bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria
Authors: Solverson Patrick , Murali Sangita G. , Brinkman Adam S. , Nelson David W. , Clayton Murray K. , Yen Chi-Liang Eric , Ney Denise M.
Published: February 2012

Phenylketonuria (PKU) is caused by a mutation in the phenylalanine (phe) hydroxylase gene and requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to AA formula. Our objective was to compare growth, body composition, and energy balance in Pahenu2 (PKU) and wild-type mice fed low-phe GMP, low-phe AA, or high-phe casein diets from 3–23 wk of age. The 2 × 2 × 3 design included main effects of genotype, sex, and diet. Fat and lean mass were assessed by dual-energy X-ray absorptiometry, and acute energy balance was assessed by indirect calorimetry. PKU mice showed growth and lean mass similar to wild-type littermates fed the GMP or AA diets; however, they exhibited a 3–15% increase in energy expenditure, as reflected in oxygen consumption, and a 3–30% increase in food intake. The GMP diet significantly reduced energy expenditure, food intake, and plasma phe concentration in PKU mice compared with the casein diet. The high-phe casein diet or the low-phe AA diet induced metabolic stress in PKU mice, as reflected in increased energy expenditure and intake of food and water, increased renal and spleen mass, and elevated plasma cytokine concentrations consistent with systemic inflammation. The low-phe GMP diet significantly attenuated these adverse effects. Moreover, total fat mass, %body fat, and the respiratory exchange ratio (CO2 produced/O2 consumed) were significantly lower in PKU mice fed GMP compared with AA diets. In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice.
Treatment with a sphingosine-1-phosphate analog inhibits airway remodeling following repeated allergen exposure
Authors: Karmouty-Quintana Harry , Siddiqui Sana , Hassan Muhannad , Tsuchiya Kimitake , Risse Paul-Andre , Xicota-Vila Laura , Marti-Solano Maria , Martin James G.
Published: January 2012

Sphingosine-1-phosphate (S1P) is an immunomodulatory lipid mediator that plays an important role in lymphocyte trafficking. Elevated levels of S1P are found in bronchoalveolar lavage (BAL) fluid of patients with asthma; however, its role in disease is not known. FTY720, a synthetic analog of S1P, has been shown to abrogate allergic inflammation and airway hyperresponsiveness following acute allergen challenge. However, its effects on asthmatic airway remodeling induced by repeated allergen exposure are unknown. Ovalbumin (OVA)-sensitized rats were challenged on days 14, 19, and 24 after sensitization. FTY720 or vehicle (PBS) therapy was administered 1 h prior to each challenge. BAL fluid and quantitative histological analysis were performed 48 h after the last challenge. FTY720 inhibited OVA-induced features of airway remodeling including increased airway smooth muscle mass and bronchial neovascularization, without affecting lymphocyte numbers in secondary lymphoid organs. Furthermore, CD3+ cells adjacent to airway smooth muscle bundles were increased in OVA-challenged rats but the increase was inhibited by FTY720. There was an expansion of bronchus-associated lymphoid tissue following FTY720 treatment of OVA-challenged animals. Real-time quantitative PCR revealed that Th2-associated transcription factors were inhibited following FTY720 therapy. Airway remodeling is a cardinal feature of severe asthma. These results demonstrate that allergen-driven airway remodeling can be inhibited by FTY720, offering potential new therapies for the treatment of severe asthma.
Rho kinase signaling pathways during stretch in primary alveolar epithelia
Authors: DiPaolo Brian C. , Margulies Susan S.
Published: January 2012

Alveolar epithelial cells (AECs) maintain integrity of the blood-gas barrier with actin-anchored intercellular tight junctions. Stretched type I-like AECs undergo magnitude- and frequency-dependent actin cytoskeletal remodeling into perijunctional actin rings. On the basis of published studies in human pulmonary artery endothelial cells (HPAECs), we hypothesize that RhoA activity, Rho kinase (ROCK) activity, and phosphorylation of myosin light chain II (MLC2) increase in stretched type I-like AECs in a manner that is dependent on stretch magnitude, and that RhoA, ROCK, or MLC2 activity inhibition will attenuate stretch-induced actin remodeling and preserve barrier properties. Primary type I-like AEC monolayers were stretched biaxially to create a change in surface area (ΔSA) of 12%, 25%, or 37% in a cyclic manner at 0.25 Hz for up to 60 min or left unstretched. Type I-like AECs were also treated with Rho pathway inhibitors (ML-7, Y-27632, or blebbistatin) and stained for F-actin or treated with the myosin phosphatase inhibitor calyculin-A and quantified for monolayer permeability. Counter to our hypothesis, ROCK activity and MLC2 phosphorylation decreased in type I-like AECs stretched to 25% and 37% ΔSA and did not change in monolayers stretched to 12% ΔSA. Furthermore, RhoA activity decreased in type I-like AECs stretched to 37% ΔSA. In contrast, MLC2 phosphorylation in HPAECs increased when HPAECs were stretched to 12% ΔSA but then decreased when they were stretched to 37% ΔSA, similar to type I-like AECs. Perijunctional actin rings were observed in unstretched type I-like AECs treated with the Rho pathway inhibitor blebbistatin. Myosin phosphatase inhibition increased MLC2 phosphorylation in stretched type I-like AECs but had no effect on monolayer permeability. In summary, stretch alters RhoA activity, ROCK activity, and MLC2 phosphorylation in a manner dependent on stretch magnitude and cell type.
Vasculoprotective effects of heme oxygenase-1 in a murine model of hyperoxia-induced bronchopulmonary dysplasia
Authors: Fernandez-Gonzalez Angeles , Alex Mitsialis S. , Liu Xianlan , Kourembanas Stella
Published: January 2012

Bronchopulmonary dysplasia (BPD) is characterized by simplified alveolarization and arrested vascular development of the lung with associated evidence of endothelial dysfunction, inflammation, increased oxidative damage, and iron deposition. Heme oxygenase-1 (HO-1) has been reported to be protective in the pathogenesis of diseases of inflammatory and oxidative etiology. Because HO-1 is involved in the response to oxidative stress produced by hyperoxia and is critical for cellular heme and iron homeostasis, it could play a protective role in BPD. Therefore, we investigated the effect of HO-1 in hyperoxia-induced lung injury using a neonatal transgenic mouse model with constitutive lung-specific HO-1 overexpression. Hyperoxia triggered an increase in pulmonary inflammation, arterial remodeling, and right ventricular hypertrophy that was attenuated by HO-1 overexpression. In addition, hyperoxia led to pulmonary edema, hemosiderosis, and a decrease in blood vessel number, all of which were markedly improved in HO-1 overexpressing mice. The protective vascular response may be mediated at least in part by carbon monoxide, due to its anti-inflammatory, antiproliferative, and antiapoptotic properties. HO-1 overexpression, however, did not prevent alveolar simplification nor altered the levels of ferritin and lactoferrin, proteins involved in iron binding and transport. Thus the protective mechanisms elicited by HO-1 overexpression primarily preserve vascular growth and barrier function through iron-independent, antioxidant, and anti-inflammatory pathways.
A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury
Authors: Liang Jiurong , Jung Yoosun , Tighe Robert M. , Xie Ting , Liu Ningshan , Leonard Maura , Gunn Michael Dee , Jiang Dianhua , Noble Paul W.
Published: January 2012

CC chemokine ligand-2 (CCL2)/monocyte chemoattractant protein (MCP)-1 expression is upregulated during pulmonary inflammation, and the CCL2-CCR2 axis plays a critical role in leukocyte recruitment and promotion of host defense against infection. The role of CCL2 in mediating macrophage subpopulations in the pathobiology of noninfectious lung injury is unknown. The goal of this study was to examine the role of CCL2 in noninfectious acute lung injury. Our results show that lung-specific overexpression of CCL2 protected mice from bleomycin-induced lung injury, characterized by significantly reduced mortality, reduced neutrophil accumulation, and decreased accumulation of the inflammatory mediators IL-6, CXCL2 (macrophage inflammatory protein-2), and CXCL1 (keratinocyte-derived chemokine). There were dramatic increases in the recruitment of myosin heavy chain (MHC) II IA/IEintCD11cintcells, exudative macrophages, and dendritic cells in Ccl2 transgenic mouse lungs both at baseline and after bleomycin treatment compared with levels in wild-type mice. We further demonstrated that MHCII IA/IEintCD11cintcells engulfed apoptotic cells during acute lung injury. Our data suggested a previously undiscovered role for MHCII IA/IEintCD11cintcells in apoptotic cell clearance and inflammation resolution.
Prostaglandins mediate the fetal pulmonary response to intrauterine inflammation
Authors: Westover Alana J. , Hooper Stuart B. , Wallace Megan J. , Moss Timothy J. M.
Published: January 2012

Intra-amniotic (IA) lipopolysaccharide (LPS) induces intrauterine and fetal lung inflammation and increases lung surfactant and compliance in preterm sheep; however, the mechanisms are unknown. Prostaglandins (PGs) are inflammatory mediators, and PGE2 has established roles in fetal lung surfactant production. The aim of our first study was to determine PGE2 concentrations in response to IA LPS and pulmonary gene expression for PG synthetic [prostaglandin H synthase-2 (PGHS-2) and PGE synthase (PGES)] and PG-metabolizing [prostaglandin dehydrogenase (PGDH)] enzymes and PGE2 receptors. Our second study aimed to block LPS-induced increases in PGE2 with a PGHS-2 inhibitor (nimesulide) and determine lung inflammation and surfactant protein mRNA expression. Pregnant ewes received an IA saline or LPS injection at 118 days of gestation. In study 1, fetal plasma and amniotic fluid were sampled before and at 2, 4, 6, 12, and 24 h after injection and then daily, and fetuses were delivered 2 or 7 days later. Amniotic fluid PGE2 concentrations increased ( P < 0.05) 12 h and 3–6 days after LPS. Fetal lung PGHS-2 mRNA and PGES mRNA increased 2 ( P = 0.0084) and 7 ( P = 0.014) days after LPS, respectively. In study 2, maternal intravenous nimesulide or vehicle infusion began immediately before LPS or saline injection and continued until delivery 2 days later. Nimesulide inhibited LPS-induced increases in PGE2 and decreased fetal lung IL-1β and IL-8 mRNA ( P ≤ 0.002) without altering lung inflammatory cell infiltration. Nimesulide decreased surfactant protein (SP)-A ( P = 0.05), -B ( P = 0.05), and -D ( P = 0.0015) but increased SP-C mRNA ( P = 0.023). Thus PGHS-2 mediates, at least in part, fetal pulmonary responses to inflammation.
Inhibitory effects of theophylline on the peroxynitrite-augmented release of matrix metalloproteinases by lung fibroblasts
Authors: Sugiura Hisatoshi , Kawabata Hiroki , Ichikawa Tomohiro , Koarai Akira , Yanagisawa Satoru , Kikuchi Takashi , Minakata Yoshiaki , Matsunaga Kazuto , Nakanishi Masanori , Hirano Tsunahiko , Akamatsu Keiichiro , Furukawa Kanako , Ichinose Masakazu
Published: January 2012

The anti-inflammatory effects of theophylline have been reported to include inhibition of the release of proinflammatory mediators from macrophages and neutrophils. Overproduction of reactive nitrogen species (RNS) has been reported in the airways of patients with chronic obstructive pulmonary disease (COPD), and this causes tissue inflammation and injury. We investigated whether peroxynitrite stimulated the release of matrix metalloproteinases 2 and 9 (MMP-2 and -9; gelatinases) from human fetal lung fibroblasts (HFL-1 cell line) and whether theophylline inhibited the peroxynitrite-augmented release of MMPs. HFL-1 cells and primary lung fibroblasts were treated with peroxynitrite (an RNS), and gelatinases levels were evaluated by gelatin zymography. The inhibitory effect of theophylline on the peroxynitrite-augmented release of MMP-2 and MMP-9 was also investigated. To explore the cell signaling pathways involved in the peroxynitrite-induced gelatinases release and the inhibitory effect of theophylline, transforming growth factor-β1(TGF-β1), nuclear factor-κB (NF-κB), and histone deacetylase (HDAC) were measured. Peroxynitrite significantly augmented the release of MMP-2 and MMP-9 by fibroblasts ( P < 0.01), as well as TGF-β1release ( P < 0.01), NF-κB activation ( P < 0.01), and HDAC2 inactivation ( P < 0.01). An NF-κB inhibitor diminished the RNS-augmented release of MMPs and TGF-β1( P < 0.01), and a neutralizing TGF-β antibody also diminished MMP release ( P < 0.01). Theophylline significantly inhibited the peroxynitrite-augmented release of MMP-2 and MMP-9 in HFL-1 cells and normal adult lung fibroblasts, and it also inhibited the peroxynitrite-mediated HDAC2 inactivation, NF-κB activation, and TGF-β1release in HFL-1 cells (all P < 0.01). These results suggest that peroxynitrite can influence tissue remodeling by promoting gelatinases release, while theophylline suppresses peroxynitrite-induced tissue remodeling via pathways involving NF-κB/TGF-β1and/or HDAC in the HFL-1 cell line.
Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis
Authors: Tanjore Harikrishna , Blackwell Timothy S. , Lawson William E.
Published: January 2012

While the factors that regulate the onset and progression of idiopathic pulmonary fibrosis (IPF) are incompletely understood, recent investigations have revealed that endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are prominent in alveolar epithelial cells in this disease. Initial observations linking ER stress and IPF were made in cases of familial interstitial pneumonia (FIP), the familial form of IPF, in a family with a mutation in surfactant protein C ( SFTPC). Subsequent studies involving lung biopsy specimens revealed that ER stress markers are highly expressed in the alveolar epithelium in IPF and FIP. Recent mouse modeling has revealed that induction of ER stress in the alveolar epithelium predisposed to enhanced lung fibrosis after treatment with bleomycin, which is mediated at least in part by increased alveolar epithelial cell (AEC) apoptosis. Emerging data also indicate that ER stress in AECs could impact fibrotic remodeling by altering inflammatory responses and inducing epithelial-mesenchymal transition. Although the cause of ER stress in IPF remains unknown, common environmental exposures such as herpesviruses, inhaled particulates, and cigarette smoke induce ER stress and are candidates for contributing to AEC dysfunction by this mechanism. Together, investigations to date suggest that ER stress predisposes to AEC dysfunction and subsequent lung fibrosis. However, many questions remain regarding the role of ER stress in initiation and progression of lung fibrosis, including whether ER stress or the UPR could be targeted for therapeutic benefit.
Endocytosis and Signaling: Cell Logistics Shape the Eukaryotic Cell Plan
Authors: Sigismund Sara , Confalonieri Stefano , Ciliberto Andrea , Polo Simona , Scita Giorgio , Di Fiore Pier Paolo
Published: February 2012

Our understanding of endocytosis has evolved remarkably in little more than a decade. This is the result not only of advances in our knowledge of its molecular and biological workings, but also of a true paradigm shift in our understanding of what really constitutes endocytosis and of its role in homeostasis. Although endocytosis was initially discovered and studied as a relatively simple process to transport molecules across the plasma membrane, it was subsequently found to be inextricably linked with almost all aspects of cellular signaling. This led to the notion that endocytosis is actually the master organizer of cellular signaling, providing the cell with understandable messages that have been resolved in space and time. In essence, endocytosis provides the communications and supply routes (the logistics) of the cell. Although this may seem revolutionary, it is still likely to be only a small part of the entire story. A wealth of new evidence is uncovering the surprisingly pervasive nature of endocytosis in essentially all aspects of cellular regulation. In addition, many newly discovered functions of endocytic proteins are not immediately interpretable within the classical view of endocytosis. A possible framework, to rationalize all this new knowledge, requires us to “upgrade” our vision of endocytosis. By combining the analysis of biochemical, biological, and evolutionary evidence, we propose herein that endocytosis constitutes one of the major enabling conditions that in the history of life permitted the development of a higher level of organization, leading to the actuation of the eukaryotic cell plan.
Fast Synaptic Inhibition in Spinal Sensory Processing and Pain Control
Authors: Zeilhofer Hanns Ulrich , Wildner Hendrik , Yévenes Gonzalo E.
Published: February 2012

The two amino acids GABA and glycine mediate fast inhibitory neurotransmission in different CNS areas and serve pivotal roles in the spinal sensory processing. Under healthy conditions, they limit the excitability of spinal terminals of primary sensory nerve fibers and of intrinsic dorsal horn neurons through pre- and postsynaptic mechanisms, and thereby facilitate the spatial and temporal discrimination of sensory stimuli. Removal of fast inhibition not only reduces the fidelity of normal sensory processing but also provokes symptoms very much reminiscent of pathological and chronic pain syndromes. This review summarizes our knowledge of the molecular bases of spinal inhibitory neurotransmission and its organization in dorsal horn sensory circuits. Particular emphasis is placed on the role and mechanisms of spinal inhibitory malfunction in inflammatory and neuropathic chronic pain syndromes.
Spectral Analysis of the Svalbard Temperature Record 1912–2010
Authors: Humlum Ole , Solheim Jan-Erik , Stordahl Kjell
Published: January 2012

Climate development with possible anthropogenic effects occurs on a background of natural climatic variations, which may be considerable, and especially in the Arctic. Natural climate variations however remain poorly understood, although they remain important for discriminating between natural and anthropogenic influences on current climate change. Using the Svalbard (78°N) surface air temperature record 1912–2010 as an example, we here suggest a road ahead to identify and describe such natural climate variations. By means of Fourier and wavelet analysis the record is decomposed into time-frequency space, to extract information on periodic signals and their amplitude and variation over time. By this we identify several cyclic variations on the time scale investigated. These oscillations are present in the annual record, as well as in seasonal subsets of the record. Using only three oscillations it is possible to hindcast the Svalbard temperature record well. We suggest that such persistent oscillations may be used for forecasting the overall features of future temperature changes for a limited period, about 10–25% of the record length. Our main focus is on identifying the character of recurrent natural temperature variations, but we also comment briefly on possible physical explanations for some of the identified cyclic variations.
Neuropathy Dermatitis following Surgical Nerve Injury
Authors: Sharquie Khalifa E. , Noaimi Adil A. , Alaboudi Ali S.
Published: January 2012

Background. Cutting nerve during operations like saphenous vein grafting and knee joint surgery are common surgical procedures.Objective. To report cases of dermatitis at the site of neuropathy following skin incision for saphenous vein grafting and knee joint surgery.Patients and Methods. This case report work was done in the Department of Dermatology, Baghdad Teaching Hospital, during 2009-2010, seven cases were recorded, six following saphenous vein grafting and one case after knee surgery. Five males and two females, their ages ranged from 50 to 66 (58 ± 5.033223) years. Detailed history and full clinical examination were done for each patient regarding all points related to their conditions.Results. All cases presented around 2-3 months following the operation with dermatitis at the site of operational incision. The dermatitis appeared on one side of the operational scar and at area of neuropathy, and the rash did not cross to contralateral side. The dermatitis was well-defined plaque or patch erythematous slight scaly and nonitchy and subsided within few weeks with or without topical therapy.Conclusions. Neuropathy dermatitis is apparently a new variant of dermatitis that follows nerve cut during surgery.
A Noncommutative Enumeration Problem
Authors: Bernabei Maria Simonetta , Thaler Horst
Published: January 2012

We tackle the combinatorics of coloured hard-dimer objects. This is achieved by identifying coloured hard-dimer configurations with a certain class of rooted trees that allow for an algebraic treatment in terms of noncommutative formal power series. A representation in terms of matrices then allows to find the asymptotic behaviour of these objects.
Influenza Vaccination in the Face of Immune Exhaustion: Is Herd Immunity Effective for Protecting the Elderly?
Authors: Lang Pierre Olivier , Samaras Dimitrios , Samaras Nikolaos , Govind Sheila , Aspinall Richard
Published: January 2012

At the start of the 21st century, seasonal influenza virus infection is still a major public health concern across the world. The recent body of evidence confirms that trivalent inactivated influenza vaccines (TIVs) are not optimal within the population who account for approximately 90% of all influenza-related death: elderly and chronically ill individuals regardless of age. With the ever increasing aging of the world population and the recent fears of any pandemic influenza rife, great efforts and resources have been dedicated to developing more immunogenic vaccines and strategies for enhancing protection in these higher-risk groups. This paper describes the mechanisms that shape immune response at the extreme ages of life and how they have been taken into account to design more effective immunization strategies for these vulnerable populations. Furthermore, consideration will be given to how herd immunity may provide an effective strategy in preventing the burden of seasonal influenza infection within the aged population.
Queueing Maximal Covering Location-Allocation Problem: An Extension with M/G/1 Queueing Systems
Authors: Moghadas Foroogh Moeen , Kakhki Hossein Taghizadeh
Published: January 2012

We consider the queueing maximal covering location-allocation problem (QM-CLAP) with an M/G/1 queueing system. We first formulate the problem as a binary quadratic programming problem and then propose a new solution procedure based on decomposition of the problem into smaller binary quadratic sub-problems. The heuristic procedure GRASP is used to solve the sub-problems, as well as the entire model. Some computational results are also presented.
Successful Utilization of High-Flux Hemodialysis for Treatment of Vancomycin Toxicity in a Child
Authors: Stidham Timothy , Reiter Pamela D. , Ford Douglas M. , Lum Gary M. , Albietz Joseph
Published: January 2012

Vancomycin is routinely used for empiric antibiotic therapy in children. Higher-serum-concentration targets for serious infections are now being recommended. This recommendation may result in aggressive dosing with increased potential for toxicity. We report a case of a pediatric patient who developed vancomycin toxicity and associated oliguric renal failure who was treated effectively with high-flux hemodialysis for vancomycin toxicity, clearing serum concentrations of vancomycin by over 75% in only 6 hours (213.2 mcg/mL to 51.8 mcg/mL) with subsequent return to baseline renal function and without adverse sequelae. While not historically considered a viable option for drug removal in cases of toxicity, new high-flux hemodialysis techniques can remove significant percentages of vancomycin in short periods of time.
Peptides Derived fromMycobacterium lepraeML1601c Discriminate between Leprosy Patients and Healthy Endemic Controls
Authors: Bobosha Kidist , van der Ploeg-van Schip Jolien J. , Esquenazi Danuza A. , Guimarães Marjorie M. , Martins Marcia V. , Bekele Yonas , Fantahun Yonas , Aseffa Abraham , Franken Kees L. M. C. , Gismondi Ronaldo C. , Pessolani Maria C. V. , Ottenhoff Tom H. M. , Pereira Geraldo M. B. , Geluk Annemieke
Published: January 2012

The stable incidence of new leprosy cases suggests that transmission of infection continues despite worldwide implementation of MDT. Thus, specific tools are needed to diagnose early stageMycobacterium lepraeinfection, the likely sources of transmission.M. lepraeantigens that induce T-cell responses inM. lepraeexposed and/or infected individuals thus are major targets for new diagnostic tools. Previously, we showed that ML1601c was immunogenic in patients and healthy household contacts (HHC). However, some endemic controls (EC) also recognized this protein. To improve the diagnostic potential, IFN-γresponses to ML1601c peptides were assessed using PBMC from Brazilian leprosy patients and EC. Five ML1601c peptides only induced IFN-γin patients and HHC. Moreover, 24-hour whole-blood assay (WBA), two ML1601c peptides could assess the level ofM. lepraeexposure in Ethiopian EC. Beside IFN-γ, also IP-10, IL-6, IL-1β, TNF-α, and MCP-1 were increased in EC from areas with high leprosy prevalence in response to these ML1601c peptides. Thus, ML1601c peptides may be useful for differentiatingM. lepraeexposed or infected individuals and can also be used to indicate the magnitude ofM. lepraetransmission even in the context of various HLA alleles as present in these different genetic backgrounds.
Daphnia as an Emerging Epigenetic Model Organism
Authors: Harris Kami D. M. , Bartlett Nicholas J. , Lloyd Vett K.
Published: January 2012

Daphniaoffer a variety of benefits for the study of epigenetics.Daphnia’sparthenogenetic life cycle allows the study of epigenetic effects in the absence of confounding genetic differences. Sex determination and sexual reproduction are epigenetically determined as are several other well-studied alternate phenotypes that arise in response to environmental stressors. Additionally, there is a large body of ecological literature available, recently complemented by the genome sequence of one species and transgenic technology. DNA methylation has been shown to be altered in response to toxicants and heavy metals, although investigation of other epigenetic mechanisms is only beginning. More thorough studies on DNA methylation as well as investigation of histone modifications and RNAi in sex determination and predator-induced defenses using this ecologically and evolutionarily important organism will contribute to our understanding of epigenetics.
Molecular Analysis of the Bacterial Communities in Crude Oil Samples from Two Brazilian Offshore Petroleum Platforms
Authors: Korenblum Elisa , Souza Diogo Bastos , Penna Monica , Seldin Lucy
Published: January 2012

Crude oil samples with high- and low-water content from two offshore platforms (PA and PB) in Campos Basin, Brazil, were assessed for bacterial communities by 16S rRNA gene-based clone libraries. RDP Classifier was used to analyze a total of 156 clones within four libraries obtained from two platforms. The clone sequences were mainly affiliated withGammaproteobacteria(78.2% of the total clones); however, clones associated withBetaproteobacteria(10.9%),Alphaproteobacteria(9%), and Firmicutes (1.9%) were also identified.Pseudomonadaceaewas the most common family affiliated with these clone sequences. The sequences were further analyzed by MOTHUR, yielding 81 operational taxonomic units (OTUs) grouped at 97% stringency. Richness estimators also calculated by MOTHUR indicated that oil samples with high-water content were the most diverse. Comparison of bacterial communities present in these four samples using LIBSHUFF and Principal Component Analysis (PCA) indicated that the water content significantly influenced the community structure only of crude oil obtained from PA. Differences between PA and PB libraries were observed, suggesting the importance of the oil field as a driver of community composition in this habitat.
Tree-Based Neighbor Discovery in Urban Vehicular Sensor Networks
Authors: Roh Heejun , Lee Wonjun
Published: January 2012

In urban vehicular sensor networks, vehicles equipped with onboard sensors monitor some area, and the result can be shared to neighbor vehicles to correct their own sensing data. However, due to the frequent change of vehicle topology compared to the wireless sensor network, it is required for a vehicle to discover neighboring vehicles. Therefore, efficient neighbor discovery algorithm should be designed for vehicular sensor networks. In this paper, two efficient tree-based neighbor discovery algorithms in vehicular sensor networks are proposed and analyzed. After suggesting detailed scenario and its system model, we show that the expected value of neighbor discovery delay has different characteristics depending on neighbor discovery algorithms. An interesting observation of our result is that M-binary tree-based neighbor discovery shows better performance than M-ary tree-based neighbor discovery in the parking lot scenario, which is a counterintuitive result. We analyze why such result appears extensively.
An Angiotensin II Type 1 Receptor Blocker Prevents Renal Injury via Inhibition of the Notch Pathway in Ins2 Akita Diabetic Mice
Authors: Koshizaka Masaya , Takemoto Minoru , Sato Seiya , Tokuyama Hirotake , Fujimoto Masaki , Okabe Emiko , Ishibashi Ryoichi , Ishikawa Takahiro , Tsurutani Yuya , Onishi Shunichiro , Mezawa Morito , He Peng , Honjo Satoshi , Ueda Shiro , Saito Yasushi , Yokote Koutaro
Published: January 2012

Recently, it has been reported that the Notch pathway is involved in the pathogenesis of diabetic nephropathy. In this study, we investigated the activation of the Notch pathway in Ins2 Akita diabetic mouse (Akita mouse) and the effects of telmisartan, an angiotensin II type1 receptor blocker, on the Notch pathway. The intracellular domain of Notch1 (ICN1) is proteolytically cleaved from the cell plasma membrane in the course of Notch activation. The expression of ICN1 and its ligand, Jagged1, were increased in the glomeruli of Akita mice, especially in the podocytes. Administration of telmisartan significantly ameliorated the expression of ICN1 and Jagged1. Telmisartan inhibited the angiotensin II-induced increased expression of transforming growth factorβand vascular endothelial growth factor A which could directly activate the Notch signaling pathway in cultured podocytes. Our results indicate that the telmisartan prevents diabetic nephropathy through the inhibition of the Notch pathway.
Multiple Positive Solutions of Singular Nonlinear Sturm‐Liouville Problems with Carathéodory Perturbed Term
Authors: Han Yuefeng , Zhang Xinguang , Liu Lishan , Wu Yonghong
Published: January 2012

By employing a well‐known fixed point theorem, we establish the existence of multiple positive solutions for the following fourth‐order singular differential equation Lu = p(t)f(t, u(t), u′′(t)) − g(t, u(t), u′′(t)), 0 < t < 1, α1u(0) − β1u′(0) = 0, γ1u(1) + δ1u′(1) = 0, α2u′′(0) − β2u′′′(0) = 0, γ2u′′(1) + δ2u′′′(1) = 0, with αi, βi, γi, δi ≥ 0 and βiγi + αiγi + αiδi > 0,     i = 1,2, where L denotes the linear operator Lu : = (ru′′′)′ − qu′′, r ∈ C1([0,1], (0, +∞)), and q ∈ C([0,1], [0, +∞)). This equation is viewed as a perturbation of the fourth‐order Sturm‐Liouville problem, where the perturbed term g : (0,1)×[0, +∞)×(−∞, +∞)→(−∞, +∞) only satisfies the global Carathéodory conditions, which implies that the perturbed effect of g on f is quite large so that the nonlinearity can tend to negative infinity at some singular points.
Control of Transcriptional Elongation by RNA Polymerase II: A Retrospective
Authors: Brannan Kris , Bentley David L.
Published: January 2012

The origins of our current understanding of control of transcription elongation lie in pioneering experiments that mapped RNA polymerase II on viral and cellular genes. These studies first uncovered the surprising excess of polymerase molecules that we now know to be situated at the at the 5′ ends of most genes in multicellular organisms. The pileup of pol II near transcription start sites reflects a ubiquitous bottle-neck that limits elongation right at the start of the transcription elongation. Subsequent seminal work identified conserved protein factors that positively and negatively control the flux of polymerase through this bottle-neck, and make a major contribution to control of gene expression.
Extreme Heat Resistance of Food Borne PathogensCampylobacter jejuni, Escherichia coli, andSalmonella typhimuriumon Chicken Breast Fillet during Cooking
Authors: de Jong Aarieke E.I. , van Asselt Esther D. , Zwietering Marcel H. , Nauta Maarten J. , de Jonge Rob
Published: January 2012

The aim of this research was to determine the decimal reduction times of bacteria present on chicken fillet in boiling water. The experiments were conducted withCampylobacter jejuni, Salmonella, andEscherichia coli. Whole chicken breast fillets were inoculated with the pathogens, stored overnight (4∘C), and subsequently cooked. The surface temperature reached70∘Cwithin 30 sec and85∘Cwithin one minute. Extremely high decimal reduction times of 1.90, 1.97, and 2.20 min were obtained forC. jejuni, E. coli, andS. typhimurium, respectively. Chicken meat and refrigerated storage before cooking enlarged the heat resistance of the food borne pathogens. Additionally, a high challenge temperature or fast heating rate contributed to the level of heat resistance. The data were used to assess the probability of illness (campylobacteriosis) due to consumption of chicken fillet as a function of cooking time. The data revealed that cooking time may be far more critical than previously assumed.
Distinct Proteasome Subpopulations in the Alveolar Space of Patients with the Acute Respiratory Distress Syndrome
Authors: Sixt S. U. , Alami R. , Hakenbeck J. , Adamzik M. , Kloß A. , Costabel U. , Jungblut P. R. , Dahlmann B. , Peters J.
Published: January 2012

There is increasing evidence that proteasomes have a biological role in the extracellular alveolar space, but inflammation could change their composition. We tested whether immunoproteasome protein-containing subpopulations are present in the alveolar space of patients with lung inflammation evoking the acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) supernatants and cell pellet lysate from ARDS patients (n=28) and healthy subjects (n=10) were analyzed for the presence of immunoproteasome proteins (LMP2 and LMP7) and proteasome subtypes by western blot, chromatographic purification, and 2D-dimensional gelelectrophoresis. In all ARDS patients but not in healthy subjects LMP7 and LMP2 were observed in BAL supernatants. Proteasomes purified from pooled ARDS BAL supernatant showed an altered enzyme activity ratio. Chromatography revealed a distinct pattern with 7 proteasome subtype peaks in BAL supernatant of ARDS patients that differed from healthy subjects. Total proteasome concentration in BAL supernatant was increased in ARDS (971 ng/mL±1116 versus59±25;P<0.001), and all fluorogenic substrates were hydrolyzed, albeit to a lesser extent, with inhibition by epoxomicin (P=0.0001). Thus, we identified for the first time immunoproteasome proteins and a distinct proteasomal subtype pattern in the alveolar space of ARDS patients, presumably in response to inflammation.
Stationary Dynamic Displacement Solutions for a Rectangular Load Applied within a 3D Viscoelastic Isotropic Full Space—Part I: Formulation
Authors: Mesquita Euclides , Romanini Edivaldo , Labaki Josue
Published: January 2012

A dynamic stationary semianalytical solution for a spatially constant load applied over a rectangular surface within a viscoelastic isotropic full space is presented. The solution is obtained within the frame of a double Fourier integral transform. Closed‐form solutions for general loadings within the full space are furnished in the transformed wave number domain. Expressions for three boundary value problems, associated to a normal and two tangential rectangular loadings in the original physical space, are given in terms of a double inverse Fourier integral. These inverse integral transforms must be evaluated numerically. In the second part of the present paper a strategy to evaluate these integrals is described, the procedure validated and a number of original results are reported.
On Stochastic Equations with Measurable Coefficients Driven by Symmetric Stable Processes
Authors: Kurenok V. P.
Published: January 2012

We consider a one-dimensional stochastic equation , , with respect to a symmetric stable process of index . It is shown that solving this equation is equivalent to solving of a 2-dimensional stochastic equation with respect to the semimartingale and corresponding matrix . In the case of we provide new sufficient conditions for the existence of solutions of both equations with measurable coefficients. The
existence proofs are established using the method of Krylov's estimates
for processes satisfying the 2-dimensional equation. On another hand,
the Krylov's estimates are based on some analytical facts of independent
interest that are also proved in the paper.
Mathematical Distinction in Action Potential between Primo-Vessels and Smooth Muscle
Authors: Cho Seong-Jin , Lee Sang-Hun , Zhang Wenji , Lee Sae-Bhom , Choi Kwang-Ho , Choi Sun-Mi , Ryu Yeon-Hee
Published: January 2012

We studied the action potential of Primo-vessels in rats to determine the electrophysiological characteristics of these structures. We introduced a mathematical analysis method, a normalized Fourier transform that displays the sine and cosine components separately, to compare the action potentials of Primo-vessels with those for the smooth muscle. We found that Primo-vessels generated two types of action potential pulses that differed from those of smooth muscle: (1) Type I pulse had rapid depolarizing and repolarizing phases, and (2) Type II pulse had a rapid depolarizing phase and a gradually slowing repolarizing phase.
Study of the Effects of Total Flavonoids of Astragalus on Atherosclerosis Formation and Potential Mechanisms
Authors: Wang Deqing , Zhuang Yuan , Tian Yaping , Thomas Graham Neil , Ying Mingzhong , Tomlinson Brian
Published: January 2012

Astragalus mongholicusBunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol (P<0.05to 0.01), increased HDL cholesterol levels (P<0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P<0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component ofAstragalus mongholicusBunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the atherosclerosis profile.
The Roles of Mitogen-Activated Protein Kinase Pathways in TGF-β-Induced Epithelial-Mesenchymal Transition
Authors: Gui Ting , Sun Yujing , Shimokado Aiko , Muragaki Yasuteru
Published: January 2012

The mitogen-activated protein kinase (MAPK) pathway allows cells to interpret external signals and respond appropriately, especially during the epithelial-mesenchymal transition (EMT). EMT is an important process during embryonic development, fibrosis, and tumor progression in which epithelial cells acquire mesenchymal, fibroblast-like properties and show reduced intercellular adhesion and increased motility. TGF-βsignaling is the first pathway to be described as an inducer of EMT, and its relationship with the Smad family is already well characterized. Studies of four members of the MAPK family in different biological systems have shown that the MAPK and TGF-βsignaling pathways interact with each other and have a synergistic effect on the secretion of additional growth factors and cytokines that in turn promote EMT. In this paper, we present background on the regulation and function of MAPKs and their cascades, highlight the mechanisms of MAPK crosstalk with TGF-βsignaling, and discuss the roles of MAPKs in EMT.
Ruthenium Sensitizers and Their Applications in Dye-Sensitized Solar Cells
Authors: Qin Yuancheng , Peng Qiang
Published: February 2012

Dye-sensitized solar cells (DSSCs) have attracted considerable attention in recent years due to the possibility of low-cost conversion of photovoltaic energy. The DSSCs-based ruthenium complexes as sensitizers show high efficiency and excellent stability, implying potential practical applications. This review focuses on recent advances in design and preparation of efficient ruthenium sensitizers and their applications in DSSCs, including thiocyanate ruthenium sensitizers and thiocyanate-free ruthenium sensitizers.
Infection by CXCR4-Tropic Human Immunodeficiency Virus Type 1 Is Inhibited by the Cationic Cell-Penetrating Peptide Derived from HIV-1 Tat
Authors: Keogan Shawn , Passic Shendra , Krebs Fred C.
Published: January 2012

Cell-penetrating peptides (CPP), which are short peptides that are capable of crossing the plasma membrane of a living cell, are under development as delivery vehicles for therapeutic agents that cannot themselves enter the cell. One well-studied CPP is the 10-amino acid peptide derived from the human immunodeficiency virus type 1 (HIV-1) Tat protein. In experiments to test the hypothesis that multiple cationic amino acids within Tat peptide confer antiviral activity against HIV-1, introduction of Tat peptide resulted in concentration-dependent inhibition of HIV-1 IIIB infection. Using Tat peptide variants containing arginine substitutions for two nonionic residues and two lysine residues, HIV-1 inhibition experiments demonstrated a direct relationship between cationic charge and antiviral potency. These studies of Tat peptide as an antiviral agent raise new questions about the role of Tat in HIV-1 replication and provide a starting point for the development of CPPs as novel HIV-1 inhibitors.
Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome in a Chronic Hemodialysis Patient
Authors: Yamada Shunsuke , Fuyuno Seiya , Eriguchi Masahiro , Tsuruya Kazuhiko , Kitazono Takanari
Published: January 2012

A 75-year-old male who was undergoing chronic hemodialysis developed abrupt-onset pitting edema and pain in the dorsum of both hands and feet. Biochemical analysis disclosed increased C-reactive protein, and negative rheumatoid factor and antinuclear antibody. Radiological examination showed no bony erosion. Computed tomography and gallium scintigraphy revealed no active infection or neoplasms. The clinical diagnosis was remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. The pitting edema and inflammatory response quickly subsided after low-dose prednisolone therapy. This case demonstrates that RS3PE syndrome could be a differential diagnosis in elderly patients undergoing dialysis who develop pitting edema and joint pain.
Role of the Arylhydrocarbon Receptor (AhR) in the Pathology of Asthma and COPD
Authors: Chiba Takahito , Chihara Junichi , Furue Masutaka
Published: January 2012

The dioxins and dioxin-like compounds in cigarette smoke and environmental pollutants modulate immunological responses. These environmental toxicants are known to cause lung cancer but have also recently been implicated in allergic and inflammatory diseases such as bronchitis, asthma, and chronic obstructive pulmonary disease (COPD). In a novel pathway of this response, the activation of a nuclear receptor, arylhydrocarbon receptor (AhR), mediates the effects of these toxins through the arachidonic acid cascade, cell differentiation, cell-cell adhesion interactions, cytokine expression, and mucin production that are implicated in the pathogenesis and exacerbation of asthma/COPD. We have previously reported that human bronchial epithelial cells express AhR, and AhR activation induces mucin production through reactive oxygen species. This review discusses the role of AhR in asthma and COPD, focusing in particular on inflammatory and resident cells in the lung. We describe the important impact that AhR activation may have on the inflammation phase in the pathology of asthma and COPD. In addition, crosstalk of AhR signaling with other ligand-activated transcription factors such as peroxisome proliferator-activated receptors (PPARs) has been well documented.
Maxillomandibular Advancement in the Management of Obstructive Sleep Apnea
Authors: Varghese Ranji , Adams Nathan G. , Slocumb Nancy L. , Viozzi Christopher F. , Ramar Kannan , Olson Eric J.
Published: January 2012

Maxillomandibular advancement (MMA) is a surgical option for obstructive sleep apnea (OSA). MMA involves forward-fixing the maxilla and mandible approximately 10  mm via Le Fort I maxillary and sagittal split mandibular osteotomies. We retrospectively reviewed outcomes from 24 consecutive OSA patients who underwent MMA at our institution. MMA resulted in an 83% reduction in the group mean apnea-hypopnea index (AHI) per polysomnography an average of 6.7 months after surgery. Forty-two percent of patients achieved a post-MMA AHI of less than 5 events/hour sleep and 71% achieved an AHI less than or equal to 10 events/hour sleep. The Epworth Sleepiness Scale score decreased by an average of 5 post-surgery. No parameters predictive of cure for OSA by MMA were identified.
Simulation of Spread and Control of Lesions in Brain
Authors: Thamattoor Raman Krishna Mohan
Published: January 2012

A simulation model for the spread and control of lesions in the brain is constructed using a planar network (graph) representation for the central nervous system (CNS). The model is inspired by the lesion structures observed in the case of multiple sclerosis (MS), a chronic disease of the CNS. The initial lesion site is at the center of a unit square and spreads outwards based on the success rate in damaging edges (axons) of the network. The damaged edges send out alarm signals which, at appropriate intensity levels, generate programmed cell death. Depending on the extent and timing of the programmed cell death, the lesion may get controlled or aggravated akin to the control of wild fires by burning of peripheral vegetation. The parameter phase space of the model shows smooth transition from uncontrolled situation to controlled situation. The simulations show that the model is capable of generating a wide variety of lesion growth and arrest scenarios.