bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist
Authors: Savard Martin , Labonté Julie , Dubuc Céléna , Neugebauer Witold , D’Orléans-Juste Pedro , Gobeil Fernand 
Published: February 2013

Abstract
We recently identified a novel human B2 receptor (B2R) agonist [Hyp3,Thi5,NChg7,Thi8]-bradykinin (NG291) with greater in vitro and in vivo potency and duration of action than natural bradykinin (BK). Here, we further examined its stability and selectivity toward B2R. The hypotensive, antithrombotic, and profibrinolytic functions of NG291 relative to BK and its analogue ([Hyp3,Thi5,(4-Me)Tyr8(ΨCH2NH)Arg9]-BK) (RMP-7) were also tested. Contraction assays using isolated mouse stomachs (containing kinin B1R, B2R, and kininase I- and II-like activities) showed that NG291 is a more potent contractant than BK and is inhibited by HOE-140 (B2R antagonist) but unaffected by R954 (B1R antagonist), whereas both decreased the potency of BK. In stomach tissues from B2R knockout mice, BK maintained its activity via B1R, whereas NG291 had no contractile effect, indicating that it was selective for B2R. Unlike BK, NG291 was not degraded by rabbit lung ACE. Comparing intravenously administered BK and NG291 revealed that NG291 exhibited more potent and prolonged hypotensive action and greater antithrombotic and profibrinolytic activities. These effects were of comparable magnitude to RMP-7 and were absent in B2R knockout mice. We concluded that NG291 is a novel biostable B2R-selective agonist that may prove suitable for investigating the (pre)clinical cardioprotective efficacy of B2R activation.
Plasma kallikrein-kinin system and diabetic retinopathy
Authors: Liu Jia , Feener Edward P. 
Published: February 2013

Abstract
Diabetic retinopathy (DR) occurs, to some extent, in most people with at least 20 years’ duration of diabetes mellitus. The progression of DR to its sight-threatening stages is usually associated with the worsening of underlying retinal vascular dysfunction and disease. The plasma kallikrein-kinin system (KKS) is activated during vascular injury, where it mediates important functions in innate inflammation, blood flow, and coagulation. Recent findings from human vitreous proteomics and experimental studies on diabetic animal models have implicated the KKS in contributing to DR. Vitreous fluid from people with advanced stages of DR contains increased levels of plasma KKS components, including plasma kallikrein (PK), coagulation factor XII, and high-molecular-weight kininogen. Both bradykinin B1 and B2 receptor isoforms (B1R and B2R, respectively) are expressed in human retina, and retinal B1R levels are increased in diabetic rodents. The activation of the intraocular KKS induces retinal vascular permeability, vasodilation, and retinal thickening, and these responses are exacerbated in diabetic rats. Preclinical studies have shown that the administration of PK inhibitors and B1R antagonists to diabetic rats ameliorates retinal vascular hyperpermeability and inflammation. These findings suggest that components of plasma KKS are potential therapeutic targets for diabetic macular edema.
Deciphering the emerging role of SUMO conjugation in the hypoxia-signaling cascade
Authors: Núñez-O’Mara Analía , Berra Edurne 
Published: February 2013

Abstract
By driving the primary transcriptional response, the hypoxia inducible factor (HIF) is a master player of the hypoxia-signaling cascade, activation of which is essential to maintain oxygen homeostasis. HIF is formed by the interaction of a constitutive HIF-1β subunit with a HIF-α subunit tightly regulated through the concerted action of the prolyl hydroxylase domain containing proteins (PHDs) and factor inhibiting HIF. In well-oxygenated cells, HIF-α prolyl-hydroxylation by PHDs is the recognition signal for the binding of the ubiquitin E3 ligase pVHL, allowing protein poly-ubiquitination and degradation by the proteasome. Factor inhibiting HIF-mediated asparaginyl hydroxylation prevents interaction with the CBP/p300 coactivator and hence reduces HIF-dependent transcriptional activity. Upon low oxygen availability, HIF-α hydroxylation is blocked, resulting in protein stabilization and HIF complex activation. Post-translational modifications other than hydroxylation appear to be important in the cellular response to hypoxia. Small ubiquitin-like modifier (SUMO) is a 10 kDa protein readily conjugated to the lysine (K) residues of numerous cellular substrates in a sequential process termed SUMOylation. Recent data support the idea that a fine balance in SUMOylation/deSUMOylation is required for the adequate activation of the hypoxia-signaling cascade. In the present review, we will concentrate on the mechanisms of SUMOylation and its consequences in the cellular response to hypoxia.
Role of hypoxia inducible factor-1α for interferon synthesis in mouse dendritic cells
Authors: Wobben Regina , Hüsecken Yvonne , Lodewick Claudia , Gibbert Kathrin , Fandrey Joachim , Winning Sandra 
Published: February 2013

Abstract
Dendritic cells (DCs) are an important link between innate and adaptive immunity. DCs get activated in inflamed tissues where oxygen tension is usually low, which requires the transcription factor hypoxia inducible factor (HIF)-1 for cellular adaptation. To investigate whether the HIF-1 transcriptional complex plays a pivotal role in the function of DCs, we compared the effects of exogenous inflammatory stimuli and hypoxia on HIF-1α in bone marrow-derived DCs from wild type and myeloid-specific HIF-1α knock-out mice. We showed that the Toll-like receptor ligands lipopolysaccharides and cytosine-phosphatidyl-guanines significantly induce HIF-1α mRNA and protein, leading to elevated HIF-1 target gene expression of vascular endothelial growth factor. In contrast, polyinosinic:polycytidylic acid did not show comparable effects. Furthermore the potential to up-regulate inflammatory cytokines critically influences DC function. Our data demonstrate that HIF-1α protein is needed for adequate production of interferon-α and -β. In co-cultures of DCs and cytotoxic T cells, we observed that DCs lacking active HIF-1α protein induce significantly less CD278 and granzyme B mRNA in T cells. We conclude that HIF-1α plays a crucial role in DC interferon production and T cell activation, linking the innate and adaptive immune system.
Hydroxynonenal-stimulated activity of the uncoupling protein in Acanthamoeba castellanii mitochondria under phosphorylating conditions
Authors: Woyda-Ploszczyca Andrzej , Jarmuszkiewicz Wieslawa 
Published: February 2013

Abstract
The influence of 4-hydroxy-2-nonenal (HNE), a lipid peroxidation end product, on the activity of the amoeba Acanthamoeba castellanii uncoupling protein (AcUCP) in isolated phosphorylating mitochondria was studied. Under phosphorylating conditions, exogenously added HNE induced GTP-sensitive AcUCP-mediated mitochondrial uncoupling. The HNE-induced proton leak decreased the yield of oxidative phosphorylation in an HNE concentration-dependent manner. The present study describes how the contributions of ATP synthase and HNE-induced AcUCP in phosphorylating respiration vary when the rate of succinate oxidation is decreased by limiting succinate uptake or inhibiting complex III activity within the range of a constant membrane potential. In phosphorylating mitochondria, at a given HNE concentration (100 μm), the efficiency of AcUCP in mitochondrial uncoupling increased as the respiratory rate decreased because the AcUCP contribution remained constant while the ATP synthase contribution decreased with the respiratory rate. HNE-induced uncoupling can be inhibited by GTP only when ubiquinone is sufficiently oxidized, indicating that in phosphorylating A. castellanii mitochondria, the sensitivity of AcUCP activity to GTP depends on the redox state of the membranous ubiquinone.
Hydroxylase-dependent regulation of the NF-κB pathway
Authors: Scholz Carsten C. , Taylor Cormac T. 
Published: February 2013

Abstract
Hypoxia is associated with a diverse range of physiological and pathophysiological processes, including development, wound healing, inflammation, vascular disease and cancer. The requirement that eukaryotic cells have for molecular oxygen as the terminal electron acceptor for the electron transport chain means that the maintenance of oxygen delivery is key for bioenergetic homeostasis. Metazoans have evolved an effective way to adapt to hypoxic stress at the molecular level through a transcription factor termed the hypoxia inducible factor. A family of oxygen-sensing hydroxylases utilizes molecular oxygen as a co-substrate for the hydroxylation of hypoxia inducible factor α subunits, thereby reducing its expression and transcriptional activity when oxygen is available. Recent studies have indicated that other hypoxia-responsive transcriptional pathways may also be hydroxylase-dependent. In this review, we will discuss the role of hydroxylases in the regulation of NF-κB, a key regulator of immunity and inflammation. Developing our understanding of the role of hydroxylases in hypoxic inflammation may identify novel therapeutic approaches in chronic inflammatory disease.
The human Ah receptor: hints from dioxin toxicities to deregulated target genes and physiological functions
Authors: Bock Karl Walter 
Published: February 2013

Abstract
Marked species differences of dioxin toxicity prompted the review of three well-studied human dioxin toxicities (chloracne, inflammation and cancer) and deregulated Ah receptor (AhR) target genes to obtain hints as to the physiological functions of this receptor. Dioxin here stands for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Microarray analysis of dermal cysts from a dioxin-poisoned patient revealed, in addition to induced CYP1A1, increased expression of gremlin, an antagonist of bone morphogenetic proteins. Dioxin-mediated skin and intestinal inflammation is associated with deregulated T cell differentiation. In the supernatant of CD4+ T cells obtained from the dioxin-poisoned patient, increased interleukin-22 was detected, a cytokine that may be controlled in part by AhR-regulated Notch. Cancer is one of the long-term consequences of chronic inflammation. In line with dioxin-sensitive lymphoid tissue, enhanced death of lymphoid cancer was observed in the dioxin-exposed Seveso population 25 years after poisoning. Accumulating evidence suggests that endogenous AhR ligands, notably the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole, in contrast to TCDD, is rapidly metabolized by AhR-induced CYP1A1. The feedback loop between 6-formylindolo[3,2-b]carbazole, AhR and CYP1A1 guarantees transient activation that, in contrast to sustained activation by TCDD, may be essential for a putative role of the AhR in stem/progenitor cell homeostasis.
Recent advances in the electrochemistry and spectroelectrochemistry of membrane proteins
Authors: Melin Frederic , Hellwig Petra 
Published: February 2013

Abstract
Integral membrane proteins are encountered in fundamental natural processes, such as photosynthesis and respiration. The relation between the structure of the proteins and their function and dynamics are still not clear in most cases. Once fully understood, these processes could ultimately help researchers to develop alternative methods for producing energy, either from light or biomass. They could also lead to more efficient antibiotics, which would selectively inhibit a specific membrane protein of pathogenic bacteria. Since the chemical reactions involved in both photosynthesis and respiration are redox reactions, electrochemical methods can play a considerable role in uncovering their mechanisms. The electrochemical characterization of membrane proteins is, however, quite challenging. An overview on the techniques used for the characterization of membrane proteins, including classical approaches such as voltammetry and spectroelectrochemistry, and recent developments, such as their combination with surface-enhanced techniques is given.
Cannabinoid hyperemesis syndrome: a specific cause of cyclical vomiting
Authors: Morris Reshmi , Fisher Martin 
Published: February 2013

Abstract
Cyclical vomiting syndrome (CVS) is a disorder that occurs mostly in children, adolescents and young adults in which episodes of nausea and vomiting occur up to six to 12 times per year. In the past decade, one specific cause of cyclical vomiting syndrome, referred to as cannabinoid hyperemesis syndrome (CHS), has been described in a subset of patients who report chronic marijuana use. Of interest, almost all of these patients report compulsive bathing in hot water as part of the syndrome. In this report, we present the case of a 20-year-old female with CHS, review the issues generally encountered in CVS and discuss the known details of CHS. This is an important syndrome that needs to be considered as a potential diagnosis when patients present with cyclical vomiting.
Experiences of returning to elite alpine skiing after ACL injury and ACL reconstruction
Authors: Nordahl Birgitta , Sjöström Rita , Westin Maria , Werner Suzanne , Alricsson Marie 
Published: February 2013

AbstractAim:To explore the experiences of alpine skiing at the elite level after anterior cruciate ligament (ACL) injury and reconstruction.Design:A qualitative approach where semi-structured interviews were conducted, and an analysis of the manifest content was performed.Participants:Five ski high school students, two male and three female skiers, who had suffered ACL injuries and undergone ACL reconstructions.Results: Seven categories were identified. The participants described their perceived opportunities with regard to returning to alpine skiing after ACL injury and reconstruction as something positive to do with self-belief, being mentally and physically prepared, regaining confidence in their own ability, being given time and using active strategies. In contrast, perceived barriers to a return to elite alpine skiing gave rise to negative feelings, for example, fear, disheartenment, a total lack of or ambivalent confidence in their own ability and the use of passive strategies.Conclusion:The two male skiers returned to alpine skiing. They reported confidence in their own ability, active strategies and support on all levels, as well as enhanced physical ability. The female skiers did not return to their pre-injury level of competitive alpine skiing. They stated a lack of support on all levels, deterioration in their physical ability and two out of three reported passive strategies and no or ambivalent confidence in their own ability. The most important factors were family support, support on all levels, access to a physiotherapist and time given.
Why is the nanoscale special (or not)? Fundamental properties and how it relates to the design of nano-enabled drug delivery systems
Authors: Otto Daniel P. , de Villiers Melgardt M. 
Published: February 2013

AbstractNanoscience studies describe natural phenomena at the submicron scale. Below a critical nanoscale limit, the physical, chemical, and biological properties of materials show a marked departure in their behavior compared to the bulk. At the nanoscale, energy conversion is dominated by phonons, whereas at larger scales, electrons determine the process. The surface-to-volume ratio at the nanoscale is immense, and interfacial interactions are markedly more important than at the macroscopic level, where the majority of the material is shielded from the surface. These properties render the nanoparticles to be significantly different from their larger counterparts. Nano-enabled drug delivery systems have resulted from multidisciplinary cooperation aimed at improving drug delivery. Significant improvements in the thermodynamic and delivery properties are seen due to nanotechnology. Hybrid nanodelivery systems, i.e., membranes with nanopores that can gate stimuli-responsive drug release could be a future development. Nanotechnology will improve current drug delivery and create novel future delivery systems. The fundamental properties and challenges of nanodelivery systems are discussed in this review.
Learning the core ideas of scanning probe microscopy by toy model inquiries
Authors: Lindell Anssi , Kähkönen Anna-Leena 
Published: February 2013

AbstractAtomic force microscopy has developed from an atomic level imaging technique to a large family of nanoscientific research setups called scanning probe microscopy. Following this trend, we also need to develop our education from instructions to use the instrument for imaging into an approach of deeper understanding of the science behind the technologies. In this article, we describe our new university level scanning probe microscopy laboratory unit to learn the main scientific principles and applications of the instruments. Three inquiries using toy models were designed to cover the core ideas of scanning probe microscopy. Learning outcomes were analyzed and categorized into levels from the research reports of nine students. We found that practically every student learned atomic force imaging basics: scanning and essential properties of the topography image. One-third of the students showed good understanding in image artifacts and probe calibration, but just one of the students reached the level beyond the topography images to scanning force microscopy and combined force and topography techniques in his report. Also, the connection between scanning probe techniques and human senses was considered an important objective in design of this laboratory unit, although with modest success in learning so far.
Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches
Authors: Le Trequesser Quentin , Seznec Hervé , Delville Marie-Hélène 
Published: February 2013

AbstractThe successful development of nanomaterials illustrates the considerable interest in the development of new molecular probes for medical diagnosis and imaging. Substantial progress was made in the synthesis protocol and characterization of these materials, whereas toxicological issues are sometimes incomplete. Nanoparticle-based contrast agents (CAs) tend to become efficient tools for enhancing medical diagnostics and surgery for a wide range of imaging modalities. The multimodal nanoparticles (NPs) are much more efficient than the conventional molecular-scale CAs. They provide new abilities for in vivo detection and enhanced targeting efficiencies through longer circulation times, designed clearance pathways, and multiple binding capacities. Properly protected, they can safely be used for the fabrication of various functional systems with targeting properties, reduced toxicity, and proper removal from the body. This review mainly describes the advances in the development of mono- to multimodal NPs and their in vitro and in vivo relevant biomedical applications ranging from imaging and tracking to cancer treatment. Besides the specific applications for classical imaging (magnetic resonance imaging, positron emission tomography, computed tomography, ultrasound, and photoacoustic imaging), the less common imaging techniques such as terahertz molecular imaging (THMI) or ion beam analysis (IBA) are mentioned. The perspectives on the multimodal theranostic NPs and their potential for clinical advances are also mentioned.
Bioorthogonal chemistries for nanomaterial conjugation and targeting
Authors: Rahim Maha K. , Kota Rajesh , Lee Sumi , Haun Jered B. 
Published: February 2013

AbstractBioorthogonal chemistries are covalent reaction pairs that proceed in the presence of biological components with complete specificity. A suite of reactions has been described to date that provides scientists and engineers with diverse operational characteristics for different applications. Nanomaterials in particular have benefitted from these new capabilities, resulting in improved coupling efficiencies and multifunctionality. In this review, we will discuss the application of bioorthogonal chemistries to different nanomaterial systems, highlighting the advantages and limitations for use in bioconjugation. We will also describe how recent improvements in the reaction speed of catalyst-free bioorthogonal chemistries have enabled the successful coupling of nanomaterials directly to live cells. Using a recently developed reaction pair, tetrazine and trans-cyclooctene, the direct covalent coupling to cells has been shown to occur on time-scales that are relevant for biological studies and diagnostic applications and can even amplify nanomaterial binding greater than tenfold relative to traditional immunoconjugates. This powerful technique still maintains exquisite specificity, however, yielding robust results in clinical diagnostic applications using human tissue and blood samples. Future work will likely focus on further advancement of the in situ amplification technique, such as increasing nanomaterial binding, enabling multiplexed detection through the use of orthogonal reaction systems and extension to applications in vivo.
Mechanical and wear behavior of vinyl ester-carbon/cement by-pass dust particulate filled homogeneous and their functionally graded composites
Authors: Gangil Brijesh , Patnaik Amar , Kumar Anoop 
Published: February 2013

Abstract
The paper presents the processing, mechanical and sliding wear characterization of particulate filled cement by-pass dust and carbon fiber (fixed) reinforced homogeneous and functionally graded vinyl ester composites. Homogeneous and graded composites are fabricated by simple mechanical stirring and vertical centrifugal casting technique, respectively. Among the physical and mechanical properties, void content, hardness and impact strength are found to increase with increase in filler content in case of functionally graded materials (FGMs), whereas tensile strength and flexural strength are found to deteriorate for both FGMs and homogeneous composites as compared to the neat composites. Sliding wear characteristics are studied with the help of pin-on-disc test employing the design of experiments approach based on Taguchi’s orthogonal arrays. The present study reveals that graded composites exhibit good mechanical and wear characteristics compared to homogeneous composites. Scanning electron microscopy confirms the dispersion of carbon fiber in the matrix in graded composites.