Search

Materials in nature have fascinating properties that serve as a continuous source of inspiration for materials scientists. Accordingly, bio-mimetic and bio-inspired approaches have yielded remarkable structural and functional materials for a plethora of applications. Despite these advances, many properties of natural materials remain challenging or yet impossible to incorporate into synthetic materials. Natural materials are produced by living cells, which sense and process environmental cues and conditions by means of signaling and genetic programs, thereby controlling the biosynthesis, remodeling, functionalization, or degradation of the natural material. In this context, synthetic biology offers unique opportunities in materials sciences by providing direct access to the rational engineering of how a cell senses and processes environmental information and translates them into the properties and functions of materials. Here, we identify and review two main directions by which synthetic biology can be harnessed to provide new impulses for the biologization of the materials sciences: first, the engineering of cells to produce precursors for the subsequent synthesis of materials. This includes materials that are otherwise produced from petrochemical resources, but also materials where the bio-produced substances contribute unique properties and functions not existing in traditional materials. Second, engineered living materials that are formed or assembled by cells or in which cells contribute specific functions while remaining an integral part of the living composite material. We finally provide a perspective of future scientific directions of this promising area of research and discuss science policy that would be required to support research and development in this field., Materials Today Bio, 11, ISSN:2590-0064

Resume Objectif Depuis la promulgation de la loi sur la transparence sur la securite nucleaire en juin 2006, les activites nucleaires francaises sont soumises a de nombreux reglements. La marine nationale, qui est sujette aux memes exigences de transparence que ses homologues publics ou prives, a donc mis en place un systeme complet de surveillance. Methode Le present article decrit les senseurs et instruments de mesure mis en œuvre sur le site militaire de la base navale de Cherbourg et propose de detailler les resultats d’analyses pratiquees sur les prelevements environnementaux de l’annee 2013. Resultats La dose annuelle liee aux activites de la marine nationale dans la region de Cherbourg est extremement faible, au regard des doses auxquelles exposent les activites medicales ou le rayonnement naturel cosmique et tellurique.

Fe2+/Fe3+ ratio versus sediment depth values have been determined for ten lakes in British Columbia. The values often reflect the local topography of the lakes, the weathering history of the deposited minerals, and the diagenesis of the minerals after deposition in the lake.

Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer-related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies-(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician-scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framework.

X-ray diffraction and Mossbauer techniques have been utilized to study the late-glacial and post-glacial sediments of a core obtained from Georgie Lake, northeastern Vancouver Island. The Mossbauer data clearly shows there is a substantive drop in the Fe2+/Fe3+ ratio at the transition from glacial to post-glacial sediments.

The design, computed performance using linear and nonlinear modeling, and experimental results of a DC 18-GHz high-isolation ultrafast monolithic SPST (single-pole single-throw) switch with driver are presented. A nonlinear simulation of the SPST and of the driver was carried out in order to predict the switching time of the overall circuit. The monolithic SPST design uses GaAs FETs and the driver uses GaAs devices in order to achieve a very short switching time. Insertion loss of less than 2.4 dB, a typical isolation of 50 dB, and a switching time of less than 1 ns, driver included, were obtained. The validity of the nonlinear models used was demonstrated by the good agreement obtained between the simulated and the measured performance. >

Biochemical experiments over the past 40 years have shown that nucleoside diphosphate (NDP) kinase activity, which catalyzes phosphoryl transfer from a nucleoside triphosphate to a nucleoside diphosphate, is ubiquitously found in organisms from bacteria to human. Over the past 10 years, eight human genes of the nm23/NDP kinase family have been discovered that can be separated into two groups based on analysis of their sequences. In addition to catalysis, which may not be exhibited by all isoforms, evidence for regulatory roles has come recently from the discovery of the genes nm23 and awd, which encode NDP kinases and are involved in tumor metastasis and Drosophila development, respectively. Current work shows that the human NDP kinase genes are differentially expressed in tissues and that their products are targeted to different subcellular locations. This suggests that Nm23/NDP kinases possess different, but specific, functions within the cell, depending on their localization. The roles of NDP kinases in metabolic pathways and nucleic acid synthesis are discussed.

Fine particles of alpha -Fe or Fe(Co) are prepared by the reduction in H/sub 2/ of gamma -FeOOH or Co-ferrite particles which have been wrapped in monomolecular layers of exfoliated MoS/sub 2/. The presence of the MoS/sub 2/ restricts coalescence of the starting particles while allowing the reduction to take place. Magnetic moments and coercivities are determined at temperature during processing. Results are given for magnetization measurements, electron microscopy, Mossbauer effect spectroscopy, and X-ray diffraction. Enhanced coercivities are observed when MoS/sub 2/ is present. Surface pinning is deduced from the approach to magnetic saturation. >

Cobalt ferrite, CoxFe3−xO4 with 0.55≤x≤0.8, is produced by precipitation from aqueous solutions. Drying and annealing at temperatures below 300 °C results in a coercivity that increases with increasing temperature. Mossbauer effect spectroscopy and magnetic measurements are consistent with the interpretation that these Co ferrites have a (mostly) normal spinel structure as made. These convert to a (mostly) inverse spinel structure on thermal aging. No significant morphological changes occur during this transformation. Coercivities as high as μ0Hc=0.2 T are observed.

Monomolecular layers of exfoliated MoS2 are incorporated in the process of the formation of Co ferrite from aqueous solutions. The presence of MoS2 is found to limit the coalescence of particles during reduction to Fe(Co) metal. That MoS2 inhibits the full conversion to metal is confirmed by Mossbauer effect spectroscopy. Magnetization measurements are interpreted on the basis of noncollinear magnetization patterns resulting from competing surface anisotropies.

Tumor suppressor genes have a pivotal role in normal cells regulating cell cycle processes negatively. Furthermore, the inhibition of cell proliferation is a crucial step in the achievement of cell differentiation. Increasing evidence suggests that the nm23 genes, initially documented as suppressors of the invasive phenotype in some cancer types, are involved in the control of normal development and differentiation. In this review, we summarize some data concerning the involvement of the nm23 genes in development and differentiation, attempting to delineate an overall view of many facets of their biological role.

Mossbauer effect spectroscopy (MES) and x‐ray diffraction are used to characterize the various phases present in samples of FeCx prepared by thermal decomposition of a solution of Fe(CO)5 containing exfoliated monolayers of MoS2. MES is used to determine how these phases change their structural and magnetic properties with thermal annealing.

Fe(Co)5 is thermally reduced to Fe(C) in the presence of monomolecular flakes of MoS2. The magnetic properties of particles produced by the decomposition of Fe(CO)5 and subsequent thermal annealing are described. Comparison of the properties of primarily χ‐Fe5C2 carbides prepared with and without the presence of MoS2 flakes show that enhanced coercivity is achieved by including MoS2 in the processing.

Monomolecular layers of MoS2 are used as substrates for the preparation of fine particles of magnetic materials. Particles of Ni, Co, and Fe and their alloys and various ferrites, hydroxides, and carbides have been produced. Some of these particles have magnetizations and coercivity values suitable for use in information storage technologies. Although attempts to produce multilayers of (MoS2/Fen)m by chemical methods have not succeeded, new pathways to improved magnetic materials have been found.

We have identified a cDNA encoding a 212 amino acid protein (Nm23-H5) with 27-31% identity to the human members of the nm23/nucleoside diphosphate (NDP) kinase gene family. The nm23-H5 gene is located on chromosome 5q23-31 and is transcribed as one main transcript of 1.1 kb which is highly and specifically expressed in testis, in the spermatogonia and early spermatocytes. Nm23-H5 possesses most of the residues conserved among NDP kinases plus an additional COOH-terminus end of 55 amino acids unique to this protein. However, under usual assay conditions, Nm23-H5 expressed in Escherichia coli did not exhibit NDP kinase activity. These results suggest that Nm23-H5 is specifically involved in early stages of spermatogenesis.

Despite the clinical relevance of prostate cancer, few aspects regarding the molecular alterations involved in the process of prostate carcinogenesis are clearly understood. Cytogenetic and molecular genetic studies have identified specific abnormalities in prostate tumors, mainly on chromosomes 8, 10 and 16. On the basis of these findings, we designed a study to further characterize the altered regions on chromosome 10, using 15 microsatellite markers on a population composed of 20 paired normal and primary non-metastatic prostatic-tumor samples. Overall, 65% (13/20) of the cases analyzed showed molecular alterations, mainly rearrangements and deletions. The locus presenting the highest rate of abnormalities was D1OS221, which maps to 10q23-q24. Another region with frequent alterations was 10q21, at the DIOS109 locus. There was no statistical association between microsatellite abnormalities and Gleason grade or tumor stage in the prostate cancer cases studied. These results suggest that microsatellite alterations on the long arm of chromosome 10 are non-random events occurring in prostate cancer and that they may play a role in the process of tumorigenesis in these neoplasms.

The nm23-H1 gene encoding the nucleoside diphosphate (NDP) kinase A has been proposed as a tumor metastasis suppressor. Two important features emerge from published data: 1) an inverse correlation between the metastatic invasion and the level of NDP kinase/Nm23 was observed in melanomas, hepatocellular carcinomas and, in some studies, on breast carcinomas; 2) an overexpression of NDP kinase/Nm23 was observed in several solid tumors as compared to normal surrounding tissues, positively correlated with aggressiveness in the case of neuroblastomas. The level of NDP kinase/Nm23 in tumors appears to be altered in different ways, related or not to the metastatic potential, depending on the tissue of origin. Its evaluation as a prognostic or diagnostic marker of tumor invasion and aggressiveness deserves further study.

The X-ray structure of a point mutant of nucleoside diphosphate kinase (NDP kinase) from Dictyostelium discoideum has been determined to 2.2 A resolution. The enzyme is a hexamer made of identical subunits with a novel mononucleotide binding fold. Each subunit contains an alpha/beta domain with a four stranded, antiparallel beta-sheet. The topology is different from adenylate kinase, but identical to the allosteric domain of Escherichia coli ATCase regulatory subunits, which bind mononucleotides at an equivalent position. Dimer contacts between NDP kinase subunits within the hexamer are similar to those in ATCase. Trimer contacts involve a large loop of polypeptide chain that bears the site of the Pro----Ser substitution in Killer of prune (K-pn) mutants of the highly homologous Drosophila enzyme. Properties of Drosophila NDP kinase, the product of the awd developmental gene, and of the human enzyme, the product of the nm23 genes in tumorigenesis, are discussed in view of the three-dimensional structure and of possible interactions of NDP kinase with other nucleotide binding proteins.

A lambda gt11 cDNA library from Dictyostelium discoideum was screened by direct labeling of filter replicas with [35S]guanosine 5'-O-(thiotriphosphate) (GTP gamma S). A positive clone was obtained and used as probe to isolate additional clones from which a complete cDNA sequence was determined. The cDNA hybridizes to a single copy gene that is expressed as a 0.6-kilobase mRNA in vegetatively growing amoeba. The open reading frame encodes a protein of 155 amino acids (calculated Mr 16,775), devoid of cysteine residues. The protein contains most of the short consensus motifs characteristic of the catalytic domain of protein kinases although the overall homology with this class of enzymes is not greater than 20%. Its size and amino acid composition indicated that it could be the monomer of a nucleoside diphosphate (NDP) kinase, an enzyme which catalyzes the phosphate transfer from triphospho- to diphosphonucleotides. Indeed, specific NDP kinase activity was found in extracts of bacteria transformed with a plasmid expressing the protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the extracts incubated in the presence of [35S]GTP gamma S revealed a single 35S-labeled band of size corresponding to the protein, which likely represents the stable thiophosphorylated reaction intermediate characteristic for the ping-pong reaction mechanism of NDP kinases. The formation of this labeled intermediate probably allowed the detection of the enzyme on the filters during the screening procedure. Although NDP kinases from a great variety of sources have been characterized, the primary structure of the D. discoideum NDP kinase is the first reported for an enzyme of eukaryotic origin.

Guanylate cyclase activity (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2.), measured in purified rat liver plasma membranes, was markedly increased by treatment with various purified proteases. The effect was maximal with trypsin, alpha-chymotrypsin, papain, and thermolysin (6- to 8-fold increase with 5 to 20 microgram of protease/ml) and lower with subtilisin and elastase (3- to 4-fold increase). The activation was due to an increase in the maximal velocity of the cyclizing reaction. No modification was observed either in the apparent affinity for the substrate MnGTP or in the cooperative behavior of the enzyme kinetics which displayed Hill coefficients of 1.6 for both basal and activated states. The Triton X-100-dispersed guanylate cyclase remained sensitive to papain, which suggests that the action of proteases was not restricted to an indirect action upon the membranous environment of the guanylate cyclase. In contrast, the cytosolic soluble guanylate cyclase, assayed in the presence or absence of sodium azide, was absolutely insensitive to papain. Thus, proteolysis represents a previously undescribed mechanism for activating membranous guanylate cyclase systems, which might be of importance in the physiological regulation of this enzyme.

The cyclic nucleotide phosphodiesterase of Dictyostelium discoideum functions to maintain the responsiveness of cells to the chemoattractant cAMP during the aggregation phase of development. We have prepared a cDNA library and have isolated clones which contain a portion of the 5' untranslated region and the entire coding and 3' untranslated portions of the cyclic nucleotide phosphodiesterase gene. The primary structure of the extracellular cyclic nucleotide phosphodiesterase precursor has been deduced from the nucleotide sequence. The molecule is composed of 452 amino acids and was calculated to have a molecular mass of 51,078 daltons. Forty-nine amino-terminal residues which contain a hydrophobic leader sequence are not present in the mature extracellular enzyme. Four potential asparagine-linked glycosylation sites were found within the phosphodiesterase. An amino acid sequence homology search revealed no closely related proteins. Phosphodiesterase mRNA levels are low in growing cells and first increase soon after the onset of development. The amount of transcript then decreases before rising in abundance to maximum levels during the terminal stages of cell aggregation and apical tip formation. During formation of the fruiting body, levels of phosphodiesterase mRNA decrease. Exposure of cells to cAMP increases the amount of phosphodiesterase mRNA. Increases of mRNA abundance are correlated with increases in enzyme activity, suggesting regulation at the level of transcription.

The epinephrine sensitivity in vitro of the adenylate cyclase system in liver plasma membranes from adrenalectomized rats was increased by the addition of 1 to 100 muM GTP or GDP in the incubation medium. Basal and glucagon-stimulated cyclase activities were also enhanced by GTP and GDP. These effects occurred even in the absence of an ATP-regenerating system. They were mimicked by 5'-guanyl diphosphonate and a series of guanyl derivatives, indicating that the structural requirement for the GTP action is not very stringent. Guanyl nucleotides did not increase the affinity of the adenylate cyclase system for the activating hormones, nor did they protect the enzyme activity against denaturation. Their synergic effect was due to an enhancement of the affinity of the enzyme for the substrate MgATP and also to an increase of the maximal velocity of the reaction. It is proposed that the guanyl nucleotides act directly and primarily upon the catalytic component of the cyclase system, independently of their effects on the binding of the activating hormones to liver plasma membrane. Since the activating effects of epinephrine and glucagon are similar in the presence of GTP, but not in its absence, it is suggested that the lower efficiency of epinephrine under normal conditions is not due to intrinsic membrane characteristics, but rather, to superimposed extraneous modulations.

Resume La structure du bis-peroxyde 5 , forme par photoxydation du benzhydrylidene-cyclobutane 1 , est demontree par un certain nombre de transformations, notamment acidolyse selective (en hydroperoxydes 11 ), reductions variees du bis-peroxyde 5 (en diols 6 , 8 et tetrol 9 ) et de ses derives (en diols 7 , 21 et derives, epoxyde 12 , alcool 13 , triol 14 , tetrols 15 , 22 ), et degradations oxydatives partielles (en bis-hemiacetal 17 , hemiacetal-lactone 18 , cetol 19 , lactones 27 , 28 , 29 ). Les configurations et les conformations de tous les derives sont determinees par etude de leurs spectres de RMN, particulierement en utilisant un complexe d'europium.

We have previously reported that treatment of rat liver plasma membranes with various proteases led to activation and solubilization of membrane-bound guanylate cyclase. We report here that the guanylate cyclase solubilized by proteolysis differed from the cytosolic cyclase and rather was similar to the membrane-bound form of the enzyme in that it exhibited a sigmoidal MnGTP concentration dependence and was not activated by an excess Mn2+ or by nitrosocompounds. Also, whereas the cytosolic guanylate cyclase activity was completely abolished by 10 to 100 microM Cd2+, a dithiol reagent, no inhibitory effect was observed on the trypsin-solubilized enzyme. Therefore, the differences in kinetic properties between cytosolic and membrane-bound rat liver guanylate cyclase reside in structural differences between both forms of the enzyme rather than in differences in their environment.

It has been previously shown that trypsin treatment of rat liver plasma membranes causes the solubilization of a guanylate cyclase of Mr = 140,000 (Lacombe, M. L., Haguenauer-Tsapis, R., Stengel, D., Ben Salah, A., and Hanoune, J. (1980) FEBS Lett. 116, 79-84). In this study, we observed that addition of Mn-GTP during this step greatly protected the enzyme from proteolytic degradation. This effect was specific for guanine nucleotides, being weaker for other nucleotides triphosphate and GDP, and absent for cyclic GMP and GMP. Metal-GTP complex was required with a strict specificity for Mn2+. In addition to the Mr = 140,000 enzyme, trypsin solubilization in the presence of Mn-GTP led to the formation of a small and active form of guanylate cyclase. Based on its behavior on Ultrogel AcA 34 and sucrose gradients, its apparent Mr was calculated to be 68,000. Both forms could be well separated by high performance liquid chromatography and were shown to be sequentially solubilized (the larger appearing before the smaller species). Mr = 140,000 species, but not the cytosolic enzyme, was able to generate the Mr = 68,000 enzyme upon tryptic treatment in the presence of Mn-GTP. The Mr = 140,000 and 68,000 enzymes exhibited Michaelis-Menten kinetics (Hill coefficient = 1) with Km for Mn-GTP of 130 and 70 microM, respectively. The proteolytically solubilized enzymes were strickingly heat labile and highly protected by Mn-GTP. These results support the hypothesis that the rat liver membrane-bound guanylate cyclase has a dimeric structure similar to that of the cytosolic enzyme. They also suggest a possible role for GTP in limiting the degradation rate of membrane guanylate cyclase in vivo and, thus, in regulating the active enzyme concentration.

Various 2-alkyl-alpha-methyl- and 2-alkylindan-5-acetic acids have been prepared. The acids, which can exist in two diastereoisomeric forms that cannot be separated by crystallization or chromatography, can be analyzed in their mixture by NMR in the presence of Eu(dpm)3. It has been possible to reconstitute the two pure racemic 2-isopropyl-alpha-methylindan-5-acetic acids from their enantiomers obtained after resolution of the mixtures through salts with various active bases. The relative configuration of the two asymmetric centers of one of the diastereoisomers salts with various active bases. The relative configuration of the two asymmetric centers of one of the diastereoisomers has been determined by X-ray crystallography. The absolute configurations of the resolved acids have been established by a comparative study of their CD curves. The antiinflammatory and analgesic properties of these compounds as functions of their structure and stereochemistry are discussed.