Home About us Contact
|
Home About us Contact | ||
|
|
||
Likely Candidate (likely + candidate)
Selected AbstractsThe role of steroid hormones in the regulation of vasopressin and oxytocin release and mRNA expression in hypothalamo neurohypophysial explants from the ratEXPERIMENTAL PHYSIOLOGY, Issue 2000Celia D. Sladek Vasopressin and oxytocin release from the neural lobe, and the vasopressin and oxytocin mRNA contents of the supraoptic and paraventricular nuclei are increased by hypertonicity of the extracellular fluid. The factors regulating these parameters can be conveniently studied in perifused explants of the hypothalamo-neurohypophysial system that include the supraoptic nucleus (but not the paraventricular nucleus) with its axonal projections to the neural lobe. Vasopressin and oxytocin release and the mRNA content of these explants respond appropriately to increases in the osmolality of the perifusate. This requires synaptic input from the region of the organum vasculosum of the lamina terminalis. Glutamate is a likely candidate for transmitting osmotic information from the organum vasculosum of the lamina terminalis to the magnocellular neurones, because agonists for excitatory amino acid receptors stimulate vasopressin and oxytocin release, and because increased vasopressin release and mRNA content induced in hypothalamo-neurohypophysial explants by a ramp increase in osmolality are blocked by antagonists of both NMDA (N -methyl-D-aspartate) and non-NMDA glutamate receptors. Osmotically stimulated vasopressin release is also blocked by testosterone, dihydrotestosterone, oestradiol and corticosterone. Both oestrogen and dihydrotestosterone block NMDA stimulation of vasopressin release, and in preliminary studies oestradiol blocked AMPA stimulation of vasopressin release. Thus, steroid inhibition of osmotically stimulated vasopressin secretion may reflect inhibition of mechanisms mediated by excitatory amino acids. Recent studies have demonstrated numerous mechanisms by which steroid hormones may impact upon neuronal function. Therefore, additional work is warranted to understand these effects of the steroid hormones on vasopressin and oxytocin secretion and to elucidate the potential contribution of these mechanisms to regulation of hormone release in vivo. [source] Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin 1a receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNAGENES, BRAIN AND BEHAVIOR, Issue 3 2008A. Knafo Human altruism is a widespread phenomenon that puzzled evolutionary biologists since Darwin. Economic games illustrate human altruism by showing that behavior deviates from economic predictions of profit maximization. A game that most plainly shows this altruistic tendency is the Dictator Game. We hypothesized that human altruistic behavior is to some extent hardwired and that a likely candidate that may contribute to individual differences in altruistic behavior is the arginine vasopressin 1a (AVPR1a) receptor that in some mammals such as the vole has a profound impact on affiliative behaviors. In the current investigation, 203 male and female university students played an online version of the Dictator Game, for real money payoffs. All subjects and their parents were genotyped for AVPR1a RS1 and RS3 promoter-region repeat polymorphisms. Parents did not participate in online game playing. As variation in the length of a repetitive element in the vole AVPR1a promoter region is associated with differences in social behavior, we examined the relationship between RS1 and RS3 repeat length (base pairs) and allocation sums. Participants with short versions (308,325 bp) of the AVPR1a RS3 repeat allocated significantly (likelihood ratio = 14.75, P = 0.001, df = 2) fewer shekels to the ,other' than participants with long versions (327,343 bp). We also implemented a family-based association test, UNPHASED, to confirm and validate the correlation between the AVPR1a RS3 repeat and monetary allocations in the dictator game. Dictator game allocations were significantly associated with the RS3 repeat (global P value: likelihood ratio ,2 = 11.73, df = 4, P = 0.019). The association between the AVPR1a RS3 repeat and altruism was also confirmed using two self-report scales (the Bardi,Schwartz Universalism and Benevolence Value-expressive Behavior scales). RS3 long alleles were associated with higher scores on both measures. Finally, long AVPR1a RS3 repeats were associated with higher AVPR1a human post-mortem hippocampal messenger RNA levels than short RS3 repeats (one-way analysis of variance (ANOVA): F = 15.04, P = 0.001, df = 14) suggesting a functional molecular genetic basis for the observation that participants with the long RS3 repeats allocate more money than participants with the short repeats. This is the first investigation showing that a common human polymorphism, with antecedents in lower mammals, contributes to decision making in an economic game. The finding that the same gene contributing to social bonding in lower animals also appears to operate similarly in human behavior suggests a common evolutionary mechanism. [source] Dynamic Models in Space and TimeGEOGRAPHICAL ANALYSIS, Issue 2 2001J. Paul Elhorst This paper presents a first-order autoregressive distributed lag model in both space and time. It is shown that this model encompasses a wide series of simpler models frequently used in the analysis of space-time data as well as models that better fit the data and have never been used before. A framework is developed to determine which model is the most likely candidate to study space-time data. As an application, the relationship between the labor force participation rate and the unemployment rate is estimated using regional data of Germany, France, and the United Kingdom derived from Eurostat, 1983,1993. [source] Individual distinctiveness in the mobbing call of a cooperative bird, the noisy miner Manorina melanocephalaJOURNAL OF AVIAN BIOLOGY, Issue 5 2009Robert A. W. Kennedy Individual differentiation is usually advantageous in maximising the fitness benefits of interactions with conspecifics. In social species, where intraspecific interactions are frequent, this is likely to be particularly important. Indeed, some form of differentiation underpins most hypotheses proposed to account for cooperative behaviour in birds. The auditory modality is a likely candidate for this function, particularly for species where individuals are widely spaced and in dense vegetation. In this study, we examined the acoustic structure of a distinctive mobbing signal, the ,chur' call, of the cooperatively breeding noisy miner Manorina melanocephala. Using 250,calls from 25 individuals, a combination of spectrographic-based measurement of call parameters, cross-correlation and multi-dimensional scaling was used to test for systematic individual differences in call structure. Strong differences between individuals were observed in all measures, indicating that this call encodes sufficient information to facilitate individual differentiation. We then conducted a series of field playbacks to test the effect of the behaviour on conspecifics. Results demonstrated that the call, in isolation, has a clear attractant effect. Given that chur calls are synonymous with the characteristic cooperative mobbing behaviour of this species, these findings suggest they are likely to have an important function in coordinating complex social behaviour. [source] Genetic Analysis and Molecular Mapping of a Rolling Leaf Mutation Gene in RiceJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 12 2007Ji-Cai Yi Abstract A rice mutant with rolling leaf, namely ,- rl, was obtained from M2 progenies of a native indica rice stable strain Qinghuazhan (QHZ) from mutagenesis of dry seeds by ,-rays. Genetic analysis using the F2 population from a cross between this mutant and QHZ indicated the mutation was controlled by a single recessive gene. In order to map the locus for this mutation, another F2 population with 601 rolling leaf plants was constructed from a cross between ,- rl and a japonica cultivar 02428. After primary mapping with SSR (simple sequence repeats) markers, the mutated locus was located at the short arm of chromosome 3, flanked by RM6829 and RM3126. A number of SSR, InDel (insertion/deletion) and SNP (single nucleotide polymorphism) markers within this region were further developed for fine mapping. Finally, two markers, SNP121679 and InDel422395, were identified to be flanked to this locus with genetic distances of 0.08 cM and 0.17 cM respectively, and two SNP markers, SNP75346 and SNP110263, were found to be co-segregated with this locus. These results suggested that this locus was distinguished from all loci for the rolling leaf mutation in rice reported so far, and thus renamed rl10(t). By searching the rice genome database with closely linked markers using BLAST programs, an e -physical map covering rl10(t) locus spanning about a 50 kb region was constructed. Expression analysis of the genes predicted in this region showed that a gene encoding putative flavin-containing monooxygenase (FMO) was silenced in ,- rl, thus this is the most likely candidate responsible for the rolling leaf mutation. [source] Influence of muscular activity on local mineralization patterns in metatarsals of the embryonic mouseJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2000E. Tanck This study addressed the theory that local mechanical loading may influence the development of embryonic long bones. Embryonic mouse metatarsal rudiments were cultured as whole organs, and the geometry of the primary ossification center was compared with that of rudiments that had developed in utero. The mineralization front in vivo was found to be nearly straight, whereas in vitro it acquired a more convex shape due to a slower mineralization rate at the periphery of the mineralized cylinder. A poroelastic finite element analysis was performed to calculate the local distributions of distortional strain and fluid pressure at the mineralization front in the metatarsal during loading in vivo as a result of muscle contractions in the embryonic hindlimbs. The distribution of fluid pressure from the finite element analysis could not explain the difference in mineralization shape. The most likely candidate for the difference was the distortional strain, resulting from muscle contraction, which is absent in vitro, because its value at the periphery was significantly higher than in the center of the tissue. Without external loads, the mineralization process may be considered as pre-programmed, starting at the center of the tissue and resulting in a spherical mineralization front. Strain modulates the rate of the mineralization process in vivo, resulting in the straight mineralization front. These results confirm that disturbances in muscle development are likely to produce disturbed mineralization patterns, resulting in a disordered osteogenic process. [source] CHARACTERIZATION OF A DINOFLAGELLATE CRYPTOCHROME BLUE-LIGHT RECEPTOR WITH A POSSIBLE ROLE IN CIRCADIAN CONTROL OF THE CELL CYCLE,JOURNAL OF PHYCOLOGY, Issue 3 2007Stephanie A. Brunelle Karenia brevis (C. C. Davis) G. Hansen et Moestrup is a dinoflagellate responsible for red tides in the Gulf of Mexico. The signaling pathways regulating its cell cycle are of interest because they are the key to the formation of toxic blooms that cause mass marine animal die-offs and human illness. Karenia brevis displays phased cell division, in which cells enter S phase at precise times relative to the onset of light. Here, we demonstrate that a circadian rhythm underlies this behavior and that light quality affects the rate of cell-cycle progression: in blue light, K. brevis entered the S phase early relative to its behavior in white light of similar intensity, whereas in red light, K. brevis was not affected. A data base of 25,000 K. brevis expressed sequence tags (ESTs) revealed several sequences with similarity to cryptochrome blue-light receptors, but none related to known red-light receptors. We characterized the K. brevis cryptochrome (Kb CRY) and modeled its three-dimensional protein structure. Phylogenetic analysis of the photolyase/CRY gene family showed that Kb CRY is a member of the cryptochrome DASH (CRY DASH) clade. Western blotting with an antibody designed to bind a conserved peptide within Kb CRY identified a single band at ,55 kDa. Immunolocalization showed that Kb CRY, like CRY DASH in Arabidopsis, is localized to the chloroplast. This is the first blue-light receptor to be characterized in a dinoflagellate. As the Kb CRY appears to be the only blue-light receptor expressed, it is a likely candidate for circadian entrainment of the cell cycle. [source] Personal view: food for thought , western lifestyle and susceptibility to Crohn's disease.ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2005The FODMAP hypothesis Summary Susceptibility to the development of Crohn's disease involves a combination of genetic and environmental factors. The association of Crohn's disease with westernization has implicated lifestyle factors in pathogenesis. While diet is a likely candidate, evidence for specific changes in dietary habits and/or intake has been lacking. A new hypothesis is proposed, by which excessive delivery of highly fermentable but poorly absorbed short-chain carbohydrates and polyols (designated FODMAPs , Fermentable Oligo-, Di- and Mono-saccharides And Polyols) to the distal small intestinal and colonic lumen is a dietary factor underlying susceptibility to Crohn's disease. The subsequent rapid fermentation of FODMAPs in the distal small and proximal large intestine induces conditions in the bowel that lead to increased intestinal permeability, a predisposing factor to the development of Crohn's disease. Evidence supporting this hypothesis includes the increasing intake of FODMAPs in western societies, the association of increased intake of sugars in the development of Crohn's disease, and the previously documented effects of the ingestion of excessive FODMAPs on the bowel. This hypothesis provides potential for the design of preventive strategies and raises concern about current enthusiasm for putative health-promoting effects of FODMAPs. One of the greatest challenges in defining the pathogenesis of Crohn's disease is to identify predisposing environmental factors. Such an achievement might lead to the development of preventive strategies for, and the definition of, possible target for changing the natural history of this serious disease. The present paper describes a new hypothesis for one such environmental factor. [source] The sodium tail of MercuryMETEORITICS & PLANETARY SCIENCE, Issue 9 2002A. E. POTTER However, when the angle of the ecliptic is near maximum in the northern hemisphere, and Mercury is near its greatest eastern elongation, it can be seen against the western sky for about a half hour after sunset. During these times, we were able to map sodium D2 emission streaming from the planet, forming a long comet-like tail. On 2001 May 26 (U.T.) we mapped the tail downstream to a distance of ,40 000 km. Sodium velocities in the tail increased to ,11 km s,1 at 40 000 km as the result of radiation pressure acceleration. On 2000 June 5 (U.T.) we mapped the cross-sectional extent of the tail at a distance of ,17 500 km downstream. At this distance, the half-power full-width of the emission was ,20 000 km. We estimated the transverse velocity of sodium in the tail to range from 2 to 4 km s,1. The velocities we observed imply source velocities from the planet surface of the order of 5 km s,1, or 4 eV. Particle sputtering is a likely candidate for production of sodium atoms at these velocities. The total flux of sodium in the tail was ,1 times 1023 atoms s,1, which corresponds to 1 to 10% of the estimated total production rate of sodium on the planet. [source] Metastability in multicomponent oxide transistorsPHYSICA STATUS SOLIDI (A) APPLICATIONS AND MATERIALS SCIENCE, Issue 3 2010Warren B. Jackson Abstract Results of an investigation of bias stress metastability of multicomponent, zinc,indium and zinc,tin oxides, transistors are investigated. The bias stress as a function of various dielectrics, passivation layers, and illumination conditions indicate that for negative gate bias stressing defects often are created in the semiconductor, probably near or at the surface, particularly if the devices are unpassivated. Oxygen vacancy formation is a likely candidate. For many dielectrics, the positive gate bias metastability appears to be dominated by charge trapping within the insulator. For zinc,tin oxide devices, the kinetics of the metastability follows a stretched exponential behavior with a power law dependence on gate voltage. Correcting for the observed Meyer,Neldel behavior, the activation energy of , is about 1.2,eV for defect generation and the disorder energy from , is about 0.06,eV. By using passivation, the best gate dielectrics and annealing protocols, we have reduced the bias stress metastability to about 0.1,V for a 25,000,s stress at 22,°C. [source] The dual role of a loop with low loop contact distance in folding and domain swappingPROTEIN SCIENCE, Issue 7 2002Apichart Linhananta Abstract , helices, , strands, and loops are the basic building blocks of protein structure. The folding kinetics of , helices and , strands have been investigated extensively. However, little is known about the formation of loops. Experimental studies show that for some proteins, the formation of a single loop is the rate-determining step for folding, whereas for others, a loop (or turn) can misfold to serve as the hinge loop region for domain-swapped species. Computer simulations of an all-atom model of fragment B of Staphylococcal protein A found that the formation of a single loop initiates the dominant folding pathway. On the other hand, the stability analysis of intermediates suggests that the same loop is a likely candidate to serve as a hinge loop for domain swapping. To interpret the simulation result, we developed a simple structural parameter: the loop contact distance (LCD), or the sequence distance of contacting residues between a loop and the rest of the protein. The parameter is applied to a number of other proteins, including SH3 domains and prion protein. The results suggest that a locally interacting loop (low LCD) can either promote folding or serve as the hinge region for domain swapping. Thus, there is an intimate connection between folding and domain swapping, a possible cause of misfolding and aggregation. [source] The radiation of the Cape flora, southern AfricaBIOLOGICAL REVIEWS, Issue 4 2003H. P. LINDER ABSTRACT The flora of the south-western tip of southern Africa, the Cape flora, with some 9000 species in an area of 90 000 km2 is much more speciose than can be expected from its area or latitude, and is comparable to that expected from the most diverse equatorial areas. The endemism of almost 70%, on the other hand, is comparable to that found on islands. This high endemism is accounted for by the ecological and geographical isolation of the Cape Floristic Region, but explanations for the high species richness are not so easily found. The high species richness is accentuated when its taxonomic distribution is investigated: almost half of the total species richness of the area is accounted for by 33,Cape floral clades'. These are clades which may have initially diversified in the region, and of which at least half the species are still found in the Cape Floristic Region. Such a high contribution by a very small number of clades is typical of island floras, not of mainland floras. The start of the radiation of these clades has been dated by molecular clock techniques to between 18 million years ago (Mya)(Pelargonium) and 8 Mya (Phylica), but only six radiations have been dated to date. The fossil evidence for the dating of the radiation is shown to be largely speculative. The Cenozoic environmental history of southern Africa is reviewed in search of possible triggers for the radiations, climatic changes emerge as the most likely candidate. Due to a very poor fossil record, the climatic history has to be inferred from larger scale patterns, these suggest large-scale fluctuations between summer wet (Palaeocene, Early Miocene)and summer dry climates (Oligocene, Middle Miocene to present). The massive speciation in the Cape flora might be accounted for by the diverse limitations to gene flow (dissected landscapes, pollinator specialisation, long flowering times allowing much phenological specialisation), as well as a richly complex environment providing a diversity of selective forces (geographically variable climate, much altitude variation, different soil types, rocky terrain providing many micro-niches, and regular fires providing both intermediate disturbances, as well as different ways of surviving the fires). However, much of this is based on correlation, and there is a great need for (a)experimental testing of the proposed speciation mechanisms, (b)more molecular clock estimates of the age and pattern of the radiations, and (c)more fossil evidence bearing on the past climates. [source] Maximizing anticholinergic therapy for overactive bladder: has the ceiling been reached?BJU INTERNATIONAL, Issue 2007Scott A. MacDiarmid SUMMARY Urinary incontinence affects an estimated 20,33% of adults the USA and 55% of the country's elderly [1], having a more substantial impact on the physical and mental dimension of quality of life than other common chronic diseases. Muscarinic receptor antagonists, including oxybutynin, tolterodine, trospium chloride, darifenacin, and solifenacin, are front-line therapies for overactive bladder (OAB), with an efficacy of 65,75% in reducing major symptoms. Strategies to increase the therapeutic index have included behavioural therapy, flexible dosing, and dose escalation, as well as newer formulations that reduce anticholinergic side-effects. Among approved OAB agents, the oxybutynin transdermal-delivery system has been associated with a lower incidence of dry mouth than immediate- and extended-release formulations of traditional agents. With a low propensity for drug interactions and dry mouth, it is a likely candidate for older patients taking multiple medications. The transdermal patch bypasses systemic and first-pass metabolism, avoiding higher plasma concentrations of the active metabolite (N -desethyloxybutynin) thought to be associated with dry mouth symptoms. Anticholinergics have a significant role to play in the management of OAB; newer drugs targeted toward muscarinic receptors, and novel delivery systems, continue to increase the therapeutic index for this condition. [source] Bacteria divert resources from growth for magellanic penguin chicksECOLOGY LETTERS, Issue 6 2002Jaime Potti Abstract The influence of bacteria on the growth of their wild avian hosts is unknown. We tested experimentally whether administration of a wide-spectrum antibiotic (cephalosporine) during early development of magellanic penguin (Spheniscus magellanicus) chicks had any effect on their growth rates in the wild. Chicks that were injected in two occasions with cephalosporine grew faster than control untreated chicks. The positive effect of medication on nestling growth disappeared after the treatment ceased, did not alter haematological indices indicative of health status, had no influence on chick survival until near independence and was related to a changed bacterial composition of the faecal microbiota of treated chicks when compared with that from control chicks. These results were similar to those obtained for poultry with antimicrobials promoting growth and chick nutrient assimilation rates. Gram-positive bacilli in the diphtheroid genus Corynebacterium are likely candidates to cause decreased growth rates in magellanic penguin chicks. [source] The microanatomy of the distal arrector pili: possible role for ,1,1 and ,5,1 integrins in mediating cell-cell adhesion and anchorage to the extracellular matrixJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2000Jeri Kersten Mendelson The arrector pili (AP) muscle is a small band of smooth muscle that attaches proximally to the bulge area of the pilosebaceous apparatus in the reticular dermis and extends up toward the epidermis. The distal anatomy of the AP and the anchorage mechanism allowing hair erection have not been previously described. Integrins are likely candidates mediating this attachment. Immunohistochemical techniques were used to determine the distribution of the following integrins: ,1, ,2, ,3, ,4, ,5, ,6 and ,1 as well as fibronectin. Frozen human scalp tissue was sectioned in traditional planes, obliquely and horizontally to visualize microanatomy in three dimensions. Histological examination revealed that the distal portions of smooth muscle fibers splay extensively between collagen bundles of the upper dermis. Integrin subunits ,1, ,5 and ,1 were expressed by the AP muscle. Analysis of the relative density of immunoreactivity in digitized sections revealed increased ,5 subunit expression at the extracellular matrix (ECM)-muscle interface. These data suggest that anchorage of the AP muscle to the ECM is via ,5,1 integrin and ,1,1 integrin functions in muscle cell-cell adhesion. Extensive splaying of smooth muscle fibers may allow increased surface area contact between the ECM and smooth muscle cells expressing peripherally situated ,5 integrin. [source] Human skin permeation of ,8 -tetrahydrocannabinol, cannabidiol and cannabinolJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2004Audra L. Stinchcomb ABSTRACT The purpose of this study was to quantify the in-vitro human skin transdermal flux of ,8 -tetrahydrocannabinol (,8 -THC), cannabidiol (CBD) and cannabinol (CBN). These cannabinoids are of interest because they are likely candidates for transdermal combination therapy. Differential thermal analysis and in-vitro diffusion studies with human tissue were completed for the compounds. Heats of fusion, melting points and relative thermodynamic activities were determined for the crystalline compounds, CBD and CBN. Flux, permeability, tissue concentration and lag times were measured in the diffusion experiments. CBN had a lower heat of fusion and corresponding higher calculated relative thermodynamic activity than CBD. Ethanol concentrations of 30 to 33% significantly increased the transdermal flux of ,8 -THC and CBD. Tissue concentrations of ,8 -THC were significantly higher than for CBN. Lag times for CBD were significantly smaller than for CBN. The permeabilities of CBD and CBN were 10-fold higher than for ,8 -THC. Combinations of these cannabinoids with ethanol will be further studied in transdermal patch formulations in vitro and in vivo, as significant flux levels of all the drugs were obtained. CBD, the most polar of the three drugs, and other more polar cannabinoids will also be the focus of future drug design studies for improved transdermal delivery rates. [source] The Social Responsibility of Professional SocietiesMETAPHILOSOPHY, Issue 5 2002David L. Hull A consistent position for professional societies with respect to social and moral issues is difficult to forge. The most consistent position is that professional societies qua professional societies should avoid getting involved in any and all social or moral issues. Professional societies should be praised or blamed only on the basis of their success or failure to achieve their professional goals. If, however, we do think that professional societies deserve moral praise and blame with respect to broader moral issues, then the situation gets much more complicated. One contrast explored in this article is between scientific and philosophical societies getting involved in social and moral issues. A second contrast is between individual and group responsibility. If groups are to be praised or blamed, smaller well,integrated groups are the most likely candidates. [source] Mammalian tooth marks on the bones of dinosaurs and other Late Cretaceous vertebratesPALAEONTOLOGY, Issue 4 2010NICHOLAS R. LONGRICH Abstract:, We describe bones from the Late Cretaceous of Alberta , including bones of large dinosaurs, a femur from the aquatic reptile Champsosaurus, and a dentary from the marsupial Eodelphis, that bear tooth marks made by animals with opposing pairs of teeth. Of the animals known from the Late Cretaceous of North America, only mammals are capable of making such tooth marks. In particular, multituberculates, which have paired upper and lower incisors, are the most likely candidates for the makers of these traces. The traces described here represent the oldest known mammalian tooth marks. Although it is possible that some of these tooth marks represent feeding traces, the tooth marks often penetrate deep into the dense cortices of the bone. This raises the possibility that, much as extant mammals gnaw bone and antler, some Cretaceous mammals may have consumed the bones of dinosaurs and other vertebrates as a source of minerals. However, none of the tooth marks described here resemble the extensive gnaw traces produced by Cenozoic multituberculates or rodents. This suggests that specialized gnawing forms may have been rare or absent in the Late Cretaceous of North America. [source] Structure and dynamics of translation initiation factor aIF-1A from the archaeon Methanococcus jannaschii determined by NMR spectroscopyPROTEIN SCIENCE, Issue 12 2001Wei Li Abstract Translation initiation factor 1A (aIF-1A) from the archaeon Methanococcus jannaschii was expressed in Escherichia coli, purified, and characterized in terms of its structure and dynamics using multidimensional NMR methods. The protein was found to be a member of the OB-fold family of RNA-associated proteins, containing a barrel of five beta-strands, a feature that is shared with the homologous eukaryotic translation initiation factor 1A (eIF-1A), as well as the prokaryotic translation initiation factor IF1. External to the , barrel, aIF-1A contains an ,-helix at its C-terminal and a flexible loop at its N-terminal, features that are qualitatively similar to those found in eIF-1A, but not present in prokaryotic IF1. The structural model of aIF-1A, when used in combination with primary sequence information for aIF-1A in divergent species, permitted the most-conserved residues on the protein surface to be identified, including the most likely candidates for direct interaction with the 16S ribosomal RNA and other components of the translational apparatus. Several of the conserved surface residues appear to be unique to the archaea. Nitrogen-15 relaxation and amide exchange rate data were used to characterize the internal motions within aIF-1A, providing evidence that the protein surfaces that are most likely to participate in intermolecular interactions are relatively flexible. A model is proposed, suggesting some specific interactions that may occur between aIF-1A and the small subunit of the archaeal ribosome. [source] Differences in Endolymphatic Sac Mitochondria-Rich Cells Indicate Specific FunctionsTHE LARYNGOSCOPE, Issue 3 2002Theo A. Peters MSc Abstract Objective/Hypothesis The purpose of the study was to examine the specific involvement of endolymphatic sac mitochondria-rich cells in endolymph homeostasis. Study Design Transmission electron microscopy and immunohistochemistry were performed on the endolymphatic sac of young adult rats, and two important developmental stages were also investigated. Methods Ultrastructural characteristics of endolymphatic sac mitochondria-rich cells were studied more concisely and compared with renal mitochondria-rich cells (i.e., the intercalated cells). In addition, expression of cytokeratins 7 and 19 was determined. Results Until birth, only one type of mitochondria-rich cell is observed in the rat endolymphatic sac. In young adult animals, distinct differences in mitochondria-rich cell ultrastructure in the endolymphatic sac enables classification into subtypes or configurations. Comparison of endolymphatic sac mitochondria-rich cells with renal intercalated cells reveals striking similarities and provides additional information on their specific function in endolymph homeostasis. Furthermore, differences in cytokeratin expression are determined in endolymphatic sac mitochondria-rich cells. Conclusions Differences in morphology of endolymphatic sac mitochondria-rich cells develop after birth and may reflect a distinct functional or physiological state of the cell. In analogy to renal intercalated cells, the distribution patterns of H+ -adenosine triphosphatase and Cl,/HCO3, exchanger may differ between subtypes. We propose that subtype A mitochondria-rich cells, from which protruding A mitochondria-rich cells are the activated state, are involved in proton secretion (apical H+ -adenosine triphosphatase) and thus are potential candidates for hearing loss accompanying renal tubular acidosis. Subtype B mitochondria-rich cells are the most likely candidates to be affected in Pendred syndrome because of the assumed function of pendrin as apical Cl,/HCO3, exchanger. [source] The granin family of uniquely acidic proteins of the diffuse neuroendocrine system: comparative and functional aspectsBIOLOGICAL REVIEWS, Issue 4 2004Karen B. Helle ABSTRACT The chromogranins A (CgA) and B (CgB) and secretogranin II (SgII) constitute the main members of a family of uniquely acidic secretory proteins in elements of the diffuse neuroendocrine system. These genetically distinct proteins, CgA, CgB, SgII and the less well known secretogranins III,VII are collectively referred to as,granins'and characterised by numerous pairs of basic amino acids as potential cleavage sites for processing by the co-stored prohormone converting enzymes PC 1/3 and PC2. This review is directed towards comparative and functional aspects of the granins with emphasis on their phylogenetically conserved sequences. Recent developments provide ample evidence of widely different effects and targets for the intact granins and their derived peptides, intracellularly in the directed trafficking of storage components during granule maturation and extracellularly in autocrine, paracrine and endocrine interactions. Most of the effects assigned to the granin derived peptides fit into patterns of direct or indirect inhibitory modulations of major functions. So far, peptides derived from CgA (vasostatins, chromacin, pancreastatin, WE-14, catestatin and parastatin), CgB (secretolytin) and SgII (secretoneurin) are the most likely candidates for granin-derived regulatory peptides, of postulated relevance not only for homeostatic processes, but also for tissue assembly and repair, inflammatory responses and the first line of defence against invading microorganisms. [source] Alteration of the Diastereoselectivity of 3-Methylaspartate Ammonia Lyase by Using Structure-Based MutagenesisCHEMBIOCHEM, Issue 13 2009Hans Raj Abstract 3-Methylaspartate ammonia-lyase (MAL) catalyzes the reversible amination of mesaconate to give both (2S,3S)-3-methylaspartic acid and (2S,3R)-3-methylaspartic acid as products. The deamination mechanism of MAL is likely to involve general base catalysis, in which a catalytic base abstracts the C3 proton of the respective stereoisomer to generate an enolate anion intermediate that is stabilized by coordination to the essential active-site MgII ion. The crystal structure of MAL in complex with (2S,3S)-3-methylaspartic acid suggests that Lys331 is the only candidate in the vicinity that can function as a general base catalyst. The structure of the complex further suggests that two other residues, His194 and Gln329, are responsible for binding the C4 carboxylate group of (2S,3S)-3-methylaspartic acid, and hence are likely candidates to assist the MgII ion in stabilizing the enolate anion intermediate. In this study, the importance of Lys331, His194, and Gln329 for the activity and stereoselectivity of MAL was investigated by site-directed mutagenesis. His194 and Gln329 were replaced with either an alanine or arginine, whereas Lys331 was mutated to a glycine, alanine, glutamine, arginine, or histidine. The properties of the mutant proteins were investigated by circular dichroism (CD) spectroscopy, kinetic analysis, and 1H NMR spectroscopy. The CD spectra of all mutants were comparable to that of wild-type MAL, and this indicates that these mutations did not result in any major conformational changes. Kinetic studies demonstrated that the mutations have a profound effect on the values of kcat and kcat/KM; this implicates Lys331, His194 and Gln329 as mechanistically important. The 1H NMR spectra of the amination and deamination reactions catalyzed by the mutant enzymes K331A, H194A, and Q329A showed that these mutants have strongly enhanced diastereoselectivities. In the amination direction, they catalyze the conversion of mesaconate to yield only (2S,3S)-3-methylaspartic acid, with no detectable formation of (2S,3R)-3-methylaspartic acid. The results are discussed in terms of a mechanism in which Lys331, His194, and Gln329 are involved in positioning the substrate and in formation and stabilization of the enolate anion intermediate. [source] A new autosomal dominant Peters' anomaly phenotype expanding the anterior segment dysgenesis spectrumACTA OPHTHALMOLOGICA, Issue 1 2009Nilufer Berker Abstract. Purpose:, To test the association of genes involved in anterior segment development in a family with autosomal dominantly inherited Peters' anomaly (PA) with a unique ocular phenotype. Methods:, Six members of a five-generation family with PA were extensively phenotyped and linkage analysis of candidate genes, namely, PAX6, PITX2, FOXC1, CYP1B1 and MAF, was performed. Results:, The complete pedigree consisted of 38 members, 19 of whom were affected. The six probands examined had bilateral microcornea, corneal opacity, iridocorneal adhesions, nystagmus and strabismus, but cataract, keratolenticular adhesions, glaucoma and posterior embryotoxon were absent. PAX6 gene mutations had been previously excluded in one of the affected members. DNA markers for candidate genes CYP1B1 on 2p22, PITX2 on 4q25, PAX6 on 11p13, MAF on 16q23 and FOXC1 on 6p25 were genotyped. Highly negative lod scores were obtained for all markers. Conclusions:, The exclusion of these genes as likely candidates supports the hypothesis that the ocular phenotype associated with PA segregating in this family is a distinct, new, autosomal dominant entity in the anterior segment dysgenesis spectrum. [source] Metal Ion Coordination to Azole NucleosidesCHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2005Jens Müller Dr. Abstract To evaluate the possibility of introducing azole nucleosides as building blocks for metal-mediated base pairs in artificial oligonucleotides, imidazole nucleoside, 1,2,4-triazole nucleoside and tetrazole nucleoside have been synthesized and characterized. The X-ray crystal structures of p -toluoyl-protected 1,2,4-triazole and tetrazole nucleosides are reported. Contrary to the situation primarily found for deoxyribonucleosides, the sugar moieties adopt C3,- endo conformations. The acidity of the , nucleosides increases with increasing number of nitrogen ring atoms, giving pKa values of 6.01±0.05, 1.32±0.05 and <,3, respectively. This decrease in basicity results in a decreasing ability to form 2:1 complexes with linearly coordinating metal ions such as Ag+ and Hg2+. In all cases, the Ag+ complexes are of higher stability than the corresponding Hg2+ complexes. Whereas imidazole nucleoside forms highly stable 2:1 complexes with both metal ions (estimated log ,2 values of >10), only Ag+ is able to reach this coordination pattern in the case of triazole nucleoside (log ,2 = 4.3±0.1). Tetrazole nucleoside does not form 2:1 complexes at all under the experimental conditions used. These data suggest that imidazole nucleoside, and to a lesser extent 1,2,4-triazole nucleoside, are likely candidates for successful incorporation as ligands in oligonucleotides based on metal-mediated base pairs. DFT calculations further corroborate this idea, providing model complexes for such base pairs with glycosidic bond distances (10.8,11.0 Å) resembling those in idealized B-DNA (10.85 Å). [source] | ||||||||||||||||||||||