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Functional
Kinds of Functional Terms modified by Functional Selected AbstractsEVOLUTION ON A LOCAL SCALE: DEVELOPMENTAL, FUNCTIONAL, AND GENETIC BASES OF DIVERGENCE IN BILL FORM AND ASSOCIATED CHANGES IN SONG STRUCTURE BETWEEN ADJACENT HABITATSEVOLUTION, Issue 8 2008Alexander V. Badyaev Divergent selection on traits involved in both local adaptation and the production of mating signals can strongly facilitate population differentiation. Because of its links to foraging morphologies and cultural inheritance song of birds can contribute particularly strongly to maintenance of local adaptations. In two adjacent habitats,native Sonoran desert and urban areas,house finches (Carpodacus mexicanus) forage on seeds that are highly distinct in size and shell hardness and require different bite forces and bill morphologies. Here, we first document strong and habitat-specific natural selection on bill traits linked to bite force and find adaptive modifications of bite force and bill morphology and associated divergence in courtship song between the two habitats. Second, we investigate the developmental basis of this divergence and find that early ontogenetic tissue transformation in bill, but not skeletal traits, is accelerated in the urban population and that the mandibular primordia of the large-beaked urban finches express bone morphogenetic proteins (BMP) earlier and at higher level than those of the desert finches. Further, we show that despite being geographically adjacent, urban and desert populations are nevertheless genetically distinct corroborating findings of early developmental divergence between them. Taken together, these results suggest that divergent selection on function and development of traits involved in production of mating signals, in combination with localized learning of such signals, can be very effective at maintaining local adaptations, even at small spatial scales and in highly mobile animals. [source] EFFECT OF LACTIC ACID FERMENTATION OF CASSAVA ON FUNCTIONAL AND SENSORY CHARACTERISTICS OF FUFU FLOURJOURNAL OF FOOD PROCESSING AND PRESERVATION, Issue 4 2008A.O. SOBOWALE ABSTRACT The effects of lactic acid fermentation of cassava on the functional and sensory characteristic of fufu flour were investigated. Two strains of Lactobacillus plantarum were used as starter cultures for the fermentation of cassava to fufu for 96 h. The resultant wet fufu samples were dried at 65C in a cabinet dryer for 48 h, and were analyzed for functional and sensory characteristics. Fermentation reduced the water-binding capacity of the fufu flour from 176.6% to between 118 and 125%. The pasting characteristics of the traditional and starter culture-fermented fufu flour samples were not significantly different from that of the unfermented cassava flour. When subjected to sensory evaluation, the traditional and starter culture-fermented cassava fufu flour were not significantly different in terms of color, odor and texture, but the cassava fufu flour produced, using starter culture SL19, had the highest overall acceptability (P < 0.05). PRACTICAL APPLICATIONS Traditionally, processing of cassava to fufu is usually carried out by using the old stock from a previous fermentation to initiate the fermentation of a new batch. This old method usually results in fufu that has a strong odor that may not be acceptable to some consumers. The use of starter culture like Lactobacillus plantarum will reduce the strong odor of fufu; this will increase its acceptability by consumers and ensure the overall quality. Also, the functional properties of fufu are not affected. The development of lactobacilli strains could help in optimizing the traditional processes, therefore increasing the economic returns. [source] EFFECT OF THE PHOSPHODIESTERASE 5 INHIBITORS SILDENAFIL, TADALAFIL AND VARDENAFIL ON RAT ANOCOCCYGEUS MUSCLE: FUNCTIONAL AND BIOCHEMICAL ASPECTSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2009Haroldo A Toque SUMMARY 1The anococcygeus muscle is part of the erectile machinery in male rodents. Phosphodiesterase (PDE) 5 inhibitors enhance and prolong the effects of cGMP, which has a key role in penile erection. The aim of the present study was to provide a functional and biochemical comparison of the three PDE5 inhibitors, namely sildenafil, tadalafil and vardenafil, in the rat anococcygeus muscle. 2Muscle strips were mounted in 4 mL organ baths and isometric force recorded. Levels of cGMP were measured using an enzyme immunoassay kit. Western blots were used to determine PDE5 protein expression. 3The PDE5 inhibitors concentration-dependently relaxed carbachol-precontracted anococcygeus muscle; however, vardenafil was more potent (pEC50 = 8.11 ± 0.05) than sildenafil (7.72 ± 0.06) or tadalafil (7.69 ± 0.05). Addition of NG -nitro- l -arginine methyl ester (100 µmol/L) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 µmol/L) to the organ baths caused significant rightward shifts in concentration,response curves for all PDE5 inhibitors. 4Sildenafil, tadalafil and vardenafil (all at 0.1 µmol/L) caused leftward shifts in the glyceryl trinitrate (GTN) concentration-response curves (by 4.0-, 3.7- and 5.5-fold, respectively). In addition, all three PDE5 inhibitors significantly potentiated relaxation responses to both GTN (0.01,10 µmol/L) and electrical field stimulation (EFS; 1,32 Hz), with vardenafil having more pronounced effects. 5All three PDE5 inhibitors reduced EFS-evoked contractions in a concentration-dependent manner over the concentration range 0.001,1 µmol/L. There were no significant differences between the effects of the three PDE5 inhibitors. 6Vardenafil (0.01,0.1 µmol/L) was more potent in preventing cGMP degradation in vitro than sildenafil (0.01,0.1 µmol/L) and tadalafil (0.01,0.1 µmol/L). 7Under control conditions, the expression of PDE5 was higher in the anococcygeus muscle than in the corpus cavernosum. 8In conclusion, PDE5 inhibitors enhance exogenous and endogenous nitric oxide-mediated relaxation in the rat anococcygeus muscle. The potency of vardenafil was greater than that of either sildenafil or tadalafil. [source] Quantitative Comparison of Approximate Solution Sets for Bi-criteria Optimization Problems,DECISION SCIENCES, Issue 1 2003W. Matthew Carlyle ABSTRACT We present the Integrated Preference Functional (IPF) for comparing the quality of proposed sets of near-pareto-optimal solutions to bi-criteria optimization problems. Evaluating the quality of such solution sets is one of the key issues in developing and comparing heuristics for multiple objective combinatorial optimization problems. The IPF is a set functional that, given a weight density function provided by a decision maker and a discrete set of solutions for a particular problem, assigns a numerical value to that solution set. This value can be used to compare the quality of different sets of solutions, and therefore provides a robust, quantitative approach for comparing different heuristic, a posteriori solution procedures for difficult multiple objective optimization problems. We provide specific examples of decision maker preference functions and illustrate the calculation of the resulting IPF for specific solution sets and a simple family of combined objectives. [source] Sex determination in fish: Lessons from the sex-determining gene of the teleost medaka, Oryzias latipesDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 5-6 2003Masaru Matsuda Although sex determination systems in animals are diverse, sex-determining genes have been identified only in mammals and some invertebrates. Recently, DMY (DM domain gene on the Y chromosome) has been found in the sex-determining region on the Y chromosome of the teleost medaka fish, Oryzias latipes. Functional and expression analyses of DMY show it to be the leading candidate for the male-determining master gene of the medaka. Although some work is required to define DMY as the master sex-determining gene, medaka is expected to be a good experimental animal for investigating the precise mechanisms involved in primary sex determination in non-mammalian vertebrates. In this article, the process of identification of DMY and is summarized and the origins of DMY and sexual development of the medaka's gonads are reviewed. In addition, putative functions of DMY are discussed. [source] N-cadherin prodomain cleavage regulates synapse formation in vivoDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2009Nazlie S. Latefi Abstract Cadherins are initially synthesized bearing a prodomain that is thought to limit adhesion during early stages of biosynthesis. Functional cadherins lack this prodomain, raising the intriguing possibility that cells may utilize prodomain cleavage as a means to temporally or spatially regulate adhesion after delivery of cadherin to the cell surface. In support of this idea, immunostaining for the prodomain of zebrafish N-cadherin revealed enriched labeling at neuronal surfaces at the soma and along axonal processes. To determine whether post-translational cleavage of the prodomain affects synapse formation, we imaged Rohon-Beard cells in zebrafish embryos expressing GFP-tagged wild-type N-cadherin (NCAD-GFP) or a GFP-tagged N-cadherin mutant expressing an uncleavable prodomain (PRON-GFP) rendering it nonadhesive. NCAD-GFP accumulated at synaptic microdomains in a developmentally regulated manner, and its overexpression transiently accelerated synapse formation. PRON-GFP was much more diffusely distributed along the axon and its overexpression delayed synapse formation. Our results support the notion that N-cadherin serves to stabilize pre- to postsynaptic contacts early in synapse development and suggests that regulated cleavage of the N-cadherin prodomain may be a mechanism by which the kinetics of synaptogenesis are regulated. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source] Functional and molecular evidence of adenosine A2A receptor in coronary arteriolar dilation to adenosineDRUG DEVELOPMENT RESEARCH, Issue 1-2 2001Lih Kuo Abstract Adenosine is a potent vasodilator implicated in the regulation of coronary microvascular diameter during metabolic stress. However, the specific adenosine receptors and underlying mechanism responsible for the dilation of coronary microvessels to adenosine remains to be elucidated. Thus, pig subepicardial coronary arterioles (<100 ,m) were isolated, cannulated, and pressurized without flow for in vitro study. All vessels developed basal tone and dilated concentration-dependently to adenosine. Disruption of endothelium and inhibition of nitric oxide (NO) synthase by L-NAME produced identical attenuation of adenosine-induced dilation. KATP channel inhibitor glibenclamide further reduced the dilation of denuded vessels. cAMP antagonist Rp-8-Br-cAMP blocked vasodilation to forskolin, but failed to inhibit vasodilation to adenosine. Coronary dilation to adenosine was blocked by a selective adenosine A2A receptor antagonist ZM241385, but was not altered by an A1 receptor antagonist, DPCPX. Reverse transcription-polymerase chain reaction study revealed that A2A receptor mRNA was expressed in microvessels but not in cardiac myocytes; A1 receptor expression was observed only in cardiac myocytes. These results suggest that adenosine-induced dilation of coronary arterioles is mediated predominantly by A2A receptors. Activation of these receptors elicits vasodilation by endothelial release of NO and by smooth muscle opening of KATP channels in a cAMP-independent manner. Drug Dev. Res. 52:350,356, 2001. © 2001 Wiley-Liss, Inc. [source] Extensive HLA class I allele promiscuity among viral CTL epitopesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007Nicole Frahm Abstract Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals' HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development. [source] Phenotypic classification of human CD8+ T,cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector functionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2004Hiroko Tomiyama Abstract Phenotypic classification of human CD8+ T,cells using three cell surface markers, CD27, CD28 and CD45RA, was recently suggested to be useful for identification of naive, memory and effector CD8+ T,cells. However, it still remains unclear whether such classification precisely reflects functional classification of CD8+ T,cells. To clarify this, we characterized each CD27CD28CD45RA subset of total and human cytomegalovirus (HCMV)-specific CD8+ T,cells by analyzing the expression of perforin and two chemokine receptors, CCR5 and CCR7, as well as their function. An inverse correlation between perforin and CD27 expression was found in all four CD28CD45RA subsets. Therefore, to achieve a phenotypic classification of CD8+ T,cells that moreprecisely reflects their function, the CD27+ subset was divided into CD27low and CD27high subsets based on the expression level of CD27. Functional and flow cytometric analyses of CD27CD28CD45RA subsets showed that this phenotypic classification reflects functional classification of CD8+ T,cells. HCMV-specific CD8+ T,cells from healthy HCMV-seropositive individuals were predominantly found in effector and memory/effector subsets, indicating that HCMV-specific effector CD8+ T,cells are actively induced by HCMV replication in healthy HCMV carriers. Phenotypic analyses of CD8+ T,cells using this classification will enable the characterization of antigen-specific CD8+ T,cells. [source] A Dinuclear Double-Stranded Oxido Complex of ReV with a Bis(benzene- o -dithiolato) LigandEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 27 2009Jorge S. Gancheff Abstract The reaction of [ReOCl3(PPh3)2] with 1,2-bis(2,3-dimercaptobenzamido)ethane (H4 - 1) in the presence of Na2CO3 in methanol under anaerobic conditions affords the dinuclear ReV oxido complex [PPh4]2[ReO(1)]2 containing two distorted square-pyramidal {ReVOS4} units bridged by the ligand strands in a double-stranded fashion. The coordinationgeometry around the metal centers is similar to the one observed for [ReO(bdt)2],. The ReS4 planes are arranged in a coplanar fashion and are not twisted around the metal,metal vector, which prevents the complex to adopt a helical structure. Luminescence studies show the presence of emission bands, which are assigned to singlet-singlet transitions exhibiting very fast decays (ca. 10 ns). Theoretical Density Functional (DFT) studies on geometry and electronic properties were performed employing the hybrid B3LYP and PBE1PBE functionals. While the general trends observed in the experimental data are well reproduced in all cases, a good agreement was obtained using PBE1PBE, in particular for the Re,S bonds. Natural Bond Orbitals (NBO) analysis indicates the presence of polarized Re,O and Re,S bonds, both of them polarized toward the non-metal. The calculation show that the molecular orbitals of the ReV are doubly degenerated, the occupied 5d orbital of rhenium lying beneath occupied sulfur-based MOs due to the rigid geometry imposed by the C,C backbone of the bis(benzene- o -dithiolato) ligands. The origin of all absorption bands is ascribed to a ligand-to-metal charge transfer (LMCT), in which occupied sulfur-based orbitals and unoccupied rhenium-centered orbitals are involved.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Angiotensin-Converting Enzyme Genotype Affects the Response of Human Skeletal Muscle to Functional OverloadEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Jonathan Folland The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now, have remained unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin-converting enzyme (ACE) genotype is an important factor in the hypertrophic response of cardiac muscle to exercise and could also be involved in skeletal muscle hypertrophy , an important factor in the response to functional overload. Subjects were 33 healthy male volunteers with no experience of strength training. We examined the effect of ACE genotype upon changes in strength of quadriceps muscles in response to 9 weeks of specific strength training (isometric or dynamic). There was a significant interaction between ACE genotype and isometric training with greater strength gains shown by subjects with the D allele (mean ± S.E.M.: II, 9.0 ± 1.7%; ID, 17.6 ± 2.2%; DD, 14.9 ± 1.3%, ANOVA, P 0.05). A consistent genotype and training interaction (ID DD II) was observed across all of the strength measures, and both types of training. ACE genotype is the first genetic factor to be identified in the response of skeletal muscle to strength training. The association of the ACE I/D polymorphism with the responses of cardiac and skeletal muscle to functional overload indicates that they may share a common mechanism. These findings suggest a novel mechanism, involving the renin-angiotensin system, in the response of skeletal muscle to functional overload and may have implications for the management of conditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function. [source] Functional overlap between RecA and MgsA (RarA) in the rescue of stalled replication forks in Escherichia coliGENES TO CELLS, Issue 3 2005Tatsuya Shibata Escherichia coli RecA protein plays a role in DNA homologous recombination, recombination repair, and the rescue of stalled or collapsed replication forks. The mgsA (rarA) gene encodes a highly conserved DNA-dependent ATPase, whose yeast orthologue, MGS1, plays a role in maintaining genomic stability. In this study, we show a functional relationship between mgsA and recA during DNA replication. The mgsA recA double mutant grows more slowly and has lower viability than a recA single mutant, but they are equally sensitive to UV-induced DNA damage. Mutations in mgsA and recA cause lethality in DNA polymerase I deficient cells, and suppress the temperature-dependent growth defect of dnaE486 (Pol III ,-catalytic subunit). Moreover, recAS25P, a novel recA allele identified in this work, does not complement the slow growth of ,mgsA ,recA cells or the lethality of polA12 ,recA, but is proficient in DNA repair, homologous recombination, SOS mutagenesis and SOS induction. These results suggest that RecA and MgsA are functionally redundant in rescuing stalled replication forks, and that the DNA repair and homologous recombination functions of RecA are separated from its function to maintain progression of replication fork. [source] Layer-By-Layer Dendritic Growth of Hyperbranched Thin Films for Surface Sol,Gel Syntheses of Conformal, Functional, Nanocrystalline Oxide Coatings on Complex 3D (Bio)silica TemplatesADVANCED FUNCTIONAL MATERIALS, Issue 17 2009Guojie Wang Abstract Here, a straightforward and general method for the rapid dendritic amplification of accessible surface functional groups on hydroxylated surfaces is described, with focus on its application to 3D biomineral surfaces. Reaction of hydroxyl-bearing silica surfaces with an aminosilane, followed by alternating exposure to a dipentaerythritol-derived polyacrylate solution and a polyamine solution, allows the rapid, layer-by-layer (LBL) build-up of hyperbranched polyamine/polyacrylate thin films. Characterization of such LBL-grown thin films by AFM, ellipsometry, XPS, and contact angle analyses reveals a stepwise and spatially homogeneous increase in film thickness with the number of applied layers. UV,Vis absorption analyses after fluorescein isothiocyanate labeling indicate that significant amine amplification is achieved after the deposition of only 2 layers with saturation achieved after 3,5 layers. Use of this thin-film surface amplification technique for hydroxyl-enrichment of biosilica templates facilitates the conformal surface sol,gel deposition of iron oxide that, upon controlled thermal treatment, is converted into a nanocrystalline (,9.5,nm) magnetite (Fe3O4) coating. The specific adsorption of arsenic onto such magnetite-coated frustules from flowing, arsenic-bearing aqueous solutions is significantly higher than for commercial magnetite nanoparticles (,50,nm in diameter). [source] Functional (GT)n polymorphisms in promoter region of N -methyl- d -aspartate receptor 2A subunit (GRIN2A) gene affect hippocampal and amygdala volumesGENES, BRAIN AND BEHAVIOR, Issue 3 2010H. Inoue The glutamate system including N -methyl- d -aspartate (NMDA) affects synaptic formation, plasticity and maintenance. Recent studies have shown a variable (GT)n polymorphism in the promoter region of the NMDA subunit gene (GRIN2A) and a length-dependent inhibition of transcriptional activity by the (GT)n repeat. In the present study, we examined whether the GRIN2A polymorphism is associated with regional brain volume especially in medial temporal lobe structures, in which the NMDA-dependent synaptic processes have been most extensively studied. Gray matter regions of interest (ROIs) for the bilateral amygdala and hippocampus were outlined manually on the magnetic resonance images of 144 healthy individuals. In addition, voxel-based morphometry (VBM) was conducted to explore the association of genotype with regional gray matter volume from everywhere in the brain in the same sample. The manually measured hippocampal and amygdala volumes were significantly larger in subjects with short allele carriers (n = 89) than in those with homozygous long alleles (n = 55) when individual differences in intracranial volume were accounted for. The VBM showed no significant association between the genotype and regional gray matter volume in any brain region. These findings suggest that the functional GRIN2A (GT)n polymorphism could weakly but significantly impact on human medial temporal lobe volume in a length-dependent manner, providing in vivo evidence of the role of the NMDA receptor in human brain development. [source] Reverse facial artery,submental artery mandibular osteomuscular flap for the reconstruction of maxillary defects following the removal of benign tumorsHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2009Wei-Liang Chen DDS Abstract Background. Functional and aesthetic restoration in maxillary reconstruction remains a challenge. Although many free flap procedures have become popular in maxillary reconstruction, these microsurgical methods have certain limitations and risks. This study assessed the reliability of the reverse facial artery,submental artery mandibular osteomuscular flap for reconstructing maxillary defects. Methods. Eight maxillary defects following benign tumor ablation were repaired with reverse facial artery,submental artery mandibular osteomuscular flaps. The patients ranged in age from 16 to 33 years; 5 were male and 3 were female. Maxillary odontogenic myxoma was present in 3 cases, maxillary fibrous dysplasia and ameloblastoma in 2 cases each, and chondromyxoid fibroma in 1 case. The defects were classified as class 2a. Results. Primary reconstruction of the maxilla was carried out using a pedicled mandibular osteomuscular flap. No flap failures occurred. Dental reconstruction was successful in all patients. Proper aesthetics and complete functionality were obtained, and there were no donor-site problems. The patients were followed for 12 to 24 months, with an average of 18.6 months, and no recurrence was encountered. Conclusion. The reverse facial artery,submental artery mandibular osteomuscular flap is safe, quick, and simple to elevate. The flap can be used reliably for reconstructing maxillary defects. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] Efficacy of Eletriptan in Migraine-Related Functional Impairment: Functional and Work Productivity OutcomesHEADACHE, Issue 5 2007Stephen D. Silberstein MD Objective.,To provide a multidimensional assessment of the extent of functional impairment during an acute migraine attack, and of the improvement in functioning in response to treatment, using 4 concurrently administered scales: the 7-item work productivity questionnaire (PQ-7), the functional assessment in migraine (FAIM) activities and participation (FAIM-A&P) subscale, the FAIM-impact of migraine on mental functioning (FAIM-IMMF) subscale, and the traditional 4-point global functional impairment scale (FIS). Methods.,Outpatients with an International Classification of Headache Disorders diagnosis of migraine were randomized to double-blind treatment of a single attack with either oral eletriptan 20 mg (n = 192) once-daily, eletriptan 40 mg (N = 213) once-daily, or placebo (n = 208). Patients were encouraged to take study medication as soon as they were sure they were experiencing a typical migraine headache, after the aura phase (if present) had ended. Patients with moderate-to-severe functional impairment were identified on each of the 4 disability scales, and 2-hour functional response was compared between treatments. Results.,At baseline, the PQ-7 and FAIM-IMMF items that assessed ability to perform tasks requiring concentration, sustained work or attention, and ability to think quickly or spontaneously, were especially sensitive to the effects of mild headache pain, with 27% to 48% of patients (n = 92-112) reporting moderate-to-severe impairment. Only 11.3% of patients (n = 112) reported this level of impairment due to mild pain on the FIS. Functional response at 2 hours was significantly higher on eletriptan 40 mg versus placebo on the FAIM-A&P (63% vs 36%; n = 218; P < .0001); on the PQ-7 (56% vs 34%; n = 116; P= .0052); and on the FAIM-IMMF (50% vs 34%; n = 215; P= .017). These rates were all lower than the functional response rates on the FIS for eletriptan 40 mg (75%) and eletriptan 20 mg (70%) versus placebo (45%; P < .001). Conclusions.,In this exploratory analysis, use of multidimensional scales was found to provide a sensitive measure of headache-related functional impairment, especially for detecting clinically meaningful cognitive effects, and for detecting drug versus placebo differences. [source] Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophreniaHUMAN BRAIN MAPPING, Issue 12 2009Bumseok Jeong Abstract Functional studies in schizophrenia demonstrate prominent abnormalities within the left inferior frontal gyrus (IFG) and also suggest the functional connectivity abnormalities in language network including left IFG and superior temporal gyrus during semantic processing. White matter connections between regions involved in the semantic network have also been indicated in schizophrenia. However, an association between functional and anatomical connectivity disruptions within the semantic network in schizophrenia has not been established. Functional (using levels of processing paradigm) as well as diffusion tensor imaging data from 10 controls and 10 chronic schizophrenics were acquired and analyzed. First, semantic encoding specific activation was estimated, showing decreased activation within the left IFG in schizophrenia. Second, functional time series were extracted from this area, and left IFG specific functional connectivity maps were produced for each subject. In an independent analysis, tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) values between groups, and to correlate these values with functional connectivity maps. Schizophrenia patients showed weaker functional connectivity within the language network that includes left IFG and left superior temporal sulcus/middle temporal gyrus. FA was reduced in several white matter regions including left inferior frontal and left internal capsule. Finally, left inferior frontal white matter FA was positively correlated with connectivity measures of the semantic network in schizophrenics, but not in controls. Our results indicate an association between anatomical and functional connectivity abnormalities within the semantic network in schizophrenia, suggesting further that the functional abnormalities observed in this disorder might be directly related to white matter disruptions. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Functional and structural analysis of five mutations identified in methylmalonic aciduria cbIB type,HUMAN MUTATION, Issue 9 2010Ana Jorge-Finnigan Abstract ATP:cob(I)alamin adenosyltransferase (ATR, E.C.2.5.1.17) converts reduced cob(I)alamin to the adenosylcobalamin cofactor. Mutations in the MMAB gene encoding ATR are responsible for the cblB type methylmalonic aciduria. Here we report the functional analysis of five cblB mutations to determine the underlying molecular basis of the dysfunction. The transcriptional profile along with minigenes analysis revealed that c.584G>A, c.349-1G>C, and c.290G>A affect the splicing process. Wild-type ATR and the p.I96T (c.287T>C) and p.R191W (c.571C>T) mutant proteins were expressed in a prokaryote and a eukaryotic expression systems. The p.I96T protein was enzymatically active with a KM for ATP and KD for cob(I)alamin similar to wild-type enzyme, but exhibited a 40% reduction in specific activity. Both p.I96T and p.R191W mutant proteins are less stable than the wild-type protein, with increased stability when expressed under permissive folding conditions. Analysis of the oligomeric state of both mutants showed a structural defect for p.I96T and also a significant impact on the amount of recovered mutant protein that was more pronounced for p.R191W that, along with the structural analysis, suggest they might be misfolded. These results could serve as a basis for the implementation of pharmacological therapies aimed at increasing the residual activity of this type of mutations. Hum Mutat 31:1033,1042, 2010. © 2010 Wiley-Liss, Inc. [source] Serotonin and Sleep: Molecular, Functional and Clinical Aspects.HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2008B. L. Jacobs, D. J. Nutt., Edited by J. M. Monti, S. R. Pandi-Perumal No abstract is available for this article. [source] Characterization of CC-chemokine receptor 7 expression on murine T cells in lymphoid tissuesIMMUNOLOGY, Issue 2 2003Olle Bjorkdahl Summary Expression of the lymph node homing and CC-chemokine receptor 7 (CCR7), with L-selectin (CD62L), has been shown to divide human memory T cells into two functionally distinct subsets. We generated a polyclonal antibody against murine CCR7 and used this antibody to study CCR7 expression on murine T-cell subsets. Using flow cytometric staining of T cells for visualisation expression of CCR7 in association with CD62L and CD44, a major population of CD4 or CD8 T cells expressing CCR7 were found to be CD62Lhigh CD44low, which would suggest a naďve cell phenotype. By analogy with human studies, memory cells could be subdivided into CCR7high CD62Lhigh CD44high (central memory) and CCR7low CD62Llow CD44high (effector memory). The proportions of these populations were different in lymph node, blood and spleen. Functional, short-term in vitro polyclonal stimulation of blood, spleen and lymph node cells from naive mice demonstrated that CCR7high CD4 T cells produced predominantly interleukin (IL)-2, whereas CCR7low CD4 T cells produced both IL-2 and interferon-, (IFN-,). However, in contrast to previously published reports, the CCR7high CD8 T-cell subpopulation produced both IFN-, and IL-2. Analysis of effector T cells, induced by immunization in vivo, showed that a proportion of activated naďve CD4 T cells down-regulated CCR7 only after multiple cell divisions, and this coincided with the down-regulation of CD62L and production of IL-4 and IFN-,. Finally, analysis of effector T cells during the phase of maximal clonal expansion of secondary immune responses in vivo indicated that the vast majority of both IL-2- and IFN-,-producing cells are CCR7low, while few cytokine-expressing CCR7high T cells were detected. Our results support the hypothesis, developed from studies with human cells, that CCR7 may separate functionally different murine memory T-cell subpopulations, but indicate additional complexity in that CCR7high CD8 T cells also may produce IFN-,. [source] Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell linesINTERNATIONAL JOURNAL OF CANCER, Issue 10 2009Shailesh Singh Abstract Chemokines and chemokine receptors have been shown to be involved in metastatic process of prostate cancer (PCa). In this study, we show primary PCa tissues and cell lines (LNCaP and PC3) express CXCR5, a specific chemokine receptor for CXCL13. Expression of CXCR5 was significantly higher (p < 0.001) in PCa cases than compared to normal match (NM) tissues. CXCR5 intensity correlated (R2 = 0.97) with Gleason score. While prostate tumor tissues with Gleason scores , 7, displayed predominantly nuclear CXCR5 expression patterns, PCa specimens with Gleason scores , 6 showed predominantly membrane and cytoplasmic expression patterns that were comparable to benign prostatic hyperplasia (BPH). Similar to tissue expression, PCa cell lines expressed significantly more CXCR5 than normal prostatic epithelial cells (PrECs), and CXCR5 expression was distributed among intracellular and extracellular compartments. Functional in vitro assays showed higher migratory and invasive potentials toward CXCL13, an effect that was mediated by CXCR5. In both PCa cell lines, CXCL13 treatment increased the expression of collagenase-1 or matrix metalloproteinase-1 (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), stromelysin-2 (MMP-10) and stromelysin-3 (MMP-11). These data demonstrate the clinical and biological relevance of the CXCL13-CXCR5 pathway and its role in PCa cell invasion and migration. © 2009 UICC [source] Functional and structural properties and in vitro digestibility of acylated hemp (Cannabis sativa L.) protein isolatesINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 12 2009Shou-Wei Yin Summary The effects of succinylation and acetylation on some functional, structural properties and in vitro trypsin digestibility of hemp protein isolate (HPI) were investigated. The extent of acylation gradually increased from 0 to 60,70%, with the anhydride-to-protein ratio increasing from 0 to 1.0 g g,1. Size exclusion chromatography showed that succinylation led to formation of more soluble protein aggregate than acetylation, especially at anhydride levels higher than 0.1 g g,1. Succinylation led to gradual increase in protein solubility (PS) from 30 to 85,90%, while in the acetylation case, the PS was improved only at low anhydride levels, increasing from 30 to about 50% with anhydride-to-protein ratio increasing from 0 to 0.2 g g,1. At neutral pH, the emulsifying activity indexes (EAI) of HPI was 22.1 m2 g,1, and the EAI linearly and significantly increased with the extent of acylation. The EAIs of succinylated and acetylated HPI (1.0 g g,1) were 119.0 and 54.4 m2 g,1, respectively. Differential scanning calorimetry (DSC) and intrinsic fluorescence spectrum analyses indicated gradual structural unfolding of proteins, or exposure of hydrophobic clusters to the solvent, especially at higher anhydride levels. Additionally, the in vitro trypsin digestibility was significantly improved by the succinylation. The results indicated that the chemical acylation treatment (especially succinylation) could be applied to modify some selected functional properties of hemp proteins, especially PS and emulsifying ability. [source] Iron-overload and genotypic expression of HFE mutations H63D/C282Y and transferrin receptor Hin6I and BanI polymorphism in German patients with hereditary haemochromatosisINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2000R. Gottschalk Gene variations of HFE, a HLA-class I like molecule, are highly associated with hereditary haemochromatosis (HH). Functional as well as molecular studies of the HFE protein have indicated that the molecule is involved in iron metabolism and that the HFE gene variations observed among HH patients affect its interaction with the transferrin receptor (TfR). In the present study, we have therefore analysed the relationship between the HFE gene variants, C282Y and H63D, and body iron status among 85 German HH patients. In addition, two TfR gene polymorphism, TfR-Hin6I and TfR-BanI, were typed that have been reported to define ethnically distinct haplotypes. As controls we used 251/159 healthy German blood donors. Seventy-eight (92%) patients were C292Y homozygous, the H63D mutation was present in five (6%) patients with none of the patients being H63D homozygous. Serum transferrin, transferrin saturation and liver iron content were determined prior to therapeutic intervention. Among C282Y homozygous patients serum ferritin levels (2294 ± 3174 vs. 463 ± 224 µg L,1, P < 0.0001) and transferrin saturation (86 ± 18% vs. 62 ± 25%, P = 0.048) were elevated significantly compared with C282Y and/or H63D heterozygous patients. In addition, the liver iron content (291 ± 165 vs. 138 ± 95 µmol g,1, P = 0.028) and liver iron index (6.4 ± 2.8 vs. 3.2 ± 2.3, P = 0.019) were increased among C282Y homozygotes compared with C282Y heterozygotes. In contrast, no difference was observed between patients and controls regarding the distribution of TfR- Hin6I and TfR- BanI alleles. These data indicate that the iron intake is higher among C282Y homozygous patients compared with C282Y heterozygous or C282Y/H63D compound heterozygous individuals and supports the functional role of the HFE protein in iron metabolism whereas the TfR gene variants seem to have no influence on iron uptake. [source] Orthogonal Chemical Genetic Approaches for Unraveling Signaling PathwaysIUBMB LIFE, Issue 6 2005Kavita Shah Abstract While chemical genetic approach uses small molecules to probe protein functions in cells or organisms, orthogonal chemical genetics refers to strategies that utilize reengineered protein-small molecule interfaces, to alter specificities, in order to probe their functions. The advantage of orthogonal chemical genetics is that the changes at the interfaces are generally so minute that it goes undetected by natural processes, and thus depicts a true physiological picture of biological phenomenon. This review highlights the recent advances in the area of orthogonal chemical genetics, especially those designed to probe signaling processes. Dynamic protein-protein and enzyme-substrate interactions following stimuli form the foundation of signal transduction. These processes not only break spatial and temporal boundaries between interacting proteins, but also impart distinct regulatory properties by creating functional diversity at the interfaces. Functional and temporal modulation of these dynamic interactions by specific chemical probes provides extremely powerful tools to initiate, ablate, decouple and deconvolute different components of a signaling pathway at multiple stages. Not surprisingly, multiple receptor-ligand reengineering approaches have been developed in the last decade to selectively manipulate these transient interactions with the aim of unraveling signaling events. However, given the diversity of protein-protein interactions and novel chemical genetic probes developed to perturb these processes, a short review cannot do adequate justice to all aspects of signaling. For this reason, this review focuses on some orthogonal chemical-genetic strategies that are developed to study signaling processes involving enzyme-substrate interactions. IUBMB Life, 57: 397-405, 2005 [source] The Oldest Old in the Last Year of Life: Population-Based Findings from Cambridge City over-75s Cohort Study Participants Aged 85 and Older at DeathJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2010Jun Zhao MSc OBJECTIVES: To characterize people of advanced old age in their last year of life and compare those dying in their late 80s with those dying aged 90 and older to inform policy and planning. DESIGN: Retrospective analysis of prospectively collected population-based data from the Cambridge City over-75s Cohort (CC75C) Study, United Kingdom. PARTICIPANTS: Men and women aged 85 and older at death who died less than 1 year after taking part in any CC75C survey (N=321). MEASUREMENTS: Physical health, functional disability, self-rated health, cognitive status. RESULTS: Functional and cognitive impairments were markedly higher for those who died aged 90 and older, predominantly women,than for those who died aged 85 to 89. At least half (49.4,93.6%) of subjects aged 90 and older needed maximum assistance in virtually every daily activity; those aged 85 to 89 needed this only for shopping and laundry. Disability in basic and instrumental activities rose from 59.1% before to 85.4% after the age of 90 and cognitive impairment (Mini-Mental State Examination score ,21) from 41.7% to 69.4%. Despite this and proximity to death, 60.5% and 67.0%, respectively, rated their health positively. Only one in five reported needing more help. CONCLUSION: This study provides new data identifying high levels of physical and cognitive disability in very old people in the year before death. As the very old population rises, so will support needs for people dying in extreme old age. The mismatch between health perceptions and functional limitations suggests that these vulnerable older adults may not seek help from which they could benefit. These findings have major policy and planning implications for end-of-life care for the oldest old. [source] Functional and Cognitive Consequences of Silent Stroke Discovered Using Brain Magnetic Resonance Imaging in an Elderly PopulationJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2004Wolf-Peter Schmidt MD Objectives: To evaluate the prevalence of silent stroke and its associated consequences on physical, cognitive, and emotional functioning in an elderly population. Design: Population-based cross-sectional survey. Setting: The Memory and Morbidity in Augsburg Elderly project in the Augsburg region of southern Germany. Participants: Two hundred sixty-seven community-dwelling persons aged 65 to 83. Measurements: The presence of silent stroke was determined using magnetic resonance imaging brain scan and a single question asking for physician-diagnosed stroke in each participant. The health effect of silent stroke was assessed using rating scales for self-perceived health status (36-item short-form health survey), activities of daily living (ADLs) and instrumental ADLs, cognitive function, and depression (Center for Epidemiologic Studies Depression scale). Results: Just fewer than 13% (12.7%) of participants were affected by silent stroke. Silent stroke was associated with a history of hypertension, heart surgery, and elevated C-reactive protein. Individuals with silent stroke showed impairments on the Mini-Mental State Examination test and in the cognitive domains of memory, procedural speed, and motor performance. Conclusion: The presence of silent stroke has a considerable effect on cognitive performance in those affected. Determining the presence of silent stroke using brain imaging may contribute to identifying individuals at risk for developing gradual neurological deficits. [source] Diabetes Mellitus in a Subgroup of Older Mexicans: Prevalence, Association with Cardiovascular Risk Factors, Functional and Cognitive Impairment, and MortalityJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2002Joel Rodríguez-Saldańa MD OBJECTIVES: To examine the prevalence and effects of diabetes mellitus in a subgroup of older Mexicans to allow comparisons to older persons of Mexican origin living in the United States. DESIGN: Longitudinal study. SETTING: High-rise retirement housing in Mexico City. PARTICIPANTS: Seven hundred eighty-five public servants and their family members aged 65 and older. MEASUREMENTS: Geriatric survey of function; mental status and depression; a physical examination; and blood samples for glucose and cholesterol. RESULTS: The prevalence of diabetes mellitus in this population was 15.1%, substantially lower than the prevalence reported in people of Mexican origin living in the United States. Nondiabetics were more obese than diabetics. Diabetes mellitus was more common in men than women. The mortality rate was greater in diabetics than nondiabetics (relative risk = 1.73, P < .05). Diabetics had more coronary artery disease and were more likely to die from myocardial infarction and neoplasms than nondiabetics. Diabetics were more likely to be functionally impaired (P < .0001) but no more likely to fall or to have fractures. Diabetics did not differ from nondiabetics in cognitive impairment or level of dysphoria. CONCLUSION: These studies highlight some important similarities and differences in comparing a middle class subgroup of older diabetics in Mexico City with diabetics of Mexican origin living in the United States. [source] Functional, genetic and chemical characterization of biosurfactants produced by plant growth-promoting Pseudomonas putida 267JOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2009Marco Kruijt Abstract Aims:, Plant growth-promoting Pseudomonas putida strain 267, originally isolated from the rhizosphere of black pepper, produces biosurfactants that cause lysis of zoospores of the oomycete pathogen Phytophthora capsici. The biosurfactants were characterized, the biosynthesis gene(s) partially identified, and their role in control of Phytophthora damping-off of cucumber evaluated. Methods and Results:, The biosurfactants were shown to lyse zoospores of Phy. capsici and inhibit growth of the fungal pathogens Botrytis cinerea and Rhizoctonia solani. In vitro assays further showed that the biosurfactants of strain 267 are essential in swarming motility and biofilm formation. In spite of the zoosporicidal activity, the biosurfactants did not play a significant role in control of Phytophthora damping-off of cucumber, since both wild type strain 267 and its biosurfactant-deficient mutant were equally effective, and addition of the biosurfactants did not provide control. Genetic characterization revealed that surfactant biosynthesis in strain 267 is governed by homologues of PsoA and PsoB, two nonribosomal peptide synthetases involved in production of the cyclic lipopeptides (CLPs) putisolvin I and II. The structural relatedness of the biosurfactants of strain 267 to putisolvins I and II was supported by LC-MS and MS-MS analyses. Conclusions:, The biosurfactants produced by Ps. putida 267 were identified as putisolvin-like CLPs; they are essential in swarming motility and biofilm formation, and have zoosporicidal and antifungal activities. Strain 267 provides excellent biocontrol activity against Phytophthora damping-off of cucumber, but the lipopeptide surfactants are not involved in disease suppression. Significance and Impact of the Study:,Pseudomonas putida 267 suppresses Phy. capsici damping-off of cucumber and provides a potential supplementary strategy to control this economically important oomycete pathogen. The putisolvin-like biosurfactants exhibit zoosporicidal and antifungal activities, yet they do not contribute to biocontrol of Phy. capsici and colonization of cucumber roots by Ps. putida 267. These results suggest that Ps. putida 267 employs other, yet uncharacterized, mechanisms to suppress Phy. capsici. [source] Identifying the Relative Contributions of Rac1 and Rac2 to Osteoclastogenesis,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2008Yongqiang Wang Abstract Rac small GTPases may play an important regulatory role in osteoclastogenesis. Our in vitro and in vivo results show that both Rac1 and Rac2 are required for optimal osteoclast differentiation, but Rac1 is more critical. Rac1 is the key Rac isoform responsible for regulating ROS generation and the actin cytoskeleton during the multiple stages of osteoclast differentiation. Introduction: Recent evidence suggests that the Rac small GTPases may play an important regulatory role in osteoclastogenesis. This finding is important because bisphosphonates may regulate their antiresorptive/antiosteoclast effects through the modification of Rho family of small GTPases. Materials and Methods: To elucidate the specific roles of the Rac1 and Rac2 isoforms during osteoclastogenesis, we used mice deficient in Rac1, Rac2, or both Rac1 and Rac2 in monocyte/osteoclast precursors. Macrophage-colony stimulating factor (M-CSF), and RANKL-mediated osteoclastogenesis in vitro was studied by using bone marrow-derived mononucleated preosteoclast precursors (MOPs). The expression of osteoclast-specific markers was examined using quantitative real-time PCR and Western blot analysis. Free actin barbed ends in bone marrow MOPs after M-CSF stimulation was determined. The ability of MOPs to migrate toward M-CSF was assayed using Boyden chambers. Margin spreading on heparin sulfate-coated glass and RANKL-induced reactive oxygen species generation were also performed. Functional assays of in vitro-generated osteoclasts were ascertained using dentine sections from narwal tusks. Osteoclast levels in vivo were counted in TRACP and immunohistochemically stained distal tibial sections. In vivo microarchitexture of lumbar vertebrate was examined using ,CT 3D imaging and analysis. Results: We show here that, although both Rac isoforms are required for normal osteoclast differentiation, Rac1 deletion results in a more profound reduction in osteoclast formation in vitro because of its regulatory role in pre-osteoclast M-CSF-mediated chemotaxis and actin assembly and RANKL-mediated reactive oxygen species generation. This Rac1 cellular defect also manifests at the tissue level with increased trabecular bone volume and trabeculae number compared with wildtype and Rac2-null mice. This unique mouse model has shown for the first time that Rac1 and Rac2 play different and nonoverlapping roles during osteoclastogenesis and will be useful for identifying the key roles played by these two proteins during the multiple stages of osteoclast differentiation. Conclusions: Rac1 and Rac2 play different and nonoverlapping roles during osteoclastogenesis. This model showed that Rac1 is the key Rac isoform responsible for regulating ROS generation and the actin cytoskeleton during the multiple stages of osteoclast differentiation. [source] Novel UBA Domain Mutations of SQSTM1 in Paget's Disease of Bone: Genotype Phenotype Correlation, Functional Analysis, and Structural ConsequencesJOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2004Lynne J Hocking Abstract Three novel missense mutations of SQSTM1 were identified in familial PDB, all affecting the UBA domain. Functional and structural analysis showed that disease severity was related to the type of mutation but was unrelated to the polyubiquitin-binding properties of the mutant UBA domain peptides. Introduction: Mutations affecting the ubiquitin-associated (UBA) domain of Sequestosome 1 (SQSTM1) gene have recently been identified as a common cause of familial Paget's disease of bone (PDB), but the mechanisms responsible are unclear. We identified three novel SQSTM1 mutations in PDB, conducted functional and structural analyses of all PDB-causing mutations, and studied the relationship between genotype and phenotype. Materials and Methods: Mutation screening of the SQSTM1 gene was conducted in 70 kindreds with familial PDB. We characterized the effect of the mutations on structure of the UBA domain by protein NMR, studied the effects of the mutant UBA domains on ubiquitin binding, and looked at genotype-phenotype correlations. Results and Conclusions: Three novel missense mutations affecting the SQSTM1 UBA domain were identified, including a missense mutation at codon 411 (G411S), a missense mutation at codon 404 (M404V), and a missense mutation at codon 425 (G425R). We also identified a deletion leading to a premature stop codon at 394 (L394X). None of the mutations were found in controls. Structural analysis showed that M404V and G425R involved residues on the hydrophobic surface patch implicated in ubiquitin binding, and consistent with this, the G425R and M404V mutants abolished the ability of mutant UBA domains to bind polyubiquitin chains. In contrast, the G411S and P392L mutants bound polyubiquitin chains normally. Genotype-phenotype analysis showed that patients with truncating mutations had more extensive PDB than those with missense mutations (bones involved = 6.05 ± 2.71 versus 3.45 ± 2.46; p < 0.0001). This work confirms the importance of UBA domain mutations of SQSTM1 as a cause of PDB but shows that there is no correlation between the ubiquitin-binding properties of the different mutant UBA domains and disease occurrence or extent. This indicates that the mechanism of action most probably involves an interaction between SQSTM1 and a hitherto unidentified protein that modulates bone turnover. [source] | |||||||||||||||||||||||||||||||