New Functions (new + function)

Distribution by Scientific Domains
Distribution within Life Sciences


Selected Abstracts


Speaking Softly Without Big Sticks: Meta-Regulation and Public Sector Audit

LAW & POLICY, Issue 3 2003
Colin Scott
Australian government has undergone an "audit explosion" in the last twenty years. This article observes, first, that the constitutional function of public sector audit institutions (AIs) gives them a strong cultural commitment to the assessment of the regularity and legality of public expenditure. New functions connected with performance audit and evaluation of nonfinancial performance indicators are liable to be interpreted through the lens of these more traditional concerns. The second observation is that, if we think in terms of "regimes" of financial control, we find that AIs form only part of the overall regulatory regime. This calls into question the coherence and potential for effectiveness of regimes of financial control. However, AIs could also be conceived as "meta-regulators" with the capacity to steer the self-regulatory capacities of public sector organizations in respect of financial controls. Auditors may be effective as meta-regulators through speaking softly, even though they demonstrably lack big sticks. [source]


New functions for the ancient globin family: bacterial responses to nitric oxide and nitrosative stress

MOLECULAR MICROBIOLOGY, Issue 4 2000
MicroReview
Globin-like oxygen-binding proteins occur in bacteria, yeasts and other fungi, and protozoa. The simplest contain protohaem as sole prosthetic group, but show considerable variation in their similarity to the classical animal globins and plant globins. Flavohaemoglobins comprise a haem domain homologous to classical globins and a ferredoxin-NADP+ reductase (FNR)-like domain that converts the globin into an NAD(P)H-oxidizing protein with diverse reductase activities. In Escherichia coli, the prototype flavohaemoglobin (Hmp) is clearly involved in responses to nitric oxide (NO) and nitrosative stress: (i) the structural gene hmp is upregulated by NO and nitrosating agents; (ii) purified Hmp binds NO avidly, but also converts it to nitrate (aerobically) or nitrous oxide (anaerobically); (iii) hmp mutants are hypersensitive to NO and nitrosative stresses. Here, we review recent advances in E. coli and the growing number of microbes in which globins are known, draw particular attention to the essential chemistry of NO and related reactive species and their interactions with globins, and suggest that microbial globins have additional functions unrelated to ,NO' stresses. [source]


Dynamic ankle,foot orthoses as a part of treatment in children with spastic diplegia , Parents' perceptions

PHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 2 2003
Annika Näslund
Abstract Background and Purpose Dynamic ankle,foot orthoses (DAFOs) are often recommended for children with spastic diplegia in order to facilitate better function. The aim of the present study was to explore how the parents of children with diplegic cerebral palsy experience the use of DAFOs. Method A qualitative interview study with a broad research question: ,How do you perceive that DAFOs influence your child?' The parents of 15 children, aged 4,18 years, who all had spastic diplegia and wore DAFOs were interviewed. Results Content analysis resulted in the following categories: ,Physical effects'; ,New functions and activities'; ,The orthosis as a part of the treatment'; ,Opportunity for independence and play'; and ,Problems with DAFOs'. According to the parents, DAFOs appeared to contribute to the (mechanical) changes in posture affecting the muscular system. They meant that when wearing DAFOs the foot and ankle are more stable. This in turn enables postural control and alignment, contributing to functional activities under more favourable physiological conditions. The psychosocial effects were regarded by parents as being just as important as the physical effects. Conclusion In clinical practice, DAFOs may (according to parents) be regarded as a suitable complement to other treatments in children with diplegic cerebral palsy. Copyright © 2003 Whurr Publishers Ltd. [source]


Emx3 is required for the differentiation of dorsal telencephalic neurons

DEVELOPMENTAL DYNAMICS, Issue 8 2009
Gudrun Viktorin
Abstract emx3 is first expressed in prospective telencephalic cells at the anterior border of the zebrafish neural plate. Knockdown of Emx3 function by morpholino reduces the expression of markers specific to dorsal telencephalon, and impairs axon tract formation. Rescue of both early and late markers requires low-level expression of emx3 at the one- or two-somite stage. Higher emx3 expression levels cause dorsal telencephalic markers to expand ventrally, which points to a possible role of emx3 in specifying dorsal telencephalon and a potential new function for Wnt/beta-catenin pathway activation. In contrast to mice, where Emx2 plays a major role in dorsal telencephalic development, knockdown of zebrafish Emx2 apparently does not affect telencephalic development. Similarly, Emx1 knockdown has little effect. Previously, emx3 was thought to be fish-specific. However, we found all three emx orthologs in Xenopus tropicalis and opossum (Monodelphis domestica) genomes, indicating that emx3 was present in an ancestral tetrapod genome. Developmental Dynamics 238:1984,1998, 2009. © 2009 Wiley-Liss, Inc. [source]


A new function for LAT and CD8 during CD8-mediated apoptosis that is independent of TCR signal transduction

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2009
Raedun L. Clarke
Abstract The majority (>95%) of thymocytes undergo apoptosis during selection in the thymus. Several mechanisms have been proposed to explain how apoptosis of thymocytes that are not positively selected occurs; however, it is unknown whether thymocytes die purely by "neglect" or whether signaling through a cell-surface receptor initiates an apoptotic pathway. We have previously demonstrated that on double positive thymocytes the ligation of CD8 in the absence of TCR engagement results in apoptosis and have postulated this is a mechanism to remove thymocytes that have failed positive selection. On mature single positive T cells CD8 acts as a co-receptor to augment signaling through the TCR that is dependent on the phosphorylation of the adaptor protein, linker for activation of T cells (LAT). Here, we show that during CD8-mediated apoptosis of double positive thymocytes there is an increase in the association of CD8 with LAT and an increase in LAT tyrosine phosphorylation. Decreasing LAT expression and mutation of tyrosine residues of LAT reduced apoptosis upon crosslinking of CD8. Our results identify novel functions for both CD8 and LAT that are independent of TCR signal transduction and suggest a mechanism for signal transduction leading to apoptosis upon CD8 crosslinking. [source]


MAP-kinase-activated protein kinase 2 expression and activity is induced after neuronal depolarization

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008
Tobias Thomas
Abstract Mitogen-activated protein kinase-activated protein kinase (MK)2 is one of several downstream targets of p38 mitogen-activated protein kinase and has a well documented role in inflammation. Here, we describe a possible new function of MK2. We show that triggering depolarization by potassium chloride or increasing the cellular cAMP by forskolin treatment led to elevated levels of expression and activity of mouse MK2. In both treatments, the kinase inhibitor H89 completely prevented the up-regulation of MK2 at the transcript level. By the use of different cell lines we demonstrated that the induction of MK2 expression is characteristic of neuronal cells and is absent in fibroblasts, macrophages and kidney cells. In vivo, induction of a status epilepticus by systemic administration of the chemoconvulsant kainic acid resulted in markedly reduced neurodegeneration in the pyramidal layer of the hippocampus, dentate gyrus and hilus of MK2-deficient mice compared with wild-type mice. Together, our data suggest a possible role of MK2 in the cellular response after neuronal depolarization, in particular in excitotoxicity. [source]


Sinusoidal remodeling and angiogenesis: A new function for the liver-specific pericyte?,

HEPATOLOGY, Issue 3 2007
June Sung Lee
First page of article [source]


Power function decay of hydraulic conductivity for a TOPMODEL-based infiltration routine

HYDROLOGICAL PROCESSES, Issue 18 2006
Jun Wang
Abstract TOPMODEL rainfall-runoff hydrologic concepts are based on soil saturation processes, where soil controls on hydrograph recession have been represented by linear, exponential, and power function decay with soil depth. Although these decay formulations have been incorporated into baseflow decay and topographic index computations, only the linear and exponential forms have been incorporated into infiltration subroutines. This study develops a power function formulation of the Green and Ampt infiltration equation for the case where the power n = 1 and 2. This new function was created to represent field measurements in the New York City, USA, Ward Pound Ridge drinking water supply area, and provide support for similar sites reported by other researchers. Derivation of the power-function-based Green and Ampt model begins with the Green and Ampt formulation used by Beven in deriving an exponential decay model. Differences between the linear, exponential, and power function infiltration scenarios are sensitive to the relative difference between rainfall rates and hydraulic conductivity. Using a low-frequency 30 min design storm with 4·8 cm h,1 rain, the n = 2 power function formulation allows for a faster decay of infiltration and more rapid generation of runoff. Infiltration excess runoff is rare in most forested watersheds, and advantages of the power function infiltration routine may primarily include replication of field-observed processes in urbanized areas and numerical consistency with power function decay of baseflow and topographic index distributions. Equation development is presented within a TOPMODEL-based Ward Pound Ridge rainfall-runoff simulation. Copyright © 2006 John Wiley & Sons, Ltd. [source]


Numerical implementation of Aristov,Pukhnachev's formulation for axisymmetric viscous incompressible flows

INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 10 2010
N. P. Moshkin
Abstract In the present work a finite-difference technique is developed for the implementation of a new method proposed by Aristov and Pukhnachev (Doklady Phys. 2004; 49(2):112,115) for modeling of the axisymmetric viscous incompressible fluid flows. A new function is introduced that is related to the pressure and a system similar to the vorticity/stream function formulation is derived for the cross-flow. This system is coupled to an equation for the azimuthal velocity component. The scheme and the algorithm treat the equations for the cross-flow as an inextricably coupled system, which allows one to satisfy two conditions for the stream function with no condition on the auxiliary function. The issue of singularity of the matrix is tackled by adding a small parameter in the boundary conditions. The scheme is thoroughly validated on grids with different resolutions. The new numerical tool is applied to the Taylor flow between concentric rotating cylinders when the upper and lower lids are allowed to rotate independently from the inner cylinder, while the outer cylinder is held at rest. The phenomenology of this flow is adequately represented by the numerical model, including the hysteresis that takes place near certain specific values of the Reynolds number. Thus, the present results can be construed to demonstrate the viability of the new model. The success can be attributed to the adequate physical nature of the auxiliary function. The proposed technique can be used in the future for in-depth investigations of the bifurcation phenomena in rotating flows. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Dock4 regulates dendritic development in hippocampal neurons

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2008
Shuhei Ueda
Abstract Dendrite development is required for establishing proper neuronal connectivity. Rho-family small GTPases have been reported to play important roles in the regulation of dendritic growth and morphology. However, the molecular mechanisms that control the activities of Rho GTPases in developing dendrites are not well understood. In the present study we found Dock4, an activator of the small GTPase Rac, to have a role in regulating dendritic growth and branching in rat hippocampal neurons. Dock4 is highly expressed in the developing rat brain, predominantly in hippocampal neurons. In dissociated cultured hippocampal neurons, the expression of Dock4 protein is up-regulated after between 3 and 8 days in culture, when dendrites begin to grow. Knockdown of endogenous Dock4 results in reduced dendritic growth and branching. Conversely, overexpression of Dock4 with its binding partner ELMO2 enhances the numbers of dendrites and dendritic branches. These morphological effects elicited by Dock4 and ELMO2 require Rac activation and the C-terminal Crk-binding region of Dock4. Indeed, Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons. These findings demonstrate a new function of the Rac activator Dock4 in dendritic morphogenesis in hippocampal neurons. © 2008 Wiley-Liss, Inc. [source]


Advances in protein turnover analysis at the global level and biological insights

MASS SPECTROMETRY REVIEWS, Issue 5 2010
Qingbo Li
Abstract The concept of a dynamic state of body constituents, a precursor of the modern term of proteome dynamics, was conceived over a century ago. But, not until recently can we examine the dynamics of individual "constituents" for example, proteins at a truly global level. The path of advancement in our understanding of protein turnover at the global level is marked by the introduction of some key technological innovations. These methods include the isotopic tracer technique in the 1930s, the two-dimensional gel electrophoresis technique in the 1970s, the sector mass spectrometer that could analyze isotopomers of peptides in the early 1990s, the 2D gel/MALDI-TOF proteomics technology in the late 1990s, the booming liquid chromatography/mass spectrometry proteomics technology in this decade, and the recently emerging protein-tagging approaches that offer single-cell resolution for protein turnover measurements. The long-standing inquiry raised in the 1950s about the existence of a dynamic state in different organisms at different physiological conditions can now be answered with an individual "constituent" resolution on a truly global scale. Now it appears that protein degradation is not necessarily an end to the protein function. Rather, it can be the start of a new function because protein degradation clears the way for the action of other proteins. Protein turnover participates in a multi-layer complex regulatory network and shares equal importance with gene transcription and protein translation. The advances in technologies for protein turnover analysis and the improved understanding of the biological role of protein turnover will likely help to solve some long-standing biomedical problems such as the tuberculosis disease that at the present day still affects one-third of the world population. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:717,736, 2010 [source]


Origin of the murine implantation serine proteinase subfamily,

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2004
Colleen M. O'Sullivan
Abstract The S1 serine protease family is one of the largest gene families known. Within this family there are several subfamilies that have been grouped together as a result of sequence comparisons and substrate identification. The grouping of related genes allows for the speculation of function for newly found members by comparison and for novel subfamilies by contrast. Analysis of the evolutionary patterns of genes indicates whether or not orthologs are likely to be identified in other species as well as potentially indicating that hypothesized orthologs are in fact not. Looking at subtle differences between subfamily members can reveal intricacies about function and expression. Previously, we have described genes encoding two novel serine proteinases, ISP1 and ISP2, which are most closely related to tryptases. The ISP1 gene encodes the embryo-derived enzyme strypsin, which is necessary for blastocyst hatching and invasion in vitro. Additionally both ISP1 and ISP2 are co-expressed in the endometrial gland during the time of hatching, suggesting that they may also both participate in zona lysis from within the uterine lumen. Here, we demonstrate that the ISPs are tandemly linked within the tryptase cluster on 17A3.3. We suggest that remarkable similarities within the 5,-untranslated and first intron regions of ISP1 and ISP2 may explain their intimate co-regulation in uterus. We also suggest that ISP genes have evolved through gene duplication and that the ISP1 gene has also begun to adopt an additional new function in the murine preimplantation embryo. Mol. Reprod. Dev. 69: 126,136, 2004. © 2004 Wiley-Liss, Inc. [source]


Planning and Optimization of a Numerical Control Machine in a Multiple Response Case

QUALITY AND RELIABILITY ENGINEERING INTERNATIONAL, Issue 5 2006
Rossella Berni
Abstract This paper focuses on a specific case of experimental planning and optimization in a multiresponse case. Particularly, our attention is dedicated to a numerical control machine and our final goal is to improve this machine's measurement accuracy for a general dental implant. This work substantially aims at addressing two issues: the optimization methods in the presence of more response variables and the related problem of weighting according to the actual importance of these variables. About simultaneous optimization, we suggest an improvement by a new function which takes care of location and dispersion effects. Copyright © 2006 John Wiley & Sons, Ltd. [source]


NONPARAMETRIC ESTIMATION OF CONDITIONAL CUMULATIVE HAZARDS FOR MISSING POPULATION MARKS

AUSTRALIAN & NEW ZEALAND JOURNAL OF STATISTICS, Issue 1 2010
Dipankar Bandyopadhyay
Summary A new function for the competing risks model, the conditional cumulative hazard function, is introduced, from which the conditional distribution of failure times of individuals failing due to cause,j,can be studied. The standard Nelson,Aalen estimator is not appropriate in this setting, as population membership (mark) information may be missing for some individuals owing to random right-censoring. We propose the use of imputed population marks for the censored individuals through fractional risk sets. Some asymptotic properties, including uniform strong consistency, are established. We study the practical performance of this estimator through simulation studies and apply it to a real data set for illustration. [source]


Relaxation of arterial smooth muscle: A new function of a water-soluble degradation product of coenzyme Q (ubiquinone)

BIOFACTORS, Issue 1-4 2003
R. Bindu
Abstract Treatment of coenzyme Q with ozone yielded a degradation product having unmodified ring that retained its spectral characteristics and a truncated side-chain that made it water-soluble. This derivative, but not the intact lipid-quinone, showed relaxation of phenylephrine-contracted rat arterial rings. This effect offers an explanation for the known hypotensive action of exogenous coenzyme Q regardless of its side-chain length. [source]


Capsule enlargement in Cryptococcus neoformans confers resistance to oxidative stress suggesting a mechanism for intracellular survival

CELLULAR MICROBIOLOGY, Issue 10 2008
Oscar Zaragoza
Summary Cryptococcus neoformans is a facultative intracellular pathogen. The most distinctive feature of C. neoformans is a polysaccharide capsule that enlarges depending on environmental stimuli. The mechanism by which C. neoformans avoids killing during phagocytosis is unknown. We hypothesized that capsule growth conferred resistance to microbicidal molecules produced by the host during infection, particularly during phagocytosis. We observed that capsule enlargement conferred resistance to reactive oxygen species produced by H2O2 that was not associated with a higher catalase activity, suggesting a new function for the capsule as a scavenger of reactive oxidative intermediates. Soluble capsular polysaccharide protected C. neoformans and Saccharomyces cerevisiae from killing by H2O2. Acapsular mutants had higher susceptibility to free radicals. Capsular polysaccharide acted as an antioxidant in the nitroblue tetrazolium (NBT) reduction coupled to ,-nicotinamide adenine dinucleotide (NADH)/phenazine methosulfate (PMS) assay. Capsule enlargement conferred resistance to antimicrobial peptides and the antifungal drug Amphotericin B. Interestingly, the capsule had no effect on susceptibility to azoles and increased susceptibility to fluconazole. Capsule enlargement reduced phagocytosis by environmental predators, although we also noticed that in this system, starvation of C. neoformans cells produced resistance to phagocytosis. Our results suggest that capsular enlargement is a mechanism that enhances C. neoformans survival when ingested by phagocytic cells. [source]


A pulse programmer for nuclear magnetic resonance spectrometers

CONCEPTS IN MAGNETIC RESONANCE, Issue 2 2007
C.C. Odebrecht
Abstract A pulse programmer (PP) designed to control a nuclear magnetic resonance (NMR) spectrometer is reported on. The heart of the PP is a computer programmable logic device (CPDL) that provides flexibility to the design and, at the same time, reduces the number of electronics components needed and the dimensions of the printed circuit board. The PP works as follow: first, a pulse sequence defined by a set of instructions is loaded into the RAM memory of the PP. Then, when the process is started, the instructions are, one by one, read, decoded, and executed. Four types of instructions (functions) were defined: PRINT A, PRINT B, WAIT, and STOP. PRINT A and PRINT B change the status of the output channels A and B, respectively, WAIT generates a time delay, and STOP terminates the sequence. The output ports A and B have 14 channels each, and the shortest pulse and resolution are both 200 ns. The design of the PP is versatile, and new functions can be added through software without modifying the printed circuit board. To control the PP from a personal computer, a program named PulseJr was developed. It contains a graphical user interface (GUI) and pulse sequences can be drawn on the monitor screen with the mouse of the computer. Once the pulse sequence is sketched, clicking a button the program compiles the pulse sequence, generates the set of instructions, loads them into the RAM memory of the PP, and starts the pulse sequence. © 2007 Wiley Periodicals, Inc. Concepts Magn Reson Part A 30A: 127,131, 2007. [source]


Identification of germ plasm-associated transcripts by microarray analysis of Xenopus vegetal cortex RNA

DEVELOPMENTAL DYNAMICS, Issue 6 2010
Tawny N. Cuykendall
Abstract RNA localization is a common mechanism for regulating cell structure and function. Localized RNAs in Xenopus oocytes are critical for early development, including germline specification by the germ plasm. Despite the importance of these localized RNAs, only approximately 25 have been identified and fewer are functionally characterized. Using microarrays, we identified a large set of localized RNAs from the vegetal cortex. Overall, our results indicate a minimum of 275 localized RNAs in oocytes, or 2,3% of maternal transcripts, which are in general agreement with previous findings. We further validated vegetal localization for 24 candidates and further characterized three genes expressed in the germ plasm. We identified novel germ plasm expression for reticulon 3.1, exd2 (a novel exonuclease-domain encoding gene), and a putative noncoding RNA. Further analysis of these and other localized RNAs will likely identify new functions of germ plasm and facilitate the identification of cis -acting RNA localization elements. Developmental Dynamics 239:1838,1848, 2010. © 2010 Wiley-Liss, Inc. [source]


The primary cilium as a gravitational force transducer and a regulator of transcriptional noise

DEVELOPMENTAL DYNAMICS, Issue 8 2008
Stephen J. Moorman
Abstract Circumstantial evidence has suggested that the primary cilium might function as a gravity sensor. Direct evidence of its gravity-sensing function has recently been provided by studies of rohon beard neurons. These neurons showed changes in the variability of gene expression levels that are linked to the cyclic changes in the Earth's gravitational field due to the Sun and Moon. These cyclic changes also cause the tides. Rohon beard neurons, after the primary cilia have been selectively destroyed, no longer show changes in gene expression variability linked to the cyclic changes in Earth's gravitational field. After the neurons regrow their primary cilia, the link between variability in gene expression levels and the Earth's changing gravitational field returns. This suggests two new functions for the primary cilia, detecting the cyclical changes in the Earth's gravitational field and transducing those changes into changes in the variability (stochastic nature) of gene expression. Developmental Dynamics 237:1955,1959, 2008. © 2008 Wiley-Liss, Inc. [source]


Beetle horns are regulated by the Hox gene, Sex combs reduced, in a species- and sex-specific manner

EVOLUTION AND DEVELOPMENT, Issue 4 2010
Bethany R. Wasik
SUMMARY Discovering the mechanisms that underlie the origin of novel features represents a major frontier in developmental and evolutionary biology. Here we begin to characterize the role of the Hox gene Sex combs reduced (Scr) during the development and evolution of a morphologically novel trait: beetle horns. Beetle horns develop as epidermal outgrowths from the prothorax and/or head, and size and location vary dramatically across species and between sexes. Using both comparative gene expression and larval RNA interference in two species of the horned beetle genus Onthophagus, we show that Scr functions in patterning adult labial mouthpart identity and suppressing wing development in the prothorax. At the same time, however, our results illustrate that Scr has acquired, within its ancestral domain of expression, additional new functions including the regulation of prepupal growth and pupal remodeling of pronotal horn primordia. Furthermore, comparative analyses of our results across both Onthophagus species, which differ in location of horn development (thoracic horns vs. thoracic and head horns) as well as patterns of sexual dimorphism (traditional vs. reversed sexual dimorphism), reveal surprising differences in exactly when, where, and to what degree Scr regulates horn formation in different sexes. These observations suggest that the interactions between Scr and its targets in the regulation of horn development can diversify quickly over remarkably short phylogenetic distances. More generally, our results suggest that the Hox complex can play an integral role in the development and evolution of novel complex traits while maintaining traditional patterning responsibilities. [source]


Expression of a homologue of the fushi tarazu (ftz) gene in a cirripede crustacean

EVOLUTION AND DEVELOPMENT, Issue 2 2002
Emmanuèle Mouchel-Vielh
SUMMARY In Metazoa, Hox genes control the identity of the body parts along the anteroposterior axis. In addition to this homeotic function, these genes are characterized by two conserved features: They are clustered in the genome, and they contain a particular sequence, the homeobox, encoding a DNA-binding domain. Analysis of Hox homeobox sequences suggests that the Hox cluster emerged early in Metazoa and then underwent gene duplication events. In arthropods, the Hox cluster contains eight genes with a homeotic function and two other Hox -like genes, zerknullt (zen)/Hox3 and fushi tarazu (ftz). In insects, these two genes have lost their homeotic function but have acquired new functions in embryogenesis. In contrast, in chelicerates, these genes are expressed in a Hox -like pattern, which suggests that they have conserved their ancestral homeotic function. We describe here the characterization of Diva, the homologue of ftz in the cirripede crustacean Sacculina carcini. Diva is located in the Hox cluster, in the same position as the ftz genes of insects, and is not expressed in a Hox -like pattern. Instead, it is expressed exclusively in the central nervous system. Such a neurogenic expression of ftz has been also described in insects. This study, which provides the first information about the Hox cluster in Crustacea, reveals that it may not be much smaller than the insect cluster. Study of the Diva expression pattern suggests that the arthropod ftz gene has lost its ancestral homeotic function after the divergence of the Crustacea/Hexapoda clade from other arthropod clades. In contrast, the function of ftz during neurogenesis is well conserved in insects and crustaceans. [source]


A novel 2D-based approach to the discovery of candidate substrates for the metalloendopeptidase meprin

FEBS JOURNAL, Issue 18 2008
Daniel Ambort
In the past, protease-substrate finding proved to be rather haphazard and was executed by in vitro cleavage assays using singly selected targets. In the present study, we report the first protease proteomic approach applied to meprin, an astacin-like metalloendopeptidase, to determine physiological substrates in a cell-based system of Madin,Darby canine kidney epithelial cells. A simple 2D IEF/SDS/PAGE-based image analysis procedure was designed to find candidate substrates in conditioned media of Madin,Darby canine kidney cells expressing meprin in zymogen or in active form. The method enabled the discovery of hitherto unkown meprin substrates with shortened (non-trypsin-generated) N- and C-terminally truncated cleavage products in peptide fragments upon LC-MS/MS analysis. Of 22 (17 nonredundant) candidate substrates identified, the proteolytic processing of vinculin, lysyl oxidase, collagen type V and annexin A1 was analysed by means of immunoblotting validation experiments. The classification of substrates into functional groups may propose new functions for meprins in the regulation of cell homeostasis and the extracellular environment, and in innate immunity, respectively. [source]


An Organic Nanoparticle Transistor Behaving as a Biological Spiking Synapse

ADVANCED FUNCTIONAL MATERIALS, Issue 2 2010
Fabien Alibart
Abstract Molecule-based devices are envisioned to complement silicon devices by providing new functions or by implementing existing functions at a simpler process level and lower cost, by virtue of their self-organization capabilities. Moreover, they are not bound to von Neuman architecture and this feature may open the way to other architectural paradigms. Neuromorphic electronics is one of them. Here, a device made of molecules and nanoparticles,a nanoparticle organic memory field-effect transistor (NOMFET),that exhibits the main behavior of a biological spiking synapse is demonstrated. Facilitating and depressing synaptic behaviors can be reproduced by the NOMFET and can be programmed. The synaptic plasticity for real-time computing is evidenced and described by a simple model. These results open the way to rate-coding utilization of the NOMFET in dynamical neuromorphic computing circuits. [source]


Secular power and its rewards in Dorset in the late eleventh and early twelfth centuries,

HISTORICAL RESEARCH, Issue 215 2009
Nicholas Karn
Secular administration was in large part the business of the readily identifiable holders of specific offices in the late eleventh and early twelfth centuries, but alongside these operated individuals who held more informal authority. Its very intangibility has made any assessment of the importance and power of those who wielded such authority difficult. Both categories of functionary, however, operated on behalf of, and were rewarded by, the crown. Through tracing the changing allocation of resource and reward to different officers, this article presents an understanding of the fluctuating relative power of sheriffs and other functionaries over decades when new functions were altering the patterns of secular administration. [source]


Molecular interactions of the neuronal GPI-anchored lipocalin Lazarillo

JOURNAL OF MOLECULAR RECOGNITION, Issue 5 2008
Diego Sanchez
Abstract Lazarillo, a glycoprotein involved in axon growth and guidance in the grasshopper embryo, is the only member of the lipocalin family that is attached to the cell surface by a GPI anchor. Recently, the study of Lazarillo homologous genes in Drosophila and mouse has revealed new functions in the regulation of lifespan, stress resistance and neurodegeneration. Here we report an analysis of biochemical properties of Lazarillo to gain insight into the molecular basis of its physiological function. Recombinant forms of the grasshopper protein were expressed in two different systems to test: (1) potential binding of several hydrophobic ligands; (2) protein,protein homophilic interactions; and (3) whether interaction with the function-blocking mAb 10E6 interferes with ligand binding. We tested 10 candidate ligands (retinoic acid, heme, bilirubin, biliverdin, ecdysterone, juvenile hormone, farnesol, arachidonic acid, linoleic acid and palmitic acid), and monitored binding using electrophoretic mobility shift, absorbance spectrum, and fluorimetry assays. Our work indicates binding to heme and retinoic acid, resulting in increased electrophoretic mobility, as well as to fatty acids, resulting in multimerization. Retinoic acid and fatty acids binding were confirmed by fluorescence titration, and heme binding was confirmed with absorbance spectrum assays. We demonstrate that Lazarillo oligomerizes in solution and can form clusters in the plasma membrane when expressed and GPI-anchored to the cell surface, however it is unable to mediate cell,cell adhesion. Finally, by ligand-mAb competition experiments we show that ligand-binding alone cannot be the key factor for Lazarillo to perform its function during axonal growth in the grasshopper embryo. Copyright © 2008 John Wiley & Sons, Ltd. [source]


The four mammalian splice variants encoded by the p21-activated kinase 3 gene have different biological properties

JOURNAL OF NEUROCHEMISTRY, Issue 3 2008
Patricia Kreis
Abstract The p21-activated kinases (PAK1), PAK2, and PAK3 are members of the PAK group I and share high sequence identity and common biochemical properties. PAK3 is specifically implicated in neuronal plasticity and also regulates cell cycle progression, neuronal migration, and apoptosis. Loss of function of PAK3 is responsible for X-linked non-syndromic mental retardation whereas gain of PAK3 function is associated with cancer. To understand the functional specificities of PAK3, we analyzed the structure of PAK3 gene products. We report here the characterization of a new alternatively spliced exon called c located upstream of the previously identified exon b. Exon b is detected in all tetrapods and not in fish, exon c is only present in mammals. Mammalian PAK3 genes encode four splice variants and the corresponding proteins were detected with specific antibodies in brain extracts. All PAK3 transcripts are specifically expressed in brain and in particular in neurons. The presence of the exons b and c renders the kinase constitutively active and decreases interaction with GTPases. The expression of the new splice variants in COS7 cells alters cell morphology and modifies the structure of focal adhesions. We propose that the appearance of new alternatively spliced exons during evolution and the resulting increase of complexity of PAK3 gene products may confer new functions to this kinase and contribute to its specific roles in neuronal signaling. [source]


Implementation of remote monitoring and diffraction evaluation systems at the Photon Factory macromolecular crystallography beamlines

JOURNAL OF SYNCHROTRON RADIATION, Issue 3 2008
Yusuke Yamada
Owing to recent advances in high-throughput technology in macromolecular crystallography beamlines, such as high-brilliant X-ray sources, high-speed readout detectors and robotics, the number of samples that can be examined in a single visit to the beamline has increased dramatically. In order to make these experiments more efficient, two functions, remote monitoring and diffraction image evaluation, have been implemented in the macromolecular crystallography beamlines at the Photon Factory (PF). Remote monitoring allows scientists to participate in the experiment by watching from their laboratories, without having to come to the beamline. Diffraction image evaluation makes experiments easier, especially when using the sample exchange robot. To implement these two functions, two independent clients have been developed that work specifically for remote monitoring and diffraction image evaluation. In the macromolecular crystallography beamlines at PF, beamline control is performed using STARS (simple transmission and retrieval system). The system adopts a client,server style in which client programs communicate with each other through a server process using the STARS protocol. This is an advantage of the extension of the system; implementation of these new functions required few modifications of the existing system. [source]


Degradation of nitroaromatic compounds: a model to study evolution of metabolic pathways

MOLECULAR MICROBIOLOGY, Issue 4 2009
Maia Kivisaar
Summary Although many nitroaromatic compounds have been in nature for only a few decades, bacteria have already evolved the ability to metabolize them. Both horizontal transfer of genes and mutagenesis induced under stressful conditions might facilitate evolution of new catabolic pathways. Nitrotoluene degradation pathways are supposedly derived from an ancestral naphthalene degradation pathway. The 2-nitrotoluene degradation genes in Acidovorax sp. strain JS42 are controlled by the transcriptional activator NtdR, which differs from NagR, the activator of the naphthalene degradation operon in Ralstonia sp. strain U2, by only five amino acids. Both regulators respond to salicylate, an intermediate of naphthalene degradation, but NtdR also recognizes a wide range of nitroaromatic compounds. In this issue of Molecular Microbiology, Ju et al. present results of site-directed mutagenesis of NtdR and NagR and show how the nitrotoluene-responsive regulator NtdR can be generated from a NagR-like ancestor by only a few mutations. The reconstructed hypothetical pathway for the evolution of NtdR from NagR demonstrates stepwise broadening of the effector range of the evolving protein without loss of the original activity. These results provide strong evidence for the idea that promiscuity of proteins is an important step in the evolution of new functions. [source]


A tale of two dead ends: origin of a potential new gene and a potential new transposable element

MOLECULAR MICROBIOLOGY, Issue 6 2007
A. John Clutterbuck
Summary An article in this issue of Molecular Microbiology by Cultrone et al. describes how a non-autonomous helitron element could arise from its autonomous parent transposon by deletion followed by readthrough into an adjacent gene and its promoter, thus providing a mechanism for distribution of a specifically regulated promoter sequence around the genome, where it would have the potential to evolve new functions. [source]


The origin and evolution of human pathogens

MOLECULAR MICROBIOLOGY, Issue 1 2005
Eduardo A. Groisman
Summary What are the genetic origins of human pathogens? An international group of scientists discussed this topic at a workshop that took place in late October 2004 in Baeza (Spain). Focusing primarily on bacterial pathogens, they examined the role that pathogenicity islands and bacteriophages play on determining the virulence properties that distinguish closely related members of a given species, such as host range and tissue specificity. They also discussed an instance in which closely related bacterial species differ in the production of a cell surface modification mediating resistance to an antibiotic as a result of the disparate regulation of homologous genes. In certain pathogens, genes normally carrying out housekeeping functions may adopt new functions, whereas in other organisms, genes that respond to stresses associated with non-host environments are silenced during infection to prevent the expression of products that interfere with the normal colonization process. The adaptive behaviour of certain pathogens relies on gene variation at certain loci that by virtue of containing polymeric repeats in regulatory or coding regions, can generate variants that may or may not express products that modify the cell surface of the organism. The meeting also addressed the properties of ORFan genes, which have no homologues in the sequence databases, as well as the creation of genes de novo by duplication and divergence. [source]