bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional status is strongly correlated with grip strength and depression in community-living elderly Japanese
Authors: Kaburagi Tomoko , Hirasawa Reiko , Yoshino Haruka , Odaka Yukino , Satomi Mariko , Nakano Mana , Fujimoto Eka , Kabasawa Kazuyuki , Sato Kazuto
Published: March 2011

Objectives

To evaluate the utility of the Mini-Nutritional Assessment (MNA) in assessing nutritional, physical and psychosocial functions in community-living elderly individuals.

Design

A cross-sectional study of elderly individuals investigated in August 2007 and August–September 2008. Nutritional status was assessed using serum biomarkers, anthropometric measurements and the MNA. Physical function was assessed by measuring grip strength and both usual and maximum walking speeds. The Geriatric Depression Scale (GDS) was used to measure the individual's depressive state.

Setting

Elder-care facilities in Tokyo, Japan.

Subjects

Community-living elderly individuals aged ≥65 years (n 130).

Results

The MNA evaluation classified twenty-seven (20·8 %) individuals as being at risk for malnutrition (MNA score ≤23·5); these at-risk individuals included a high proportion of the elderly aged ≥75 years. MNA scores correlated with nutritional biomarkers (total protein, albumin, cholinesterase, Hb) and anthropometric measurements (triceps skinfold, subscapular skinfold, mid-arm muscle area) and exhibited a strong correlation with grip strength and GDS score. Multivariate analysis revealed that grip strength, GDS score, marital status and maximum walking speed are strong predictors of MNA score.

Conclusions

The MNA is considerably useful in providing a comprehensive assessment of nutritional status in elderly, community-living Japanese. However, larger-scale epidemiological studies are needed to determine the utility and the appropriate cut-off point of the MNA as a screen for risk of malnutrition.
X‐mode suppression of artificial E region field‐aligned plasma density irregularities
Authors: Hysell D. L. , Nossa E. , McCarrick M.
Published: March 2011

Ionospheric modification experiments have been performed at the High frequency Active Auroral Research Program involving the creation and suppression of artificial field‐aligned density irregularities (AFAIs) using O‐mode and X‐mode continuous wave emissions, respectively. The emission frequencies were offset so that the O‐mode upper hybrid interaction height nearly matched the X‐mode reflection height in the ionospheric E region. AFAIs created by O‐mode heating were observed using a 30 MHz coherent scatter radar imager. Simultaneous X‐mode heating was found to suppress the AFAI intensity and increase the threshold power for excitation by approximately a factor of 5 in our experiments. The effects are attributed in part to the broadening of the upper hybrid interaction region and in part to increased O‐mode absorption, which reduces the amplitude of the standing wave pattern in that region. Preliminary estimates based on local calculations suggest that the electron temperature in the E region was increased by a factor of about 1.6 in these experiments.
Cyclosporine A, FK506, and NIM811 ameliorate prolonged CBF reduction and impaired neurovascular coupling after cortical spreading depression
Authors: Piilgaard Henning , Witgen Brent M , Rasmussen Peter , Lauritzen Martin
Published: March 2011

Cortical spreading depression (CSD) is associated with mitochondrial depolarization, increasing intracellular Ca2+, and the release of free fatty acids, which favor opening of the mitochondrial permeability transition pore (mPTP) and activation of calcineurin (CaN). Here, we test the hypothesis that cyclosporine A (CsA), which blocks both mPTP and CaN, ameliorates the persistent reduction of cerebral blood flow (CBF), impaired vascular reactivity, and a persistent rise in the cerebral metabolic rate of oxygen (CMRO2) following CSD. In addition to CsA, we used the specific mPTP blocker NIM811 and the specific CaN blocker FK506. Cortical spreading depression was induced in rat frontal cortex. Electrocortical activity was recorded by glass microelectrodes, CBF by laser Doppler flowmetry, and tissue oxygen tension with polarographic microelectrodes. Electrocortical activity, basal CBF, CMRO2, and neurovascular and neurometabolic coupling were unaffected by all three drugs under control conditions. NIM811 augmented the rise in CBF observed during CSD. Cyclosporine A and FK506 ameliorated the persistent decrease in CBF after CSD. All three drugs prevented disruption of neurovascular coupling after CSD; the rise in CMRO2 was unchanged. Our data suggest that blockade of mPTP formation and CaN activation may prevent persistent CBF reduction and vascular dysfunction after CSD.
Adenosine kinase determines the degree of brain injury after ischemic stroke in mice
Authors: Shen Hai-Ying , Lusardi Theresa A , Williams-Karnesky Rebecca L , Lan Jing-Quan , Poulsen David J , Boison Detlev
Published: March 2011

Adenosine kinase (ADK) is the major negative metabolic regulator of the endogenous neuroprotectant and homeostatic bioenergetic network regulator adenosine. We used three independent experimental approaches to determine the role of ADK as a molecular target for predicting the brain's susceptibility to ischemic stroke. First, when subjected to a middle cerebral artery occlusion model of focal cerebral ischemia, transgenic fb-Adk-def mice, which have increased ADK expression in striatum (164%) and reduced ADK expression in cortical forebrain (65%), demonstrate increased striatal infarct volume (126%) but almost complete protection of cortex (27%) compared with wild-type (WT) controls, indicating that cerebral injury levels directly correlate to levels of ADK in the CNS. Second, we demonstrate abrogation of lipopolysaccharide (LPS)-induced ischemic preconditioning in transgenic mice with brain-wide ADK overexpression (Adk-tg), indicating that ADK activity negatively regulates LPS-induced tolerance to stroke. Third, using adeno-associated virus-based vectors that carry Adk-sense or -antisense constructs to overexpress or knockdown ADK in vivo, we demonstrate increased (126%) or decreased (51%) infarct volume, respectively, 4 weeks after injection into the striatum of WT mice. Together, our data define ADK as a possible therapeutic target for modulating the degree of stroke-induced brain injury.
Making biochemistry count: life among the amino acid dehydrogenases
Authors: Engel Paul C.
Published: March 2011

The guiding principle of the IAS Medal Lecture and of the research it covered was that searching mathematical analysis, depending on good measurements, must underpin sound biochemical conclusions. This was illustrated through various experiences with the amino acid dehydrogenases. Topics covered in the present article include: (i) the place of kinetic measurement in assessing the metabolic role of GDH (glutamate dehydrogenase); (ii) the discovery of complex regulatory behaviour in mammalian GDH, involving negative co-operativity in coenzyme binding; (iii) an X-ray structure solution for a bacterial GDH providing insight into catalysis; (iv) almost total positive co-operativity in glutamate binding to clostridial GDH; (v) unexpected outcomes with mutations at the catalytic aspartate site in GDH; (vi) reactive cysteine as a counting tool in the construction of hybrid oligomers to probe the basis of allosteric interaction; (vii) tryptophan-to-phenylalanine mutations in analysis of allosteric conformational change; (viii) site-directed mutagenesis to alter substrate specificity in GDH and PheDH (phenylalanine dehydrogenase); and (ix) varying strengths of binding of the ‘wrong’ enantiomer in engineered mutant enzymes and implications for resolution of racemates.
mTOR Signalling in Health and Disease
Authors: Proud Christopher G.
Published: March 2011

The TOR (target of rapamycin) proteins are found in all eukaryotes. TOR has a protein kinase domain, as well as other domains through which it interacts with partner proteins to form at least two types of multiprotein complex, TORC1 and TORC2 (TOR complexes 1 and 2). Rapamycin, an antibiotic and immunosuppressant, inhibits functions of TORC1. Use of this drug has revealed roles for TORC1 and its mammalian counterpart, mTORC1, in promoting many anabolic processes. mTORC1 signalling is activated by growth factors and nutrients. It is highly active in many cancers and plays a role in tumorigenesis and in other diseases. Much less is known so far about the functions and regulation of (m)TORC2. The goal of this meeting was to bring together researchers studying the roles of mTORC1/2 in normal cell and animal physiology in diverse systems, as well as scientists exploring the therapeutic value of inhibiting mTOR (mammalian TOR) signalling.
Blocking the mTOR pathway: a drug discovery perspective
Authors: Garcia-Echeverria Carlos
Published: March 2011

Substantial drug discovery efforts have been devoted, over the last few years, to identifying and developing mTOR (mammalian target of rapamycin) kinase modulators. This has resulted in a number of mTOR inhibitors with different mechanisms of action and/or distinct protein and lipid kinase selectivity profiles. As briefly reviewed in the present paper, these compounds have provided us with a better understanding of the roles of mTOR and other phosphoinositide 3-kinase/mTOR pathway components in human cancer biology, and a few of them have already demonstrated clinical benefit in cancer patients.
A longer and healthier life with TOR down-regulation: genetics and drugs
Authors: Bjedov Ivana , Partridge Linda
Published: March 2011

Genetic down-regulation of a major nutrient-sensing pathway, TOR (target of rapamycin) signalling, can improve health and extend lifespan in evolutionarily distant organisms such as yeast and mammals. Recently, it has been demonstrated that treatment with a pharmacological inhibitor of the TOR pathway, rapamycin, can replicate those findings and improve aging in a variety of model organisms. The proposed underlying anti-aging mechanisms are down-regulated translation, increased autophagy, altered metabolism and increased stress resistance.
ATP-competitive inhibitors of mTOR: new perspectives in the treatment of renal cell carcinoma
Authors: Roulin Didier , Demartines Nicolas , Dormond Olivier
Published: March 2011

Targeting mTOR (mammalian target of rapamycin) is an effective approach in the treatment of advanced RCC (renal cell carcinoma). Rapamycin-like drugs (rapalogues) have shown clinical activities and have been approved for the treatment of RCC. Recently, with the development of ATP-competitive inhibitors of mTOR, therapies targeting mTOR have entered a new era. Here, we discuss the biological relevance of blocking mTOR in RCC and review the mechanisms of action of rapalogues in RCC. We also advance some perspectives on the use of ATP-competitive inhibitors of mTOR in RCC.
The complexity of tetraspanins
Authors: Rubinstein Eric
Published: March 2011

Tetraspanins compose a family of structurally related molecules with four transmembrane domains. A total of 33 tetraspanins are present in the human genome, and tetraspanins are also found in plants and certain fungi. A well-known property of tetraspanins is their ability to interact with one another and many other surface proteins, which led to the suggestion that they organize a network of molecular interaction referred to as the ‘tetraspanin web’, and that they play a role in membrane compartmentalization. Recent studies of the dynamics of these molecules provided important new information that helped refining the models of this ‘web’. Several genetic studies in mammals and invertebrates have demonstrated key physiological roles for some of the tetraspanins, in particular in immune response, sperm–egg fusion, photoreceptor function and the normal function of certain epitheliums or vascular development. However, in several examples, the phenotypes of tetraspanin-knockout mice are relatively mild or restricted to a particular organ, despite a wide tissue distribution.
Tetraspanins in the humoral immune response
Authors: van Spriel Annemiek B.
Published: March 2011

The tetraspanins represent a large superfamily of four-transmembrane proteins that are expressed on all nucleated cells. Tetraspanins play a prominent role in the organization of the plasma membrane by co-ordinating the spatial localization of transmembrane proteins and signalling molecules into ‘tetraspanin microdomains’. In immune cells, tetraspanins interact with key leucocyte receptors [including MHC molecules, integrins, CD4/CD8 and the BCR (B-cell receptor) complex] and as such can modulate leucocyte receptor activation and downstream signalling pathways. There is now ample evidence that tetraspanins on B-lymphocytes are important in controlling antibody production. The tetraspanin CD81 interacts with the BCR complex and is critical for CD19 expression and IgG production, whereas the tetraspanin CD37 inhibits IgA production and is important for IgG production. By contrast, the tetraspanins CD9, Tssc6 and CD151 appear dispensable for humoral immune responses. Thus individual tetraspanin family members have specific functions in B-cell biology, which is evidenced by recent studies in tetraspanin-deficient mice and humans. The present review focuses on tetraspanins expressed by B-lymphocytes and discusses novel insights into the function of tetraspanins in the humoral immune response.
Structural characterization of CD81–Claudin-1 hepatitis C virus receptor complexes
Authors: Bonander Nicklas , Jamshad Mohammed , Hu Ke , Farquhar Michelle J. , Stamataki Zania , Balfe Peter , McKeating Jane A. , Bill Roslyn M.
Published: March 2011

Tetraspanins are thought to exert their biological function(s) by co-ordinating the lateral movement and trafficking of associated molecules into tetraspanin-enriched microdomains. A second four-TM (transmembrane) domain protein family, the Claudin superfamily, is the major structural component of cellular TJs (tight junctions). Although the Claudin family displays low sequence homology and appears to be evolutionarily distinct from the tetraspanins, CD81 and Claudin-1 are critical molecules defining HCV (hepatitis C virus) entry; we recently demonstrated that CD81–Claudin-1 complexes have an essential role in this process. To understand the molecular basis of CD81–Claudin-1 complex formation, we produced and purified milligram quantities of full-length CD81 and Claudin-1, alone and in complex, in both detergent and lipid contexts. Structural characterization of these purified proteins will allow us to define the mechanism(s) underlying virus–cell interactions and aid the design of therapeutic agents targeting early steps in the viral life cycle.
Membrane proteases and tetraspanins
Authors: Yáñez-Mó María , Sánchez-Madrid Francisco , Cabañas Carlos
Published: March 2011

TEMs (tetraspanin-enriched microdomains) are specialized platforms in the plasma membrane that include adhesion receptors and enzymes. Insertion into TEMs dictates the local concentration of these molecules, regulates their internalization rate, their interaction and cross-talk with other receptors at the plasma membrane and provides links with certain signalling pathways. We focus on the associations described for tetraspanins with membrane proteases and their substrates, reviewing the emerging evidence in the literature that suggests that TEMs might be essential platforms for regulating protein shedding, RIP (regulated intramembrane proteolysis) and matrix degradation and assembly.
Exosome target cell selection and the importance of exosomal tetraspanins: a hypothesis
Authors: Rana Sanyukta , Zöller Margot
Published: March 2011

Exosomes are derived from limiting membranes of MVBs (multivesicular bodies). They carry and transfer selected membrane and cytoplasmic proteins, mRNA and microRNA into target cells. It is due to this shipping of information that exosomes are considered to be the most promising therapeutic tool for multiple diseases. However, whereas knowledge on the composition of exosomes is rapidly increasing, the mode of selective recruitment into exosomes as well as target cell selection is poorly understood. We suggest that at least part of this task is taken over by tetraspanins. Tetraspanins, which are involved in morphogenesis, fission and fusion processes, are enriched in exosomes, and our previous work revealed that the recruitment of distinct tetraspanins into exosomes follows very selective routes, including a rearrangement of the tetraspanin web. Furthermore, only exosomes expressing a defined set of tetraspanins and associated molecules target endothelial cells, thereby contributing to angiogenesis and vasculogenesis. On the basis of these findings we hypothesize (i) that the protein assembly of exosomes and possibly the recruitment of microRNA will be regulated to a large extent by tetraspanins and (ii) that tetraspanins account for target cell selection and the tight interaction/uptake of exosomes by the target cell. Exosomes herald an unanticipated powerful path of cell–cell communication. An answer to how exosomes collect and transfer information will allow the use of Nature's concept to cope with malfunctions.
Tetraspanin CD9 in cell migration
Authors: Powner Dale , Kopp Petra M. , Monkley Susan J. , Critchley David R. , Berditchevski Fedor
Published: March 2011

Tetraspanin CD9 is associated with integrin adhesion receptors and it was reported that CD9 regulates integrin-dependent cell migration and invasion. Pro- and anti-migratory effects of CD9 have been linked to adhesion-dependent signalling pathways, including phosphorylation of FAK (focal adhesion kinase) and activation of phosphoinositide 3-kinase, p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase). In the present paper, we describe a novel mechanism whereby CD9 specifically controls localization of talin1, one of the critical regulators of integrin activation, to focal adhesions: CD9-deficiency leads to impaired localization of talin1 to focal adhesions and correlates with increased motility of breast cancer cells.
The effect of cell–ECM adhesion on signalling via the ErbB family of growth factor receptors
Authors: Alexi Xanthippi , Berditchevski Fedor , Odintsova Elena
Published: March 2011

Integrins and growth factor receptors of the ErbB family are involved in the regulation of cellular interactions with the extracellular microenvironment. Cross-talk between these two groups of transmembrane receptors is essential for cellular responses and can be regulated through the formation of multimolecular complexes. Tetraspanins as facilitators and building blocks of specialized microdomains may be involved in this process. In the present study, we demonstrated that, in contrast with previous reports, integrin-mediated adhesion did not stimulate ligand-independent activation of ErbB receptors in epithelial cells. However, integrin-dependent adhesion potentiated ligand-induced activation of EGFR (epidermal growth factor receptor) and ErbB2 and facilitated receptor homo- and hetero-dimerization. The actin cytoskeleton appeared to play a critical role in this phenomenon.
COMBREX: COMputational BRidge to EXperiments
Authors: Roberts Richard J.
Published: March 2011

COMBREX (computational bridges to experimentation) is a project to engage the biological community in providing better functional annotation of genomes. In essence, the project involves the generation by computational biologists of a database of predicted functions for genes in bacterial genomes. Those genes for which no functional assignments have been proven experimentally are then open for bids by biochemists to test the predicted functions. High-priority genes are those for which no previous functional assignment has been made as well as those where uncharacterized examples are present in many genomes. A pilot project is running that focuses on bacterial and archaeal genomes.
Cell-cycle-specific activators of the Mec1/ATR checkpoint kinase
Authors: Navadgi-Patil Vasundhara M. , Burgers Peter M.
Published: March 2011

Mec1 [ATR (ataxia telangiectasia mutated- and Rad3-related) in humans] is the principle kinase responsible for checkpoint activation in response to replication stress and DNA damage in Saccharomyces cerevisiae. The heterotrimeric checkpoint clamp, 9-1-1 (checkpoint clamp of Rad9, Rad1 and Hus1 in humans and Ddc1, Rad17 and Mec3 in S. cerevisiae; Ddc1-Mec3-Rad17) and the DNA replication initiation factor Dpb11 (human TopBP1) are the two known activators of Mec1. The 9-1-1 clamp functions in checkpoint activation in G1- and G2-phase, but its employment differs between these two phases of the cell cycle. The Ddc1 (human Rad9) subunit of the clamp directly activates Mec1 in G1-phase, an activity identified only in S. cerevisiae so far. However, in G2-phase, the 9-1-1 clamp activates the checkpoint by two mechanisms. One mechanism includes direct activation of Mec1 by the unstructured C-terminal tail of Ddc1. The second mech-anism involves the recruitment of Dpb11 by the phosphorylated C-terminal tail of Ddc1. The latter mechanism is highly conserved and also functions in response to replication stress in higher eukaryotes. In S. cerevisiae, however, both the 9-1-1 clamp and the Dpb11 are partially redundant for checkpoint activation in response to replication stress, suggesting the existence of additional activators of Mec1.
Helicases that underpin replication of protein-bound DNA in Escherichia coli
Authors: McGlynn Peter
Published: March 2011

A pre-requisite for successful cell division in any organism is synthesis of an accurate copy of the genetic information needed for survival. This copying process is a mammoth task, given the amount of DNA that must be duplicated, but potential blocks to replication fork movement also pose a challenge for genome duplication. Damage to the template inhibits the replication machinery but proteins bound to the template such as RNA polymerases also present barriers to replication. This review discusses recent results from Escherichia coli that shed light on the roles of helicases in overcoming protein–DNA barriers to replication and that may illustrate fundamental aspects of how duplication of protein-bound DNA is underpinned in all organisms.
Sequence-specific covalent labelling of DNA
Authors: Gottfried Anna , Weinhold Elmar
Published: March 2011

Sequence-specific DNA modification is of significance for applications in bio- and nano-technology, medical diagnostics and fundamental life sciences research. Preferentially, labelling should be performed covalently, which avoids doubts about label dissociation from the DNA under various conditions. Several methods to label native DNA have been developed in the last two decades. Triple-helix-forming oligodeoxynucleotides and hairpin polyamides that bind DNA sequences specifically in the major and minor groove respectively were used as targeting devices for subsequent covalent labelling. In addition, enzyme-directed labelling approaches utilizing nicking endonucleases in combination with DNA polymerases or DNA methyltransferases have been employed. This review summarizes various techniques useful for functionalization of long native DNA.
Formation of stable DNA triplexes
Authors: Fox Keith R. , Brown Tom
Published: March 2011

Triple-helical nucleic acids are formed by binding an oligonucleotide within the major groove of duplex DNA. These complexes offer the possibility of designing oligonucleotides which bind to duplex DNA with considerable sequence specificity. However, triple-helix formation with natural nucleotides is limited by (i) the requirement for low pH, (ii) the requirement for homopurine target sequences, and (iii) their relatively low affinity. We have prepared modified oligonucleotides to overcome these limitations, including the addition of positive charges to the sugar and/or base, the inclusion of cytosine analogues, the development of nucleosides for recognition of pyrimidine interruptions and the attachment of one or more cross-linking groups. By these means we are able to generate triplexes which have high affinities at physiological pH at sequences that contain pyrimidine interruptions.
DNA acting like RNA
Authors: Brown Robert V. , Hurley Laurence H.
Published: March 2011

Over the last decade or so, secondary non-B-DNA structures such as G-quadruplexes and i-motifs have come into focus as biologically functioning moieties that are potentially involved in telomeric interactions and the control of gene expression. In the present short review, we first describe the structural and dynamic parallels with complex RNA structures, including the importance of sequence and ions in folding, and then we describe the biological consequences of the folded structures. We conclude that there are considerable parallels between secondary and tertiary structures in RNA and DNA from both the folding and the biological perspectives.
Catalysis by the nucleolytic ribozymes
Authors: Lilley David M.J.
Published: March 2011

The nucleolytic ribozymes use general acid–base catalysis to contribute significantly to their rate enhancement. The VS (Varkud satellite) ribozyme uses a guanine and an adenine nucleobase as general base and acid respectively in the cleavage reaction. The hairpin ribozyme is probably closely similar, while the remaining nucleolytic ribozymes provide some interesting contrasts.
Interactions of the c-di-GMP riboswitch with its second messenger ligand
Authors: Smith Kathryn D. , Strobel Scott A.
Published: March 2011

The c-di-GMP [bis-(3′–5′)-cyclic dimeric guanosine monophosphate] riboswitch is a macromolecular target in the c-di-GMP second messenger signalling pathway. It regulates many genes related to c-di-GMP metabolism as well as genes involved in bacterial motility, virulence and biofilm formation. The riboswitch makes asymmetric contacts to the bases and phosphate backbone of this symmetric dinucleotide. The phylogenetics suggested and mutagenesis has confirmed that this is a flexible motif where variants can make alternative interactions with each of the guanine bases of c-di-GMP. A mutant riboswitch has been designed that can bind a related molecule, c-di-AMP, confirming the most important contacts made to the ligand. The binding kinetics reveal that this is a kinetically controlled riboswitch and mutations to the riboswitch lead to increases in the off-rate. This riboswitch is therefore flexible in sequence as well as kinetic properties.
Identification of novel ligands for thiamine pyrophosphate (TPP) riboswitches
Authors: Cressina Elena , Chen Liuhong , Moulin Michael , Leeper Finian J. , Abell Chris , Smith Alison G.
Published: March 2011

Riboswitches are regions of mRNA to which a metabolite binds in the absence of proteins, resoulting in alteration of transcription, translation or splicing. The most widespread forms of riboswitches are those responsive to TPP (thiamine pyrophosphate) the active form of vitamin B1, thiamine. TPP-riboswitches have been found in all bacterial genomes examined, and are the only ones found in eukaryotes. In each case, the riboswitch appears to regulate the expression of a gene involved in synthesis or uptake of the vitamin. Riboswitches offer an attractive target for chemical intervention, and identification of novel ligands would allow a detailed study on structure–activity relationships, as well as potential leads for the development of antimicrobial compounds. To this end, we have developed a medium-throughput methodology for screening libraries of small molecules using biophysical methods.
The ribosome as a molecular machine: the mechanism of tRNA–mRNA movement in translocation
Authors: Rodnina Marina V. , Wintermeyer Wolfgang
Published: March 2011

Translocation of tRNA and mRNA through the ribosome is one of the most dynamic events during protein synthesis. In the cell, translocation is catalysed by EF-G (elongation factor G) and driven by GTP hydrolysis. Major unresolved questions are: how the movement is induced and what the moving parts of the ribosome are. Recent progress in time-resolved cryoelectron microscopy revealed trajectories of tRNA movement through the ribosome. Driven by thermal fluctuations, the ribosome spontaneously samples a large number of conformational states. The spontaneous movement of tRNAs through the ribosome is loosely coupled to the motions within the ribosome. EF-G stabilizes conformational states prone to translocation and promotes a conformational rearrangement of the ribosome (unlocking) that accelerates the rate-limiting step of translocation: the movement of the tRNA anticodons on the small ribosomal subunit. EF-G acts as a Brownian ratchet providing directional bias for movement at the cost of GTP hydrolysis.
Inflammasome activation: from inflammatory disease to infection
Authors: Dunne Aisling
Published: March 2011

The recognition of pathogen-derived molecules by the innate immune system is mediated by a number of receptors, including members of the TLR (Toll-like receptor), RLH [RIG (retinoic acid-inducible gene)-like helicase] and the NLR (NOD-like receptor) families. NLRs in particular are also involved in the recognition of host-derived ‘danger’-associated molecules which are produced under conditions of cellular stress or injury. Activation of these receptors leads to the assembly of high-molecular-mass complexes called inflammasomes which in turn leads to the generation of active caspase 1 and to the production of mature IL-1β (interleukin 1β). The discovery that NLRP3 (NLR-related protein 3) can recognize host-derived particulate matter such as uric acid and cholesterol crystals has led to this inflammasome being implicated in a number of inflammatory diseases, including gout, atherosclerosis and Type 2 diabetes. In addition, aberrant NLRP3 activation has also been observed in a number of heritable disorders now referred to as cryopyrinopathies. On the other hand, a number of studies have reported that recognition of both viral and bacterial products by NLRs is required for effective pathogen clearance. The present review discusses both aspects of NLR activation and will highlight the role of additional inflammasome complexes in sensing infection.
The interaction of IQGAPs with calmodulin-like proteins
Authors: Pathmanathan Sevvel , Hamilton Elaine , Atcheson Erwan , Timson David J.
Published: March 2011

Since their identification over 15 years ago, the IQGAP (IQ-motif-containing GTPase-activating protein) family of proteins have been implicated in a wide range of cellular processes, including cytoskeletal reorganization, cell–cell adhesion, cytokinesis and apoptosis. These processes rely on protein–protein interactions, and understanding these (and how they influence one another) is critical in determining how the IQGAPs function. A key group of interactions is with calmodulin and the structurally related proteins myosin essential light chain and S100B. These interactions occur primarily through a series of IQ motifs, which are α-helical segments of the protein located towards the middle of the primary sequence. The three human IQGAP isoforms (IQGAP1, IQGAP2 and IQGAP3) all have four IQ motifs. However, these have different affinities for calmodulin, myosin light chain and S100B. Whereas all four IQ motifs of IQGAP1 interact with calmodulin in the presence of calcium, only the last two do so in the absence of calcium. IQ1 (the first IQ motif) interacts with the myosin essential light chain Mlc1sa and the first two undergo a calcium-dependent interaction with S100B. The significance of the interaction between Mlc1sa and IQGAP1 in mammals is unknown. However, a similar interaction involving the Saccharomyces cerevisiae IQGAP-like protein Iqg1p is involved in cytokinesis, leading to speculation that there may be a similar role in mammals.
An accurate assessment of habitat loss and current threats to the mahogany glider (Petaurus gracilis)
Authors: Jackson Stephen M. , Morgan Gethin , Kemp Jeanette E. , Maughan Mirjam , Stafford Cherie M.
Published: March 2011

Despite the establishment of legislation to protect the remaining habitat of the endangered mahogany glider (Petaurus gracilis) there is an urgent need to understand where habitat remains and how it should be managed. Regional ecosystem mapping was used to identify the true extent of habitat loss from clearing and the extent of habitat degradation due to the transition to rainforest (where rainforest develops within in a sclerophyll community) and sclerophyll thickening (where saplings of local sclerophyllous species form a thick secondary tree layer). The total area of habitat available to mahogany gliders decreased by 49%, from 276 880 to 141 122 ha, as a result of clearing of vegetation for agriculture and other human activities. Of the habitat remaining, 51 870 ha was the most structurally complex and floristically diverse habitat type ‘Mixed Open Forest’, 55 760 ha was the more open and less diverse ‘Mixed Woodland’, 29 988 ha consisted of mainly single-canopy-species vegetation ‘Monotypic Stands’ and 3504 ha was classed as having only Emergent trees (trees emergent from a rainforest canopy) suitable for the mahogany glider. The loss of habitat occurred mostly on freehold land where it has decreased from 129 435 ha to 26 852 ha. Within the remaining Mixed Open Forest habitat, 45% is considered to have decreasing habitat suitability for the mahogany glider as a result of sclerophyll thickening or transition to rainforest, as is 26% of Mixed Woodland habitat, 33% of Monotypic Stands habitat and 8% of Emergent habitat. The impact of a large reduction in habitat area and decreasing habitat suitability has been compounded by habitat fragmentation. The remaining habitat must be actively managed to ensure its usefulness to the mahogany glider by implementing an appropriate fire regime and ensuring that habitat connectivity is maintained or increased.
The Angular Diameter and Fundamental Parameters of Sirius A
Authors: Davis J. , Ireland M. J. , North J. R. , Robertson J. G. , Tango W. J. , Tuthill P. G.
Published: March 2011

The Sydney University Stellar Interferometer (SUSI) has been used to make a new determination of the angular diameter of Sirius A. The observations were made at an effective wavelength of 694.1 nm and the new value for the limb-darkened angular diameter is 6.048 ± 0.040 mas (± 0.66%). This new result is compared with previous measurements and is found to be in excellent agreement with a conventionally calibrated measurement made with the European Southern Observatory's Very Large Telescope Interferometer (VLTI) at 2.176 μm (but not with a second globally calibrated VLTI measurement). A weighted mean of the SUSI and first VLTI results gives the limb-darkened angular diameter of Sirius A as 6.041 ± 0.017 mas (± 0.28%). Combination with the Hipparcos parallax gives the radius equal to 1.713 ± 0.009 R⊙. The bolometric flux has been determined from published photometry and spectrophotometry and, combined with the angular diameter, yields the emergent flux at the stellar surface equal to (5.32 ± 0.14) × 108 W m−2 and the effective temperature equal to 9845 ± 64 K. The luminosity is 24.7 ± 0.7 L⊙.
Subtraction of Bright Point Sources from Synthesis Images of the Epoch of Reionization
Authors: Pindor B. , Wyithe J. S. B. , Mitchell D. A. , Ord S. M. , Wayth R. B. , Greenhill L. J.
Published: March 2011

Bright point sources associated with extragalactic active galactic nuclei and radio galaxies are an important foreground for low-frequency radio experiments aimed at detecting the redshifted 21-cm emission from neutral hydrogen during the epoch of reionization. The frequency dependence of the synthesized beam implies that the sidelobes of these sources will move across the field of view as a function of observing frequency, hence frustrating line-of-sight foreground subtraction techniques. We describe a method for subtracting these point sources from dirty maps produced by an instrument such as the MWA. This technique combines matched filters with an iterative centroiding scheme to locate and characterize point sources in the presence of a diffuse background. Simulations show that this technique can improve the dynamic range of epoch-of-reionization maps by 2—3 orders of magnitude.
Community engagement in regional development: a case study of a systems approach to tourism in central Australia
Authors: Friedel Margaret , Chewings Vanessa
Published: March 2011

We report a case study of community involvement in industry and regional development which took a whole-system approach to growing the tourist industry in central Australia. All stages of the study are presented beginning with the initial creation of a systems model of the industry in collaboration with the tourism industry, government agencies and the wider community in Stage 1. The process of engaging support for Stage 2 is described and attempts to refine the components of the model and develop an information system in the second stage are outlined.
Neither a refinement of the tourism simulator model nor a functional information system were achieved, although extensive information was gathered and interpreted as part of the process. The outcomes were constrained by institutional difficulties despite clear goodwill among the participants. Contrary to expectations, data that would help build the sub-models were not found. An events and attractions investment sub-model was developed as fully as possible to explore data constraints. Information provided by interviewees was synthesised as far as possible to develop relationships describing economic impacts, but different ways of estimating outcomes were not compatible, even within a single sub-model. A review of recent literature showed that effective modelling required much more sophisticated data gathering than was possible within this study to indicate sustainable yield from different investment strategies.
The study provided a practical demonstration of the challenges involved in genuinely engaging a regional rangeland community in industry and regional development, and the limited benefits of systems dynamics modelling, especially where resources and data are constrained. A useful outcome was the identification of the particular activities which elicited the greatest response from participants – the systems workshops, trialling the demonstration tourism simulator and one-on-one sharing of information. These should form the basis of future community involvement in regional development rather than any attempt to refine modelling tools.
Effects of nitrogen and phosphorus on vegetation dynamics of a degraded native grassland in semi-arid south-eastern Australia
Authors: Hacker R. B. , Toole I. D. , Melville G. J.
Published: March 2011

The roles of nitrogen (N) and phosphorus (P) in controlling vegetation transitions in a degraded semi-arid grassland were investigated in a factorial experiment that combined two initial levels of perennial plant density (low and high), three levels of N (N+, N0 and N–) and two levels of P (P+ and P0). Increased levels of both N and P were achieved by fertiliser addition while sucrose was used to reduce the level of N. Vegetation dynamics were driven primarily by soil N rather than P. Addition of sucrose, which was inferred to result in the immobilisation of mineral N, reduced the growth of annual species and facilitated the establishment and growth of native perennial grasses. Addition of P generally had no significant effect on dry matter production, either in total or for species grouped as forbs, annual grasses and perennial grasses, or on recruitment and mortality of perennial grasses. However, at some times of observation addition of P increased ground cover and/or the basal circumference of some perennial grass species. Basal circumference for Enteropogon acicularis was also increased by addition of N. Soil biological activity, measured by decomposition of cotton strips, was increased by addition of N, which maintained vegetation in an annual-dominated condition, and was not affected by addition of P. Carbon addition has the potential to assist restoration of this grassland. However, the capacity of some native grass species to respond to increased fertility suggests that once restoration is achieved some increase in fertility may be beneficial for pastoral production.
The diet of the dingo (Canis lupus dingo) in north-eastern Australia with comments on its conservation implications
Authors: Brook L. A. , Kutt A. S.
Published: March 2011

The dingo (Canis lupus dingo and hybrids) is the top mammalian predator on the Australian mainland and is thought to control and suppress populations of native herbivores and smaller mesopredators, including the introduced feral cat (Felis catus). Dingoes have been persecuted as a threat to domestic livestock, and local population decreases have been linked to increasing mesopredator populations, which in turn may cause the decline of small native mammals. There is little data on the dingo’s dietary composition in northern Australia. We examined the diet of dingoes in north-eastern Queensland via scat collection and analysis. A total of 178 scats were examined between 1994 and 2000, comprised of 185 prey items and representing 21 discrete prey types. Native mammal prey was the most frequent dietary component (69.7%), with large- to medium-sized macropods (Macropus spp. and Wallabia bicolor) present in the majority of samples (51.1%). Critical Weight Range species were found in 18.0% of the records. Introduced species such as the European hare/rabbit (Lepus capensis/Oryctolagus cuniculus) and cattle (Bos taurus) were found in smaller amounts (14.6 and 10.1%, respectively). These results suggest that dingoes prey considerably on large- to medium-sized macropods in our study area (north-eastern Australia). Dingo diet tends to differ regionally where dingoes prey on native species that are locally common or abundant. Finally, the diets of the dingo and feral cat do not appear to considerably overlap in our study area, which may have implications for mesopredator suppression.
Two new species and one reapplied name in Sesbania Scop. (Fabaceae, Sesbanieae) for Australia
Authors: Gross C. L.
Published: March 2011

For over 40 years, the names Sesbania benthamiana Domin, S. javanica Miq. and S. sesban (L.) Merr. have been applied to Australian plant specimens. A review of the types assigned to these taxa has resolved that the names S. javanica Miq. and S. sesban (L.) Merr. do not apply to species native to Australia and S. benthamiana has been misapplied. The name S. burbidgei is proposed to account for specimens previously identified as S. sesban and S. muelleri is proposed to account for specimens previously assigned as S. benthamiana. The name S. benthamiana is reapplied to material previously known as S. javanica.
Lysine methyltransferase G9a is required for de novo DNA methylation and the establishment, but not the maintenance, of proviral silencing
Authors: Leung Danny C. , Dong Kevin B. , Maksakova Irina A. , Goyal Preeti , Appanah Ruth , Lee Sandra , Tachibana Makoto , Shinkai Yoichi , Lehnertz Bernhard , Mager Dixie L. , Rossi Fabio , Lorincz Matthew C.
Published: March 2011

Methylation on lysine 9 of histone H3 (H3K9me) and DNA methylation play important roles in the transcriptional silencing of specific genes and repetitive elements. Both marks are detected on class I and II endogenous retroviruses (ERVs) in murine embryonic stem cells (mESCs). Recently, we reported that the H3K9-specific lysine methyltransferase (KMTase) Eset/Setdb1/KMT1E is required for H3K9me3 and the maintenance of silencing of ERVs in mESCs. In contrast, G9a/Ehmt2/KMT1C is dispensable, despite the fact that this KMTase is required for H3K9 dimethylation (H3K9me2) and efficient DNA methylation of these retroelements. Transcription of the exogenous retrovirus (XRV) Moloney murine leukemia virus is rapidly extinguished after integration in mESCs, concomitant with de novo DNA methylation. However, the role that H3K9 KMTases play in this process has not been addressed. Here, we demonstrate that G9a, but not Suv39h1 or Suv39h2, is required for silencing of newly integrated Moloney murine leukemia virus–based vectors in mESCs. The silencing defect in
G9a
−/−
cells is accompanied by a reduction of H3K9me2 at the proviral LTR, indicating that XRVs are direct targets of G9a. Furthermore, de novo DNA methylation of newly integrated proviruses is impaired in the
G9a
−/−
line, phenocopying proviral DNA methylation and silencing defects observed in Dnmt3a-deficient mESCs. Once established, however, maintenance of silencing of XRVs, like ERVs, is dependent exclusively on the KMTase Eset. Taken together, these observations reveal that in mESCs, the H3K9 KMTase G9a is required for the establishment, but not for the maintenance, of silencing of newly integrated proviruses.
Politeness in a Japanese intra-organisational meeting
Authors: Tanaka Hiromasa
Published: March 2011

This paper examines data collected during an intra-organisational meeting in a Japanese company. It illustrates how, in a situation involving potential conflicts, some Japanese managers switch between different linguistic codes in order to construct situational meaning. The interlocutors’ code-switch indicates constant vertical and horizontal change of their footing by sometimes strengthening solidarity with subordinates and mitigating potential face threatening acts (FTAs). This finding indicates that the use of honorifics and other social indexical forms in Japanese is not pre-determined by existing social conventions; but rather it is subject to situational evaluation of the fluid local context where relationships are constructed and negotiated.
Stereotypes in the making
Authors: Ladegaard Hans J.
Published: March 2011

This article analyzes how a group of Hong Kong students talk about people in other countries in an informal group discussion. The focus is on the discursive construction of outgroup stereotypes, and the analyses show that the attitudes discussed in the group are highly variable, even contradictory — across as well as within individual group members. Discursive Psychology is used as the theoretically informed analytic approach for the analysis, and Social Identity Theory (Tajfel) and Self-Categorization Theory (Turner) are proposed as the overall theoretical frameworks which seem to encompass the different themes uncovered in the analyses. The article argues that personal experience, rhetorical ends, and group dynamics are salient factors in terms of explaining the construction and nature of the stereotypes. Furthermore, it is argued that intergroup differentiation is important in accounting for the process of stereotype-construction, and that cognitive dissonance, as well as accusations of prejudiced identities, appear to have little noticeable effect on individual group members or intra-group harmony. Finally, the article argues that this group discussion could be seen as an example of predominant discourses and ideological positions about Western and Asian ‘others’ which exist in contemporary Hong Kong society.
A generalized Poincaré inequality for a class of constant coefficient differential operators
Authors: Gustafson Derek
Published: March 2011

We study first order differential operators

P

=

P

(
D
)

\mathcal {P} = \mathcal {P}(D)

with constant coefficients. The main question is under what conditions the following full gradient

L
p

L^p

estimate holds:
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="double-vertical-bar upper D left-parenthesis f minus f 0 right-parenthesis double-vertical-bar Subscript upper L Sub Superscript p Subscript Baseline less-than-or-equal-to upper C double-vertical-bar script upper P f double-vertical-bar Subscript upper L Sub Superscript p Subscript Baseline comma for some f 0 element-of kernel script upper P period">

‖
D
(
f
−

f
0

)

‖

L
p

≤
C
‖

P

f

‖

L
p

,
 

for some 

f
0

∈
ker
⁡

P

.

\|D(f-f_0)\|_{L^p} \leq C \|\mathcal {P} f\|_{L^p},\ \textrm {for some } f_0 \in \ker \mathcal {P}.

\]
We show that the constant rank condition is sufficient. The concept of the Moore-Penrose generalized inverse of a matrix comes into play.