bluuebunny/crossref_metadata_2025 huggingface dataset:
Sugar Allocation to Metabolic Pathways is Tightly Regulated and Affects the Virulence of Streptococcus mutans
Authors: Kawada-Matsuo Miki , Oogai Yuichi , Komatsuzawa Hitoshi
Published: December 2016

Bacteria take up and metabolize sugar as a carbohydrate source for survival. Most bacteria can utilize many sugars, including glucose, sucrose, and galactose, as well as amino sugars, such as glucosamine and N-acetylglucosamine. After entering the cytoplasm, the sugars are mainly allocated to the glycolysis pathway (energy production) and to various bacterial component biosynthesis pathways, including the cell wall, nucleic acids and amino acids. Sugars are also utilized to produce several virulence factors, such as capsule and lipoteichoic acid. Glutamine-fructose-6-phosphate aminotransferase (GlmS) and glucosamine-6-phosphate deaminase (NagB) have crucial roles in sugar distribution to the glycolysis pathway and to cell wall biosynthesis. In Streptococcus mutans, a cariogenic pathogen, the expression levels of glmS and nagB are coordinately regulated in response to the presence or absence of amino sugars. In addition, the disruption of this regulation affects the virulence of S. mutans. The expression of nagB and glmS is regulated by NagR in S. mutans, but the precise mechanism underlying glmS regulation is not clear. In Staphylococcus aureus and Bacillus subtilis, the mRNA of glmS has ribozyme activity and undergoes self-degradation at the mRNA level. However, there is no ribozyme activity region on glmS mRNA in S. mutans. In this review article, we summarize the sugar distribution, particularly the coordinated regulation of GlmS and NagB expression, and its relationship with the virulence of S. mutans.
Food and Nutrition Insecurity in Selected Rural Communities of KwaZulu-Natal, South Africa—Linking Human Nutrition and Agriculture
Authors: Govender Laurencia , Pillay Kirthee , Siwela Muthulisi , Modi Albert , Mabhaudhi Tafadzwanashe
Published: December 2016

Lack of access to nutritious and balanced diets remains a major impediment to the health and well-being of people living in rural areas. The study utilizes a qualitative systematic approach to conduct an environmental scan and review of scientific literature of studies conducted in South Africa, specifically KwaZulu-Natal (KZN). Availability and access to nutritious, diverse and balanced diets were identified as key constraints for achieving food and nutrition security as well as for human health and well-being. This has led to both under- and over-nutrition, with the former, in particular stunting, affecting children under 5 years. A high incidence of over-nutrition, both overweight and obesity, was observed among black African females. In South Africa, poor people rely mostly on social grants and cannot afford a balanced diet. Under these circumstances, agriculture could be used to increase availability and access to diverse and nutritious foods for the attainment of a balanced diet. The wider use of traditional vegetable crops and pulses could improve availability and access to healthy and locally available alternatives. The promotion of household and community food gardens, and the use of nutrient dense crops with low levels of water use, i.e., high nutritional water productivity, offers prospects for addressing malnutrition in poor rural areas.
Do Not “Let Them Eat Cake”: Correlation of Food-Consumption Patterns among Rural Primary School Children from Welfare and Non-Welfare Households
Authors: Terry Daniel , Ervin Kaye , Soutter Erin , Spiller Renata , Dalle Nogare Nicole , Hamilton Andrew
Published: December 2016

Physical and financial access impacts food choice and consumption, while educational attainment, employment, income, gender, and socioeconomic status are also influential. Within this context, the aim of the paper is to examine the association between various foods consumed and eating patterns of children between low and higher income households. A paper-based survey was completed by parents/carers of children in 41 primary schools in rural and regional areas of Victoria. Data collected included demographics and the consumption of fruit, vegetable, and other foods including drinks. Ordinal data were analysed using Spearman’s rank-order correlation. The main findings were that children who consumed more fruit and vegetables tended to have a higher intake of healthy drinks (plain milk and water) as well as a lower intake of unhealthy snacks and drinks (sugar sweetened drinks). Those who perceived that fruit and vegetables cost too much reported greater consumption of unhealthy snacks and sugar-sweetened beverages, which was more prominent in low-income households. Changing food consumption behaviours requires a complex systems-based approach that addresses more than just individual issues variables. A participatory approach that works with local communities and seeks to build an understanding of unique challenges within sub-groups has potential for embedding long-lasting and meaningful change in eating behaviours.
Stem Cells and Labeling for Spinal Cord Injury
Authors: Gazdic Marina , Volarevic Vladislav , Arsenijevic Aleksandar , Erceg Slaven , Moreno-Manzano Victoria , Arsenijevic Nebojsa , Stojkovic Miodrag
Published: December 2016

Spinal cord injury (SCI) is a devastating condition that usually results in sudden and long-lasting locomotor and sensory neuron degeneration below the lesion site. During the last two decades, the search for new therapies has been revolutionized with the improved knowledge of stem cell (SC) biology. SCs therapy offers several attractive strategies for spinal cord repair. The transplantation of SCs promotes remyelination, neurite outgrowth and axonal elongation, and activates resident or transplanted progenitor cells across the lesion cavity. However, optimized growth and differentiation protocols along with reliable safety assays should be established prior to the clinical application of SCs. Additionally, the ideal method of SCs labeling for efficient cell tracking after SCI remains a challenging issue that requires further investigation. This review summarizes the current findings on the SCs-based therapeutic strategies, and compares different SCs labeling approaches for SCI.
Metal-Free Carbon-Based Materials: Promising Electrocatalysts for Oxygen Reduction Reaction in Microbial Fuel Cells
Authors: Sawant Sandesh , Han Thi , Cho Moo
Published: December 2016

Microbial fuel cells (MFCs) are a promising green approach for wastewater treatment with the simultaneous advantage of energy production. Among the various limiting factors, the cathodic limitation, with respect to performance and cost, is one of the main obstacles to the practical applications of MFCs. Despite the high performance of platinum and other metal-based cathodes, their practical use is limited by their high cost, low stability, and environmental toxicity. Oxygen is the most favorable electron acceptor in the case of MFCs, which reduces to water through a complicated oxygen reduction reaction (ORR). Carbon-based ORR catalysts possessing high surface area and good electrical conductivity improve the ORR kinetics by lowering the cathodic overpotential. Recently, a range of carbon-based materials have attracted attention for their exceptional ORR catalytic activity and high stability. Doping the carbon texture with a heteroatom improved their ORR activity remarkably through the favorable adsorption of oxygen and weaker molecular bonding. This review provides better insight into ORR catalysis for MFCs and the properties, performance, and applicability of various metal-free carbon-based electrocatalysts in MFCs to find the most appropriate cathodic catalyst for the practical applications. The approaches for improvement, key challenges, and future opportunities in this field are also explored.
Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection
Authors: Ledet Grace , Biswas Shukla , Kumar Vidya , Graves Richard , Mitchner Demaurian , Parker Taylor , Bostanian Levon , Ghosh Sanchita , Mandal Tarun
Published: December 2016

The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrienol was incorporated into a nanoemulsion and lyophilized with lactose. Ultra performance liquid chromatography–mass spectroscopy (UPLC–MS) was used to monitor the chemical stability of GT3 over time, the particle size and ζ potential, and scanning electron microscopy (SEM) were used to study the physical stability of the nanoemulsion. Radioprotective and toxicity studies were performed in mice. The liquid formulation exhibited GT3 degradation at all storage temperatures. Lyophilization, in the presence of lactose, significantly reduced GT3 degradation. Both the liquid and lyophilized nanoemulsions had stable particle size and ζ potential when stored at 4 °C. Toxicity studies of the nanoemulsion resulted in no observable toxicity in mice at an oral dose of 600 mg/kg GT3. The nano-formulated GT3 (300 mg/kg) demonstrated enhanced survival efficacy compared to GT3 alone (200 and 400 mg/kg) in CD2F1 mice exposed to total body gamma radiation. The optimal long-term storage of formulated GT3 is as a powder at −20 °C to preserve drug and formulation integrity. Formulation of GT3 as a nanoemulsion for oral delivery as a prophylactic radioprotectant shows promise and warrants further investigation.
Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues
Authors: Al-Jazzar Ahmed , Javaheri Behzad , Prideaux Matt , Boyde Alan , Scudamore Cheryl , Cherifi Chahrazad , Hay Eric , Hopkinson Mark , Boyd Michael , Cohen-Solal Martine , Farquharson Colin , Pitsillides Andrew
Published: December 2016

Mice harbouring a dentin matrix protein 1 (Dmp1) promoter-driven human diphtheria toxin (DT) receptor (HDTR) transgene (Tg) have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT) treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT) littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2), was also found in many non-skeletal tissues in Tg mice; indicative of direct “off-target” DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.
Mobilization of Nuclear Copper by Green Tea Polyphenol Epicatechin-3-Gallate and Subsequent Prooxidant Breakage of Cellular DNA: Implications for Cancer Chemotherapy
Authors: Farhan Mohd , Oves Mohammad , Chibber Sandesh , Hadi Sheikh , Ahmad Aamir
Published: December 2016

Epidemiological as well as experimental evidence exists in support of chemopreventive and anticancer properties of green tea and its constituents. The gallocatechin, epicatechin-3-gallate is a major polyphenol present in green tea, shown responsible for these effects. Plant-derived polyphenolic compounds are established natural antioxidants which are capable of catalyzing oxidative DNA degradation of cellular DNA, alone as well as in the presence of transition metal ions, such as copper. Here we present evidence to support that, similar to various other polyphenoic compounds, epicatechin-3-gallate also causes oxidative degradation of cellular DNA. Single cell alkaline gel electrophoresis (Comet assay) was used to assess DNA breakage in lymphocytes that were exposed to various concentrations of epicatechin-3-gallate. Inhibition of DNA breakage in the presence of scavengers of reactive oxygen species (ROS) suggested involvement of ROS generation. Addition of neocuproine (a cell membrane permeable Cu(I) chelator) inhibited DNA degradation, dose-dependently, in intact lymphocytes. In contrast, bathocuproine, which does not permeate cell membrane, was observed to be ineffective. We further show that epicatechin-3-gallate degrades DNA in cell nuclei, which can also be inhibited by neocuproine, suggesting mobilization of nuclear copper in this reaction as well. Our results are indicative of ROS generation, possibly through mobilization of endogenous copper ions, and support our long-standing hypothesis of a prooxidant activity of plant-derived polyphenols as a mechanism for their documented anticancer properties.
Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer
Authors: Swets Marloes , Zaalberg Anniek , Boot Arnoud , Van Wezel Tom , Frouws Martine , Bastiaannet Esther , Gelderblom Hans , Van de Velde Cornelis , Kuppen Peter
Published: December 2016

Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03–2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13–3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated.
Brain Monitoring in Critically Neurologically Impaired Patients
Authors: Jones Salazar , Schwartzbauer Gary , Jia Xiaofeng
Published: December 2016

Assessment of neurologic injury and the evolution of severe neurologic injury is limited in comatose or critically ill patients that lack a reliable neurologic examination. For common yet severe pathologies such as the comatose state after cardiac arrest, aneurysmal subarachnoid hemorrhage (aSAH), and severe traumatic brain injury (TBI), critical medical decisions are made on the basis of the neurologic injury. Decisions regarding active intensive care management, need for neurosurgical intervention, and withdrawal of care, depend on a reliable, high-quality assessment of the true state of neurologic injury, and have traditionally relied on limited assessments such as intracranial pressure monitoring and electroencephalogram. However, even within TBI there exists a spectrum of disease that is likely not captured by such limited monitoring and thus a more directed effort towards obtaining a more robust biophysical signature of the individual patient must be undertaken. In this review, multimodal monitoring including the most promising serum markers of neuronal injury, cerebral microdialysis, brain tissue oxygenation, and pressure reactivity index to access brain microenvironment will be discussed with their utility among specific pathologies that may help determine a more complete picture of the neurologic injury state for active intensive care management and long-term outcomes. Goal-directed therapy guided by a multi-modality approach appears to be superior to standard intracranial pressure (ICP) guided therapy and should be explored further across multiple pathologies. Future directions including the application of optogenetics to evaluate brain injury and recovery and even as an adjunct monitoring modality will also be discussed.
Obatoclax, a Pan-BCL-2 Inhibitor, Targets Cyclin D1 for Degradation to Induce Antiproliferation in Human Colorectal Carcinoma Cells
Authors: Or Chi-Hung , Chang Yachu , Lin Wei-Cheng , Lee Wee-Chyan , Su Hong-Lin , Cheung Muk-Wing , Huang Chang-Po , Ho Cheesang , Chang Chia-Che
Published: December 2016

Colorectal cancer is the third most common cancer worldwide. Aberrant overexpression of antiapoptotic BCL-2 (B-cell lymphoma 2) family proteins is closely linked to tumorigenesis and poor prognosis in colorectal cancer. Obatoclax is an inhibitor targeting all antiapoptotic BCL-2 proteins. A previous study has described the antiproliferative action of obatoclax in one human colorectal cancer cell line without elucidating the underlying mechanisms. We herein reported that, in a panel of human colorectal cancer cell lines, obatoclax inhibits cell proliferation, suppresses clonogenicity, and induces G1-phase cell cycle arrest, along with cyclin D1 downregulation. Notably, ectopic cyclin D1 overexpression abrogated clonogenicity suppression but also G1-phase arrest elicited by obatoclax. Mechanistically, pre-treatment with the proteasome inhibitor MG-132 restored cyclin D1 levels in all obatoclax-treated cell lines. Cycloheximide chase analyses further revealed an evident reduction in the half-life of cyclin D1 protein by obatoclax, confirming that obatoclax downregulates cyclin D1 through induction of cyclin D1 proteasomal degradation. Lastly, threonine 286 phosphorylation of cyclin D1, which is essential for initiating cyclin D1 proteasomal degradation, was induced by obatoclax in one cell line but not others. Collectively, we reveal a novel anticancer mechanism of obatoclax by validating that obatoclax targets cyclin D1 for proteasomal degradation to downregulate cyclin D1 for inducing antiproliferation.
Contribution of Gray and White Matter Abnormalities to Cognitive Impairment in Multiple Sclerosis
Authors: Zhang Xiaofei , Zhang Fangfang , Huang Dehui , Wu Lei , Ma Lin , Liu Hua , Zhao Yujun , Yu Shengyuan , Shi Jiong
Published: December 2016

Patients with multiple sclerosis (MS) commonly exhibit cognitive impairments (CI). However, the neural mechanisms underlying CI remain unclear. The current study applied diffusion tensor imaging (DTI) and voxel-based morphometric (VBM) magnetic resonance imaging (MRI) techniques to evaluate differences in white matter (WM) integrity and gray matter (GM) volume between MS patients with CI and MS patients with cognitive preservation (CP). Neuropsychological assessment and MRI were obtained from 39 relapsing-remitting MS (RRMS) patients and 29 healthy controls (HCs). Patients were classified as CI or CP according to cognitive ability, and demographic characteristics and MRI images were compared. Compared with HCs, MS patients exhibited widespread damage in WM integrity, and GM loss in several regions. Compared with CP patients, CI patients exhibited more extensive WM impairments, particularly in the corpus callosum, cerebellar peduncle, corona radiata, optic radiation, superior longitudinal fasciculus, anterior limb of the internal capsule, and cingulate, as well as decreased GM volume in the bilateral caudate, left insula and right temporal lobe. MS patients with CI exhibited more significant structural abnormalities than those with CP. Widespread impairments of WM integrity and selective GM atrophy both appear to be associated with impaired cognition in RRMS.
Bispecific Antibodies as a Development Platform for New Concepts and Treatment Strategies
Authors: Yang Fa , Wen Weihong , Qin Weijun
Published: December 2016

With the development of molecular cloning technology and the deep understanding of antibody engineering, there are diverse bispecific antibody formats from which to choose to pursue the optimal biological activity and clinical purpose. The single-chain-based bispecific antibodies usually bridge tumor cells with immune cells and form an immunological synapse because of their relatively small size. Bispecific antibodies in the IgG format include asymmetric bispecific antibodies and homodimerized bispecific antibodies, all of which have an extended blood half-life and their own crystalline fragment (Fc)-mediated functions. Besides retargeting effector cells to the site of cancer, new applications were established for bispecific antibodies. Bispecific antibodies that can simultaneously bind to cell surface antigens and payloads are a very ideal delivery system for therapeutic use. Bispecific antibodies that can inhibit two correlated signaling molecules at the same time can be developed to overcome inherent or acquired resistance and to be more efficient angiogenesis inhibitors. Bispecific antibodies can also be used to treat hemophilia A by mimicking the function of factor VIII. Bispecific antibodies also have broad application prospects in bone disorders and infections and diseases of the central nervous system. The latest developments of the formats and application of bispecific antibodies will be reviewed. Furthermore, the challenges and perspectives are summarized in this review.
In-Depth Two-Year Study of Phenolic Profile Variability among Olive Oils from Autochthonous and Mediterranean Varieties in Morocco, as Revealed by a LC-MS Chemometric Profiling Approach
Authors: Bajoub Aadil , Medina-Rodríguez Santiago , Olmo-García Lucía , Ajal El , Monasterio Romina , Hanine Hafida , Fernández-Gutiérrez Alberto , Carrasco-Pancorbo Alegría
Published: December 2016

Olive oil phenolic fraction considerably contributes to the sensory quality and nutritional value of this foodstuff. Herein, the phenolic fraction of 203 olive oil samples extracted from fruits of four autochthonous Moroccan cultivars (“Picholine Marocaine”, “Dahbia”, “Haouzia” and “Menara”), and nine Mediterranean varieties recently introduced in Morocco (“Arbequina”, “Arbosana”, “Cornicabra”, “Frantoio”, “Hojiblanca”, “Koroneiki”, “Manzanilla”, “Picholine de Languedoc” and “Picual”), were explored over two consecutive crop seasons (2012/2013 and 2013/2014) by using liquid chromatography-mass spectrometry. A total of 32 phenolic compounds (and quinic acid), belonging to five chemical classes (secoiridoids, simple phenols, flavonoids, lignans and phenolic acids) were identified and quantified. Phenolic profiling revealed that the determined phenolic compounds showed variety-dependent levels, being, at the same time, significantly affected by the crop season. Moreover, based on the obtained phenolic composition and chemometric linear discriminant analysis, statistical models were obtained allowing a very satisfactory classification and prediction of the varietal origin of the studied oils.
Transcriptional Regulation and Transport of Terpenoid Indole Alkaloid in Catharanthus roseus: Exploration of New Research Directions
Authors: Liu Jiaqi , Cai Junjun , Wang Rui , Yang Shihai
Published: December 2016

As one of the model medicinal plants for exploration of biochemical pathways and molecular biological questions on complex metabolic pathways, Catharanthus roseus synthesizes more than 100 terpenoid indole alkaloids (TIAs) used for clinical treatment of various diseases and for new drug discovery. Given that extensive studies have revealed the major metabolic pathways and the spatial-temporal biosynthesis of TIA in C. roseus plant, little is known about subcellular and inter-cellular trafficking or long-distance transport of TIA end products or intermediates, as well as their regulation. While these transport processes are indispensable for multi-organelle, -tissue and -cell biosynthesis, storage and their functions, great efforts have been made to explore these dynamic cellular processes. Progress has been made in past decades on transcriptional regulation of TIA biosynthesis by transcription factors as either activators or repressors; recent studies also revealed several transporters involved in subcellular and inter-cellular TIA trafficking. However, many details and the regulatory network for controlling the tissue-or cell-specific biosynthesis, transport and storage of serpentine and ajmalicine in root, catharanthine in leaf and root, vindoline specifically in leaf and vinblastine and vincristine only in green leaf and their biosynthetic intermediates remain to be determined. This review is to summarize the progress made in biosynthesis, transcriptional regulation and transport of TIAs. Based on analysis of organelle, tissue and cell-type specific biosynthesis and progresses in transport and trafficking of similar natural products, the transporters that might be involved in transport of TIAs and their synthetic intermediates are discussed; according to transcriptome analysis and bioinformatic approaches, the transcription factors that might be involved in TIA biosynthesis are analyzed. Further discussion is made on a broad context of transcriptional and transport regulation in order to guide our future research.
Targeting Notch3 in Hepatocellular Carcinoma: Molecular Mechanisms and Therapeutic Perspectives
Authors: Giovannini Catia , Bolondi Luigi , Gramantieri Laura
Published: December 2016

The Notch signaling pathway is a very conserved system that controls embryonic cell fate decisions and the maintenance of adult stem cells through cell to cell communication. Accumulating evidence support the relevance of Notch signaling in different human diseases and it is one of the most commonly activated signaling pathways in cancer. This review focuses mainly on the role of Notch3 signaling in hepatocellular carcinoma and its potential therapeutic applications against this malignancy. In this regard, the crosstalk between Notch and p53 may play an important role.
Symmetries in Genetic Systems and the Concept of Geno-Logical Coding
Authors: Petoukhov Sergey , Petukhova Elena
Published: December 2016

The genetic code of amino acid sequences in proteins does not allow understanding and modeling of inherited processes such as inborn coordinated motions of living bodies, innate principles of sensory information processing, quasi-holographic properties, etc. To be able to model these phenomena, the concept of geno-logical coding, which is connected with logical functions and Boolean algebra, is put forward. The article describes basic pieces of evidence in favor of the existence of the geno-logical code, which exists in p­arallel with the known genetic code of amino acid sequences but which serves for transferring inherited processes along chains of generations. These pieces of evidence have been received due to the analysis of symmetries in structures of molecular-genetic systems. The analysis has revealed a close connection of the genetic system with dyadic groups of binary numbers and with other mathematical objects, which are related with dyadic groups: Walsh functions (which are algebraic characters of dyadic groups), bit-reversal permutations, logical holography, etc. These results provide a new approach for mathematical modeling of genetic structures, which uses known mathematical formalisms from technological fields of noise-immunity coding of information, binary analysis, logical holography, and digital devices of artificial intellect. Some opportunities for a development of algebraic-logical biology are opened.
A Systematic Review of the Role of Dysfunctional Wound Healing in the Pathogenesis and Treatment of Idiopathic Pulmonary Fibrosis
Authors: Betensley Alan , Sharif Rabab , Karamichos Dimitrios
Published: December 2016

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disorder showcasing an interaction between genetic predisposition and environmental risks. This usually involves the coaction of a mixture of cell types associated with abnormal wound healing, leading to structural distortion and loss of gas exchange function. IPF bears fatal prognosis due to respiratory failure, revealing a median survival of approximately 2 to 3 years. This review showcases the ongoing progress in understanding the complex pathophysiology of IPF and it highlights the latest potential clinical treatments. In IPF, various components of the immune system, particularly clotting cascade and shortened telomeres, are highly involved in disease pathobiology and progression. This review also illustrates two US Food and Drug Administration (FDA)-approved drugs, nintedanib (OFEV, Boehringer Ingelheim, Ingelheim am Rhein, Germany) and pirfenidone (Esbriet, Roche, Basel, Switzerland), that slow IPF progression, but unfortunately neither drug can reverse the course of the disease. Although the mechanisms underlying IPF remain poorly understood, this review unveils the past and current advances that encourage the detection of new IPF pathogenic pathways and the development of effective treatment methods for the near future.
A Comprehensive Study of Photorefractive Properties in Poly(ethylene glycol) Dimethacrylate— Ionic Liquid Composites
Authors: Ellabban Mostafa , Glavan Gašper , Klepp Jürgen , Fally Martin
Published: December 2016

A detailed investigation of the recording, as well as the readout of transmission gratings in composites of poly(ethylene glycol) dimethacrylate (PEGDMA) and ionic liquids is presented. Gratings with a period of about 5.8 micrometers were recorded using a two-wave mixing technique with a coherent laser beam of a 355-nm wavelength. A series of samples with grating thicknesses d 0 = 10 … 150 micrometers, each for two different exposure times, was prepared. The recording kinetics, as well as the post-exposure properties of the gratings were monitored by diffracting a low intensity probe beam at a wavelength of 633 nm for Bragg incidence. To obtain a complete characterization, two-beam coupling experiments were conducted to clarify the type and the strength of the recorded gratings. Finally, the diffraction efficiency was measured as a function of the readout angle at different post-exposure times. We found that, depending on the parameters, different grating types (pure phase and/or mixed) are generated, and at elevated thicknesses, strong light-induced scattering develops. The measured angular dependence of the diffraction efficiency can be fitted using a five-wave coupling theory assuming an attenuation of the gratings along the thickness. For grating thicknesses larger than 85 microns, light-induced scattering becomes increasingly important. The latter is an obstacle for recording thicker holograms, as it destroys the recording interference pattern with increasing sample depth. The obtained results are valuable in particular when considering PEGDMA-ionic liquid composites in the synthesis of advanced polymer composites for applications, such as biomaterials, conductive polymers and holographic storage materials.
Simulation-Aided Design of Tubular Polymeric Capsules for Self-Healing Concrete
Authors: Šavija Branko , Feiteira João , Araújo Maria , Chatrabhuti Sutima , Raquez Jean-Marie , Van Tittelboom Kim , Gruyaert Elke , De Belie Nele , Schlangen Erik
Published: December 2016

Polymeric capsules can have an advantage over glass capsules used up to now as proof-of-concept carriers in self-healing concrete. They allow easier processing and afford the possibility to fine tune their mechanical properties. Out of the multiple requirements for capsules used in this context, the capability of rupturing when crossed by a crack in concrete of a typical size is one of the most relevant, as without it no healing agent is released into the crack. This study assessed the fitness of five types of polymeric capsules to fulfill this requirement by using a numerical model to screen the best performing ones and verifying their fitness with experimental methods. Capsules made of a specific type of poly(methyl methacrylate) (PMMA) were considered fit for the intended application, rupturing at average crack sizes of 69 and 128 μm, respectively for a wall thickness of ~0.3 and ~0.7 mm. Thicker walls were considered unfit, as they ruptured for crack sizes much higher than 100 μm. Other types of PMMA used and polylactic acid were equally unfit for the same reason. There was overall good fitting between model output and experimental results and an elongation at break of 1.5% is recommended regarding polymers for this application.
A Novel, Energy-Aware Task Duplication-Based Scheduling Algorithm of Parallel Tasks on Clusters
Authors: Liang Aihua , Pang Yu
Published: December 2016

Increasing energy has become an important issue in high performance clusters. To balance the energy and performance, we proposed a novel, energy-aware duplication-based scheduling (NEADS). An existing energy-aware duplication-based algorithm replicates all qualified predecessor tasks in a bottom-up manner. Some tasks without direct relation may be replicated to the same processor, which cannot reduce the communication energy. Instead, the computation overhead may be increased. In contrast, the proposed algorithm only replicates the directly correlated predecessor tasks in the energy threshold range without lengthening the schedule length. The proposed algorithm is compared with the non-duplication algorithm and existing duplicated-based algorithm. Extensive experimental results show that the proposed algorithm can effectively reduce energy consumption in various applications. It has advantages over other algorithms on computation-intensive applications.
Novel Peptide with Specific Calcium-Binding Capacity from Schizochytrium sp. Protein Hydrolysates and Calcium Bioavailability in Caco-2 Cells
Authors: Cai Xixi , Lin Jiaping , Wang Shaoyun
Published: December 2016

Peptide-calcium can probably be a suitable supplement to improve calcium absorption in the human body. In this study, a specific peptide Phe-Tyr (FY) with calcium-binding capacity was purified from Schizochytrium sp. protein hydrolysates through gel filtration chromatography and reversed phase HPLC. The calcium-binding capacity of FY reached 128.77 ± 2.57 μg/mg. Results of ultraviolet spectroscopy, fluorescence spectroscopy, and infrared spectroscopy showed that carboxyl groups, amino groups, and amido groups were the major chelating sites. FY-Ca exhibited excellent thermal stability and solubility, which were beneficial to be absorbed and transported in the basic intestinal tract of the human body. Moreover, the calcium bioavailability in Caco-2 cells showed that FY-Ca could enhance calcium uptake efficiency by more than three times when compared with CaCl2, and protect calcium ions against dietary inhibitors, such as tannic acid, oxalate, phytate, and Zn2+. Our findings further the progress of algae-based peptide-calcium, suggesting that FY-Ca has the potential to be developed as functionally nutraceutical additives.
Concentration of Tea Extracts by Osmotic Evaporation: Optimisation of Process Parameters and Effect on Antioxidant Activity
Authors: Marques Marisa , Alves Vítor , Coelhoso Isabel
Published: December 2016

In this work, the concentration process of three different tea extracts (medicinal Rosil No. 6, Black, and Forest Fruit teas) using the osmotic evaporation (OE) process, was studied. The effect of the OE process on the content of phenolic compounds and antioxidant activity was evaluated. The concentration process was carried out in a hollow-fibre membrane contactor with an effective surface area of 0.54 m2. The tea extract was circulated through the shell side of the contactor, while a concentrated osmotic solution (CaCl2 5 M) was circulated inside the fibres. The flux, the driving force, and the mass transfer coefficient were evaluated. A decrease of the water flux over time was observed and was attributed only to the decrease of the driving force, caused by the dilution of the osmotic solution. Using a surface area/feed volume ratio of 774 m2·m−3, it is possible to reach a tea concentration of 40% (w/w) in 5 h, with a constant water flux and without losing the phenolic content and antioxidant potential in most teas.
Application of Lectin Array Technology for Biobetter Characterization: Its Correlation with FcγRIII Binding and ADCC
Authors: Roucka Markus , Zimmermann Klaus , Fido Markus , Nechansky Andreas
Published: December 2016

Lectin microarray technology was applied to compare the glycosylation pattern of the monoclonal antibody MB311 expressed in SP2.0 cells to an antibody-dependent cellular cytotoxic effector function (ADCC)-optimized variant (MB314). MB314 was generated by a plant expression system that uses genetically modified moss protoplasts (Physcomitrella patens) to generate a de-fucosylated version of MB311. In contrast to MB311, no or very low interactions of MB314 with lectins Aspergillus oryzae l-fucose (AOL), Pisum sativum agglutinin (PSA), Lens culinaris agglutinin (LCA), and Aleuria aurantia lectin (AAL) were observed. These lectins are specific for mono-/biantennary N-glycans containing a core fucose residue. Importantly, this fucose indicative lectin-binding pattern correlated with increased MB314 binding to CD16 (FcγRIII; receptor for the constant region of an antibody)—whose affinity is mediated through core fucosylation—and stronger ADCC. In summary, these results demonstrate that lectin microarrays are useful orthogonal methods during antibody development and for characterization.
Quality Evaluation of Pseudostellariae Radix Based on Simultaneous Determination of Multiple Bioactive Components Combined with Grey Relational Analysis
Authors: Hua Yujiao , Wang Shengnan , Chai Chuan , Liu Zixiu , Liu Xunhong , Zou Lisi , Wu Qinan , Zhao Hui , Ying Yan
Published: December 2016

Pseudostellariae Radix (PR) is an important traditional Chinese herbal medicine (TCM) with vast clinical consumption because of its positive effects. However, little attention has been devoted to simultaneous analysis of its bioactive components for quality control of PR based on its different harvesting times, different growing habitats, and different processing methods. In this research, the quality of PR was evaluated based on simultaneous determination of multiple bioactive components combined with grey relational analysis (GRA). A reliable method based on ultra-fast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-QTRAP-MS/MS) was established to simultaneously determine the contents of 30 components in PR, including two cyclopeptides, 12 nucleosides, and 16 amino acids. Furthermore, grey relational analysis was performed to evaluate the quality of PR samples according to the contents of these 30 components. The results showed that the quality of PR harvested in 6 August 2013, cultivated in Jurong, Jiangsu, and treated by oven drying 60 °C was better than that of other PR samples. The proposed method is useful for the overall assessment on the quality of PR, and this study provides valuable information for revealing the dynamic change laws of metabolite accumulation in PR and choosing the most suitable harvesting time and reasonable processing method of PR to obtain the best quality.
Meadowsweet Teas as New Functional Beverages: Comparative Analysis of Nutrients, Phytochemicals and Biological Effects of Four Filipendula Species
Authors: Olennikov Daniil , Kashchenko Nina , Chirikova Nadezhda
Published: December 2016

In recent years, the increased popularity of functional beverages such as herbal teas and decoctions has led to the search for new sources of raw materials that provide appropriate taste and functionality to consumers. The objective of this study was to investigate the nutritional, phytochemical profiles and bioactivities of possible functional beverages produced from F. ulmaria and its alternative substitutes (F. camtschatica, F. denudata, F. stepposa). The investigated decoctions were analyzed regarding their macronutrient, carbohydrate, organic acid, amino acid and mineral composition. Quantification of the main phenolic compounds in the decoctions of meadowsweet floral teas was performed by a microcolumn RP-HPLC-UV procedure; the highest content was revealed in F. stepposa tea. The investigation of the essential oil of four meadowsweet teas revealed the presence of 28 compounds, including simple phenols, monoterpenes, sesquiterpenes and aliphatic components. The dominance of methyl salicylate and salicylaldehyde was noted in all samples. Studies on the water soluble polysaccharides of Filipendula flowers allowed us to establish their general affiliation to galactans and/or arabinogalactans with an admixture of glucans of the starch type and galacturonans as minor components. The bioactivity data demonstrated a good ability of meadowsweet teas to inhibit amylase, α-glucosidase and AGE formation. Tea samples showed antioxidant properties by the DPPH•, ABTS•+ and Br• free radicals scavenging assays and the carotene bleaching assay, caused by the presence of highly active ellagitannins. The anti-complement activity of the water-soluble polysaccharide fraction of meadowsweet teas indicated their possible immune-modulating properties. Filipendula beverage formulations can be expected to deliver beneficial effects due to their unique nutritional and phytochemical profiles. Potential applications as health-promoting functional products may be suggested.
Time-Resolved Fluorescence Spectroscopy and Fluorescence Lifetime Imaging Microscopy for Characterization of Dendritic Polymer Nanoparticles and Applications in Nanomedicine
Authors: Boreham Alexander , Brodwolf Robert , Walker Karolina , Haag Rainer , Alexiev Ulrike
Published: December 2016

The emerging field of nanomedicine provides new approaches for the diagnosis and treatment of diseases, for symptom relief and for monitoring of disease progression. One route of realizing this approach is through carefully constructed nanoparticles. Due to the small size inherent to the nanoparticles a proper characterization is not trivial. This review highlights the application of time-resolved fluorescence spectroscopy and fluorescence lifetime imaging microscopy (FLIM) for the analysis of nanoparticles, covering aspects ranging from molecular properties to particle detection in tissue samples. The latter technique is particularly important as FLIM allows for distinguishing of target molecules from the autofluorescent background and, due to the environmental sensitivity of the fluorescence lifetime, also offers insights into the local environment of the nanoparticle or its interactions with other biomolecules. Thus, these techniques offer highly suitable tools in the fields of particle development, such as organic chemistry, and in the fields of particle application, such as in experimental dermatology or pharmaceutical research.
Activity of Zearalenone in the Porcine Intestinal Tract
Authors: Gajęcka Magdalena , Zielonka Łukasz , Gajęcki Maciej
Published: December 2016

This study demonstrates that low doses (somewhat above the No Observed Adverse Effect Level, NOAEL) of the mycoestrogen zearalenone (ZEN) and its metabolites display multispecificity towards various biological targets in gilts. The observed responses in gilts were surprising. The presence of ZEN and zearalenols (ZELs) did not evoke a response in the porcine gastrointestinal tract, which was attributed to dietary tolerance. Lymphocyte proliferation was intensified in jejunal mesenteric lymph nodes, and lymphocyte counts increased in the jejunal epithelium with time of exposure. In the distal digestive tract, fecal bacterial counts decreased, the activity of fecal bacterial enzymes and lactic acid bacteria increased, and cecal water was characterized by higher genotoxicity. The accompanying hyperestrogenism led to changes in mRNA activity of selected enzymes (cytochrome P450, hydroxysteroid dehydrogenases, nitric oxide synthases) and receptors (estrogen and progesterone receptors), and it stimulated post-translational modifications which play an important role in non-genomic mechanisms of signal transmission. Hyperestrogenism influences the regulation of the host’s steroid hormones (estron, estradiol and progesteron), it affects the virulence of bacterial genes encoding bacterial hydroxysteroid dehydrogenases (HSDs), and it participates in detoxification processes by slowing down intestinal activity, provoking energy deficits and promoting antiporter activity at the level of enterocytes. In most cases, hyperestrogenism fulfils all of the above roles. The results of this study indicate that low doses of ZEN alleviate inflammatory processes in the digestive system, in particular in the proximal and distal intestinal tract, and increase body weight gains in gilts.
Glycosaminoglycans and Their Mimetics
Authors: Ferro Vito
Published: December 2016

Glycosaminoglycans (GAGs) are linear, polyanionic polysaccharides that are ubiquitous on the mammalian cell surface and in the extracellular matrix and are generally found attached to a protein core as part of a proteoglycan.[...]
Rate of Homologous Desensitization and Internalization of the GLP-1 Receptor
Authors: Shaaban Ghina , Oriowo Mabayoje , Al-Sabah Suleiman
Published: December 2016

The glucagon-like peptide-1 receptor (GLP-1R) is an important target in the treatment of type 2 diabetes mellitus. The aim of this study was to compare the rate of agonist stimulated desensitization and internalization of GLP-1R. To this end, an N-terminally myc-tagged GLP-1R was stably expressed in HEK-293 cells. Homologous desensitization was assessed by measuring the cAMP response to agonist stimulation following pre-incubation with agonist for up to 120 min. Receptor internalization was monitored using an indirect ELISA-based method and confocal microscopy. Pre-incubation with GLP-1 resulted in a time-dependent loss of response to a second stimulation. Washing cells following pre-incubation failed to bring cAMP levels back to basal. Taking this into account, two desensitization rates were calculated: “apparent” (t1/2 = 19.27 min) and “net” (t1/2 = 2.99 min). Incubation of cells with GLP-1 also resulted in a time-dependent loss of receptor cell surface expression (t1/2 = 2.05 min). Rapid agonist-stimulated internalization of GLP-1R was confirmed using confocal microscopy. Stimulation of GLP-1R with GLP-1 results in rapid desensitization and internalization of the receptor. Interestingly, the rate of “net” desensitization closely matches the rate of internalization. Our results suggest that agonist-bound GLP-1R continues to generate cAMP after it has been internalized.