bluuebunny/crossref_metadata_2025 huggingface dataset:
Prelamin A-mediated nuclear envelope dynamics in normal and laminopathic cells
Authors: Lattanzi Giovanna
Published: November 2011

Prelamin A is the precursor protein of lamin A, a major constituent of the nuclear lamina in higher eukaryotes. Increasing attention to prelamin A processing and function has been given after the discovery, from 2002 to 2004, of diseases caused by prelamin A accumulation. These diseases, belonging to the group of laminopathies and mostly featuring LMNA mutations, are characterized, at the clinical level, by different degrees of accelerated aging, and adipose tissue, skin and bone abnormalities. The outcome of studies conducted in the last few years consists of three major findings. First, prelamin A is processed at different rates under physiological conditions depending on the differentiation state of the cell. This means that, for instance, in muscle cells, prelamin A itself plays a biological role, besides production of mature lamin A. Secondly, prelamin A post-translational modifications give rise to different processing intermediates, which elicit different effects in the nucleus, mostly by modification of the chromatin arrangement. Thirdly, there is a threshold of toxicity, especially of the farnesylated form of prelamin A, whose accumulation is obviously linked to cell and organism senescence. The present review is focused on prelamin A-mediated nuclear envelope modifications that are upstream of chromatin dynamics and gene expression mechanisms regulated by the lamin A precursor.
The LINC complex and human disease
Authors: Meinke Peter , Nguyen Thuy Duong , Wehnert Manfred S.
Published: November 2011

The LINC (linker of nucleoskeleton and cytoskeleton) complex is a proposed mechanical link tethering the nucleo- and cyto-skeleton via the NE (nuclear envelope). The LINC components emerin, lamin A/C, SUN1, SUN2, nesprin-1 and nesprin-2 interact with each other at the NE and also with other binding partners including actin filaments and B-type lamins. Besides the mechanostructural functions, the LINC complex is also involved in signalling pathways and gene regulation. Emerin was the first LINC component associated with a human disease, namely EDMD (Emery–Dreifuss muscular dystrophy). Later on, other components of the LINC complex, such as lamins A/C and small isoforms of nesprin-1 and nesprin-2, were found to be associated with EDMD, reflecting a genetic heterogeneity that has not been resolved so far. Only approximately 46% of the EDMD patients can be linked to genes of LINC and non-LINC components, pointing to further genes involved in the pathology of EDMD. Obvious candidates are the LINC proteins SUN1 and SUN2. Recently, screening of binding partners of LINC components as candidates identified LUMA (TMEM43), encoding a binding partner of emerin and lamins, as a gene involved in atypical EDMD. Nevertheless, such mutations contribute only to a very small fraction of EDMD patients. EDMD-causing mutations in STA/EMD (encoding emerin) that disrupt emerin binding to Btf (Bcl-2-associated transcription factor), GCL (germ cell-less) and BAF (barrier to autointegration factor) provide the first glimpses into LINC being involved in gene regulation and thus opening new avenues for functional studies. Thus the association of LINC with human disease provides tools for understanding its functions within the cell.
In vitro pathological modelling using patient-specific induced pluripotent stem cells: the case of progeria
Authors: Nissan Xavier , Blondel Sophie , Peschanski Marc
Published: November 2011

Progeria, also known as HGPS (Hutchinson–Gilford progeria syndrome), is a rare fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (C1804T) of the gene encoding lamins A and C, LMNA, leading to the production of a truncated form of the protein called progerin. Owing to their unique potential to self-renew and to differentiate into any cell types of the organism, pluripotent stem cells offer a unique tool to study molecular and cellular mechanisms related to this global and systemic disease. Recent studies have exploited this potential by generating human induced pluripotent stem cells from HGPS patients' fibroblasts displaying several phenotypic defects characteristic of HGPS such as nuclear abnormalities, progerin expression, altered DNA-repair mechanisms and premature senescence. Altogether, these findings provide new insights on the use of pluripotent stem cells for pathological modelling and may open original therapeutic perspectives for diseases that lack pre-clinical in vitro human models, such as HGPS.
UnLINCing the nuclear envelope: towards an understanding of the physiological significance of nuclear positioning
Authors: Razafsky David , Zang Shulun , Hodzic Didier
Published: November 2011

Appropriate tissue morphogenesis strictly requires the developmental regulation of different types of nuclear movements. LINC (linker of nucleoskeleton and cytoskeleton) complexes are macromolecular scaffolds that span the nuclear envelope and physically connect the nuclear interior to different cytoskeletal elements and molecular motors, thereby playing essential roles in nucleokinesis. Recent studies dedicated to the in vivo disruption of LINC complexes not only confirmed their widespread role in nuclear dynamics, but also led to a vigorous regain of interest in the physiological relevance of nuclear positioning within cells and syncitia. In the present paper, we review the results of LINC complex disruption in vivo across different organisms and the potential implications of observed phenotypes in human diseases.
An unexpected tail of VEGF and PlGF in pre-eclampsia
Authors: Bates David O.
Published: November 2011

PET (pre-eclamptic toxaemia), characterized by pregnancy-related hypertension and proteinuria, due to widespread endothelial dysfunction, is a primary cause of maternal morbidity. Altered circulating factors, particularly the VEGF (vascular endothelial growth factor) family of proteins and their receptors, are thought to be key contributors to this disease. Plasma from patients with PET induces numerous cellular and physiological changes in endothelial cells, indicating the presence of a circulating imbalance of the normal plasma constituents. These have been narrowed down to macromolecules of the VEGF family of proteins and receptors. It has been shown that responses of endothelial cells in intact vessels to plasma from patients with pre-eclampsia is VEGF-dependent. It has recently been shown that this may be specific to the VEGF165b isoform, and blocked by addition of recombinant human PlGF (placental growth factor). Taken together with results that show that sVEGFR1 (soluble VEGF receptor 1) levels are insufficient to bind VEGF-A in human plasma from patients with pre-eclampsia, and that other circulating macromolecules bind, but do not inactivate, VEGF-A, this suggests that novel hypotheses involving altered bioavailability of VEGF isoforms resulting from reduced or bound PlGF, or increased sVEGFR1 increasing biological activity of circulating plasma, could be tested. This suggests that knowing how to alter the balance of VEGF family members could prevent endothelial activation, and potentially some symptoms, of pre-eclampsia.
Is inflammation the cause of pre-eclampsia?
Authors: Ramma Wenda , Ahmed Asif
Published: November 2011

It has been proposed that either excessive inflammation or an imbalance in angiogenic factors cause pre-eclampsia. In the present review, the arguments for and against the role of inflammation and/or angiogenic imbalance as the cause of pre-eclampsia are discussed on the basis of the Bradford–Hill criteria for disease causation. Although both angiogenic imbalance and systemic inflammation are implicated in pre-eclampsia, the absence of temporality of inflammatory markers with pre-eclampsia challenges the concept that excessive inflammation is the cause of pre-eclampsia. In contrast, the elevation of anti-angiogenic factors that precede the clinical signs of pre-eclampsia fulfils the criterion of temporality. The second most important criterion is the dose–response relationship. Although such a relationship has not been proven between pro-inflammatory cytokines and pre-eclampsia, high levels of anti-angiogenic factors have been shown to correlate with increased incidence and disease severity, hence satisfying this condition. Finally, as the removal of circulating sFlt-1 (soluble Fms-like tyrosine kinase receptor-1) from pre-eclamptic patients significantly improves the clinical outcome, it fulfils the Hill's experiment principle, which states that removal of the cause by an appropriate experimental regimen should ameliorate the condition. In contrast, treatment with high doses of corticosteroid fails to improve maternal outcome in pre-eclampsia, despite suppressing inflammation. Inflammation may enhance the pathology induced by the imbalance in the angiogenic factors, but does not by itself cause pre-eclampsia. Development of therapies based on the angiogenic and cytoprotective mechanisms seems more promising.
LMNA-linked lipodystrophies: from altered fat distribution to cellular alterations
Authors: Bidault Guillaume , Vatier Camille , Capeau Jacqueline , Vigouroux Corinne , Béréziat Véronique
Published: November 2011

Mutations in the LMNA gene, encoding the nuclear intermediate filaments the A-type lamins, result in a wide variety of diseases known as laminopathies. Some of them, such as familial partial lipodystrophy of Dunnigan and metabolic laminopathies, are characterized by lipodystrophic syndromes with altered fat distribution and severe metabolic alterations with insulin resistance and dyslipidaemia. Metabolic disturbances could be due either to the inability of adipose tissue to adequately store triacylglycerols or to other cellular alterations linked to A-type lamin mutations. Indeed, abnormal prelamin A accumulation and farnesylation, which are clearly involved in laminopathic premature aging syndromes, could play important roles in lipodystrophies. In addition, gene expression alterations, and signalling abnormalities affecting SREBP1 (sterol-regulatory-element-binding protein 1) and MAPK (mitogen-activated protein kinase) pathways, could participate in the pathophysiological mechanisms leading to LMNA (lamin A/C)-linked metabolic alterations and lipodystrophies. In the present review, we describe the clinical phenotype of LMNA-linked lipodystrophies and discuss the current physiological and biochemical hypotheses regarding the pathophysiology of these diseases.
Microtubule-associated nuclear envelope proteins in interphase and mitosis
Authors: Figueroa Ricardo A. , Gudise Santhosh , Hallberg Einar
Published: November 2011

The LINC (linker of nucleoskeleton and cytoskeleton) complex forms a transcisternal bridge across the NE (nuclear envelope) that connects the cytoskeleton with the nuclear interior. This enables some proteins of the NE to communicate with the centrosome and the microtubule cytoskeleton. The position of the centrosome relative to the NE is of vital importance for many cell functions, such as cell migration and division, and centrosomal dislocation is a frequent phenotype in laminopathic disorders. Also in mitosis, a small group of transmembrane NE proteins associate with microtubules when they concentrate in a specific membrane domain associated with the mitotic spindle. The present review discusses structural and functional aspects of microtubule association with NE proteins and how this association may be maintained over the cell cycle.
DNA-damage accumulation and replicative arrest in Hutchinson–Gilford progeria syndrome
Authors: Musich Phillip R. , Zou Yue
Published: November 2011

A common feature of progeria syndromes is a premature aging phenotype and an enhanced accumulation of DNA damage arising from a compromised repair system. HGPS (Hutchinson–Gilford progeria syndrome) is a severe form of progeria in which patients accumulate progerin, a mutant lamin A protein derived from a splicing variant of the lamin A/C gene (LMNA). Progerin causes chromatin perturbations which result in the formation of DSBs (double-strand breaks) and abnormal DDR (DNA-damage response). In the present article, we review recent findings which resolve some mechanistic details of how progerin may disrupt DDR pathways in HGPS cells. We propose that progerin accumulation results in disruption of functions of some replication and repair factors, causing the mislocalization of XPA (xeroderma pigmentosum group A) protein to the replication forks, replication fork stalling and, subsequently, DNA DSBs. The binding of XPA to the stalled forks excludes normal binding by repair proteins, leading to DSB accumulation, which activates ATM (ataxia telangiectasia mutated) and ATR (ATM- and Rad3-related) checkpoints, and arresting cell-cycle progression.
The role of RhoJ in endothelial cell biology and angiogenesis
Authors: Leszczynska Katarzyna , Kaur Sukhbir , Wilson Eleanor , Bicknell Roy , Heath Victoria L.
Published: November 2011

RhoJ is an endothelially expressed member of the Cdc42 (cell division cycle 42) subfamily of small Rho GTPases. It is expressed in both the developing mammalian vasculature and the vascular beds of a number of adult tissues, with its expression regulated by the endothelial transcription factor ERG (ETS-related gene). RhoJ has been shown to regulate endothelial motility, tubulogenesis and lumen formation in vitro, and modulates the vascularization of Matrigel plugs in vivo. Both vascular endothelial growth factor and semaphorin 3E have been found to affect its activation. RhoJ has been shown to be a focal-adhesion-localized Rho GTPase which can modulate focal adhesion number, actomyosin contractility and activity of Cdc42 and Rac1. The present review discusses the biology of RhoJ with a focus on recent reports of its role in endothelial cells and angiogenesis.
Defective DNA-damage repair induced by nuclear lamina dysfunction is a key mediator of smooth muscle cell aging
Authors: Warren Derek T. , Shanahan Catherine M.
Published: November 2011

Accumulation of DNA damage is a major driving force of normal cellular aging and has recently been demonstrated to hasten the development of vascular diseases such as atherosclerosis. VSMCs (vascular smooth muscle cells) are essential for vessel wall integrity and repair, and maintenance of their proliferative capacity is essential for vascular health. The signalling pathways that determine VSMC aging remain poorly defined; however, recent evidence implicates persistent DNA damage and the A-type nuclear lamins as key regulators of this process. In the present review, we discuss the importance of the nuclear lamina in the spatial organization of nuclear signalling events, including the DNA-damage response. In particular, we focus on the evidence suggesting that prelamin A accumulation interferes with nuclear spatial compartmentalization by disrupting chromatin organization and DNA-damage repair pathways to promote VSMC aging and senescence.
A haloarchaeal ferredoxin electron donor that plays an essential role in nitrate assimilation
Authors: Zafrilla Basilio , Martínez-Espinosa Rosa María , Bonete María José , Butt Julea N. , Richardson David J. , Gates Andrew J.
Published: November 2011

In the absence of ammonium, many organisms, including the halophilic archaeon Haloferax volcanii DS2 (DM3757), may assimilate inorganic nitrogen from nitrate or nitrite, using a ferredoxin-dependent assimilatory NO3−/NO2− reductase pathway. The small acidic ferredoxin Hv-Fd plays an essential role in the electron transfer cascade required for assimilatory nitrate and nitrite reduction by the cytoplasmic NarB- and NirA-type reductases respectively. UV–visible absorbance and EPR spectroscopic characterization of purified Hv-Fd demonstrate that this protein binds a single [2Fe–2S] cluster, and potentiometric titration reveals that the cluster shares similar redox properties with those present in plant-type ferredoxins.
Physiological function and catalytic versatility of bacterial multihaem cytochromes c involved in nitrogen and sulfur cycling
Authors: Simon Jörg , Kern Melanie , Hermann Bianca , Einsle Oliver , Butt Julea N.
Published: November 2011

Bacterial MCCs (multihaem cytochromes c) represent widespread respiratory electron-transfer proteins. In addition, some of them convert substrates such as nitrite, hydroxylamine, nitric oxide, hydrazine, sulfite, thiosulfate or hydrogen peroxide. In many cases, only a single function is assigned to a specific MCC in database entries despite the fact that an MCC may accept various substrates, thus making it a multifunctional catalyst that can play diverse physiological roles in bacterial respiration, detoxification and stress defence mechanisms. The present article briefly reviews the structure, function and biogenesis of selected MCCs that catalyse key reactions in the biogeochemical nitrogen and sulfur cycles.
The production and detoxification of a potent cytotoxin, nitric oxide, by pathogenic enteric bacteria
Authors: Arkenberg Anke , Runkel Sebastian , Richardson David J. , Rowley Gary
Published: November 2011

The nitrogen cycle is based on several redox reactions that are mainly accomplished by prokaryotic organisms, some archaea and a few eukaryotes, which use these reactions for assimilatory, dissimilatory or respiratory purposes. One group is the Enterobacteriaceae family of Gammaproteobacteria, which have their natural habitats in soil, marine environments or the intestines of humans and other warm-blooded animals. Some of the genera are pathogenic and usually associated with intestinal infections. Our body possesses several physical and chemical defence mechanisms to prevent pathogenic enteric bacteria from invading the gastrointestinal tract. One response of the innate immune system is to activate macrophages, which produce the potent cytotoxin nitric oxide (NO). However, some pathogens have evolved the ability to detoxify NO to less toxic compounds, such as the neuropharmacological agent and greenhouse gas nitrous oxide (N2O), which enables them to overcome the host's attack. The same mechanisms may be used by bacteria producing NO endogenously as a by-product of anaerobic nitrate respiration. In the present review, we provide a brief introduction into the NO detoxification mechanisms of two members of the Enterobacteriaceae family: Escherichia coli and Salmonella enterica serovar Typhimurium. These are discussed as comparative non-pathogenic and pathogenic model systems in order to investigate the importance of detoxifying NO and producing N2O for the pathogenicity of enteric bacteria.
Nitrous oxide production by lithotrophic ammonia-oxidizing bacteria and implications for engineered nitrogen-removal systems
Authors: Chandran Kartik , Stein Lisa Y. , Klotz Martin G. , van Loosdrecht Mark C.M.
Published: November 2011

Chemolithoautotrophic AOB (ammonia-oxidizing bacteria) form a crucial component in microbial nitrogen cycling in both natural and engineered systems. Under specific conditions, including transitions from anoxic to oxic conditions and/or excessive ammonia loading, and the presence of high nitrite (NO2−) concentrations, these bacteria are also documented to produce nitric oxide (NO) and nitrous oxide (N2O) gases. Essentially, ammonia oxidation in the presence of non-limiting substrate concentrations (ammonia and O2) is associated with N2O production. An exceptional scenario that leads to such conditions is the periodical switch between anoxic and oxic conditions, which is rather common in engineered nitrogen-removal systems. In particular, the recovery from, rather than imposition of, anoxic conditions has been demonstrated to result in N2O production. However, applied engineering perspectives, so far, have largely ignored the contribution of nitrification to N2O emissions in greenhouse gas inventories from wastewater-treatment plants. Recent field-scale measurements have revealed that nitrification-related N2O emissions are generally far higher than emissions assigned to heterotrophic denitrification. In the present paper, the metabolic pathways, which could potentially contribute to NO and N2O production by AOB have been conceptually reconstructed under conditions especially relevant to engineered nitrogen-removal systems. Taken together, the reconstructed pathways, field- and laboratory-scale results suggest that engineering designs that achieve low effluent aqueous nitrogen concentrations also minimize gaseous nitrogen emissions.
Vascular remodelling in human skeletal muscle
Authors: Gustafsson Thomas
Published: November 2011

Exercise-induced angiogenesis in skeletal muscle involves both non-sprouting and sprouting angiogenesis and results from the integrated responses of multiple systems and stimuli. VEGF-A (vascular endothelial growth factor A) levels are increased in exercised muscle and have been demonstrated to be critical for exercise-induced capillary growth. Only limited information is available regarding the role of other angiogenic and angiostatic factors in exercise, but changes in the angiopoietin family following repetitive bouts of exercise occur in a pattern that is favourable for angiogenesis. Results from other angiogenic model systems, indicate that miRNAs (microRNAs) are important factors in the regulation of angiogenesis and thus to explore their role as regulators of exercise induced angiogenesis will be an important avenue of study in the future. ECM (extracellular matrix) remodelling and activation of MMPs (matrix metalloproteinases) are, to some extent, overlooked players in skeletal muscle adaptation. Degradation of ECM proteins liberates angiogenic factors from immobilized matrix stores and make cell migration possible. In fact, it is known that MMPs become activated by a single bout of exercise in humans, rapid interstitial changes occur long before any changes in gene transcription could result in protein synthesis and inhibition of MMP activity completely abolishes sprouting angiogenesis. A growing body of evidence suggests that circulating and resident progenitor cells, in addition to other cell types located in skeletal muscle tissue, participate in skeletal muscle angiogenesis by various mechanisms. However, more studies are needed before these can be confirmed as mechanisms of exercise-induced capillary growth.
Intravital two-photon microscopy of lymphatic vessel development and function using a transgenic Prox1 promoter-directed mOrange2 reporter mouse
Authors: Hägerling René , Pollmann Cathrin , Kremer Ludmila , Andresen Volker , Kiefer Friedemann
Published: November 2011

Lymphatic vessels, the second vascular system of higher vertebrates, are indispensable for fluid tissue homoeostasis, dietary fat resorption and immune surveillance. Not only are lymphatic vessels formed during fetal development, when the lymphatic endothelium differentiates and separates from blood endothelial cells, but also lymphangiogenesis occurs during adult life under conditions of inflammation, wound healing and tumour formation. Under all of these conditions, haemopoietic cells can exert instructive influences on lymph vessel growth and are essential for the vital separation of blood and lymphatic vessels. LECs (lymphatic endothelial cells) are characterized by expression of a number of unique genes that distinguish them from blood endothelium and can be utilized to drive reporter genes in a lymph endothelial-specific fashion. In the present paper, we describe the Prox1 (prospero homeobox protein 1) promoter-driven expression of the fluorescent protein mOrange2, which allows the specific intravital visualization of lymph vessel growth and behaviour during mouse fetal development and in adult mice.
The nitric oxide response in plant-associated endosymbiotic bacteria
Authors: Cabrera Juan J. , Sánchez Cristina , Gates Andrew J. , Bedmar Eulogio J. , Mesa Socorro , Richardson David J. , Delgado María J.
Published: November 2011

Nitric oxide (NO) is a gaseous signalling molecule which becomes very toxic due to its ability to react with multiple cellular targets in biological systems. Bacterial cells protect against NO through the expression of enzymes that detoxify this molecule by oxidizing it to nitrate or reducing it to nitrous oxide or ammonia. These enzymes are haemoglobins, c-type nitric oxide reductase, flavorubredoxins and the cytochrome c respiratory nitrite reductase. Expression of the genes encoding these enzymes is controlled by NO-sensitive regulatory proteins. The production of NO in rhizobia–legume symbiosis has been demonstrated recently. In functioning nodules, NO acts as a potent inhibitor of nitrogenase enzymes. These observations have led to the question of how rhizobia overcome the toxicity of NO. Several studies on the NO response have been undertaken in two non-dentrifying rhizobial species, Sinorhizobium meliloti and Rhizobium etli, and in a denitrifying species, Bradyrhizobium japonicum. In the present mini-review, current knowledge of the NO response in those legume-associated endosymbiotic bacteria is summarized.
Tied down: tethering redox proteins to the outer membrane in Neisseria and other genera
Authors: Li Xi , Parker Steven , Deeudom Manu , Moir James W.
Published: November 2011

Typically, the redox proteins of respiratory chains in Gram-negative bacteria are localized in the cytoplasmic membrane or in the periplasm. An alternative arrangement appears to be widespread within the betaproteobacterial genus Neisseria, wherein several redox proteins are covalently associated with the outer membrane. In the present paper, we discuss the structural properties of these outer membrane redox proteins and the functional consequences of this attachment. Several tethered outer membrane redox proteins of Neisseria contain a weakly conserved repeated structure between the covalent tether and the redox protein globular domain that should enable the redox cofactor-containing domain to extend from the outer membrane, across the periplasm and towards the inner membrane. It is argued that the constraints imposed on the movement and orientation of the globular domains by these tethers favours the formation of electron-transfer complexes for entropic reasons. The attachment to the outer membrane may also affect the exposure of the host to redox proteins with a moonlighting function in the host–microbe interaction, thus affecting the host response to Neisseria infection. We identify putative outer membrane redox proteins from a number of other bacterial genera outside Neisseria, and suggest that this organizational arrangement may be more common than previously recognized.
Anammox bacteria in different compartments of recirculating aquaculture systems
Authors: van Kessel Maartje A.H.J. , Harhangi Harry R. , Flik Gert , Jetten Mike S.M. , Klaren Peter H.M. , Op den Camp Huub J.M.
Published: November 2011

Strict environmental restrictions force the aquaculture industry to guarantee optimal water quality for fish production in a sustainable manner. The implementation of anammox (anaerobic ammonium oxidation) in biofilters would result in the conversion of both ammonium and nitrite (both toxic to aquatic animals) into harmless dinitrogen gas. Both marine and freshwater aquaculture systems contain populations of anammox bacteria. These bacteria are also present in the faeces of freshwater and marine fish. Interestingly, a new planctomycete species appears to be present in these recirculation systems too. Further exploitation of anammox bacteria in different compartments of aquaculture systems can lead to a more environmentally friendly aquaculture practice.
Nuclear Envelope Disease and Chromatin Organization
Authors: Ellis Juliet A. , Shackleton Sue
Published: November 2011

The fifth U.K. meeting on nuclear envelope disease and chromatin brought together international experts from across the field of nuclear envelope biology to discuss the advancements in a class of tissue-specific degenerative diseases called the laminopathies. Clinically, these range from relatively mild fat-wasting disorders to the severe premature aging condition known as Hutchinson–Gilford progeria syndrome. Since the first association of the nuclear envelope with human inherited disease in 1994, there has been an exponential increase in an unexpected variety of functions associated with nuclear envelope proteins, ranging from mechanical support and nucleocytoskeletal connections to regulation of chromatin organization and gene expression. This Biochemical Society Focused Meeting reinforced the functional complexity of nuclear-associated diseases, revealed new avenues to be investigated and highlighted the signalling pathways suitable as therapeutic targets.
Shear stress, tip cells and regulators of endothelial migration
Authors: Zhuang Xiaodong , Cross Darren , Heath Victoria L. , Bicknell Roy
Published: November 2011

We have in recent years described several endothelial-specific genes that mediate cell migration. These include Robo4 (roundabout 4), CLEC14A (C-type lectin 14A) and ECSCR (endothelial cell-specific chemotaxis regulator) [formerly known as ECSM2 (endothelial cell-specific molecule 2)]. Loss of laminar shear stress induces Robo4 and CLEC14A expression and an endothelial ‘tip cell’ phenotype. Low shear stress is found not only at sites of vascular occlusion such as thrombosis and embolism, but also in the poorly structured vessels that populate solid tumours. The latter probably accounts for strong expression of Robo4 and CLEC14A on tumour vessels. The function of Robo4 has, in the past, aroused controversy. However, the recent identification of Unc5B as a Robo4 ligand has increased our understanding and we hypothesize that Robo4 function is context-dependent. ECSCR is another endothelial-specific protein that promotes filopodia formation and migration, but, in this case, expression is independent of shear stress. We discuss recent papers describing ECSCR, including intracellular signalling pathways, and briefly contrast these with signalling by Robo4.
Advances in the Cellular and Molecular Biology of Angiogenesis
Authors: Egginton Stuart , Bicknell Roy
Published: November 2011

Capillaries have been recognized for over a century as one of the most important components in regulating tissue oxygen transport, and their formation or angiogenesis a pivotal element of tissue remodelling during development and adaptation. Clinical interest stems from observations that both excessive and inadequate vascular growth plays a major role in human diseases, and novel developments in treatments for cancer and eye disease increasingly rely on anti-angiogenic therapies. Although the discovery of VEGF (vascular endothelial growth factor) provided the first clue for specificity of signalling in endothelial cell activation, understanding the integrative response that drives angiogenesis requires a much broader perspective. The Advances in the Cellular and Molecular Biology of Angiogenesis meeting brought together researchers at the forefront of this rapidly moving field to provide an update on current understanding, and the most recent insights into molecular and cellular mechanisms of vascular growth. The plenary lecture highlighted the integrative nature of the angiogenic process, whereas invited contributions from basic and clinician scientists described fundamental mechanisms and disease-associated issues of blood vessel formation, grouped under a number of themes to aid discussion. These articles will appeal to academic, clinical and pharmaceutical scientists interested in the molecular and cellular basis of angiogenesis, their modulation or dysfunction in human diseases, and application of these findings towards translational medicine.
Acoustic double layer structures in dense magnetized electron-positron-ion plasmas
Authors: Akhtar N. , Mahmood S.
Published: November 2011

The acoustic double layer structures are studied using quantum hydrodynamic model in dense magnetized electron-positron-ion plasmas. The extended Korteweg-de Vries is derived using reductive perturbation method. It is found that increase in the ion concentration in dense magnetized electron-positron plasmas increases the amplitude as well as the steepness of the double layer structure. However, increase in the magnetic field strength and decrease in the obliqueness of the nonlinear acoustic wave enhances only the steepness of the double layer structures. The numerical results have also been shown by using the data of the outer layer regions of white dwarfs given in the literature.
Arbitrary amplitude ion-acoustic waves in a multicomponent plasma with superthermal species
Authors: El-Tantawy S. A. , Moslem W. M.
Published: November 2011

Properties of fully nonlinear ion-acoustic waves in a multicomponent plasma consisting of warm positive ions, superthermal electrons, as well as positrons, and dust impurities have been investigated. By using the hydrodynamic model for ions and superthermal electron/positron distribution, a Sagdeev potential has been derived. Existence conditions for large amplitude solitary and shock waves are presented. In order to show that the characteristics of the solitary and shock waves are influenced by the plasma parameters, the relevant numerical analysis of the Sagdeev potential is presented. The nonlinear structures, as predicted here, may be associated with the electrostatic perturbations in interstellar medium.
Mechanisms of impulsive magnetic reconnection: Global and local aspects
Authors: Yamada Masaaki
Published: November 2011

The global and local aspects of mechanisms of impulsive magnetic reconnection are discussed focusing on results from a dedicated laboratory experiment, MRX (Magnetic Reconnection Experiment), as well as fusion experiments. Possible application of the present analysis to reconnection phenomena in solar and space plasmas is also discussed. An external force which drives internal current in a fusion plasma causes magnetic flux to accumulate in a core section of the plasma (flux build-up). When the flux build-up generates a magnetic profile that satisfies a condition for a global magnetohydrodynamic instability to develop, reconnection takes place in an induced current layer generated by the instability leading to a global self-organization of the plasma. Generally the flux build-up phase is significantly longer than the reconnection time, τH ≫ τRec, thus making the waveform of flux evolution or other plasma parameters sawtooth shaped. In the reconnection layer of collisionless plasmas, the two fluid dynamics would lead to the formation of a narrow electron current channel which tends to become unstable against micro-instabilities, leading to an unsteady or impulsive reconnection. A common feature of impulsive reconnection after flux build-up is presented.
Study on the conformational equilibrium of the alanine dipeptide in water solution by using the averaged solvent electrostatic potential from molecular dynamics methodology
Authors: García-Prieto Francisco F. , Galván Ignacio Fdez. , Aguilar Manuel A. , Martín M. Elena
Published: November 2011

The ASEP/MD method has been employed for studying the solvent effect on the conformational equilibrium of the alanine dipeptide in water solution. MP2 and density functional theory (DFT) levels of theory were used and results were compared. While in gas phase cyclic structures showing intramolecular hydrogen bonds were found to be the most stable, the stability order is reversed in water solution. Intermolecular interaction with the solvent causes the predominance of extended structures as the stabilizing contacts dipeptide-water are favoured. Free-energy differences in solution were calculated and PPII, αR, and C5 conformers were identified as the most stable at MP2 level. Experimental data from Raman and IR techniques show discrepancies about the relative abundance of αR y C5, our results support the Raman data. The DFT level of theory agrees with MP2 in the location and stability of PPII and αR forms but fails in the location of C5. MP2 results suggest the possibility of finding traces of C7eq conformer in water solution, in agreement with recent experiments.
A tunneling field effect transistor model combining interband tunneling with channel transport
Authors: Wan J. , Le Royer C. , Zaslavsky A. , Cristoloveanu S.
Published: November 2011

We present a model for the tunneling field-effect transistor (TFET) comprising a series connection of a metal-oxide-semiconductor FET (MOSFET) with a gate-controllable tunneling diode. Through the introduction of MOSFET in the model, both operational regimes of TFET are handled correctly, with the tunneling diode dominating at low interband tunneling current and the MOSFET component dominating at high tunneling current. The comparison between our model, TCAD simulations and experimental data on TFETs with different gate oxide and channel thicknesses over the full range of gate and drain bias confirms the model’s reliability and accuracy. At low tunneling current, the model further simplifies to a compact analytical model. With minor modifications, our model can also be applied to multi-gate TFET architectures.
Trends to equilibrium for a class of relativistic diffusions
Authors: Angst Jürgen
Published: November 2011

A large class \documentclass[12pt]{minimal}\begin{document}$\mathcal C$\end{document}C of relativistic diffusions with values in the phase-space of special relativity was introduced by Angst and Franchi [J. Math. Phys. 48(8), 083101 (2007)] in order to answer some open questions concerning the asymptotic behavior of two examples of such processes. In particular, the equilibrium measures of these diffusions were explicitly computed, and their hydrodynamic limit was shown to be Brownian. In this paper, we address the question of the trends to equilibrium of the momentum component of the diffusions of the whole class \documentclass[12pt]{minimal}\begin{document}$\mathcal C$\end{document}C. We show the existence of a spectral gap using the Lyapounov method and deduce the exponential decay of the distance to equilibrium in \documentclass[12pt]{minimal}\begin{document}$\mathbb L^2-$\end{document}L2−norm and in total variation. A similar result was obtained recently by Calogero [e-print arXiv:1009.5086v2] for a particular process of the class \documentclass[12pt]{minimal}\begin{document}$\mathcal C$\end{document}C.
On the entropy of relaxing deterministic systems
Authors: Evans Denis J. , Williams Stephen R. , Searles Debra J.
Published: November 2011

In this paper, we re-visit Gibbs’ second (unresolved) paradox, namely the constancy of the fine-grained Gibbs entropy for autonomous Hamiltonian systems. We compare and contrast the different roles played by dissipation and entropy both at equilibrium where dissipation is identically zero and away from equilibrium where entropy cannot be defined and seems unnecessary in any case. Away from equilibrium dissipation is a powerful quantity that can always be defined and that appears as the central argument of numerous exact theorems: the fluctuation, relaxation, and dissipation theorems and the newly derived Clausius inequality.
Accurate potential energy surfaces with a DFT+$U(\mathbf {R})$U(R) approach
Authors: Kulik Heather J. , Marzari Nicola
Published: November 2011

We introduce an improvement to the Hubbard U augmented density functional approach known as DFT+U that incorporates variations in the value of self-consistently calculated, linear-response U with changes in geometry. This approach overcomes the one major shortcoming of previous DFT+U studies, i.e., the use of an averaged Hubbard U when comparing energies for different points along a potential energy surface is no longer required. While DFT+U is quite successful at providing accurate descriptions of localized electrons (e.g., d or f) by correcting self-interaction errors of standard exchange correlation functionals, we show several diatomic molecule examples where this position-dependent DFT+\documentclass[12pt]{minimal}\begin{document}$U(\mathbf {R})$\end{document}U(R) provides a significant two- to four-fold improvement over DFT+U predictions, when compared to accurate correlated quantum chemistry and experimental references. DFT+\documentclass[12pt]{minimal}\begin{document}$U(\mathbf {R})$\end{document}U(R) reduces errors in binding energies, frequencies, and equilibrium bond lengths by applying the linear-response, position-dependent \documentclass[12pt]{minimal}\begin{document}$U(\mathbf {R})$\end{document}U(R) at each configuration considered. This extension is most relevant where variations in U are large across the points being compared, as is the case with covalent diatomic molecules such as transition-metal oxides. We thus provide a tool for deciding whether a standard DFT+U approach is sufficient by determining the strength of the dependence of U on changes in coordinates. We also apply this approach to larger systems with greater degrees of freedom and demonstrate how DFT+\documentclass[12pt]{minimal}\begin{document}$U(\mathbf {R})$\end{document}U(R) may be applied automatically in relaxations, transition-state finding methods, and dynamics.
Optical and luminescence properties of Co:AgCl0.2Br0.8 crystals and their potential applications as gain media for middle-infrared lasers
Authors: Zakosky-Neuberger I. , Shafir I. , Nagli L. , Katzir A.
Published: November 2011

Infrared absorption and luminescence emission of cobalt doped silver halide crystals were investigated at room temperature and at low temperatures. A broad absorption band was observed in the near-infrared (1.4–2.5 µm) and a broad emission band in the middle-infrared (3.5–5.2 µm). The emission lifetime varied between 1.73 ms at low temperatures and 5 µs at room temperature. Based on the measured parameters and theoretical calculations, we believe that there is an excellent chance that these crystals would lase in the mid-IR. Moreover, it would be possible to extrude fibers from the crystals and obtain mid-IR fiber lasers.
First-principles investigations of elastic stability and electronic structure of cubic platinum carbide under pressure
Authors: Sun Xiao-Wei , Chen Qi-Feng , Chen Xiang-Rong , Cai Ling-Cang , Jing Fu-Qian
Published: November 2011

The authors have presented a detailed investigation on the phase stabilities and electronic properties of ideal stoichiometric platinum carbide (PtC) in the rock-salt (RS) and zinc-blende (ZB) structures under high pressure. Theoretical calculations are performed using the first-principles pseudopotential density functional method, in which we employ the generalized gradient approximation (GGA) of the Perdew-Burke-Ernzerhof form and local density approximation (LDA) of Ceperly and Adler parameterized by Perdew and Zunger together with plane-wave basis sets for expanding the periodic electron density. Through a series of tests, such as the total energy as a function of volume, the Gibbs free energy as a function of pressure, the P-V equation of states, the elastic stabilities, and the electronic band structures of PtC with ZB and RS phases, we have confirmed that the recently synthesized compound PtC is crystallized in the ZB structure at zero pressure and that the RS structure is a high-pressure phase; the phase transition studied from the usual condition of equal enthalpies occurs at the pressures of 46.6 and 46.5 GPa for GGA and LDA calculations, respectively. Our conclusions are consistent with the theoretical prediction obtained from the full-potential linearized augmented plane-wave method, but are reversed with the DAC experimental results and other pseudopotential plane-wave theoretical results. Therefore, the experimental observation of the RS structure in PtC remains a puzzle, and our study indicates that further experimental and theoretical investigations need to be carried out to find the cause of the stability of the PtC.
Donor impurity states in wurtzite InGaN staggered quantum wells
Authors: Xia Congxin , Jia Yalei , Wei Shuyi , Jia Yu , Spector Harold N.
Published: November 2011

Within the framework of the effective-mass approximation, donor impurity states in wurtzite (WZ) InGaN staggered quantum wells (QWs) are investigated theoretically. Numerical results show that the donor binding energy becomes insensitive to the variation of In composition y in the WZ In0.2Ga0.8N/InyGa1−yN staggered QWs when y > 0.125 and for any impurity position. Moreover, for the impurity located at the right edge of the InyGa1−yN well layer, the donor binding energy has a minimum and it is also insensible to the variation of well width in the staggered QWs when the well width L > 3 nm.
Low noise measurement system for determination of the critical currents in superconducting tapes by a pulse method
Authors: Ciszek M. , Trojanowski S.
Published: November 2011

Steady state measurements of the high critical currents in superconducting composite wires and tapes might be burdened with some errors. The origin of the errors is mainly associated with the Joule heat generated at current leads contacts, which at high transport currents can considerably increase temperature of an investigated sample wire. To avoid this unwanted heating phenomenon pulsed current methods are widely used. A waveform of the current pulse is usually shaped by means of a series RLC circuit with the subcritical dumping condition. Measurement results (i.e., a value of current peak, its time derivative, and a voltage drop along a superconducting sample) are recorded by means of a 4-channels, 12-bit resolution, 50 ns sampling time, digital recorder. Very low noise, broadband, voltage preamplifiers, based on rf bipolar transistors, were designed and fabricated. From the data, current-voltage characteristics are plotted and then the critical currents of investigated tapes are determined. Presented in the work our home-made, low noise, measurement setup allows to obtain a current pulse of about 4000 A at duration time of several milliseconds.
Dielectric and tunable properties of columnar Ba0.6Sr0.4TiO3-MgO composites prepared by spark plasma sintering
Authors: Liao Wanfang , Liang Ruihong , Wang Genshui , Cao Fei , Dong Xianlin
Published: November 2011

The ferroelectric Ba0.6Sr0.4TiO3 (BST) and dielectric MgO composites with three different structures: columnar, layered, and spherical inclusion were prepared by spark plasma sintering (SPS). The microstructure and dielectric properties were investigated. Results show that the columnar composite exhibits an appreciable tunability (44.3%) as high as that of pure BST while the permittivity has been reduced from 5872 to 3998 at 10 kHz at room temperature, leading to a reduction of permittivity without deterioration of tunability in the bulk ceramics. This is a feasible way to balance the permittivity and the tunability, which is very promising for tunable devices application.
Note: High precision angle generator using multiple ultrasonic motors and a self-calibratable encoder
Authors: Kim Jong-Ahn , Kim Jae Wan , Kang Chu-Shik , Jin Jonghan , Bong Eom Tae
Published: November 2011

We present an angle generator with high resolution and accuracy, which uses multiple ultrasonic motors and a self-calibratable encoder. A cylindrical air bearing guides a rotational motion, and the ultrasonic motors achieve high resolution over the full circle range with a simple configuration. The self-calibratable encoder can compensate the scale error of a divided circle (signal period: 20″) effectively by applying the equal-division-averaged method. The angle generator configures a position feedback control loop using the readout of the encoder. By combining the ac and dc operation mode, the angle generator produced stepwise angular motion with 0.005″ resolution. We also evaluated the performance of the angle generator using a precision angle encoder and an autocollimator. The expanded uncertainty (k = 2) in the angle generation was estimated less than 0.03″, which included the calibrated scale error and the nonlinearity error.