Kośliński, Piotr; Jarzemski, Piotr; Markuszewski, Michał J; Kaliszan, Roman
2014-03-01
Pterins are a class of potential cancer biomarkers. New methods involving hydrophilic interaction liquid chromatography (HILIC) and reversed phase (RP) high-performance liquid chromatography have been developed for analysis of eight pterin compounds: 6,7-dimethylpterin, pterin, 6-OH-methylpterin, biopterin, isoxanthopterin, neopterin, xanthopterin, and pterin-6-carboxylic acid. The effect of mobile phase composition, buffer type, pH and concentration on retention using HILIC, C8 and C18 RP stationary phases were examined. Separation of pterins on RP and HILIC stationary phase was performed and optimized. Eight pterins were successfully separated on HILIC Luna diol-bonded phases, Aquasil C18 RP column and LiChrospher C8 RP column. Determination and separation of the pterins from urine samples were performed on HILIC Luna and LiChrospher C8 RP columns which were chosen as the most appropriate ones. Finally, LiChrospher C8 RP column with fluorescence detection was selected for further validation of the method. The optimum chromatographic condition was mobile phase methanol (A)/phosphoric buffer pH 7, 10mM (B), isocratic elution 0-15min 5% A flow=0.5ml/min 15-17min. 5% A, flow=0.5-1ml/min the linearity (R(2)>0.997) and retention time repeatability (RSD%<1) were at satisfactory level. The precision of peak areas expressed as RSD in % was between 0.55 and 14. Pterins detection limits varied from 0.041ng/ml to 2.9ng/ml. Finally, HPLC method was used for the analysis of pterins in urine samples with two different oxidation procedures. Concentration levels of pterin compounds in bladder cancer patients and healthy subjects were compared. Copyright © 2013 Elsevier B.V. All rights reserved.
Rutowski, R.L; Macedonia, J.M; Morehouse, N; Taylor-Taft, L
2005-01-01
Animal colouration is typically the product of nanostructures that reflect or scatter light and pigments that absorb it. The interplay between these colour-producing mechanisms may influence the efficacy and potential information content of colour signals, but this notion has received little empirical attention. Wing scales in the male orange sulphur butterfly (Colias eurytheme) possess ridges with lamellae that produce a brilliant iridescent ultraviolet (UV) reflectance via thin-film interference. Curiously, these same scales contain pterin pigments that strongly absorb wavelengths below 550 nm. Given that male UV reflectance functions as a sexual signal in C. eurytheme, it is paradoxical that pigments in the wing scales are highly UV absorbing. We present spectrophotometric analyses of the wings before and after pterin removal that show that pterins both depress the amplitude of UV iridescence and suppress a diffuse UV reflectance that emanates from the scales. This latter effect enhances the directionality and spectral purity of the iridescence, and increases the signal's chromaticity and potential signal content. Our findings also suggest that pterins amplify the contrast between iridescent UV reflectance and scale background colour as a male's wings move during flight. PMID:16191648
Rutowski, R L; Macedonia, J M; Morehouse, N; Taylor-Taft, L
2005-11-07
Animal colouration is typically the product of nanostructures that reflect or scatter light and pigments that absorb it. The interplay between these colour-producing mechanisms may influence the efficacy and potential information content of colour signals, but this notion has received little empirical attention. Wing scales in the male orange sulphur butterfly (Colias eurytheme) possess ridges with lamellae that produce a brilliant iridescent ultraviolet (UV) reflectance via thin-film interference. Curiously, these same scales contain pterin pigments that strongly absorb wavelengths below 550 nm. Given that male UV reflectance functions as a sexual signal in C. eurytheme, it is paradoxical that pigments in the wing scales are highly UV absorbing. We present spectrophotometric analyses of the wings before and after pterin removal that show that pterins both depress the amplitude of UV iridescence and suppress a diffuse UV reflectance that emanates from the scales. This latter effect enhances the directionality and spectral purity of the iridescence, and increases the signal's chromaticity and potential signal content. Our findings also suggest that pterins amplify the contrast between iridescent UV reflectance and scale background colour as a male's wings move during flight.
Evaluation of Pterin, a Promising Drug Candidate from Cyanide Degrading Bacteria.
Mahendran, Ramasamy; Thandeeswaran, Murugesan; Kiran, Gopikrishnan; Arulkumar, Mani; Ayub Nawaz, K A; Jabastin, Jayamanoharan; Janani, Balraj; Anto Thomas, Thomas; Angayarkanni, Jayaraman
2018-06-01
Pterin is a member of the compounds known as pteridines. They have the same nucleus of 2-amino-4-hydroxypteridine (pterin); however, the side-chain is different at the position 6, and the state of oxidation of the ring may exist in different form viz. tetrahydro, dihydro, or a fully oxidized form. In the present study, the microorganisms able to utilize cyanide, and heavy metals have been tested for the efficient production of pterin compound. The soil samples contaminated with cyanide and heavy metals were collected from Salem steel industries, Tamil Nadu, India. Out of 77 isolated strains, 40 isolates were found to utilize sodium cyanate as nitrogen source at different concentrations. However, only 13 isolates were able to tolerate maximum concentration (60 mM) of sodium cyanate and were screened for pterin production. Among the 13 isolates, only 1 organism showed maximum production of pterin, and the same was identified as Bacillus pumilus SVD06. The compound was extracted and purified by preparative high-performance liquid chromatography and analyzed by UV/visible, FTIR, and fluorescent spectrum. The antioxidant property of the purified pterin compound was determined by cyclic voltammetry. In addition, antimicrobial activity of pterin was also studied which was substantiated by antagonistic activity against Escherichia coli, and Pseudomonas aeruginosa. Besides that the pterin compound was proved to inhibit the formation of biofilm. The extracted pterin compounds could be proposed further not only for antioxidant and antimicrobial but also for its potency to aid as anticancer and psychotic drugs in future.
Nitric-oxide Synthase Forms N-NO-pterin and S-NO-Cys
Rosenfeld, Robin J.; Bonaventura, Joseph; Szymczyna, Blair R.; MacCoss, Michael J.; Arvai, Andrew S.; Yates, John R.; Tainer, John A.; Getzoff, Elizabeth D.
2010-01-01
Inducible nitric-oxide synthase (iNOS) produces biologically stressful levels of nitric oxide (NO) as a potent mediator of cellular cytotoxicity or signaling. Yet, how this nitrosative stress affects iNOS function in vivo is poorly understood. Here we define two specific non-heme iNOS nitrosation sites discovered by combining UV-visible spectroscopy, chemiluminescence, mass spectrometry, and x-ray crystallography. We detected auto-S-nitrosylation during enzymatic turnover by using chemiluminescence. Selective S-nitrosylation of the ZnS4 site, which bridges the dimer interface, promoted a dimer-destabilizing order-to-disorder transition. The nitrosated iNOS crystal structure revealed an unexpected N-NO modification on the pterin cofactor. Furthermore, the structurally defined N-NO moiety is solvent-exposed and available to transfer NO to a partner. We investigated glutathione (GSH) as a potential transnitrosation partner because the intracellular GSH concentration is high and NOS can form S-nitrosoglutathione. Our computational results predicted a GSH binding site adjacent to the N-NO-pterin. Moreover, we detected GSH binding to iNOS with saturation transfer difference NMR spectroscopy. Collectively, these observations resolve previous paradoxes regarding this uncommon pterin cofactor in NOS and suggest means for regulating iNOS activity via N-NO-pterin and S-NO-Cys modifications. The iNOS self-nitrosation characterized here appears appropriate to help control NO production in response to cellular conditions. PMID:20659888
Structure-based design of bacterial nitric oxide synthase inhibitors
Holden, Jeffrey K.; Kang, Soosung; Hollingsworth, Scott A.; ...
2014-12-18
Inhibition of bacterial nitric oxide synthase (bNOS) has the potential to improve the efficacy of antimicrobials used to treat infections by Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis. However, inhibitor specificity toward bNOS over the mammalian NOS (mNOS) isoforms remains a challenge because of the near identical NOS active sites. One key structural difference between the NOS isoforms is the amino acid composition of the pterin cofactor binding site that is adjacent to the NOS active site. Previously, we demonstrated that a NOS inhibitor targeting both the active and pterin sites was potent and functioned as an antimicrobial. Here wemore » present additional crystal structures, binding analyses, and bacterial killing studies of inhibitors that target both the active and pterin sites of a bNOS and function as antimicrobials. Lastly, these data provide a framework for continued development of bNOS inhibitors, as each molecule represents an excellent chemical scaffold for the design of isoform selective bNOS inhibitors.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
White, R.H.
1990-06-05
The biosynthetic pathway for the generation of the methylated pterin in methanopterins was determined for the methanogenic bacteria Methanococcus volta and Methanobacterium formicicum. Extracts of M. volta were found to readily cleave L-7,8-dihydroneopterin to 7,8-dihydro-6-(hydroxymethyl)pterin, which was confirmed to be a precursor of the pterin portion of the methanopterin. (methylene{sup 2}H)-6-(hydroxymethyl)pterin was incorporated into methanopterin by growing cells of M. volta to an extent of 30%. Both the C-11 and C-12 methyl groups of methanopterin originate from (methyl-{sup 2}H{sub 3})methionine. Cells grown in the presence of (methylene-{sup 2}H)-6-(hydroxymethyl)pterin, (ethyl-{sup 2}H{sub 4})-6-(1 (RS)-hydroxyethyl)pterin, (methyl-{sup 2}H{sub 3})-6-(hydroxymethyl)-7-methylpterin, (ethyl-{sup 2}H{sub 4}, methyl-{sup 2}H{submore » 3})-6-(1 (RS)-hydroxyethyl)-7-methylpterin, and (1-ethyl-{sup 3}H)-6-(1 (RS)-hydroxyethyl)-7-methylpterin showed that only the non-7-methylated pterins were incorporated into methanopterin. Cells extracts of M. formicicum readily condensed synthetic (methylene-{sup 3}H)-7,8-H{sub 2}-6-(hydroxymethyl)pterin-PP with methaniline to generate demethylated methanopterin, which is then methylated to methanopterin by the cell extract in the presence of S-adenosylmethionine. These observations indicate that the pterin portion of methanopterin is biosynthetically derived from 7,8-H{sub 2}-6-(hydroxymethyl)pterin, which is coupled to methaniline by a pathway analogous to the biosynthesis of folic acid. This pathway for the biosynthesis of methanopterin represents the first example of the modification of the specificity of a coenzyme through a methylation reaction.« less
Chartier, François J M; Couture, Manon
2004-09-01
We have used resonance Raman spectroscopy to probe the heme environment of a recently discovered NOS from the pathogenic bacterium Staphylococcus aureus, named SANOS. We detect two forms of the CO complex in the absence of L-arginine, with nu(Fe-CO) at 482 and 497 cm(-1) and nu(C-O) at 1949 and 1930 cm(-1), respectively. Similarly to mammalian NOS, the binding of L-arginine to SANOS caused the formation of a single CO complex with nu(Fe-CO) and nu(C-O) frequencies at 504 and 1,917 cm(-1), respectively, indicating that L-arginine induced an electrostatic/steric effect on the CO molecule. The addition of pterins to CO-bound SANOS modified the resonance Raman spectra only when they were added in combination with L-arginine. We found that (6R) 5,6,7,8 tetra-hydro-L-biopterin and tetrahydrofolate were not required for the stability of the reduced protein, which is 5-coordinate, and of the CO complex, which does not change with time to a form with a Soret band at 420 nm that is indicative of a change of the heme proximal coordination. Since SANOS is stable in the absence of added pterin, it suggests that the role of the pterin cofactor in the bacterial NOS may be limited to electron/proton transfer required for catalysis and may not involve maintaining the structural integrity of the protein as is the case for mammalian NOS.
Morehouse, Nathan I; Vukusic, Peter; Rutowski, Ron
2006-01-01
A small but growing literature indicates that many animal colours are produced by combinations of structural and pigmentary mechanisms. We investigated one such complex colour phenotype: the highly chromatic wing colours of pierid butterflies including oranges, yellows and patterns which appear white to the human eye, but strongly absorb the ultraviolet (UV) wavelengths visible to butterflies. Pierids produce these bright colours using wing scales that contain collections of minute granules. However, to date, no work has directly characterized the molecular composition or optical properties of these granules. We present results that indicate these granules contain pterin pigments. We also find that pterin granules increase light reflection from single wing scales, such that wing scales containing denser granule arrays reflect more light than those with less dense granule collections. As male wing scales contain more pterin granules than those of females, the sexual dichromatism found in many pierid species can be explained by differences in wing scale pterin deposition. Additionally, the colour pattern elements produced by these pterins are known to be important during mating interactions in a number of pierid species. Therefore, we discuss the potential relevance of our results within the framework of sexual selection and colour signal evolution. PMID:17164199
Estébanez, Sandra; Lorente, Carolina; Kaufman, Teodoro S; Larghi, Enrique L; Thomas, Andrés H; Serrano, Mariana P
2018-05-04
Pterin derivatives are heterocyclic compounds which are present in different biological systems. Neutral aqueous solutions of pterins presents acid-base and keto-enol equilibria. These compounds under UV-A radiation fluoresce, undergo photooxidation, generate reactive oxygen species, and photoinduce the oxidation of biological substrates. As photosensitizers, they may act through different mechanisms; mainly through an electron-transfer initiated process (type I mechanism), but they also produce singlet molecular oxygen ( 1 O 2 ) upon irradiation (type II mechanism). In general, upon UV-A excitation two triplet states, corresponding to the lactim and lactam tautomers, are formed, but only the last one is the responsible for the photosensitized reactions of biomolecules. We present a study of the photochemical properties of 3-methylpterin (3-Mep) which, in contrast to most pterin derivatives, exists only in the lactam form. Also an improvement in the synthesis of 3-Mep is reported. The spectroscopic properties 3-Mep in aqueous solution were similar to those of the unsubstituted pterin derivative (Ptr) in its acid form, such as absorption, fluorescent and phosphorescent emission spectra. Experiments using 2'-deoxyguanosine 5'-monophosphate (dGMP) as oxidizable target, demonstrated that methylation at C-3 position of the pterin moiety does not affect significantly the efficiency of photosensitization, but results in a more photostable sensitizer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Characterization of pterin deaminase from Mucor indicus MTCC 3513
NASA Astrophysics Data System (ADS)
Thandeeswaran, M.; Karthika, P.; Mahendran, R.; Palaniswamy, M.; Angayarkanni, J.
2018-03-01
Pterin deaminase is an amidohydrolase enzyme which hydrolyses pteridines to produce lumazine derivatives and ammonia. Even though the enzyme was shown as early as 1959 for its anticancer efficacy there was a long gap in the communique after that which was in 2013. In our study we have chosen Mucor indicus MTCC 3513 which was a promising strain for production of different industrial products.The pterin deaminase enzyme was harvested and extracellular from M. indicus. The extracellular sample was partially purified by using ethanol precipitation and ion exchange column (Hi-Trap QFF) in Fast Protein Liquid Chromatography. The molecular weight of the purified pterin deaminase enzyme was apparently determined by SDS-PAGE. The purified enzyme was further biochemically characterized. Molecular docking studies with the predicted sequence showed higher binding affinity towards folic acid interaction. The structure of this protein may open the windows for new drug targets for cancer therapy.
Durairaju Nisshanthini, S; Teresa Infanta S, Antony K; Raja, Duraisamy Senthil; Natarajan, Karuppannan; Palaniswamy, M; Angayarkanni, Jayaraman
2015-04-01
Soil and water samples were collected from various regions of SIPCOT and nearby Vanappadi Lake, Ranipet, Tamilnadu, India. Based on their colony morphology and their stability during subculturing, 72 bacteria were isolated, of which 14 isolates were actinomycetes. Preliminary selection was carried out to exploit the ability of the microorganisms to utilize sodium cyanate as nitrogen source. Those organisms that were able to utilize cyanate were subjected to secondary screening viz., utilization of sodium cyanide as the nitrogen source. The oxygenolytic cleavage of cyanide is dependent on cyanide monooxygenase which obligately requires pterin cofactor for its activity. Based on this, the organisms capable of utilizing sodium cyanide were tested for the presence of pterin. Thin layer chromatography (TLC) of the cell extracts using n-butanol: 5 N glacial acetic acid (4:1) revealed that 10 out of 12 organisms that were able to utilize cyanide had the pterin-related blue fluorescent compound in the cell extract. The cell extracts of these 10 organisms were subjected to high performance thin layer chromatography (HPTLC) for further confirmation using a pterin standard. Based on the incubation period, cell biomass yield, peak height and area, strain VPW3 was selected and was identified as Bacillus subtilis. The Rf value of the cell extract was 0.73 which was consistent with the 0.74 Rf value of the pterin standard when scanned at 254 nm. The compound was extracted and purified by preparative High Performance Liquid Chromatography (HPLC). Characterization of the compound was performed by ultraviolet spectrum, fluorescence spectrum, Electrospray Ionization-Mass Spectrometry (ESI-MS), and Nuclear Magnetic Resonance spectroscopy (NMR). The compound is proposed to be 6-propionyl pterin (2-amino-6-propionyl-3H-pteridin-4-one).
Association studies to transporting proteins of fac-ReI(CO)3(pterin)(H2O) complex.
Ragone, Fabricio; Saavedra, Héctor H Martínez; García, Pablo F; Wolcan, Ezequiel; Argüello, Gerardo A; Ruiz, Gustavo T
2017-01-01
A new synthetic route to acquire the water soluble complex fac-Re I (CO) 3 (pterin)(H 2 O) was carried out in aqueous solution. The complex has been obtained with success via the fac-[Re I (CO) 3 (H 2 O) 3 ]Cl precursor complex. Re I (CO) 3 (pterin)(H 2 O) has been found to bind strongly with bovine and human serum albumins (BSA and HSA) with intrinsic-binding constants, K b , of 6.5 × 10 5 M -1 and 5.6 × 10 5 M -1 at 310 K, respectively. The interactions of serum albumins with Re I (CO) 3 (pterin)(H 2 O) were evaluated employing UV-vis fluorescence and absorption spectroscopy and circular dichroism. The results suggest that the serum albumins-Re I (CO) 3 (pterin)(H 2 O) interactions occurred in the domain IIA-binding pocket without loss of helical stability of the proteins. The comparison of the fluorescence quenching of BSA and HSA due to the binding to the Re(I) complex suggested that local interaction around the Trp 214 residue had taken place. The analysis of the thermodynamic parameters ΔG 0 , ΔH 0 , and ΔS 0 indicated that the hydrophobic interactions played a major role in both HSA-Re(I) and BSA-Re(I) association processes. All these experimental results suggest that these proteins can be considered as good carriers for transportation of Re I (CO) 3 (pterin)(H 2 O) complex. This is of significant importance in relation to the use of this Re(I) complex in several biomedical fields, such as photodynamic therapy and radiopharmacy.
NASA Astrophysics Data System (ADS)
Smyth, Ciarán A.; Mehigan, Sam; Rakovich, Yury P.; Bell, Steven E. J.; McCabe, Eithne M.
2011-07-01
Optical techniques toward the realization of sensitive and selective biosensing platforms have received considerable attention in recent times. Techniques based on interferometry, surface plasmon resonance, and waveguides have all proved popular, while spectroscopy in particular offers much potential. Raman spectroscopy is an information-rich technique in which the vibrational frequencies reveal much about the structure of a compound, but it is a weak process and offers poor sensitivity. In response to this problem, surface-enhanced Raman scattering (SERS) has received much attention, due to significant increases in sensitivity instigated by bringing the sample into contact with an enhancing substrate. Here we discuss a facile and rapid technique for the detection of pterins using SERS-active colloidal silver suspensions. Pterins are a family of biological compounds that are employed in nature in color pigmentation and as facilitators in metabolic pathways. In this work, small volumes of xanthopterin, isoxanthopterin, and 7,8-dihydrobiopterin have been examined while adsorbed to silver colloids. Limits of detection have been examined for both xanthopterin and isoxanthopterin using a 10-s exposure to a 12 mW 532 nm laser, which, while showing a trade-off between scan time and signal intensity, still provides the opportunity for the investigation of simultaneous detection of both pterins in solution.
Sariego-Jamardo, Andrea; García-Cazorla, Angels; Artuch, Rafael; Castejón, Esperanza; García-Arenas, Dolores; Molero-Luis, Marta; Ormazábal, Aida; Sanmartí, Francesc Xavier
2015-11-01
The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet. We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown. Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed. The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not. Copyright © 2015 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thiaville, Jennifer J.; Frelin, Océane; García-Salinas, Carolina
Tetrahydrofolate (THF) and its one-carbon derivatives, collectively termed folates, are essential cofactors, but are inherently unstable. While it is clear that chemical oxidation can cleave folates or damage their pterin precursors, very little is known about enzymatic damage to these molecules or about whether the folate biosynthesis pathway responds adaptively to damage to its end-products. The presence of a duplication of the gene encoding the folate biosynthesis enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (FolK) in many sequenced bacterial genomes combined with a strong chromosomal clustering of the folK gene with panB, encoding the 5,10-methylene-THF-dependent enzyme ketopantoate hydroxymethyltransferase, led us to infer that PanBmore » has a side activity that cleaves 5,10-methylene-THF, yielding a pterin product that is recycled by FolK. Genetic and metabolic analyses of Escherichia coli strains showed that overexpression of PanB leads to accumulation of the likely folate cleavage product 6-hydroxymethylpterin and other pterins in cells and medium, and—unexpectedly—to a 46% increase in total folate content. In silico modeling of the folate biosynthesis pathway showed that these observations are consistent with the in vivo cleavage of 5,10-methylene-THF by a side-activity of PanB, with FolK-mediated recycling of the pterin cleavage product, and with regulation of folate biosynthesis by folates or their damage products.« less
Shanmuganathan, Muthusamy V.; Krishnan, Subramanian; Fu, Xiaowei; Prasadarao, Nemani V.
2013-01-01
Macrophages serve as permissive niches for Escherichia coli (E. coli) K1 to attain high grade bacteremia in the pathogenesis of meningitis in neonates. Although pterin levels are a diagnostic marker for immune activation, the role of macrophages in pterin production and in the establishment of meningitis is unknown. Here, we demonstrate that macrophages infected with E. coli K1 produce both neopterin and biopterin through increased expression of GTP-cyclohydrolase 1 (GCH1). Of note, increased production of biopterin enhances the expression of Fc-gamma receptor I (CD64), which in turn, aided the entry of E. coli K1 in macrophages while increased neopterin suppresses reactive oxygen species (ROS), thereby aiding bacterial survival. Inhibition of GCH1 by 2, 4-Diamino-6-hydroxypyrimidine (DAHP) prevented the E. coli K1 induced expression of CD64 in macrophages in vitro and the development of bacteremia in a newborn mouse model of meningitis. These studies suggest that targeting GCH1 could be therapeutic strategy for preventing neonatal meningitis by E. coli K1. PMID:24161960
Chen, Hong; Li, Laishen; Zhang, Yang; Zhou, Rendan
2012-10-01
A new magnolol-bonded silica gel stationary phase (MSP) was used to separate the basic drugs including four purines, eight pyrimidines, four pterins and five flavonoids as polar representative samples by high performance liquid chromatography (HPLC). To clarify the separation mechanism, a commercial ODS column was also tested under the same chromatographic conditions. The high selectivities and fast baseline separations of the above drugs were achieved by using simple mobile phases on MSP. Although there is no end-caped treatment, the peak shapes of basic drugs containing nitrogen such as purines, pyrimidines and pterins were rather symmetrical on MSP, which indicated the the magnolol as ligand with multi-sites could shield the side effect of residual silanol groups on the surface of silica gel. Although somewhat different in the separation resolution, it was found that the elution orders of some drugs were generally similar on both MSP and ODS. The hydrophobic interaction should play a significant role in the separations of the above basic drugs, which was attributed to their reversed-phase property in the nature. However, MSP could provide the additional sites for many polar solutes, which was a rational explanation for the high selectivity of MSP. For example, in the separation of purines, pyrimidines and pterins on MSP, hydrogen-bonding and dipole-dipole interactions played leading roles besides hydrophobic interaction. Some solute molecules (such as mercaptopurine, vitexicarpin) and MSP can form the strong pi-pi stacking in the separation process. All enhanced the retention and improved the separation selectivity of MSP, which facilitated the separation of the basic drugs.
Armarego, W L; Randles, D; Taguchi, H
1983-01-01
The Km and kcat. values for [6,6,7,7-2H]7,8(6H)-dihydropterin and 2,6-diamino-5-iminopyrimidin-4-one were determined for dihydropteridine reductase (EC 1.6.99.10) from two sources. The parameters of the pterin are of the same order as those of the most effective substrates of dihydropteridine reductase. The Km values of the pterin are one order of magnitude smaller than those of the pyrimidinone, although the kcat. values are of the same order. PMID:6870836
Shanmuganathan, Muthusamy V; Krishnan, Subramanian; Fu, Xiaowei; Prasadarao, Nemani V
2014-02-01
Macrophages serve as permissive niches for Escherichia coli (E. coli) K1 to attain high grade bacteremia in the pathogenesis of meningitis in neonates. Although pterin levels are a diagnostic marker for immune activation, the role of macrophages in pterin production and in the establishment of meningitis is unknown. Here, we demonstrate that macrophages infected with E. coli K1 produce both neopterin and biopterin through increased expression of GTP-cyclohydrolase 1 (GCH1). Of note, increased production of biopterin enhances the expression of Fc-gamma receptor I (CD64), which in turn, aided the entry of E. coli K1 in macrophages while increased neopterin suppresses reactive oxygen species (ROS), thereby aiding bacterial survival. Inhibition of GCH1 by 2, 4-Diamino-6-hydroxypyrimidine (DAHP) prevented the E. coli K1 induced expression of CD64 in macrophages in vitro and the development of bacteremia in a newborn mouse model of meningitis. These studies suggest that targeting GCH1 could be therapeutic strategy for preventing neonatal meningitis by E. coli K1. Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Schwarz, Günter; Schulze, Jutta; Bittner, Florian; Eilers, Thomas; Kuper, Jochen; Bollmann, Gabriele; Nerlich, Andrea; Brinkmann, Henner; Mendel, Ralf R.
2000-01-01
Molybdenum (Mo) plays an essential role in the active site of all eukaryotic Mo-containing enzymes. In plants, Mo enzymes are important for nitrate assimilation, phytohormone synthesis, and purine catabolism. Mo is bound to a unique metal binding pterin (molybdopterin [MPT]), thereby forming the active Mo cofactor (Moco), which is highly conserved in eukaryotes, eubacteria, and archaebacteria. Here, we describe the function of the two-domain protein Cnx1 from Arabidopsis in the final step of Moco biosynthesis. Cnx1 is constitutively expressed in all organs and in plants grown on different nitrogen sources. Mo-repairable cnxA mutants from Nicotiana plumbaginifolia accumulate MPT and show altered Cnx1 expression. Transformation of cnxA mutants and the corresponding Arabidopsis chl-6 mutant with cnx1 cDNA resulted in functional reconstitution of their Moco deficiency. We also identified a point mutation in the Cnx1 E domain of Arabidopsis chl-6 that causes the molybdate-repairable phenotype. Recombinant Cnx1 protein is capable of synthesizing Moco. The G domain binds and activates MPT, whereas the E domain is essential for activating Mo. In addition, Cnx1 binds to the cytoskeleton in the same way that its mammalian homolog gephyrin does in neuronal cells, which suggests a hypothetical model for anchoring the Moco-synthetic machinery by Cnx1 in plant cells. PMID:11148290
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hill, Shannon E.; Nguyen, Elaine; Ukachukwu, Chiamaka U.
Dihydroneopterin triphosphate pyrophosphatase (DHNTPase), a member of the Mg2+ dependent Nudix hydrolase superfamily, is the recently-discovered enzyme that functions in the second step of the pterin branch of the folate biosynthetic pathway in E. coli. DHNTPase is of interest because inhibition of enzymes in bacterial folate biosynthetic pathways is a strategy for antibiotic development. We determined crystal structures of DHNTPase with and without activating, Mg2+-mimicking metals Co2+ and Ni2+. Four metal ions, identified by anomalous scattering, and stoichiometrically confirmed in solution by isothermal titration calorimetry, are held in place by Glu56 and Glu60 within the Nudix sequence motif, Glu117, waters,more » and a sulfate ion, of which the latter is further stabilized by a salt bridge with Lys7. In silico docking of the DHNTP substrate reveals a binding mode in which the pterin ring moiety is nestled in a largely hydrophobic pocket, the β-phosphate activated for nucleophilic attack overlays with the crystallographic sulfate and is in line with an activated water molecule, and remaining phosphate groups are stabilized by all four identified metal ions. The structures and binding data provide new details regarding DHNTPase metal requirements, mechanism, and suggest a strategy for efficient inhibition.« less
Ukachukwu, Chiamaka U.; Freeman, Dana M.; Quirk, Stephen
2017-01-01
Dihydroneopterin triphosphate pyrophosphatase (DHNTPase), a member of the Mg2+ dependent Nudix hydrolase superfamily, is the recently-discovered enzyme that functions in the second step of the pterin branch of the folate biosynthetic pathway in E. coli. DHNTPase is of interest because inhibition of enzymes in bacterial folate biosynthetic pathways is a strategy for antibiotic development. We determined crystal structures of DHNTPase with and without activating, Mg2+-mimicking metals Co2+ and Ni2+. Four metal ions, identified by anomalous scattering, and stoichiometrically confirmed in solution by isothermal titration calorimetry, are held in place by Glu56 and Glu60 within the Nudix sequence motif, Glu117, waters, and a sulfate ion, of which the latter is further stabilized by a salt bridge with Lys7. In silico docking of the DHNTP substrate reveals a binding mode in which the pterin ring moiety is nestled in a largely hydrophobic pocket, the β-phosphate activated for nucleophilic attack overlays with the crystallographic sulfate and is in line with an activated water molecule, and remaining phosphate groups are stabilized by all four identified metal ions. The structures and binding data provide new details regarding DHNTPase metal requirements, mechanism, and suggest a strategy for efficient inhibition. PMID:28742822
Investigation of early molybdopterin biosynthetic intermediates
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wuebbens, M.M.; Rajagopalan, K.V.
1991-03-11
Little information is available regarding the early steps in the biosynthetic pathway of molybdopterin (MPT). In order to explore these early reactions, and in particular to investigate the origin of the ring and side chain carbons of MPT, a metabolic approach employing the incorporation of {sup 14}C label was chosen. This method was facilitated by the recent purification and characterization of desulfomolybdopterin 2{prime},4{prime}-cyclic phosphate, the precursor which is converted directly to active molybdopterin in Escherichia coli by the addition of vicinal sulfurs to the side chain. This labile precursor readily oxidizes to Compound Z, a stable 6-alkyl pterin which retainsmore » all of the carbon atoms present in molybdopterin. Compound Z, rather than molybdopterin itself was chosen as the end product for labeling due to its overproduction in some MPT-deficient strains, as well as its stability and ease of purification. The authors report here the isolation of {sup 14}C-labelled Compound Z from E.coli chlN cells cultured in minimal media supplemented with U-{sup 14}C guanosine. Successive cleavage of the side chain carbons by permanganate treatment and UV light produced a decrease in the specific radioactivity of the resulting pterins. These data indicate that the early portion of the molybdopterin biosynthetic pathway may be similar to that of the bioactive pterins folate and biopterin, both of which are derived from guanosine triphosphate.« less
Lindsay, A; Healy, J; Mills, W; Lewis, J; Gill, N; Draper, N; Gieseg, S P
2016-03-01
Muscle damage caused through impacts in rugby union is known to increase oxidative stress and inflammation. Pterins have been used clinically as markers of oxidative stress, inflammation, and neurotransmitter synthesis. This study investigates the release of myoglobin from muscle tissue due to force-related impacts and how it is related to the subsequent oxidation of 7,8-dihydroneopterin to specific pterins. Effects of iron and myoglobin on 7,8-dihydroneopterin oxidation were examined in vitro via strong cation-exchange high-performance liquid chromatography (SCX-HPLC) analysis of neopterin, xanthopterin, and 7,8-dihydroxanthopterin. Urine samples were collected from 25 professional rugby players pre and post four games and analyzed for myoglobin by enzyme-linked immunosorbent assay, and 7,8-dihydroneopterin oxidation products by HPLC. Iron and myoglobin oxidized 7,8-dihydroneopterin to neopterin, xanthopterin, and 7,8-dihydroxanthopterin at concentrations at or above 10 μM and 50 μg/mL, respectively. All four games showed significant increases in myoglobin, neopterin, total neopterin, biopterin, and total biopterin, which correlated between each variable (P < 0.05). Myoglobin and iron facilitate 7,8-dihydroneopterin oxidation to neopterin and xanthopterin. In vivo delocalization of myoglobin due to muscle damage may contribute to oxidative stress and inflammation after rugby. Increased concentrations of biopterin and total biopterin may indicate production of nitric oxide and monoamine neurotransmitters in response to the physical stress. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Eudes, Aymerick; Kunji, Edmund R. S.; Noiriel, Alexandre; Klaus, Sebastian M. J.; Vickers, Tim J.; Beverley, Stephen M.; Gregory, Jesse F.; Hanson, Andrew D.
2010-01-01
The Synechocystis Slr0642 protein and its plastidial Arabidopsis (Arabidopsis thaliana) ortholog At2g32040 belong to the folate-biopterin transporter (FBT) family within the major facilitator superfamily. Both proteins transport folates when expressed in Escherichia coli. Because the structural requirements for transport activity are not known for any FBT protein, we applied mutational analysis to identify residues that are critical to transport and interpreted the results using a comparative structural model based on E. coli lactose permease. Folate transport was assessed via the growth of an E. coli pabA abgT strain, which cannot synthesize or take up folates or p-aminobenzoylglutamate. In total, 47 residues were replaced with Cys or Ala. Mutations at 22 positions abolished folate uptake without affecting Slr0642 expression in membranes, whereas other mutations had no effect. Residues important for function mostly line the predicted central cavity and are concentrated in the core α-helices H1, H4, H7, and H10. The essential residue locations are consistent with a folate-binding site lying roughly equidistant from both faces of the transporter. Arabidopsis has eight FBT proteins besides At2g32040, often lacking conserved critical residues. When six of these proteins were expressed in E. coli or in Leishmania folate or pterin transporter mutants, none showed evidence of folate or pterin transport activity, and only At2g32040 was isolated by functional screening of Arabidopsis cDNA libraries in E. coli. Such negative data could reflect roles in transport of other substrates. These studies provide the first insights into the native structure and catalytic mechanism of FBT family carriers. PMID:19923217
Shanmuganathan, Muthusamy V; Krishnan, Subramanian; Fu, Xiaowei; Prasadarao, Nemani V
2013-01-01
Elevated levels of pterins and nitric oxide (NO) are observed in patients with septic shock and bacterial meningitis. We demonstrate that Escherichia coli K1 infection of human brain microvascular endothelial cells (HBMECs) induces the expression of guanosine triphosphate cyclohydrolase (GCH1), the rate-limiting enzyme in pterin synthesis, thereby elevating levels of biopterin. DAHP (2,4-diamino hydroxyl pyrimidine), a specific inhibitor of GCH1, prevented biopterin and NO production and invasion of E. coli K1 in HBMECs. GCH1 interaction with Ecgp96, the receptor for outer membrane protein A of E. coli K1, also increases on infection, and suppression of Ecgp96 expression prevents GCH1 activation and biopterin synthesis. Pretreatment of newborn mice with DAHP prevented the production of biopterin and the development of meningitis. These results suggest a novel role for biopterin synthesis in the pathogenesis of E. coli K1 meningitis.
Shanmuganathan, Muthusamy V.; Krishnan, Subramanian; Fu, Xiaowei; Prasadarao, Nemani V.
2013-01-01
Elevated levels of pterins and nitric oxide (NO) are observed in patients with septic shock and bacterial meningitis. We demonstrate that Escherichia coli K1 infection of human brain microvascular endothelial cells (HBMECs) induces the expression of guanosine triphosphate cyclohydrolase (GCH1), the rate-limiting enzyme in pterin synthesis, thereby elevating levels of biopterin. DAHP (2,4-diamino hydroxyl pyrimidine), a specific inhibitor of GCH1, prevented biopterin and NO production and invasion of E. coli K1 in HBMECs. GCH1 interaction with Ecgp96, the receptor for outer membrane protein A of E. coli K1, also increases on infection, and suppression of Ecgp96 expression prevents GCH1 activation and biopterin synthesis. Pretreatment of newborn mice with DAHP prevented the production of biopterin and the development of meningitis. These results suggest a novel role for biopterin synthesis in the pathogenesis of E. coli K1 meningitis. PMID:23100563
Wheatley, Nicole M.; Sundberg, Christopher D.; Gidaniyan, Soheil D.; Cascio, Duilio; Yeates, Todd O.
2014-01-01
Carboxysomes are proteinaceous bacterial microcompartments that increase the efficiency of the rate-limiting step in carbon fixation by sequestering reaction substrates. Typically, α-carboxysomes are genetically encoded as a single operon expressing the structural proteins and the encapsulated enzymes of the microcompartment. In addition, depending on phylogeny, as many as 13 other genes are found to co-occur near or within α-carboxysome operons. One of these genes codes for a protein with distant homology to pterin-4α-carbinolamine dehydratase (PCD) enzymes. It is present in all α-carboxysome containing bacteria and has homologs in algae and higher plants. Canonical PCDs play an important role in amino acid hydroxylation, a reaction not associated with carbon fixation. We determined the crystal structure of an α-carboxysome PCD-like protein from the chemoautotrophic bacterium Thiomonas intermedia K12, at 1.3-Å resolution. The protein retains a three-dimensional fold similar to canonical PCDs, although the prominent active site cleft present in PCD enzymes is disrupted in the α-carboxysome PCD-like protein. Using a cell-based complementation assay, we tested the PCD-like proteins from T. intermedia and two additional bacteria, and found no evidence for PCD enzymatic activity. However, we discovered that heterologous co-expression of the PCD-like protein from Halothiobacillus neapolitanus with RuBisCO and GroELS in Escherichia coli increased the amount of soluble, assembled RuBisCO recovered from cell lysates compared with co-expression of RuBisCO with GroELS alone. We conclude that this conserved PCD-like protein, renamed here α-carboxysome RuBisCO assembly factor (or acRAF), is a novel RuBisCO chaperone integral to α-carboxysome function. PMID:24459150
Wheatley, Nicole M; Sundberg, Christopher D; Gidaniyan, Soheil D; Cascio, Duilio; Yeates, Todd O
2014-03-14
Carboxysomes are proteinaceous bacterial microcompartments that increase the efficiency of the rate-limiting step in carbon fixation by sequestering reaction substrates. Typically, α-carboxysomes are genetically encoded as a single operon expressing the structural proteins and the encapsulated enzymes of the microcompartment. In addition, depending on phylogeny, as many as 13 other genes are found to co-occur near or within α-carboxysome operons. One of these genes codes for a protein with distant homology to pterin-4α-carbinolamine dehydratase (PCD) enzymes. It is present in all α-carboxysome containing bacteria and has homologs in algae and higher plants. Canonical PCDs play an important role in amino acid hydroxylation, a reaction not associated with carbon fixation. We determined the crystal structure of an α-carboxysome PCD-like protein from the chemoautotrophic bacterium Thiomonas intermedia K12, at 1.3-Å resolution. The protein retains a three-dimensional fold similar to canonical PCDs, although the prominent active site cleft present in PCD enzymes is disrupted in the α-carboxysome PCD-like protein. Using a cell-based complementation assay, we tested the PCD-like proteins from T. intermedia and two additional bacteria, and found no evidence for PCD enzymatic activity. However, we discovered that heterologous co-expression of the PCD-like protein from Halothiobacillus neapolitanus with RuBisCO and GroELS in Escherichia coli increased the amount of soluble, assembled RuBisCO recovered from cell lysates compared with co-expression of RuBisCO with GroELS alone. We conclude that this conserved PCD-like protein, renamed here α-carboxysome RuBisCO assembly factor (or acRAF), is a novel RuBisCO chaperone integral to α-carboxysome function.
Alvarez, Florencia; Grillo, Claudiaa; Schilardi, Patricial; Rubert, Aldo; Benítez, Guillermo; Lorente, Carolina; de Mele, Mónica Fernández Lorenzo
2013-01-23
The copper intrauterine device (IUD) based its contraceptive action on the release of cupric ions from a copper wire. Immediately after the insertion, a burst release of copper ions occurs, which may be associated to a variety of side effects. 6-Mercaptopurine (6-MP) and pterin (PT) have been proposed as corrosion inhibitors to reduce this harmful release. Pretreatments with 1 × 10(-4) M 6-MP and 1 × 10(-4) M PT solutions with 1h and 3h immersion times were tested. Conventional electrochemical techniques, EDX and XPS analysis, and cytotoxicity assays with HeLa cell line were employed to investigate the corrosion behavior and biocompatibility of copper with and without treatments. Results showed that copper samples treated with PT and 6-MP solutions for 3 and 1 h, respectively, are more biocompatible than those without treatment. Besides, the treatment reduces the burst release effect of copper in simulated uterine solutions during the first week after the insertion. It was concluded that PT and 6-MP treatments are promising strategies able to reduce the side effects related to the "burst release" of copper-based IUD without altering the contraceptive action.
Gravireception of the sporangiophore of Phycomyces blakesleeanus
NASA Astrophysics Data System (ADS)
Galland, P.; Grolig, F.; Schmidt, W.
The sporangiophore of the zygomycete Phycomyces blakesleeanus displays negative gravitropism that manisfests with a latency of some 5 to 15 min after stimulation Sporangiophores possess an apical organell that consists of some 200 lipid globules held together in a spherical complex of a dense mesh of F-actin The lipid globules possess an average diameter of 2 to 2 5 mu m and a density of 0 791 g cm -3 In the absence of lipid globules the gravitropic response of the sporangiophore is substantially reduced The complex of lipid globules meets basic physical criteria for a function as gravisusceptor that operates by buoyancy Fluorescence and absorption properties of the lipid globules indicate the presence of beta -carotene phytofluene as well as flavins and pterins None of these pigments appear however to be required for gravireception The negative gravitropism of Phycomyces can be modulated by blue and red light and also by the geomagnetic field The gravireception of sporangiophores is associated with gravity-induced absorbance changes GIACs that represent primary responses of gravitropism and that may involve the reduction of cytochromes We have characterized these GIACs in further detail by dual-wavelength spectrometry in earthbound experiments and during parabola flights that generated micro- and hypergravity GIACs of sporangiophores were measured in vivo with a micro-dual wavelength spectrometer MDWS at 460 and 655 nm Vertical sporangiophores that were stimulated gravitropically by placing them
Electronic structure and reactivity of high-spin iron--alkyl- and--pterinperoxo complexes.
Lehnert, Nicolai; Fujisawa, Kiyoshi; Solomon, Edward I
2003-01-27
The spectroscopic properties and electronic structure of the four-coordinate high-spin [FeIII(L3)(OOtBu)]+ complex (1; L3 = hydrotris(3-tert-butyl-5-isopropyl-1-pyrazolyl)borate; tBu = tert-butyl) are investigated and compared to the six-coordinated high-spin [Fe(6-Me3TPA)(OHx)(OOtBu)]x+ system (TPA = tris(2-pyridylmethyl)amine, x = 1 or 2) studied earlier [Lehnert, N.; Ho, R. Y. N.; Que, L., Jr.; Solomon, E. I. J. Am. Chem. Soc. 2001, 123, 12802-12816]. Complex 1 is characterized by Raman features at 889 and 830 cm-1 which are assigned to the O-O stretch (mixed with the symmetric C-C stretch) and a band at 625 cm-1 that corresponds to nu(Fe-O). The UV-vis spectrum shows a charge-transfer (CT) transition at 510 nm from the alkylperoxo pi v* (v = vertical to C-O-O plane) to a d orbital of Fe(III). A second CT is identified from MCD at 370 nm that is assigned to a transition from pi h* (h = horizontal to C-O-O plane) to an Fe(III) d orbital. For the TPA complex the pi v* CT is at 560 nm while the pi h* CT is to higher energy than 250 nm. These spectroscopic differences between four- and six-coordinate Fe(III)-OOR complexes are interpreted on the basis of their different ligand fields. In addition, the electronic structure of Fe-OOPtn complexes with the biologically relevant pterinperoxo ligand are investigated. Substitution of the tert-butyl group in 1 by pterin leads to the corresponding Fe(III)-OOPtn species (2), which shows a stronger electron donation from the peroxide to Fe(III) than 1. This is related to the lower ionization potential of pterin. Reduction of 2 by one electron leads to the Fe(II)-OOPtn complex (3), which is relevant as a model for potential intermediates in pterin-dependent hydroxylases. However, in the four-coordinate ligand field of 3, the additional electron is located in a nonbonding d orbital of iron. Hence, the pterinperoxo ligand is not activated for heterolytic cleavage of the O-O bond in this system. This is also evident from the calculated reaction energies that are endothermic by at least 20 kcal/mol.
Xiaochao, Gu; Jin, Tian; Xiaoyun, Li; Bin, Zhou; Xujing, Zheng; Jin, Xu
2018-01-01
The three-dimensional electro-Fenton method was used in the folic acid wastewater pretreatment process. In this study, we researched the degradation of folic acid and the effects of different parameters such as the air sparging rate, current density, pH and reaction time on chemical oxygen demand (COD) removal in folic acid wastewater. A four-level and four-factor orthogonal test was designed and optimal reaction conditions to pretreat folic acid wastewater by three-dimensional electrode were determined: air sparge rate 0.75 l min−1, current density 10.26 mA cm−2, pH 5 and reaction time 90 min. Under these conditions, the removal of COD reached 94.87%. LC-MS results showed that the electro-Fenton method led to an initial folic acid decomposition into p-aminobenzoyl-glutamic acid (PGA) and xanthopterin (XA); then part of the XA was oxidized to pterine-6-carboxylic acid (PCA) and the remaining part of XA was converted to pterin and carbon dioxide. The kinetics analysis of the folic acid degradation process during pretreatment was carried out by using simulated folic acid wastewater, and it could be proved that the degradation of folic acid by using the three-dimensional electro-Fenton method was a second-order reaction process. This study provided a reference for industrial folic acid treatment. PMID:29410807
A Murine Model for Human Sepiapterin-Reductase Deficiency
Yang, Seungkyoung; Lee, Young Jae; Kim, Jin-Man; Park, Sean; Peris, Joanna; Laipis, Philip; Park, Young Shik; Chung, Jae Hoon; Oh, S. Paul
2006-01-01
Tetrahydrobiopterin (BH4) is an essential cofactor for several enzymes, including all three forms of nitric oxide synthases, the three aromatic hydroxylases, and glyceryl-ether mono-oxygenase. A proper level of BH4 is, therefore, necessary for the metabolism of phenylalanine and the production of nitric oxide, catecholamines, and serotonin. BH4 deficiency has been shown to be closely associated with diverse neurological psychiatric disorders. Sepiapterin reductase (SPR) is an enzyme that catalyzes the final step of BH4 biosynthesis. Whereas the number of cases of neuropsychological disorders resulting from deficiencies of other catalytic enzymes involved in BH4 biosynthesis and metabolism has been increasing, only a handful of cases of SPR deficiency have been reported, and the role of SPR in BH4 biosynthesis in vivo has been poorly understood. Here, we report that mice deficient in the Spr gene (Spr−/−) display disturbed pterin profiles and greatly diminished levels of dopamine, norepinephrine, and serotonin, indicating that SPR is essential for homeostasis of BH4 and for the normal functions of BH4-dependent enzymes. The Spr−/− mice exhibit phenylketonuria, dwarfism, and impaired body movement. Oral supplementation of BH4 and neurotransmitter precursors completely rescued dwarfism and phenylalanine metabolism. The biochemical and behavioral characteristics of Spr−/− mice share striking similarities with the symptoms observed in SPR-deficient patients. This Spr mutant strain of mice will be an invaluable resource to elucidate many important issues regarding SPR and BH4 deficiencies. PMID:16532389
Feiz, Leila; Williams-Carrier, Rosalind; Belcher, Susan; Montano, Monica; Barkan, Alice; Stern, David B
2014-12-01
Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) plays a critical role in sustaining life by catalysis of carbon fixation in the Calvin-Benson pathway. Incomplete knowledge of the assembly pathway of chloroplast Rubisco has hampered efforts to fully delineate the enzyme's properties, or seek improved catalytic characteristics via directed evolution. Here we report that a Mu transposon insertion in the Zea mays (maize) gene encoding a chloroplast dimerization co-factor of hepatocyte nuclear factor 1 (DCoH)/pterin-4α-carbinolamine dehydratases (PCD)-like protein is the causative mutation in a seedling-lethal, Rubisco-deficient mutant named Rubisco accumulation factor 2 (raf2-1). In raf2 mutants newly synthesized Rubisco large subunit accumulates in a high-molecular weight complex, the formation of which requires a specific chaperonin 60-kDa isoform. Analogous observations had been made previously with maize mutants lacking the Rubisco biogenesis proteins RAF1 and BSD2. Chemical cross-linking of maize leaves followed by immunoprecipitation with antibodies to RAF2, RAF1 or BSD2 demonstrated co-immunoprecipitation of each with Rubisco small subunit, and to a lesser extent, co-immunoprecipitation with Rubisco large subunit. We propose that RAF2, RAF1 and BSD2 form transient complexes with the Rubisco small subunit, which in turn assembles with the large subunit as it is released from chaperonins. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.
Hartmann, Anja D; Wilhelm, Natalie; Erfle, Volker; Hartmann, Katrin
2016-12-05
The bee venom melittin shows an antiviral efficacy against the human immunodeficiency virus in cell culture. It was shown to be non-toxic for cats. Aim of this pilot study was to investigate the clinical efficacy and side-effects of melittin in cats naturally infected with feline immunodeficiency virus (FIV). The study was performed as a prospective, placebo-controlled double-blinded trial. Twenty cats were included, of which 10 cats each were treated with either melittin (500 µg/kg body weight) or phosphate-buffered saline (placebo) subcutaneously twice per week. During the treatment period of 6 weeks, the cats' general health status, determined by the Karnofsky's score, and the severity of clinical signs (conjunctivitis and stomatitis) using a clinical scoring system were evaluated. Haematology, biochemistry profiles, lymphocyte subpopulations, CD4/CD8 ratio, and pterines (biopterine, 7-xanthopterine) as surrogate parameters were also compared. The general health status and the clinical scores for conjunctivitis and stomatitis improved in cats treated with melittin. A statistically significant improvement however could only be detected for conjunctivitis in cats treated with melittin compared to cats treated with placebo which was likely due to different scores between both groups at the beginning. No influence on the lymphocyte subpopulations, CD4/CD8 ratio, and pterine concentrations was observed. No side effects occurred in this study. In the protocol used in the present study, no significant efficacy of melittin could be detected. However, efficacy of melittin, especially if applied in a higher dosage as in the present study or for a longer period, could be evaluated in further studies. Synergistic effects if used in combination with classic antiretroviral drugs could be an interesting future approach.
Vibrational spectroscopic analyses of unique yellow feather pigments (spheniscins) in penguins.
Thomas, Daniel B; McGoverin, Cushla M; McGraw, Kevin J; James, Helen F; Madden, Odile
2013-06-06
Many animals extract, synthesize and refine chemicals for colour display, where a range of compounds and structures can produce a diverse colour palette. Feather colours, for example, span the visible spectrum and mostly result from pigments in five chemical classes (carotenoids, melanins, porphyrins, psittacofulvins and metal oxides). However, the pigment that generates the yellow colour of penguin feathers appears to represent a sixth, poorly characterized class of feather pigments. This pigment class, here termed 'spheniscin', is displayed by half of the living penguin genera; the larger and richer colour displays of the pigment are highly attractive. Using Raman and mid-infrared spectroscopies, we analysed yellow feathers from two penguin species (king penguin, Aptenodytes patagonicus; macaroni penguin, Eudyptes chrysolophus) to further characterize spheniscin pigments. The Raman spectrum of spheniscin is distinct from spectra of other feather pigments and exhibits 17 distinctive spectral bands between 300 and 1700 cm(-1). Spectral bands from the yellow pigment are assigned to aromatically bound carbon atoms, and to skeletal modes in an aromatic, heterocyclic ring. It has been suggested that the penguin pigment is a pterin compound; Raman spectra from yellow penguin feathers are broadly consistent with previously reported pterin spectra, although we have not matched it to any known compound. Raman spectroscopy can provide a rapid and non-destructive method for surveying the distribution of different classes of feather pigments in the avian family tree, and for correlating the chemistry of spheniscin with compounds analysed elsewhere. We suggest that the sixth class of feather pigments may have evolved in a stem-lineage penguin and endowed modern penguins with a costly plumage trait that appears to be chemically unique among birds.
Vibrational spectroscopic analyses of unique yellow feather pigments (spheniscins) in penguins
Thomas, Daniel B.; McGoverin, Cushla M.; McGraw, Kevin J.; James, Helen F.; Madden, Odile
2013-01-01
Many animals extract, synthesize and refine chemicals for colour display, where a range of compounds and structures can produce a diverse colour palette. Feather colours, for example, span the visible spectrum and mostly result from pigments in five chemical classes (carotenoids, melanins, porphyrins, psittacofulvins and metal oxides). However, the pigment that generates the yellow colour of penguin feathers appears to represent a sixth, poorly characterized class of feather pigments. This pigment class, here termed ‘spheniscin’, is displayed by half of the living penguin genera; the larger and richer colour displays of the pigment are highly attractive. Using Raman and mid-infrared spectroscopies, we analysed yellow feathers from two penguin species (king penguin, Aptenodytes patagonicus; macaroni penguin, Eudyptes chrysolophus) to further characterize spheniscin pigments. The Raman spectrum of spheniscin is distinct from spectra of other feather pigments and exhibits 17 distinctive spectral bands between 300 and 1700 cm−1. Spectral bands from the yellow pigment are assigned to aromatically bound carbon atoms, and to skeletal modes in an aromatic, heterocyclic ring. It has been suggested that the penguin pigment is a pterin compound; Raman spectra from yellow penguin feathers are broadly consistent with previously reported pterin spectra, although we have not matched it to any known compound. Raman spectroscopy can provide a rapid and non-destructive method for surveying the distribution of different classes of feather pigments in the avian family tree, and for correlating the chemistry of spheniscin with compounds analysed elsewhere. We suggest that the sixth class of feather pigments may have evolved in a stem-lineage penguin and endowed modern penguins with a costly plumage trait that appears to be chemically unique among birds. PMID:23516063
Reduction and Oxidation of the Active Site Iron in Tyrosine Hydroxylase: Kinetics and Specificity†
Frantom, Patrick A.; Seravalli, Javier; Ragsdale, Stephen W.; Fitzpatrick, Paul F.
2006-01-01
Tyrosine hydroxylase (TyrH) is a pterin-dependent enzyme that catalyzes the hydroxylation of tyrosine to form dihydroxyphenylalanine. The oxidation state of the active site iron atom plays a central role in the regulation of the enzyme. The kinetics of reduction of ferric TyrH by several reductants were determined by anaerobic stopped-flow spectroscopy. Anaerobic rapid freeze–quench EPR confirmed that the change in the near-UV absorbance of TyrH upon adding reductant corresponded to iron reduction. Tetrahydrobiopterin reduces wild-type TyrH following a simple second-order mechanism with a rate constant of 2.8 ± 0.1 mM−1 s−1. 6-Methyltetrahydropterin reduces the ferric enzyme with a second-order rate constant of 6.1 ± 0.1 mM−1 s−1 and exhibits saturation kinetics. No EPR signal for a radical intermediate was detected. Ascorbate, glutathione, and 1,4-benzoquinone all reduce ferric TyrH, but much more slowly than tetrahydrobiopterin, suggesting that the pterin is a physiological reductant. E332A TyrH, which has an elevated Km for tetrahydropterin in the catalytic reaction, is reduced by tetrahydropterins with the same kinetic parameters as those of the wild-type enzyme, suggesting that BH4 does not bind in the catalytic conformation during the reduction. Oxidation of ferrous TyrH by molecular oxygen can be described as a single-step second-order reaction, with a rate constant of 210 mM−1 s−1. S40E TyrH, which mimics the phosphorylated state of the enzyme, has oxidation and reduction kinetics similar to those of the wild-type enzyme, suggesting that phosphorylation does not directly regulate the interconversion of the ferric and ferrous forms. PMID:16475826
Werner-Felmayer, G; Werner, E R; Fuchs, D; Hausen, A; Reibnegger, G; Wachter, H
1990-05-15
Determination of neopterin [D-erythro-6-(1',2',3'-trihydroxypropyl)pterin] in body fluids is a powerful diagnostic tool in a variety of diseases in which activation of cellular immune mechanisms is involved, such as certain malignancies, allograft rejection, and autoimmune and infectious diseases. In vitro, neopterin is released into the supernatant by peripheral blood-derived monocytes/macrophages upon stimulation with gamma-interferon. In parallel, cleavage of tryptophan by indoleamine 2,3-dioxygenase is induced. We report here that the human myelomonocytic cell line THP-1 forms neopterin and degrades tryptophan upon treatment with gamma-interferon. Like in macrophages alpha-interferon and beta-interferon induce these pathways only to a much smaller degree. The action of interferons is enhanced by cotreatment with tumor necrosis factor alpha, lipopolysaccharide, or dexamethasone. gamma-Interferon-induced neopterin formation and indoleamine 2,3-dioxygenase activity are increased by raising extracellular tryptophan concentrations. The pattern of intracellularly formed pteridines upon stimulation with gamma-interferon shows the unique characteristics of human monocytes/macrophages. Neopterin, monapterin, and biopterin are produced in a 50:2:1 ratio. Thus, the THP-1 cell line provides a permanent, easily accessible in vitro system for studying the induction and mechanism of neopterin formation.
Oyen, David; Fenwick, R Bryn; Aoto, Phillip C; Stanfield, Robyn L; Wilson, Ian A; Dyson, H Jane; Wright, Peter E
2017-08-16
The rate-determining step in the catalytic cycle of E. coli dihydrofolate reductase is tetrahydrofolate (THF) product release, which can occur via an allosteric or an intrinsic pathway. The allosteric pathway, which becomes accessible when the reduced cofactor NADPH is bound, involves transient sampling of a higher energy conformational state, greatly increasing the product dissociation rate as compared to the intrinsic pathway that obtains when NADPH is absent. Although the kinetics of this process are known, the enzyme structure and the THF product conformation in the transiently formed excited state remain elusive. Here, we use side-chain proton NMR relaxation dispersion measurements, X-ray crystallography, and structure-based chemical shift predictions to explore the structural basis of allosteric product release. In the excited state of the E:THF:NADPH product release complex, the reduced nicotinamide ring of the cofactor transiently enters the active site where it displaces the pterin ring of the THF product. The p-aminobenzoyl-l-glutamate tail of THF remains weakly bound in a widened binding cleft. Thus, through transient entry of the nicotinamide ring into the active site, the NADPH cofactor remodels the enzyme structure and the conformation of the THF to form a weakly populated excited state that is poised for rapid product release.
Pribat, Anne; Noiriel, Alexandre; Morse, Alison M.; Davis, John M.; Fouquet, Romain; Loizeau, Karen; Ravanel, Stéphane; Frank, Wolfgang; Haas, Richard; Reski, Ralf; Bedair, Mohamed; Sumner, Lloyd W.; Hanson, Andrew D.
2010-01-01
Tetrahydropterin-dependent aromatic amino acid hydroxylases (AAHs) are known from animals and microbes but not plants. A survey of genomes and ESTs revealed AAH-like sequences in gymnosperms, mosses, and algae. Analysis of full-length AAH cDNAs from Pinus taeda, Physcomitrella patens, and Chlamydomonas reinhardtii indicated that the encoded proteins form a distinct clade within the AAH family. These proteins were shown to have Phe hydroxylase activity by functional complementation of an Escherichia coli Tyr auxotroph and by enzyme assays. The P. taeda and P. patens AAHs were specific for Phe, required iron, showed Michaelian kinetics, and were active as monomers. Uniquely, they preferred 10-formyltetrahydrofolate to any physiological tetrahydropterin as cofactor and, consistent with preferring a folate cofactor, retained activity in complementation tests with tetrahydropterin-depleted E. coli host strains. Targeting assays in Arabidopsis thaliana mesophyll protoplasts using green fluorescent protein fusions, and import assays with purified Pisum sativum chloroplasts, indicated chloroplastic localization. Targeting assays further indicated that pterin-4a-carbinolamine dehydratase, which regenerates the AAH cofactor, is also chloroplastic. Ablating the single AAH gene in P. patens caused accumulation of Phe and caffeic acid esters. These data show that nonflowering plants have functional plastidial AAHs, establish an unprecedented electron donor role for a folate, and uncover a novel link between folate and aromatic metabolism. PMID:20959559
Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wolff, J.A.; Fisher, L.J.; Xu, L.
1989-11-01
Rat fibroblasts were infected with a retroviral vector containing the cDNA for rat tyrosine hydroxylase. A TH-positive clone was identified by biochemical assay and immunohistochemical staining. When supplemented in vitro with pterin cofactors required for TH activity, these cells produced L-dopa and released it into the cell cultured medium. Uninfected control cells and fibroblasts infected with the TH vector were grafted separately to the caudate of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Only grafts containing TH-expressing fibroblasts were found to reduce rotational asymmetry. These results have general implications for the application of gene therapy to human neurologicalmore » disease and specific implications for Parkinson disease.« less
Wang, Dongli; Coco, Matthew W.; Rose, Robert B.
2014-12-23
Pterin-4a-carbinolamine dehydratase (PCD) is a highly conserved enzyme that evolved a second, unrelated function in mammals, as a transcriptional coactivator. As a coactivator, PCD is known as DCoH or dimerization cofactor of the transcription factor HNF-1. These two activities are associated with a change in oligomeric state: from two dimers interacting as an enzyme in the cytoplasm to a dimer interacting with a dimer of HNF-1 in the nucleus. The same interface of DCoH forms both complexes. To determine how DCoH partitions between its two functions, we studied in this paper the folding and stability of the DCoH homotetramer. Wemore » show that the DCoH1 homotetramer is kinetically trapped, meaning once it forms it will not dissociate to interact with HNF-1. In contrast, DCoH2, a paralog of DCoH1, unfolds within hours. A simple mutation in the interface of DCoH2 from Ser-51 to Thr, as found in DCoH1, increases the kinetic stability by 9 orders of magnitude, to τ½ ~2 million years. This suggests that the DCoH1·HNF-1 complex must co-fold to interact. We conclude that simple mutations can dramatically affect the dissociation kinetics of a complex. Residue 51 represents a “kinetic hot spot” instead of a “thermodynamic hot spot.” Kinetic regulation allows PCD to adopt two distinct functions. Finally, mutations in DCoH1 associated with diabetes affect both functions of DCoH1, perhaps by disrupting the balance between the two DCoH complexes.« less
Galland, Paul; Tölle, Nadja
2003-10-01
Light-induced fluorescence changes (LIFCs) were detected in sporangiophores of the blue-light-sensitive fungus Phycomyces blakesleeanus (Burgeff). The LIFCs can be utilized as a spectrophotometric assay for blue-light photoreceptors and for the in vivo characterization of their photochemical primary reactions. Blue-light irradiation of sporangiophores elicited a transient decrease and subsequent regeneration of flavin-like fluorescence emission at 525 nm. The signals recovered in darkness in about 120 min. In contrast to blue light, near-UV (370 nm) caused an increase in the fluorescence emission at 525 nm. Because the LIFCs were altered in a light-insensitive madC mutant with a defective photoreceptor, the fluorescence changes must be associated with early photochemical events of the transduction chain. Action spectra for the fluorescence changes at 525 nm showed major peaks near 470 and 600 nm. Double-pulse experiments involving two consecutive pulses of either blue and near-UV, blue and red, or near-UV and red showed that the responses depended on the sequence in which the different wavelengths were applied. The results indicate a blue-light receptor with intermediates in the near-UV, blue and red spectral regions. We explain the results in the framework of a general model, in which the three redox states of the flavin photoreceptor, the oxidized flavin (Fl), the flavo-semiquinone (FlH*), and the flavo-hydroquinone (FlH2) are each acting as chromophores with their own characteristic photochemical primary reactions. These consist of the photoreduction of the oxidized flavin generating semiquinone, the photoreduction of the semiquinone generating hydroquinone, and the photooxidation of the flavo-hydroquinone regenerating the pool of oxidized flavins. The proposed mechanism represents a photocycle in which two antagonistic photoreceptor forms, Fl and FlH2, determine the pool size of the biological effector molecule, the flavo-semiquinone. The redox changes that are associated with the photocycle are maintained by redox partners, pterins, that function in the near-UV as secondary chromophores.
Li, Wentian; Gong, Meixia; Shu, Rui; Li, Xin; Gao, Junshan; Meng, Yan
2015-08-01
Tetrahydrobiopterin (BH4) is an essential cofactor of aromatic amino acid hydroxylases and nitric oxide synthase so that BH4 plays a key role in many biological processes. BH4 deficiency is associated with numerous metabolic syndromes and neuropsychological disorders. BH4 concentration in mammals is maintained through a de novo synthesis pathway and a regeneration pathway. Previous studies showed that the de novo pathway of BH4 is similar between insects and mammals. However, knowledge about the regeneration pathway of BH4 (RPB) is very limited in insects. Several mutants in the silkworm Bombyx mori have been approved to be associated with BH4 deficiency, which are good models to research on the RPB in insects. In this study, homologous genes encoding two enzymes, pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR) involving in RPB have been cloned and identified from B. mori. Enzymatic activity of DHPR was found in the fat body of wild type silkworm larvae. Together with the transcription profiles, it was indicated that BmPcd and BmDhpr might normally act in the RPB of B. mori and the expression of BmDhpr was activated in the brain and sexual glands while BmPcd was expressed in a wider special pattern when the de novo pathway of BH4 was lacked in lemon. Biochemical analyses showed that the recombinant BmDHPR exhibited high enzymatic activity and more suitable parameters to the coenzyme of NADH in vitro. The results in this report give new information about the RPB in B. mori and help in better understanding insect BH4 biosynthetic networks. Copyright © 2015 Elsevier Inc. All rights reserved.
Discovery and structure determination of the orphan enzyme isoxanthopterin deaminase .
Hall, Richard S; Agarwal, Rakhi; Hitchcock, Daniel; Sauder, J Michael; Burley, Stephen K; Swaminathan, Subramanyam; Raushel, Frank M
2010-05-25
Two previously uncharacterized proteins have been identified that efficiently catalyze the deamination of isoxanthopterin and pterin 6-carboxylate. The genes encoding these two enzymes, NYSGXRC-9339a ( gi|44585104 ) and NYSGXRC-9236b ( gi|44611670 ), were first identified from DNA isolated from the Sargasso Sea as part of the Global Ocean Sampling Project. The genes were synthesized, and the proteins were subsequently expressed and purified. The X-ray structure of Sgx9339a was determined at 2.7 A resolution (Protein Data Bank entry 2PAJ ). This protein folds as a distorted (beta/alpha)(8) barrel and contains a single zinc ion in the active site. These enzymes are members of the amidohydrolase superfamily and belong to cog0402 within the clusters of orthologous groups (COG). Enzymes in cog0402 have previously been shown to catalyze the deamination of guanine, cytosine, S-adenosylhomocysteine, and 8-oxoguanine. A small compound library of pteridines, purines, and pyrimidines was used to probe catalytic activity. The only substrates identified in this search were isoxanthopterin and pterin 6-carboxylate. The kinetic constants for the deamination of isoxanthopterin with Sgx9339a were determined to be 1.0 s(-1), 8.0 muM, and 1.3 x 10(5) M(-1) s(-1) (k(cat), K(m), and k(cat)/K(m), respectively). The active site of Sgx9339a most closely resembles the active site for 8-oxoguanine deaminase (Protein Data Bank entry 2UZ9 ). A model for substrate recognition of isoxanthopterin by Sgx9339a was proposed on the basis of the binding of guanine and xanthine in the active site of guanine deaminase. Residues critical for substrate binding appear to be conserved glutamine and tyrosine residues that form hydrogen bonds with the carbonyl oxygen at C4, a conserved threonine residue that forms hydrogen bonds with N5, and another conserved threonine residue that forms hydrogen bonds with the carbonyl group at C7. These conserved active site residues were used to identify 24 other genes which are predicted to deaminate isoxanthopterin.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pejchal, Robert; Sargeant, Ryan; Ludwig, Martha L.
Methylenetetrahydrofolate reductases (MTHFRs; EC 1.7.99.5) catalyze the NAD(P)H-dependent reduction of 5,10-methylenetetrahydrofolate (CH{sub 2}-H{sub 4}folate) to 5-methyltetrahydrofolate (CH{sub 3}-H{sub 4}folate) using flavin adenine dinucleotide (FAD) as a cofactor. The initial X-ray structure of Escherichia coli MTHFR revealed that this 33-kDa polypeptide is a ({beta}{alpha}){sub 8} barrel that aggregates to form an unusual tetramer with only 2-fold symmetry. Structures of reduced enzyme complexed with NADH and of oxidized Glu28Gln enzyme complexed with CH{sub 3}-H{sub 4}folate have now been determined at resolutions of 1.95 and 1.85 {angstrom}, respectively. The NADH complex reveals a rare mode of dinucleotide binding; NADH adopts a hairpin conformationmore » and is sandwiched between a conserved phenylalanine, Phe223, and the isoalloxazine ring of FAD. The nicotinamide of the bound pyridine nucleotide is stacked against the si face of the flavin ring with C4 adjoining the N5 of FAD, implying that this structure models a complex that is competent for hydride transfer. In the complex with CH{sub 3}-H{sub 4}folate, the pterin ring is also stacked against FAD in an orientation that is favorable for hydride transfer. Thus, the binding sites for the two substrates overlap, as expected for many enzymes that catalyze ping-pong reactions, and several invariant residues interact with both folate and pyridine nucleotide substrates. Comparisons of liganded and substrate-free structures reveal multiple conformations for the loops {beta}2-{alpha}2 (L2), {beta}3-{alpha}3 (L3), and {beta}4-{alpha}4 (L4) and suggest that motions of these loops facilitate the ping-pong reaction. In particular, the L4 loop adopts a 'closed' conformation that allows Asp120 to hydrogen bond to the pterin ring in the folate complex but must move to an 'open' conformation to allow NADH to bind.« less
Ferrer, C; Solano, F; Zuasti, A
1999-04-01
We have studied the pigmentary system of the teleost Sparus aurata skin by electron microscopy and chromatographic analysis. Under electron microscopy, we found the dermis to contain the three major types of recognized chromatophores: melanophores, xanthophores and iridophores. Melanophores were more abundant in the dorsal region, whereas the iridophores were more abundant in the ventral region. The most important discovery was that of epidermal xanthophores. Epidermal xanthophores were the only chromatophores in the epidermis, something only found in S aurata and in a teleost species living in the Antartic sea. In contrast, the biochemical analysis did not establish any special characteristics: we found pteridine and flavin pigments located mostly in the pigmented dorsal region. Riboflavin and pterin were two of the most abundant coloured pigment types, but other colourless pigments such as xanthopterin and isoxanthopterin were also detected.
Sunagawa, Sumito; Shirakura, Takashi; Hokama, Noboru; Kozuka, Chisayo; Yonamine, Masato; Namba, Toyotaka; Morishima, Satoko; Nakachi, Sawako; Nishi, Yukiko; Ikema, Tomomi; Okamoto, Shiki; Matsui, Chieko; Hase, Naoki; Tamura, Mizuho; Shimabukuro, Michio; Masuzaki, Hiroaki
2018-06-03
There is a controversy whether hyperuricemia is an independent risk for cardiometabolic diseases. Serum level of uric acid is affected by a wide variety of factors involved in its production and excretion. On the other hand, evidence has accumulated that locally and systemically activated xanthine oxidase (XO), a rate limiting enzyme for production of uric acid, is linked to metabolic derangement in humans and rodents. We therefore explored the clinical implication of plasma XO activity in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). We enrolled 60 patients with T2DM and MetS. MetS was defined according to the 2005 International Diabetes Federation guidelines. Plasma XO activity was measured by highly sensitive fluorometric assay measuring the conversion of pterin to isoxanthopterin, and explored associations between the value of plasma XO activity and metabolic parameters. Value of plasma XO activity was correlated with indices of insulin resistance and level of circulating liver transaminases. On the other hand, level of serum uric acid was not correlated with indices of insulin resistance. The value of plasma XO activity was not correlated with serum uric acid level. Plasma XO activity correlates with indices of insulin resistance and liver dysfunction in Japanese patients with T2DM and MetS. Through assessing the plasma XO activity, patients demonstrating normal level of serum uric acid with higher activity of XO can be screened, thereby possibly providing a clue to uncover metabolic risks in T2DM and MetS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Supangat, Supangat; Seo, Kyung Hye; Choi, Yong Kee; Park, Young Shik; Son, Daeyoung; Han, Chang-deok; Lee, Kon Ho
2006-01-27
Sepiapterin reductase (SR) is involved in the last step of tetrahydrobiopterin (BH(4)) biosynthesis by reducing the di-keto group of 6-pyruvoyl tetrahydropterin. Chlorobium tepidum SR (cSR) generates a distinct BH(4) product, L-threo-BH(4) (6R-(1'S,2'S)-5,6,7,8-BH(4)), whereas animal enzymes produce L-erythro-BH(4) (6R-(1'R,2'S)-5,6,7,8-BH(4)) although it has high amino acid sequence similarities to the other animal enzymes. To elucidate the structural basis for the different reaction stereospecificities, we have determined the three-dimensional structures of cSR alone and complexed with NADP and sepiapterin at 2.1 and 1.7 A resolution, respectively. The overall folding of the cSR, the binding site for the cofactor NADP(H), and the positions of active site residues were quite similar to the mouse and the human SR. However, significant differences were found in the substrate binding region of the cSR. In comparison to the mouse SR complex, the sepiapterin in the cSR is rotated about 180 degrees around the active site and bound between two aromatic side chains of Trp-196 and Phe-99 so that its pterin ring is shifted to the opposite side, but its side chain position is not changed. The swiveled sepiapterin binding results in the conversion of the side chain configuration, exposing the opposite face for hydride transfer from NADPH. The different sepiapterin binding mode within the conserved catalytic architecture presents a novel strategy of switching the reaction stereospecificities in the same protein fold.
Kaufholdt, David; Baillie, Christin-Kirsty; Meinen, Rieke; Mendel, Ralf R; Hänsch, Robert
2017-01-01
Survival of plants and nearly all organisms depends on the pterin based molybdenum cofactor (Moco) as well as its effective biosynthesis and insertion into apo-enzymes. To this end, both the central Moco biosynthesis enzymes are characterized and the conserved four-step reaction pathway for Moco biosynthesis is well-understood. However, protection mechanisms to prevent degradation during biosynthesis as well as transfer of the highly oxygen sensitive Moco and its intermediates are not fully enlightened. The formation of protein complexes involving transient protein-protein interactions is an efficient strategy for protected metabolic channelling of sensitive molecules. In this review, Moco biosynthesis and allocation network is presented and discussed. This network was intensively studied based on two in vivo interaction methods: bimolecular fluorescence complementation (BiFC) and split-luciferase. Whereas BiFC allows localisation of interacting partners, split-luciferase assay determines interaction strengths in vivo . Results demonstrate (i) interaction of Cnx2 and Cnx3 within the mitochondria and (ii) assembly of a biosynthesis complex including the cytosolic enzymes Cnx5, Cnx6, Cnx7, and Cnx1, which enables a protected transfer of intermediates. The whole complex is associated with actin filaments via Cnx1 as anchor protein. After biosynthesis, Moco needs to be handed over to the specific apo-enzymes. A potential pathway was discovered. Molybdenum-containing enzymes of the sulphite oxidase family interact directly with Cnx1. In contrast, the xanthine oxidoreductase family acquires Moco indirectly via a Moco binding protein (MoBP2) and Moco sulphurase ABA3. In summary, the uncovered interaction matrix enables an efficient transfer for intermediate and product protection via micro-compartmentation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Doukov,T.; Hemmi, H.; Drennan, C.
The methyltetrahydrofolate (CH{sub 3}-H{sub 4}folate) corrinoid-ironsulfur protein (CFeSP) methyltransferase (MeTr) catalyzes transfer of the methyl group of CH3-H4folate to cob(I)amide. This key step in anaerobic CO and CO{sub 2} fixation is similar to the first half-reaction in the mechanisms of other cobalamin-dependent methyltransferases. Methyl transfer requires electrophilic activation of the methyl group of CH{sub 3}-H{sub 4}folate, which includes proton transfer to the N5 group of the pterin ring and poises the methyl group for reaction with the Co(I) nucleophile. The structure of the binary CH{sub 3}-H{sub 4}folate/MeTr complex (revealed here) lacks any obvious proton donor near the N5 group. Instead,more » an Asn residue and water molecules are found within H-bonding distance of N5. Structural and kinetic experiments described here are consistent with the involvement of an extended H-bonding network in proton transfer to N5 of the folate that includes an Asn (Asn-199 in MeTr), a conserved Asp (Asp-160), and a water molecule. This situation is reminiscent of purine nucleoside phosphorylase, which involves protonation of the purine N7 in the transition state and is accomplished by an extended H-bond network that includes water molecules, a Glu residue, and an Asn residue (Kicska, G. A., Tyler, P. C., Evans, G. B., Furneaux, R. H., Shi, W., Fedorov, A., Lewandowicz, A., Cahill, S. M., Almo, S. C., and Schramm, V. L. (2002) Biochemistry 41, 14489-14498). In MeTr, the Asn residue swings from a distant position to within H-bonding distance of the N5 atom upon CH{sub 3}-H{sub 4}folate binding. An N199A variant exhibits only {approx}20-fold weakened affinity for CH{sub 3}-H{sub 4}folate but a much more marked 20,000-40,000-fold effect on catalysis, suggesting that Asn-199 plays an important role in stabilizing a transition state or high energy intermediate for methyl transfer.« less
Identification and structural analysis of ricin inhibitors. Final report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Robertus, J.D.
1996-12-01
Ricin is a potent cytotoxin which has been used by governments and terrorists as a poison. The three-dimensional structure of this toxic molecule was solved by X-ray crystallography, including an atomic description of its active site. The goal of this project was to use computer searches and other molecular modeling techniques to identify an inhibitor or ricin A chain (RTA). The program CHEM-X was used to predict that pteroic acid (PTA) would bind to RTA. This was shown to be the case by kinetic assays, where PTA protected ribosomes against the action of RTA, and by X-ray crystallography. The affinitymore » of PTA is weak, with a Ki estimated at 600 Micrometers. The pterin group of PTA was observed to make many polar interactions with RTA within the specificity site of the enzyme, and to bind more strongly than the natural substrate adenine. Further work will be required to increase the binding affinity of this class of inhibitors, and to improve their solubility if efficacious antidotes are to be designed from this lead.« less
NASA Astrophysics Data System (ADS)
Tyagi, A.; Penzkofer, A.; Batschauer, A.; Wolf, E.
2009-06-01
The fluorescence spectroscopic behaviour of (6R,S)-5,10-methenyltetrahydrofolate (MTHF), (6R,S)-10-formyltetrahydrofolate (10-HCO-H4folate), 10-formyldihydrofolate (10-HCO-H2folate), and 10-formylfolate (10-HCO-folate) in aqueous Tris-HCl buffer at pH 8 is studied. MTHF and 10-HCO-folate were commercially available. 10-HCO-H4folate was prepared from MTHF by hydrolysis at room temperature under anaerobic conditions. 10-HCO-H2folate was prepared by oxidation of 10-HCO-H4folate under aerobic conditions. Fluorescence quantum distributions at room temperature and fluorescence signal decays at room temperature and liquid nitrogen temperature were measured. The fluorescence lifetimes determined at room temperature (liquid nitrogen temperature) are 10 ps (2.9 ns) for MTHF, 38 ps (3.7 ns) for 10-HCO-H4folate, 80 ps (10.5 ns) for 10-HCO-H2folate, and 7.1 ns (20 ns) for 10-HCO-folate. The results are discussed in terms of dyadic (pterin-benzoyl-glutamate) photo-induced electron transfer and dyadic fluorescent dynamics.
Sawada, H; Nakagoshi, M; Reinhardt, R K; Ziegler, I; Koch, P B
2002-06-01
Color patterns of butterfly wings are composed of single color points represented by each scale. In the case of Precis coenia, at the end of pupal development, different types of pigments are synthesized sequentially in the differently colored scales beginning with white (pterins) followed by red (ommatins) and then black (melanin). In order to explain how formation of these different colors is regulated, we examined the expression of an mRNA-encoding guanosine triphosphate-cyclohydrolase I (GTP-CH I; EC 3.5.4.16), the first key enzyme in the biosynthesis of pteridines, during pigment formation in the wings of P. coenia. The strongest positive signal was recognized around pigment formation one day before butterfly emergence. This GTP-CH I gene expression is paralleled by GTP-CH I enzyme activity measured in wing extracts. We also investigated the effect of 20-hydroxyecdysone on the expression of GTP-CH I mRNA and the enzyme activity during color formation. The results strongly suggest that the onset and duration of the expression of a GTP-CH I mRNA is triggered by a declining ecdysteroid hormone titer during late pupal development.
Normalization of urinary pteridines by urine specific gravity for early cancer detection.
Burton, Casey; Shi, Honglan; Ma, Yinfa
2014-08-05
Urinary biomarkers, such as pteridines, require normalization with respect to an individual's hydration status and time since last urination. Conventional creatinine-based corrections are affected by a multitude of patient factors whereas urine specific gravity (USG) is a bulk specimen property that may better resist those same factors. We examined the performance of traditional creatinine adjustments relative to USG to six urinary pteridines in aggressive and benign breast cancers. 6-Biopterin, neopterin, pterin, 6-hydroxymethylpterin, isoxanthopterin, xanthopterin, and creatinine were analyzed in 50 urine specimens with a previously developed liquid chromatography-tandem mass spectrometry technique. Creatinine and USG performance were evaluated with non-parametric Mann-Whitney hypothesis testing. USG and creatinine were moderately correlated (r=0.857) with deviations occurring in dilute and concentrated specimens. In 48 aggressive and benign breast cancers, normalization by USG significantly outperformed creatinine adjustments which marginally outperformed uncorrected pteridines in predicting pathological status. In addition, isoxanthopterin and xanthopterin were significantly higher in pathological specimens when normalized by USG. USG, as a bulk property, can provide better performance over creatinine-based normalizations for urinary pteridines in cancer detection applications. Copyright © 2014 Elsevier B.V. All rights reserved.
Lindsay, Angus; Schmiechen, Alexandra; Chamberlain, Christopher M; Ervasti, James M; Lowe, Dawn A
2018-05-23
Macrophage infiltration is a hallmark of dystrophin-deficient muscle. We tested the hypothesis that Duchenne muscular dystrophy (DMD) patients would have elevated levels of the macrophage synthesized pterins, neopterin and 7,8-dihydroneopterin compared to unaffected age-matched controls. Urinary neopterin/creatinine and 7,8-dihydroneopterin/creatinine were elevated in DMD patients and 7,8-dihydroneopterin/creatinine was associated with patient age and ambulation. 7,8-dihydroneopterin correction with specific gravity was also elevated in DMD patients. Because 7,8-dihydroneopterin is an antioxidant, we then identified a potential role for 7,8-dihydroneopterin in disease pathology. We assessed whether 7,8-dihydroneopterin could 1) protect against isometric force loss in wildtype skeletal muscle exposed to various pro-oxidants, and 2) protect wildtype and mdx muscle from eccentric contraction-induced force drop which has an oxidative component. Force drop was elicited in isolated Extensor Digitorum Longus (EDL) muscles by 10 eccentric contractions and recovery of force following the contractions was measured in the presence of exogenous 7,8-dihydroneopterin. 7,8-dihydroneopterin attenuated isometric force loss by wildtype EDL muscles when challenged by H 2 O 2 and HOCl, but exacerbated force loss when challenged by SIN-1 (NO · , O 2 · , ONOO - ). 7,8-dihydroneopterin attenuated eccentric contraction-induced force drop in mdx muscle. Isometric force by EDL muscles of mdx mice also recovered to a greater degree following eccentric contractions in the presence of 7,8-dihydroneopterin. The results corroborate macrophage activation in DMD patients, provide a potential protective role for 7,8-dihydroneopterin in the susceptibility of dystrophic muscle to eccentric contractions and indicate oxidative stress contributes to eccentric contraction-induced force drop in mdx skeletal muscle. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Sensing and Responding to UV-A in Cyanobacteria
Moon, Yoon-Jung; Kim, Seung Il; Chung, Young-Ho
2012-01-01
Ultraviolet (UV) radiation can cause stresses or act as a photoregulatory signal depending on its wavelengths and fluence rates. Although the most harmful effects of UV on living cells are generally attributed to UV-B radiation, UV-A radiation can also affect many aspects of cellular processes. In cyanobacteria, most studies have concentrated on the damaging effect of UV and defense mechanisms to withstand UV stress. However, little is known about the activation mechanism of signaling components or their pathways which are implicated in the process following UV irradiation. Motile cyanobacteria use a very precise negative phototaxis signaling system to move away from high levels of solar radiation, which is an effective escape mechanism to avoid the detrimental effects of UV radiation. Recently, two different UV-A-induced signaling systems for regulating cyanobacterial phototaxis were characterized at the photophysiological and molecular levels. Here, we review the current understanding of the UV-A mediated signaling pathways in the context of the UV-A perception mechanism, early signaling components, and negative phototactic responses. In addition, increasing evidences supporting a role of pterins in response to UV radiation are discussed. We outline the effect of UV-induced cell damage, associated signaling molecules, and programmed cell death under UV-mediated oxidative stress. PMID:23208372
Roberts, Kenneth M.; Pavon, Jorge Alex; Fitzpatrick, Paul F.
2013-01-01
Phenylalanine hydroxylase (PheH) catalyzes the key step in the catabolism of dietary phenylalanine, its hydroxylation to tyrosine using tetrahydrobiopterin (BH4) and O2. A complete kinetic mechanism for PheH was determined by global analysis of single turnover data in the reaction of PheHΔ117, a truncated form of the enzyme lacking the N-terminal regulatory domain. Formation of the productive PheHΔ117-BH4-phenylalanine complex begins with the rapid binding of BH4 (Kd = 65 µM). Subsequent addition of phenylalanine to the binary complex to form the productive ternary complex (Kd = 130 µM) is approximately ten-fold slower. Both substrates can also bind to the free enzyme to form inhibitory binary complexes. O2 rapidly binds to the productive ternary complex; this is followed by formation of an unidentified intermediate, detectable as a decrease in absorbance at 340 nm, with a rate constant of 140 s−1. Formation of the 4a-hydroxypterin and Fe(IV)O intermediates is ten-fold slower and is followed by the rapid hydroxylation of the amino acid. Product release is the rate-determining step and largely determines kcat. Similar reactions using 6-methyltetrahydropterin indicate a preference for the physiological pterin during hydroxylation. PMID:23327364
NASA Technical Reports Server (NTRS)
Bachmann, M.; Shiraishi, N.; Campbell, W. H.; Yoo, B. C.; Harmon, A. C.; Huber, S. C.; Davies, E. (Principal Investigator)
1996-01-01
Spinach leaf NADH:nitrate reductase (NR) responds to light/dark signals and photosynthetic activity in part as a result of rapid regulation by reversible protein phosphorylation. We have identified the major regulatory phosphorylation site as Ser-543, which is located in the hinge 1 region connecting the cytochrome b domain with the molybdenum-pterin cofactor binding domain of NR, using recombinant NR fragments containing or lacking the phosphorylation site sequence. Studies with NR partial reactions indicated that the block in electron flow caused by phosphorylation also could be localized to the hinge 1 region. A synthetic peptide (NR6) based on the phosphorylation site sequence was phosphorylated readily by NR kinase (NRk) in vitro. NR6 kinase activity tracked the ATP-dependent inactivation of NR during several chromatographic steps and completely inhibited inactivation/phosphorylation of native NR in vitro. Two forms of NRk were resolved by using anion exchange chromatography. Studies with synthetic peptide analogs indicated that both forms of NRk had similar specificity determinants, requiring a basic residue at P-3 (i.e., three amino acids N-terminal to the phosphorylated serine) and a hydrophobic residue at P-5. Both forms are strictly calcium dependent but belong to distinct families of protein kinases because they are distinct immunochemically.
Dong, Wei; Cheng, Zhi-jun; Lei, Cai-lin; Wang, Xiao-le; Wang, Jiu-lin; Wang, Jie; Wu, Fu-qing; Zhang, Xin; Guo, Xiu-ping; Zhai, Hu-qu; Wan, Jian-min
2014-12-01
Folate (vitamin B9) deficiency is a global health problem especially in developing countries where the major staple foods such as rice contain extremely low folates. Biofortification of rice could be an alternative complement way to fight folate deficiency. In this study, we evaluated the availability of the genes in each step of folate biosynthesis pathway for rice folate enhancement in the japonica variety kitaake genetic background. The first enzymes GTP cyclohydrolase I (GTPCHI) and aminodeoxychorismate synthase (ADCS) in the pterin and para-aminobenzoate branches resulted in significant increase in seed folate content, respectively (P < 0.01). Overexpression of two closely related enzymes dihydrofolate synthase (DHFS) and folypolyglutamate synthase (FPGS), which perform the first and further additions of glutamates, produced slightly increase in seed folate content separately. The GTPCHI transgene was combined with each of the other transgenes except ADCS to investigate the effects of gene stacking on seed folate accumulation. Seed folate contents in the gene-stacked plants were higher than the individual low-folate transgenic parents, but lower than the high-folate GTPCHI transgenic lines, pointing to an inadequate supply of para-aminobenzoic acid (PABA) precursor initiated by ADCS in constraining folate overproduction in gene-stacked plants.
Development of a lateral flow dipstick immunoassay for evaluation of folate levels in maize.
Liang, Qiuju; Yi, Chen; Jiang, Ling; Tan, Guiyu; Zhang, Chunyi; Wang, Baomin
2017-09-01
Folates (vitamin B9) are essential for all organisms as cofactors for one-carbon metabolism. However, measurement of folates is technically complicated and time-consuming. In this study, we developed a dipstick immunoassay using a folate-specific monoclonal antibody (mAb), allowing rapid and low-cost detection of folates. The indicator range of the dipstick for 5-formylterahydrofolate (5-CHO-THF), 5-methyltetrahydrofolate (5-CH 3 -THF) and their polyglutamyl forms was 100-200 ng mL -1 ; moreover, no cross-reactivity was observed with tetrahydrofolate (THF) or 5,10-methenyltetrahydrofolate (5,10-CH=THF) at 500 ng mL -1 , or with the folate precursors pterin-6-COOH, p-aminobenzoate (pABA), and L-glutamate, or with the folate analogues methotrexate and 10-formyltetrahydrofolate (10-CHO-THF) at up to 1000 ng mL -1 . The dipstick immunoassay was tested in maize seeds; the results classified the seeds into those with low, moderate, and high levels of folates, and were in agreement with those of liquid chromatography-mass spectrometry. Thus, we conclude that the dipstick assay will provide a versatile tool to facilitate large-scale screening of maize rich in folates. Graphical Abstract The dipstick based immunoassay for analyzing folate level in maize.
Metabolic features of the cell danger response.
Naviaux, Robert K
2014-05-01
The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis. © 2013. Published by Elsevier B.V. All rights reserved.
Roy, Roopali; Mukund, Swarnalatha; Schut, Gerrit J.; Dunn, Dianne M.; Weiss, Robert; Adams, Michael W. W.
1999-01-01
Pyrococcus furiosus is a hyperthermophilic archaeon which grows optimally near 100°C by fermenting peptides and sugars to produce organic acids, CO2, and H2. Its growth requires tungsten, and two different tungsten-containing enzymes, aldehyde ferredoxin oxidoreductase (AOR) and glyceraldehyde-3-phosphate ferredoxin oxidoreductase (GAPOR), have been previously purified from P. furiosus. These two enzymes are thought to function in the metabolism of peptides and carbohydrates, respectively. A third type of tungsten-containing enzyme, formaldehyde ferredoxin oxidoreductase (FOR), has now been characterized. FOR is a homotetramer with a mass of 280 kDa and contains approximately 1 W atom, 4 Fe atoms, and 1 Ca atom per subunit, together with a pterin cofactor. The low recovery of FOR activity during purification was attributed to loss of sulfide, since the purified enzyme was activated up to fivefold by treatment with sulfide (HS−) under reducing conditions. FOR uses P. furiosus ferredoxin as an electron acceptor (Km = 100 μM) and oxidizes a range of aldehydes. Formaldehyde (Km = 15 mM for the sulfide-activated enzyme) was used in routine assays, but the physiological substrate is thought to be an aliphatic C5 semi- or dialdehyde, e.g., glutaric dialdehyde (Km = 1 mM). Based on its amino-terminal sequence, the gene encoding FOR (for) was identified in the genomic database, together with those encoding AOR and GAPOR. The amino acid sequence of FOR corresponded to a mass of 68.7 kDa and is highly similar to those of the subunits of AOR (61% similarity and 40% identity) and GAPOR (50% similarity and 23% identity). The three genes are not linked on the P. furiosus chromosome. Two additional (and nonlinked) genes (termed wor4 and wor5) that encode putative tungstoenzymes with 57% (WOR4) and 56% (WOR5) sequence similarity to FOR were also identified. Based on sequence motif similarities with FOR, both WOR4 and WOR5 are also proposed to contain a tungstobispterin site and one [4Fe-4S] cluster per subunit. PMID:9973343
NASA Astrophysics Data System (ADS)
Smyth, C.; Mehigan, S.; Rakovich, Y. P.; Bell, S. E. J.; McCabe, E. M.
2011-03-01
Optical techniques towards the realisation of sensitive and selective biosensing platforms have received a considerable amount of attention in recent times. Techniques based on interferometry, surface plasmon resonance, field-effect transistors and waveguides have all proved popular, and in particular, spectroscopy offers a large range of options. Raman spectroscopy has always been viewed as an information rich technique in which the vibrational frequencies reveal a lot about the structure of a compound. The issue with Raman spectroscopy has traditionally been that its rather low cross section leads to poor limits-of-detection. In response to this problem, Surface-enhanced Raman Scattering (SERS), which increases sensitivity by bringing the sample in contact with many types of enhanceing substrates, has been developed. Here we discuss a facile and rapid technique for the detection of pterins using colloidal silver suspensions. Pteridine compounds are a family of biochemicals, heterocyclic in structure, and employed in nature as components of colour pigmentation and also as facilitators for many metabolic pathways, particularly those relating to the amino acid hydroxylases. In this work, xanthopterin, isoxanthopterin and 7,8- dihydrobiopterin have been examined whilst absorbed to SERS-active silver colloids. SERS, while far more sensitive than regular Raman spectroscopy, has its own issues relating to the reproducibility of substrates. In order to obtain quantitative data for the pteridine compounds mentioned above, exploratory studies of methods for introducing an internal standard for normalisation of the signals have been carried out.e
DOE Office of Scientific and Technical Information (OSTI.GOV)
Celeste, Lesa R.; Chai, Geqing; Bielak, Magdalena
N{sup 10}-formyltetrahydrofolate synthetase (FTHFS) is a folate enzyme that catalyzes the formylation of tetrahydrofolate (THF) in an ATP dependent manner. Structures of FTHFS from the thermophilic homoacetogen, Moorella thermoacetica, complexed with (1) a catalytic intermediate-formylphosphate (XPO) and product-ADP; (2) with an inhibitory substrate analog-folate; (3) with XPO and an inhibitory THF analog, ZD9331, were used to analyze the enzyme mechanism. Nucleophilic attack of the formate ion on the gamma phosphate of ATP leads to the formation of XPO and the first product ADP. A channel that leads to the putative formate binding pocket allows for the binding of ATP andmore » formate in random order. Formate binding is due to interactions with the gamma-phosphate moiety of ATP and additionally to two hydrogen bonds from the backbone nitrogen of Ala276 and the side chain of Arg97. Upon ADP dissociation, XPO reorients and moves to the position previously occupied by the beta-phosphate of ATP. Conformational changes that occur due to the XPO presence apparently allow for the recruitment of the third substrate, THF, with its pterin moiety positioned between Phe384 and Trp412. This position overlaps with that of the bound nucleoside, which is consistent with a catalytic mechanism hypothesis that FTHFS works via a sequential ping-pong mechanism. More specifically, a random bi uni uni bi ping-pong ter ter mechanism is proposed. Additionally, the native structure originally reported at a 2.5 {angstrom} resolution was redetermined at a 2.2 {angstrom} resolution.« less
Multiple ligand-binding modes in bacterial R67 dihydrofolate reductase
NASA Astrophysics Data System (ADS)
Alonso, Hernán; Gillies, Malcolm B.; Cummins, Peter L.; Bliznyuk, Andrey A.; Gready, Jill E.
2005-03-01
R67 dihydrofolate reductase (DHFR), a bacterial plasmid-encoded enzyme associated with resistance to the drug trimethoprim, shows neither sequence nor structural homology with the chromosomal DHFR. It presents a highly symmetrical toroidal structure, where four identical monomers contribute to the unique central active-site pore. Two reactants (dihydrofolate, DHF), two cofactors (NADPH) or one of each (R67•DHF•NADPH) can be found simultaneously within the active site, the last one being the reactive ternary complex. As the positioning of the ligands has proven elusive to empirical determination, we addressed the problem from a theoretical perspective. Several potential structures of the ternary complex were generated using the docking programs AutoDock and FlexX. The variability among the final poses, many of which conformed to experimental data, prompted us to perform a comparative scoring analysis and molecular dynamics simulations to assess the stability of the complexes. Analysis of ligand-ligand and ligand-protein interactions along the 4 ns trajectories of eight different structures allowed us to identify important inter-ligand contacts and key protein residues. Our results, combined with published empirical data, clearly suggest that multipe binding modes of the ligands are possible within R67 DHFR. While the pterin ring of DHF and the nicotinamide ring of NADPH assume a stacked endo-conformation at the centre of the pore, probably assisted by V66, Q67 and I68, the tails of the molecules extend towards opposite ends of the cavity, adopting multiple configurations in a solvent rich-environment where hydrogen-bond interactions with K32 and Y69 may play important roles.
Zhou, Hai Yan; Yan, Hong; Wang, Li Li; Yan, Wei Jia; Shui, Ying Bo; Beebe, David C
2015-08-01
The goal of this study was to quantitatively identify the differentially expressed proteins in nuclear cataracts of different ages and normal lens nuclei in humans. Forty-eight human lens nucleus samples with hardness grades III, IV were obtained during cataract surgery by extracapsular cataract extraction. Seven normal transparent human lens nuclei were obtained from fresh normal cadaver eyes during corneal transplantation surgery. Lens nuclei were divided into seven groups according to age and optic axis: Group A (average age 80.8 ± 1.2 years), Group B (average age 57.0 ± 4.0 years), Group C average age 80.3 ± 4.5 years), Group D (average age 56.9 ± 4.2 years), Group E (average age 78.1 ± 2.5 years), Group F (average age 57.6 ± 3.3 years) and Group G (seven normal transparent human lenses from normal cadaver eyes, average age 34.7 ± 4.2 years). Water-soluble, water-insoluble, and water-insoluble-urea-soluble protein fractions were extracted from samples. The three-part protein fractions from the individual lenses were combined to form the total proteins of each sample. The proteomic profiles of each group were further analyzed using 8-plex iTRAQ labeling combined with 2D-LC-MS/MS. The data were analyzed with the ProteinPilot software for peptide matching, protein identification, and quantification. Differentially expressed proteins were validated by Western blotting. We employed biological and technical replicates and selected the intersection of the two results, which included 80 proteins. Nine proteins were differentially expressed among the 80 proteins identified using proteomic techniques. In age-related nuclear cataracts (ARNC), the expression levels of fatty acid-binding protein and pterin-4-alpha-carbinolamine dehydratase were upregulated, whereas the levels of alpha-crystallin B chain (CRYAB), GSH synthetase, phakinin, gamma-crystallin C, phosphoglycerate kinase 1, betaine-homocysteine S-methyltransferase 1 (BHMT1), and spectrin beta chain were downregulated. These proteins may be associated with abnormal protein aggregation and oxidative stress. GSH synthetase and CRYAB expression levels in the nuclear cataract decreased with age. The mass spectrometric analysis results were consistent with the Western blot validation. The results indicate that CRYAB and GSH synthetase may be involved in ARNC pathogenesis. iTRAQ combined with 2D-LC-MS/MS provides new methods for future studies of pathological mechanisms and protective drug development for ARNC. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Friedebold, J; Bowien, B
1993-01-01
Organoautotrophic growth of Alcaligenes eutrophus on formate was dependent on the presence of molybdate in the medium. Supplementation of the medium with tungstate lead to growth cessation. Corresponding effects of these anions were observed for the activity of the soluble, NAD(+)-linked formate dehydrogenase (S-FDH; EC 1.2.1.2) of the organism. Lack of molybdate or presence of tungstate resulted in an almost complete loss of S-FDH activity. S-FDH was purified to near homogeneity in the presence of nitrate as a stabilizing agent. The native enzyme exhibited an M(r) of 197,000 and a heterotetrameric quaternary structure with nonidentical subunits of M(r) 110,000 (alpha), 57,000 (beta), 19,400 (gamma), and 11,600 (delta). It contained 0.64 g-atom of molybdenum, 25 g-atom of nonheme iron, 20 g-atom of acid-labile sulfur, and 0.9 mol of flavin mononucleotide per mol. The fluorescence spectrum of iodine-oxidized S-FDH was nearly identical to the form A spectrum of milk xanthine oxidase, proving the presence of a pterin cofactor. The molybdenum-complexing cofactor was identified as molybdopterin guanine dinucleotide in an amount of 0.71 mol/mol of S-FDH. Apparent Km values of 3.3 mM for formate and 0.09 mM for NAD+ were determined. The enzyme coupled the oxidation of formate to a number of artificial electron acceptors and was strongly inactivated by formate in the absence of NAD+. It was inhibited by cyanide, azide, nitrate, and Hg2+ ions. Thus, the enzyme belongs to a new group of complex molybdo-flavo Fe-S FDH that so far has been detected in only one other aerobic bacterium. Images PMID:8335630
Bailey, Steven W; Ayling, June E
2013-11-08
Although many countries have fortified their grain supplies with folic acid (FA) to decrease the incidence of neural tube defects, others have not due to concerns that this synthetic folate might have some adverse effects. Persistent unmetabolized FA has been found even in plasma from fasted subjects. To facilitate measurement of low levels of folic acid in human plasma, post-column coulometric oxidative cleavage was used to convert poorly fluorescent FA into a highly fluorescent compound determined to be 6-formyl-pterin. To minimize sample work-up and maximize recovery, column-switching HPLC transferred a window of eluate containing the FA from the first column (C8) onto a second column (phenyl-hexyl). The pH of two mobile phases were adjusted to be above and then below a pK of the FA α-carboxyl group, thus promoting separation from compounds coeluting from the C8-column. This permitted sample preparation using only a simple high recovery protein precipitation. Definitive identification of FA in human plasma was accomplished by duplicate injections of sample with the electrochemical voltage set above and below its half-potential. The LOD (S/N=3) was 0.10 nM. The intra- and inter-assay CV's were 2.3% and 5%, respectively. Comparison of these results with those obtained by HPLC/MS/MS with stable isotope internal standard showed a slope of 1.00 ± 0.019. This simple, sensitive, and repeatable assay facilitates a more thorough investigation of the response of various human populations to folic acid intake. Post-column differential coulometric electrochemistry can expand the variety of compounds amenable to fluorescence detection. Copyright © 2013 Elsevier B.V. All rights reserved.
Burton, Casey; Shi, Honglan; Ma, Yinfa
2013-11-19
Recent preliminary studies have implicated urinary pteridines as candidate biomarkers in a growing number of malignancies including breast cancer. While the developments of capillary electrophoresis-laser induced fluorescence (CE-LIF), high performance liquid chromatography (HPLC), and liquid chromatography-mass spectroscopy (LC-MS) pteridine urinalyses among others have helped to enable these findings, limitations including poor pteridine specificity, asynchronous or nonexistent renal dilution normalization, and a lack of information regarding adduct formation in mass spectrometry techniques utilizing electrospray ionization (ESI) have prevented application of these techniques to a larger clinical setting. In this study, a simple, rapid, specific, and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and optimized for simultaneous detection of six pteridines previously implicated in breast cancer and creatinine as a renal dilution factor in urine. In addition, this study reports cationic adduct formation of urinary pteridines under ESI-positive ionization for the first time. This newly developed technique separates and detects the following six urinary pteridines: 6-biopterin, 6-hydroxymethylpterin, d-neopterin, pterin, isoxanthopterin, and xanthopterin, as well as creatinine. The method detection limit for the pteridines is between 0.025 and 0.5 μg/L, and for creatinine, it is 0.15 μg/L. The method was also validated by spiked recoveries (81-105%), reproducibility (RSD: 1-6%), and application to 25 real urine samples from breast cancer positive and negative samples through a double-blind study. The proposed technique was finally compared directly with a previously reported CE-LIF technique, concluding that additional or alternative renal dilution factors are needed for proper investigation of urinary pteridines as breast cancer biomarkers.
Alternative Proofs for Inequalities of Some Trigonometric Functions
ERIC Educational Resources Information Center
Guo, Bai-Ni; Qi, Feng
2008-01-01
By using an identity relating to Bernoulli's numbers and power series expansions of cotangent function and logarithms of functions involving sine function, cosine function and tangent function, four inequalities involving cotangent function, sine function, secant function and tangent function are established.
ERIC Educational Resources Information Center
Wood, Brenna K.; Drogan, Robin R.; Janney, Donna M.
2014-01-01
Reviewers analyzed studies published from 1990 to 2012 to determine early childhood practitioner involvement in functional behavioral assessment (FBA) and function-based behavioral intervention plans (BIP) for children with challenging behavior, age 6 and younger. Coding of 30 studies included practitioner involvement in FBA and BIP processes,…
Gavin, Leslie; Wysocki, Tim
2006-06-01
The role of fathers in pediatric disease management and its associations with family functioning have rarely been the focus of empirical study. In this study, we used the Dads Active Disease Support scale (DADS), a measure of the amount and helpfulness of paternal involvement in pediatric disease management, to explore the association between father involvement and other aspects of family functioning. A sample of 190 heterosexual couples completed the DADS and measures of maternal, marital, and family functioning. Maternal report of higher ratings on DADS Helpfulness scale was associated with fewer self-reported maternal psychiatric symptoms and less perceived impact of the disease on family functioning. Both mothers' and fathers' reports indicated that more paternal involvement was related to more favorable outcomes in marital satisfaction and family functioning. More paternal involvement in disease management was associated with healthier maternal, marital, and family functioning. Longitudinal studies are needed to determine whether paternal involvement is likely to be a fruitful target for psychological intervention.
Disease management, coping, and functional disability in pediatric sickle cell disease.
Oliver-Carpenter, Gloria; Barach, Ilana; Crosby, Lori E; Valenzuela, Jessica; Mitchell, Monica J
2011-02-01
Youth with sickle cell disease (SCD) experience chronic symptoms that significantly interfere with physical, academic, and social-emotional functioning. Thus, to effectively manage SCD, youth and caregivers must work collaboratively to ensure optimal functioning. The goal of the current study was to examine the level of involvement in disease management tasks for youth with SCD and their caregivers. The study also examined the relationship between involvement in disease management tasks, daily functioning, and coping skills. The study utilized collaborative care and disease management theoretical frameworks. Youth and caregivers participated in the study during an annual research and education day event. Forty-seven patients with SCD aged 6 to 18 years and their caregivers completed questionnaires examining level of involvement in disease management tasks, youth functional disability, and youth coping strategies. Caregivers also completed a demographic and medical history form. Parents and youth agreed that parents were significantly more involved in disease management tasks than youth, although level of involvement varied by task. Decreased parent involvement was related to greater coping strategies used by patients, including massage, prayer, and positive thinking. Higher functional disability (lower functioning) was related to greater parent involvement in disease management tasks, suggesting that greater impairment may encourage increased parent involvement. Health professionals working with families of youth with SCD should discuss with parents and youth how disease management tasks and roles will be shared and transferred during adolescence. Parents and youth may also benefit from a discussion of these issues within their own families.
Özyurt, Jale; Thiel, Christiane M; Lorenzen, Anna; Gebhardt, Ursel; Calaminus, Gabriele; Warmuth-Metz, Monika; Müller, Hermann L
2014-04-01
To test memory performance and executive functions in patients with childhood craniopharyngioma and hypothalamic involvement. Using standardized neuropsychological tests, we compared cognitive performance in a group of 15 patients with childhood craniopharyngioma and known hypothalamic involvement and a group of 24 age- and intelligence-matched control subjects. In addition, we compared individual patients' results with normative data to detect abnormal performance in the clinically relevant range. Within the patient group, we further tested whether the grade of hypothalamic involvement had an impact on cognitive performance and quality of life. Relative to healthy controls, the patients demonstrated significantly lower performance scores in tests of memory and executive functioning. On the individual performance level, delayed recall performance was severely impaired in one-third of the patients. Compared with patients with low-grade hypothalamic involvement, those with high-grade hypothalamic involvement showed worse performance in executive functions and reduced functional capabilities for daily life actions, indicating lower quality of life. Our findings demonstrate that hypothalamic involvement is related to impairments in memory and executive functioning in patients with childhood craniopharyngioma and indicate that a high grade of hypothalamic involvement is related to worse outcomes. Copyright © 2014 Mosby, Inc. All rights reserved.
On computing closed forms for summations. [polynomials and rational functions
NASA Technical Reports Server (NTRS)
Moenck, R.
1977-01-01
The problem of finding closed forms for a summation involving polynomials and rational functions is considered. A method closely related to Hermite's method for integration of rational functions derived. The method expresses the sum of a rational function as a rational function part and a transcendental part involving derivatives of the gamma function.
Code of Federal Regulations, 2012 CFR
2012-10-01
... Functions. (a) The primary function of the Board is to promote safety in transportation. The Board is... involving a public and a non-public vessel or involving Coast Guard functions. The Board makes... 49 Transportation 7 2012-10-01 2012-10-01 false Functions. 800.3 Section 800.3 Transportation...
Code of Federal Regulations, 2011 CFR
2011-10-01
... Functions. (a) The primary function of the Board is to promote safety in transportation. The Board is... involving a public and a non-public vessel or involving Coast Guard functions. The Board makes... 49 Transportation 7 2011-10-01 2011-10-01 false Functions. 800.3 Section 800.3 Transportation...
Code of Federal Regulations, 2010 CFR
2010-10-01
... Functions. (a) The primary function of the Board is to promote safety in transportation. The Board is... involving a public and a non-public vessel or involving Coast Guard functions. The Board makes... 49 Transportation 7 2010-10-01 2010-10-01 false Functions. 800.3 Section 800.3 Transportation...
Code of Federal Regulations, 2014 CFR
2014-10-01
... Functions. (a) The primary function of the Board is to promote safety in transportation. The Board is... involving a public and a non-public vessel or involving Coast Guard functions. The Board makes... 49 Transportation 7 2014-10-01 2014-10-01 false Functions. 800.3 Section 800.3 Transportation...
Code of Federal Regulations, 2013 CFR
2013-10-01
... Functions. (a) The primary function of the Board is to promote safety in transportation. The Board is... involving a public and a non-public vessel or involving Coast Guard functions. The Board makes... 49 Transportation 7 2013-10-01 2013-10-01 false Functions. 800.3 Section 800.3 Transportation...
Disease Management, Coping, and Functional Disability in Pediatric Sickle Cell Disease
Oliver-Carpenter, Gloria; Barach, Ilana; Crosby, Lori E.; Valenzuela, Jessica; Mitchell, Monica J.
2016-01-01
Background Youth with sickle cell disease (SCD) experience chronic symptoms that significantly interfere with physical, academic, and social-emotional functioning. Thus, to effectively manage SCD, youth and caregivers must work collaboratively to ensure optimal functioning. The goal of the current study was to examine the level of involvement in disease management tasks for youth with SCD and their caregivers. The study also examined the relationship between involvement in disease management tasks, daily functioning, and coping skills. The study utilized collaborative care and disease management theoretical frameworks. Methods Youth and caregivers participated in the study during an annual research and education day event. Forty-seven patients with SCD aged 6 to 18 years and their caregivers completed questionnaires examining level of involvement in disease management tasks, youth functional disability and youth coping strategies. Caregivers also completed a demographic and medical history form. Results Parents and youth agreed that parents are significantly more involved in disease management tasks than youth, although level of involvement varied by task. Decreased parent involvement was related to greater coping strategies used by patients, including massage, prayer, and positive thinking. Higher functional disability (lower functioning) was related to greater parent involvement in disease management tasks, suggesting that greater impairment may encourage increased parent involvement. Conclusions Health professionals working with families of youth with SCD should discuss with parents and youth how disease management tasks and roles will be shared and transferred during adolescence. Parents and youth may also benefit from a discussion of these issues within their own families. PMID:21443065
ERIC Educational Resources Information Center
Lee, Chang-Hun; Song, Juyoung
2012-01-01
This study uses an ecological systems theory to understand bullying behavior. Emphasis is given to overcome limitations found in the literature, such as very little empirical research on functions of parental involvement and the impacts of school climate on bullying as an outcome variable. Two functions of parental involvement investigated are (a)…
García-Madruga, Juan A.; Gómez-Veiga, Isabel; Vila, José Ó.
2016-01-01
In this paper, we propose a preliminary theory of executive functions that address in a specific way their relationship with working memory (WM) and higher-level cognition. It includes: (a) four core on-line WM executive functions that are involved in every novel and complex cognitive task; (b) two higher order off-line executive functions, planning and revision, that are required to resolving the most complex intellectual abilities; and (c) emotional control that is involved in any complex, novel and difficult task. The main assumption is that efficiency on thinking abilities may be improved by specific instruction or training on the executive functions necessary to solving novel and complex tasks involved in these abilities. Evidence for the impact of our training proposal on WM's executive functions involved in higher-level cognitive abilities comes from three studies applying an adaptive program designed to improve reading comprehension in primary school students by boosting the core WM's executive functions involved in it: focusing on relevant information, switching (or shifting) between representations or tasks, connecting incoming information from text with long-term representations, updating of the semantic representation of the text in WM, and inhibition of irrelevant information. The results are consistent with the assumption that cognitive enhancements from the training intervention may have affected not only a specific but also a more domain-general mechanism involved in various executive functions. We discuss some methodological issues in the studies of effects of WM training on reading comprehension. The perspectives and limitations of our approach are finally discussed. PMID:26869961
Respiratory muscle involvement in sarcoidosis.
Schreiber, Tina; Windisch, Wolfram
2018-07-01
In sarcoidosis, muscle involvement is common, but mostly asymptomatic. Currently, little is known about respiratory muscle and diaphragm involvement and function in patients with sarcoidosis. Reduced inspiratory muscle strength and/or a reduced diaphragm function may contribute to exertional dyspnea, fatigue and reduced health-related quality of life. Previous studies using volitional and non-volitional tests demonstrated a reduced inspiratory muscle strength in sarcoidosis compared to control subjects, and also showed that respiratory muscle function may even be significantly impaired in a subset of patients. Areas covered: This review examines the evidence on respiratory muscle involvement and its implications in sarcoidosis with emphasis on pathogenesis, diagnosis and treatment of respiratory muscle dysfunction. The presented evidence was identified by a literature search performed in PubMed and Medline for articles about respiratory and skeletal muscle function in sarcoidosis through to January 2018. Expert commentary: Respiratory muscle involvement in sarcoidosis is an underdiagnosed condition, which may have an important impact on dyspnea and health-related quality of life. Further studies are needed to understand the etiology, pathogenesis and extent of respiratory muscle involvement in sarcoidosis.
Integrating Functional, Developmental and Evolutionary Biology into Biology Curricula
ERIC Educational Resources Information Center
Haave, Neil
2012-01-01
A complete understanding of life involves how organisms are able to function in their environment and how they arise. Understanding how organisms arise involves both their evolution and development. Thus to completely comprehend living things, biology must study their function, development and evolution. Previous proposals for standardized…
Linear and nonlinear stiffness and friction in biological rhythmic movements.
Beek, P J; Schmidt, R C; Morris, A W; Sim, M Y; Turvey, M T
1995-11-01
Biological rhythmic movements can be viewed as instances of self-sustained oscillators. Auto-oscillatory phenomena must involve a nonlinear friction function, and usually involve a nonlinear elastic function. With respect to rhythmic movements, the question is: What kinds of nonlinear friction and elastic functions are involved? The nonlinear friction functions of the kind identified by Rayleigh (involving terms such as theta3) and van der Pol (involving terms such as theta2theta), and the nonlinear elastic functions identified by Duffing (involving terms such as theta3), constitute elementary nonlinear components for the assembling of self-sustained oscillators, Recently, additional elementary nonlinear friction and stiffness functions expressed, respectively, through terms such as theta2theta3 and thetatheta2, and a methodology for evaluating the contribution of the elementary components to any given cyclic activity have been identified. The methodology uses a quantification of the continuous deviation of oscillatory motion from ideal (harmonic) motion. Multiple regression of this quantity on the elementary linear and nonlinear terms reveals the individual contribution of each term to the oscillator's non-harmonic behavior. In the present article the methodology was applied to the data from three experiments in which human subjects produced pendular rhythmic movements under manipulations of rotational inertia (experiment 1), rotational inertia and frequency (experiment 2), and rotational inertia and amplitude (experiment 3). The analysis revealed that the pendular oscillators assembled in the three experiments were compositionally rich, braiding linear and nonlinear friction and elastic functions in a manner that depended on the nature of the task.
ERIC Educational Resources Information Center
O'Neill, Sue; Stephenson, Jennifer
2009-01-01
This article examines literature published since 1997 on functional behaviour assessment (FBA) and behaviour intervention plans (BIPs), involving school-based personnel, for children identified as having or being at risk of emotional/behavioural disorder (E/BD) in school settings. Of interest was the level of involvement of school-based personnel…
Genetics Home Reference: CLN4 disease
... with each other. Specifically, CSPα is involved in recycling certain proteins that are involved in nerve impulse ... protein cannot perform its function, which reduces protein recycling, causing a shortage (deficiency) of functional proteins needed ...
Holt, Cheryl L.; Wang, Min Qi; Caplan, Lee; Schulz, Emily; Blake, Victor; Southward, Vivian L.
2013-01-01
The present study tested a mediational model of the role of religious involvement, spirituality, and physical/emotional functioning in a sample of African American men and women with cancer. Several mediators were proposed based on theory and previous research, including sense of meaning, positive and negative affect, and positive and negative religious coping. One hundred patients were recruited through oncologist offices, key community leaders and community organizations, and interviewed by telephone. Participants completed an established measure of religious involvement, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-SP-12 version 4), the Positive and Negative Affect Schedule (PANAS), the Meaning in Life Scale, the Brief RCOPE, and the SF-12, which assesses physical and emotional functioning. Positive affect completely mediated the relationship between religious behaviors and emotional functioning. Though several other constructs showed relationships with study variables, evidence of mediation was not supported. Mediational models were not significant for the physical functioning outcome, nor were there significant main effects of religious involvement or spirituality for this outcome. Implications for cancer survivorship interventions are discussed. PMID:21222026
Yeh, Yi-Chun; Huang, Mei-Feng; Wu, Yu-Yu; Hu, Huei-Fan; Yen, Cheng-Fang
2017-08-01
The aim of this study was to examine the relationships of pain and pain-induced functional impairment with bullying involvement, as well as the relationships between pain and mental health problems among 474 children and adolescents with ADHD. The levels of pain, pain-induced functional impairment, involvement in bullying, depression, anxiety, ADHD symptoms, and sleep quality were assessed. Both victims of verbal and relational bullying and victims of physical bullying were more likely to have pain and pain-induced functional impairment than nonvictims. The perpetrators of verbal and relational bullying were more likely to have pain than the nonperpetrators. Participants with pain and pain-induced functional impairment experienced more severe depression and anxiety and worse sleep quality than did those without pain or pain-induced functional impairment. Clinical and educational professionals should consider the possibility of involvement in bullying and comorbid depression, anxiety, and poor sleep quality among ADHD children and adolescents with pain problems.
Serotonin involvement in pituitary-adrenal function
NASA Technical Reports Server (NTRS)
Vernikos-Danellis, J.; Kellar, K. J.; Kent, D.; Gonzales, C.; Berger, P. A.; Barchas, J. D.
1977-01-01
Experiments clarifying the effects of serotonin (5-HT) in the regulation of the hypothalamic-pituitary-adrenocortical system are surveyed. Lesion experiments which seek to determine functional maps of serotonergic input to areas involved in regulation are reported. Investigations of the effects of 5-HT levels on the plasma ACTH response to stress and the diurnal variation in basal plasma corticosterone are summarized, and the question of whether serotonergic transmission is involved in the regulation of all aspects of pituitary-adrenal function is considered with attention to the stimulatory and inhibitory action of 5-HT.
ERIC Educational Resources Information Center
Green, Carolyn W.; And Others
1986-01-01
A staff supervision and classroom management program to increase involvement in functional task activities (e.g., self-help, leisure, social/communication) was implemented in three classes serving 19 students (ages 11-36) with profound mental and physical handicaps. Large increases in functional task involvement and smaller increases in student…
Some subclasses of multivalent functions involving a certain linear operator
NASA Astrophysics Data System (ADS)
Srivastava, H. M.; Patel, J.
2005-10-01
The authors investigate various inclusion and other properties of several subclasses of the class of normalized p-valent analytic functions in the open unit disk, which are defined here by means of a certain linear operator. Problems involving generalized neighborhoods of analytic functions in the class are investigated. Finally, some applications of fractional calculus operators are considered.
Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis.
de Leeuw, Christiaan; Goudriaan, Andrea; Smit, August B; Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Verheijen, Mark H G; Posthuma, Danielle
2015-11-01
Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls. The gene sets included specific synaptic, astrocytic, oligodendrocyte and microglial functions. We report association of Tourette syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte-neuron metabolic coupling may be an important contributor to Tourette syndrome pathogenesis.
Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis
de Leeuw, Christiaan; Goudriaan, Andrea; Smit, August B; Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Scharf, J M; Pauls, D L; Yu, D; Illmann, C; Osiecki, L; Neale, B M; Mathews, C A; Reus, V I; Lowe, T L; Freimer, N B; Cox, N J; Davis, L K; Rouleau, G A; Chouinard, S; Dion, Y; Girard, S; Cath, D C; Posthuma, D; Smit, J H; Heutink, P; King, R A; Fernandez, T; Leckman, J F; Sandor, P; Barr, C L; McMahon, W; Lyon, G; Leppert, M; Morgan, J; Weiss, R; Grados, M A; Singer, H; Jankovic, J; Tischfield, J A; Heiman, G A; Verheijen, Mark H G; Posthuma, Danielle
2015-01-01
Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls. The gene sets included specific synaptic, astrocytic, oligodendrocyte and microglial functions. We report association of Tourette syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte-neuron metabolic coupling may be an important contributor to Tourette syndrome pathogenesis. PMID:25735483
Different functional classes of genes are characterized by different compositional properties.
D'Onofrio, Giuseppe; Ghosh, Tapash Chandra; Saccone, Salvatore
2007-12-22
A compositional analysis on a set of human genes classified in several functional classes was performed. We found out that the GC3, i.e. the GC level at the third codon positions, of the genes involved in cellular metabolism was significantly higher than those involved in information storage and processing. Analyses of human/Xenopus ortologous genes showed that: (i) the GC3 increment of the genes involved in cellular metabolism was significantly higher than those involved in information storage and processing; and (ii) a strong correlation between the GC3 and the corresponding GCi, i.e. the GC level of introns, was found in each functional class. The non-randomness of the GC increments favours the selective hypothesis of gene/genome evolution.
Longitudinal and bulk viscosities of Lennard-Jones fluids
NASA Astrophysics Data System (ADS)
Tankeshwar, K.; Pathak, K. N.; Ranganathan, S.
1996-12-01
Expressions for the longitudinal and bulk viscosities have been derived using Green Kubo formulae involving the time integral of the longitudinal and bulk stress autocorrelation functions. The time evolution of stress autocorrelation functions are determined using the Mori formalism and a memory function which is obtained from the Mori equation of motion. The memory function is of hyperbolic secant form and involves two parameters which are related to the microscopic sum rules of the respective autocorrelation function. We have derived expressions for the zeroth-, second-and fourth- order sum rules of the longitudinal and bulk stress autocorrelation functions. These involve static correlation functions up to four particles. The final expressions for these have been put in a form suitable for numerical calculations using low- order decoupling approximations. The numerical results have been obtained for the sum rules of longitudinal and bulk stress autocorrelation functions. These have been used to calculate the longitudinal and bulk viscosities and time evolution of the longitudinal stress autocorrelation function of the Lennard-Jones fluids over wide ranges of densities and temperatures. We have compared our results with the available computer simulation data and found reasonable agreement.
ERIC Educational Resources Information Center
Reiterer, Susanne; Pereda, Ernesto; Bhattacharya, Joydeep
2009-01-01
This article examines the question of whether university-based high-level foreign language and linguistic training can influence brain activation and whether different L2 proficiency groups have different brain activation in terms of lateralization and hemispheric involvement. The traditional and prevailing theory of hemispheric involvement in…
Biological pathways and genetic mechanisms involved in social functioning.
Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G
2013-08-01
To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.
Verdejo-Román, Juan; Fornito, Alex; Soriano-Mas, Carles; Vilar-López, Raquel; Verdejo-García, Antonio
2017-02-01
Overvaluation of palatable food is a primary driver of obesity, and is associated with brain regions of the reward system. However, it remains unclear if this network is specialized in food reward, or generally involved in reward processing. We used functional magnetic resonance imaging (fMRI) to characterize functional connectivity during processing of food and monetary rewards. Thirty-nine adults with excess weight and 37 adults with normal weight performed the Willingness to Pay for Food task and the Monetary Incentive Delay task in the fMRI scanner. A data-driven graph approach was applied to compare whole-brain, task-related functional connectivity between groups. Excess weight was associated with decreased functional connectivity during the processing of food rewards in a network involving primarily frontal and striatal areas, and increased functional connectivity during the processing of monetary rewards in a network involving principally frontal and parietal areas. These two networks were topologically and anatomically distinct, and were independently associated with BMI. The processing of food and monetary rewards involve segregated neural networks, and both are altered in individuals with excess weight. Copyright © 2016 Elsevier Inc. All rights reserved.
Chang, Chia-Ming; Yang, Yi-Ping; Chuang, Jen-Hua; Chuang, Chi-Mu; Lin, Tzu-Wei; Wang, Peng-Hui; Yu, Mu-Hsien
2017-01-01
The clinical characteristics of clear cell carcinoma (CCC) and endometrioid carcinoma EC) are concomitant with endometriosis (ES), which leads to the postulation of malignant transformation of ES to endometriosis-associated ovarian carcinoma (EAOC). Different deregulated functional areas were proposed accounting for the pathogenesis of EAOC transformation, and there is still a lack of a data-driven analysis with the accumulated experimental data in publicly-available databases to incorporate the deregulated functions involved in the malignant transformation of EOAC. We used the microarray gene expression datasets of ES, CCC and EC downloaded from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database. Then, we investigated the pathogenesis of EAOC by a data-driven, function-based analytic model with the quantified molecular functions defined by 1454 Gene Ontology (GO) term gene sets. This model converts the gene expression profiles to the functionome consisting of 1454 quantified GO functions, and then, the key functions involving the malignant transformation of EOAC can be extracted by a series of filters. Our results demonstrate that the deregulated oxidoreductase activity, metabolism, hormone activity, inflammatory response, innate immune response and cell-cell signaling play the key roles in the malignant transformation of EAOC. These results provide the evidence supporting the specific molecular pathways involved in the malignant transformation of EAOC. PMID:29113136
Functional integrative levels in the human interactome recapitulate organ organization.
Souiai, Ouissem; Becker, Emmanuelle; Prieto, Carlos; Benkahla, Alia; De las Rivas, Javier; Brun, Christine
2011-01-01
Interactome networks represent sets of possible physical interactions between proteins. They lack spatio-temporal information by construction. However, the specialized functions of the differentiated cell types which are assembled into tissues or organs depend on the combinatorial arrangements of proteins and their physical interactions. Is tissue-specificity, therefore, encoded within the interactome? In order to address this question, we combined protein-protein interactions, expression data, functional annotations and interactome topology. We first identified a subnetwork formed exclusively of proteins whose interactions were observed in all tested tissues. These are mainly involved in housekeeping functions and are located at the topological center of the interactome. This 'Largest Common Interactome Network' represents a 'functional interactome core'. Interestingly, two types of tissue-specific interactions are distinguished when considering function and network topology: tissue-specific interactions involved in regulatory and developmental functions are central whereas tissue-specific interactions involved in organ physiological functions are peripheral. Overall, the functional organization of the human interactome reflects several integrative levels of functions with housekeeping and regulatory tissue-specific functions at the center and physiological tissue-specific functions at the periphery. This gradient of functions recapitulates the organization of organs, from cells to organs. Given that several gradients have already been identified across interactomes, we propose that gradients may represent a general principle of protein-protein interaction network organization.
Narvaez, Joana C M; Pechansky, Flávio; Jansen, Karen; Pinheiro, Ricardo T; Silva, Ricardo A; Kapczinski, Flávio; Magalhães, Pedro V
2015-01-01
To assess the relationship between crack cocaine use and dimensions of quality of life and social functioning in young adults. This was a cross-sectional, population-based study involving 1,560 participants in Pelotas, Brazil. Crack cocaine use and abuse were investigated using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) inventory. Outcomes of interest were quality of life, religiosity, and social functioning in terms of education, occupational status, family structure, and medical treatment history. Lifetime crack cocaine use was associated with poor quality of life, worse functioning, impaired academic performance, and lower religious involvement. A greater maternal presence and higher paternal absence were more also more pronounced in crack cocaine users, who were also more likely to seek psychological and psychiatric treatment than the general population. Quality of life was severely impacted by crack cocaine use, especially in terms of general and physical health. Social functioning also differed between the general population and crack users, who had lower educational attainment and religious involvement. Maternal presence, paternal absence, and mental health-seeking behaviors were also more frequent among crack cocaine users, although these individuals reported lower rates of treatment satisfaction. Crack cocaine users also had significant social impairment, so that interventions involving family management and a greater focus on general health, quality of life, and functioning may make crucial contributions to the recovery of this group.
Functional Measurement: An Incredibly Flexible Tool
ERIC Educational Resources Information Center
Mullet, Etienne; Morales Martinez, Guadalupe Elizabeth; Makris, Ioannis; Roge, Bernadette; Munoz Sastre, Maria Teresa
2012-01-01
Functional Measurement (FM) has been applied to a variety of settings that can be considered as "extreme" settings; that is, settings involving participants with severe cognitive disabilities or involving unusual stimulus material. FM has, as instance, been successfully applied for analyzing (a) numerosity judgments among children as…
Evaluation of Language Function under Awake Craniotomy
KANNO, Aya; MIKUNI, Nobuhiro
2015-01-01
Awake craniotomy is the only established way to assess patients’ language functions intraoperatively and to contribute to their preservation, if necessary. Recent guidelines have enabled the approach to be used widely, effectively, and safely. Non-invasive brain functional imaging techniques, including functional magnetic resonance imaging and diffusion tensor imaging, have been used preoperatively to identify brain functional regions corresponding to language, and their accuracy has increased year by year. In addition, the use of neuronavigation that incorporates this preoperative information has made it possible to identify the positional relationships between the lesion and functional regions involved in language, conduct functional brain mapping in the awake state with electrical stimulation, and intraoperatively assess nerve function in real time when resecting the lesion. This article outlines the history of awake craniotomy, the current state of pre- and intraoperative evaluation of language function, and the clinical usefulness of such functional evaluation. When evaluating patients’ language functions during awake craniotomy, given the various intraoperative stresses involved, it is necessary to carefully select the tasks to be undertaken, quickly perform all examinations, and promptly evaluate the results. As language functions involve both input and output, they are strongly affected by patients’ preoperative cognitive function, degree of intraoperative wakefulness and fatigue, the ability to produce verbal articulations and utterances, as well as perform synergic movement. Therefore, it is essential to appropriately assess the reproducibility of language function evaluation using awake craniotomy techniques. PMID:25925758
Evaluation of Language Function under Awake Craniotomy.
Kanno, Aya; Mikuni, Nobuhiro
2015-01-01
Awake craniotomy is the only established way to assess patients' language functions intraoperatively and to contribute to their preservation, if necessary. Recent guidelines have enabled the approach to be used widely, effectively, and safely. Non-invasive brain functional imaging techniques, including functional magnetic resonance imaging and diffusion tensor imaging, have been used preoperatively to identify brain functional regions corresponding to language, and their accuracy has increased year by year. In addition, the use of neuronavigation that incorporates this preoperative information has made it possible to identify the positional relationships between the lesion and functional regions involved in language, conduct functional brain mapping in the awake state with electrical stimulation, and intraoperatively assess nerve function in real time when resecting the lesion. This article outlines the history of awake craniotomy, the current state of pre- and intraoperative evaluation of language function, and the clinical usefulness of such functional evaluation. When evaluating patients' language functions during awake craniotomy, given the various intraoperative stresses involved, it is necessary to carefully select the tasks to be undertaken, quickly perform all examinations, and promptly evaluate the results. As language functions involve both input and output, they are strongly affected by patients' preoperative cognitive function, degree of intraoperative wakefulness and fatigue, the ability to produce verbal articulations and utterances, as well as perform synergic movement. Therefore, it is essential to appropriately assess the reproducibility of language function evaluation using awake craniotomy techniques.
Small-spot laser-exposure effects on visual function
NASA Astrophysics Data System (ADS)
Zwick, Harry; Robbins, David O.; Stuck, Bruce E.; Lund, David J.; Reynolds, Scottie B.; Nawim, Maqsood; Schuschereba, Steven T.
1990-07-01
Laser field exposure effects on visual function involve produc tJon of minimal spot irradiation on or near the huntan fovea. Functional effects of such exposure may involve transient or perinanent change in visual function depending upon exposure dose. While Maximun Permissible Exposure (MPE) lirrtits define exposure in terins of threshold retinal niorphological change such limits are not applicable with regard to transient changes in visual function below MPE limits induced by alteration in retinal physiological processes. Mechanisms of transient and permanent functional change reported in these exper iments point out the need to examine laser safety limits in terms of both the functional as well as the morphological disturbance induced in retinal tissue. L
2013-01-01
Background Understanding the function of a particular gene under various stresses is important for engineering plants for broad-spectrum stress tolerance. Although virus-induced gene silencing (VIGS) has been used to characterize genes involved in abiotic stress tolerance, currently available gene silencing and stress imposition methodology at the whole plant level is not suitable for high-throughput functional analyses of genes. This demands a robust and reliable methodology for characterizing genes involved in abiotic and multi-stress tolerance. Results Our methodology employs VIGS-based gene silencing in leaf disks combined with simple stress imposition and effect quantification methodologies for easy and faster characterization of genes involved in abiotic and multi-stress tolerance. By subjecting leaf disks from gene-silenced plants to various abiotic stresses and inoculating silenced plants with various pathogens, we show the involvement of several genes for multi-stress tolerance. In addition, we demonstrate that VIGS can be used to characterize genes involved in thermotolerance. Our results also showed the functional relevance of NtEDS1 in abiotic stress, NbRBX1 and NbCTR1 in oxidative stress; NtRAR1 and NtNPR1 in salinity stress; NbSOS1 and NbHSP101 in biotic stress; and NtEDS1, NbETR1, NbWRKY2 and NbMYC2 in thermotolerance. Conclusions In addition to widening the application of VIGS, we developed a robust, easy and high-throughput methodology for functional characterization of genes involved in multi-stress tolerance. PMID:24289810
Jona, Celine M H; Labuschagne, Izelle; Mercieca, Emily-Clare; Fisher, Fiona; Gluyas, Cathy; Stout, Julie C; Andrews, Sophie C
2017-01-01
Family functioning in Huntington's disease (HD) is known from previous studies to be adversely affected. However, which aspects of family functioning are disrupted is unknown, limiting the empirical basis around which to create supportive interventions. The aim of the current study was to assess family functioning in HD families. We assessed family functioning in 61 participants (38 HD gene-expanded participants and 23 family members) using the McMaster Family Assessment Device (FAD; Epstein, Baldwin and Bishop, 1983), which provides scores for seven domains of functioning: Problem Solving; Communication; Affective Involvement; Affective Responsiveness; Behavior Control; Roles; and General Family Functioning. The most commonly reported disrupted domain for HD participants was Affective Involvement, which was reported by 39.5% of HD participants, followed closely by General Family Functioning (36.8%). For family members, the most commonly reported dysfunctional domains were Affective Involvement and Communication (both 52.2%). Furthermore, symptomatic HD participants reported more disruption to Problem Solving than pre-symptomatic HD participants. In terms of agreement between pre-symptomatic and symptomatic HD participants and their family members, all domains showed moderate to very good agreement. However, on average, family members rated Communication as more disrupted than their HD affected family member. These findings highlight the need to target areas of emotional engagement, communication skills and problem solving in family interventions in HD.
Jona, Celine M.H.; Labuschagne, Izelle; Mercieca, Emily-Clare; Fisher, Fiona; Gluyas, Cathy; Stout, Julie C.; Andrews, Sophie C.
2017-01-01
Background: Family functioning in Huntington’s disease (HD) is known from previous studies to be adversely affected. However, which aspects of family functioning are disrupted is unknown, limiting the empirical basis around which to create supportive interventions. Objective: The aim of the current study was to assess family functioning in HD families. Methods: We assessed family functioning in 61 participants (38 HD gene-expanded participants and 23 family members) using the McMaster Family Assessment Device (FAD; Epstein, Baldwin and Bishop, 1983), which provides scores for seven domains of functioning: Problem Solving; Communication; Affective Involvement; Affective Responsiveness; Behavior Control; Roles; and General Family Functioning. Results: The most commonly reported disrupted domain for HD participants was Affective Involvement, which was reported by 39.5% of HD participants, followed closely by General Family Functioning (36.8%). For family members, the most commonly reported dysfunctional domains were Affective Involvement and Communication (both 52.2%). Furthermore, symptomatic HD participants reported more disruption to Problem Solving than pre-symptomatic HD participants. In terms of agreement between pre-symptomatic and symptomatic HD participants and their family members, all domains showed moderate to very good agreement. However, on average, family members rated Communication as more disrupted than their HD affected family member. Conclusion: These findings highlight the need to target areas of emotional engagement, communication skills and problem solving in family interventions in HD. PMID:28968240
Audiovisual Integration in High Functioning Adults with Autism
ERIC Educational Resources Information Center
Keane, Brian P.; Rosenthal, Orna; Chun, Nicole H.; Shams, Ladan
2010-01-01
Autism involves various perceptual benefits and deficits, but it is unclear if the disorder also involves anomalous audiovisual integration. To address this issue, we compared the performance of high-functioning adults with autism and matched controls on experiments investigating the audiovisual integration of speech, spatiotemporal relations, and…
Ruiz, Montse C; Haapanen, Saara; Tolvanen, Asko; Robazza, Claudio; Duda, Joan L
2017-08-01
This study examined the relationships between perceptions of the motivational climate, motivation regulations, and the intensity and functionality levels of athletes' pleasant and unpleasant emotional states. Specifically, we examined the hypothesised mediational role of motivation regulations in the climate-emotion relationship. We also tested a sequence in which emotions were assumed to be predicted by the motivational climate dimensions and then served as antecedents to variability in motivation regulations. Participants (N = 494) completed a multi-section questionnaire assessing targeted variables. Structural equation modelling (SEM) revealed that a perceived task-involving climate was a positive predictor of autonomous motivation and of the impact of functional anger, and a negative predictor of the intensity of anxiety and dysfunctional anger. Autonomous motivation was a partial mediator of perceptions of a task-involving climate and the impact of functional anger. An ego-involving climate was a positive predictor of controlled motivation, and of the intensity and impact of functional anger and the intensity of dysfunctional anger. Controlled motivation partially mediated the relationship between an ego-involving climate and the intensity of dysfunctional anger. Good fit to the data also emerged for the motivational climate, emotional states, and motivation regulations sequence. Findings provide support for the consideration of hedonic tone and functionality distinctions in the assessment of athletes' emotional states.
Folinic acid treatment for schizophrenia associated with folate receptor autoantibodies.
Ramaekers, V T; Thöny, B; Sequeira, J M; Ansseau, M; Philippe, P; Boemer, F; Bours, V; Quadros, E V
2014-12-01
Auto-antibodies against folate receptor alpha (FRα) at the choroid plexus that block N(5)-methyltetrahydrofolate (MTHF) transfer to the brain were identified in catatonic schizophrenia. Acoustic hallucinations disappeared following folinic acid treatment. Folate transport to the CNS prevents homocysteine accumulation and delivers one-carbon units for methyl-transfer reactions and synthesis of purines. The guanosine derivative tetrahydrobiopterin acts as common co-factor for the enzymes producing dopamine, serotonin and nitric oxide. Our study selected patients with schizophrenia unresponsive to conventional treatment. Serum from these patients with normal plasma homocysteine, folate and vitamin B12 was tested for FR autoantibodies of the blocking type on serial samples each week. Spinal fluid was analyzed for MTHF and the metabolites of pterins, dopamine and serotonin. The clinical response to folinic acid treatment was evaluated. Fifteen of 18 patients (83.3%) had positive serum FR auto-antibodies compared to only 1 in 30 controls (3.3%) (χ(2)=21.6; p<0.0001). FRα antibody titers in patients fluctuated over time varying between negative and high titers, modulating folate flux to the CNS, which explained low CSF folate values in 6 and normal values in 7 patients. The mean±SD for CSF MTHF was diminished compared to previously established controls (t-test: 3.90; p=0.0002). A positive linear correlation existed between CSF MTHF and biopterin levels. CSF dopamine and serotonin metabolites were low or in the lower normal range. Administration of folinic acid (0.3-1mg/kg/day) to 7 participating patients during at least six months resulted in clinical improvement. Assessment of FR auto-antibodies in serum is recommended for schizophrenic patients. Clinical negative or positive symptoms are speculated to be influenced by the level and evolution of FRα antibody titers which determine folate flux to the brain with up- or down-regulation of brain folate intermediates linked to metabolic processes affecting homocysteine levels, synthesis of tetrahydrobiopterin and neurotransmitters. Folinic acid intervention appears to stabilize the disease process. Copyright © 2014 Elsevier Inc. All rights reserved.
Ares, Gastón; Besio, Mariángela; Giménez, Ana; Deliza, Rosires
2010-10-01
Consumers perceive functional foods as member of the particular food category to which they belong. In this context, apart from health and sensory characteristics, non-sensory factors such as packaging might have a key role on determining consumers' purchase decisions regarding functional foods. The aims of the present work were to study the influence of different package attributes on consumer willingness to purchase regular and functional chocolate milk desserts; and to assess if the influence of these attributes was affected by consumers' level of involvement with the product. A conjoint analysis task was carried out with 107 regular milk desserts consumers, who were asked to score their willingness to purchase of 16 milk dessert package concepts varying in five features of the package, and to complete a personal involvement inventory questionnaire. Consumers' level of involvement with the product affected their interest in the evaluated products and their reaction towards the considered conjoint variables, suggesting that it could be a useful segmentation tool during food development. Package colour and the presence of a picture on the label were the variables with the highest relative importance, regardless of consumers' involvement with the product. The importance of these variables was higher than the type of dessert indicating that packaging may play an important role in consumers' perception and purchase intention of functional foods.
Functional Integrative Levels in the Human Interactome Recapitulate Organ Organization
Prieto, Carlos; Benkahla, Alia; De Las Rivas, Javier; Brun, Christine
2011-01-01
Interactome networks represent sets of possible physical interactions between proteins. They lack spatio-temporal information by construction. However, the specialized functions of the differentiated cell types which are assembled into tissues or organs depend on the combinatorial arrangements of proteins and their physical interactions. Is tissue-specificity, therefore, encoded within the interactome? In order to address this question, we combined protein-protein interactions, expression data, functional annotations and interactome topology. We first identified a subnetwork formed exclusively of proteins whose interactions were observed in all tested tissues. These are mainly involved in housekeeping functions and are located at the topological center of the interactome. This ‘Largest Common Interactome Network’ represents a ‘functional interactome core’. Interestingly, two types of tissue-specific interactions are distinguished when considering function and network topology: tissue-specific interactions involved in regulatory and developmental functions are central whereas tissue-specific interactions involved in organ physiological functions are peripheral. Overall, the functional organization of the human interactome reflects several integrative levels of functions with housekeeping and regulatory tissue-specific functions at the center and physiological tissue-specific functions at the periphery. This gradient of functions recapitulates the organization of organs, from cells to organs. Given that several gradients have already been identified across interactomes, we propose that gradients may represent a general principle of protein-protein interaction network organization. PMID:21799769
ERIC Educational Resources Information Center
Miller, Duane I.
1980-01-01
Studied how egalitaranism and success through individual achievement, were expressed in the involvement of others in consumer decisions. Results found egalitarians involved others in seeking more information. Individual achievement subjects delegated more decision responsibility for non-ego involving decisions. Suggests involvement of others could…
Variations in the perceptions of peer and coach motivational climate.
Vazou, Spiridoula
2010-06-01
This study examined (a) variations in the perceptions of peer- and coach-generated motivational climate within and between teams and (b) individual- and group-level factors that can account for these variations. Participants were 483 athletes between 12 and 16 years old. The results showed that perceptions of both peer- and coach-generated climate varied as a function of group-level variables, namely team success, coach's gender (except for peer ego-involving climate), and team type (only for coach ego-involving climate). Perceptions of peer- and coach-generated climate also varied as a function of individual-level variables, namely athletes' task and ego orientations, gender, and age (only for coach task-involving and peer ego-involving climate). Moreover, within-team variations in perceptions of peer- and coach-generated climate as a function of task and ego orientation levels were identified. Identifying and controlling the factors that influence perceptions of peer- and coach-generated climate may be important in strengthening task-involving motivational cues.
Cheng, Wei; Rolls, Edmund T; Qiu, Jiang; Liu, Wei; Tang, Yanqing; Huang, Chu-Chung; Wang, XinFa; Zhang, Jie; Lin, Wei; Zheng, Lirong; Pu, JunCai; Tsai, Shih-Jen; Yang, Albert C; Lin, Ching-Po; Wang, Fei; Xie, Peng; Feng, Jianfeng
2016-12-01
The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial orbitofrontal cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal cortex Brodmann area 36 and entorhinal cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial orbitofrontal cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The lateral orbitofrontal cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the lateral orbitofrontal cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 with these three brain areas was lower in the medicated than the unmedicated patients. This is consistent with the hypothesis that the increased functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 is related to depression. Relating the changes in cortical connectivity to our understanding of the functions of different parts of the orbitofrontal cortex in emotion helps to provide new insight into the brain changes related to depression. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Computations involving differential operators and their actions on functions
NASA Technical Reports Server (NTRS)
Crouch, Peter E.; Grossman, Robert; Larson, Richard
1991-01-01
The algorithms derived by Grossmann and Larson (1989) are further developed for rewriting expressions involving differential operators. The differential operators involved arise in the local analysis of nonlinear dynamical systems. These algorithms are extended in two different directions: the algorithms are generalized so that they apply to differential operators on groups and the data structures and algorithms are developed to compute symbolically the action of differential operators on functions. Both of these generalizations are needed for applications.
Huang, Meng; Baskin, David S; Fung, Steve
2016-05-01
Rapid word recognition and reading fluency is a specialized cortical process governed by the visual word form area (VWFA), which is localized to the dominant posterior lateral occipitotemporal sulcus/fusiform gyrus. A lesion of the VWFA results in pure alexia without agraphia characterized by letter-by-letter reading. Palinopsia is a visual processing distortion characterized by persistent afterimages and has been reported in lesions involving the nondominant occipitotemporal cortex. A 67-year-old right-handed woman with no neurologic history presented to our emergency department with acute cortical ischemic symptoms that began with a transient episode of receptive aphasia. She also reported inability to read, albeit with retained writing ability. She also saw afterimages of objects. During her stroke workup, an intra-axial circumscribed enhancing mass lesion was discovered involving her dominant posterolateral occipitotemporal lobe. Given the eloquent brain involvement, she underwent preoperative functional magnetic resonance imaging with diffusion tensor imaging tractography and awake craniotomy to maximize resection and preserve function. Many organic lesions involving these regions have been reported in the literature, but to the best of our knowledge, glioblastoma involving the VWFA resulting in both clinical syndromes of pure alexia and palinopsia with superimposed functional magnetic resonance imaging and fiber tract mapping has never been reported before. Copyright © 2015 Elsevier Inc. All rights reserved.
Empowerment through public involvement functional interactive planning (PIFIP)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Beck, J. E.; Davidson, S. A.
1993-05-01
This paper constructs a planning process that will enable private industries, government, and public interest organizations to actualize their visions. The public involvement functional interactive planning (PIFIP) model can facilitate these groups in actualizing their visions by forcing them to recognize their stakeholder`s values, interests and expectations.
Self-Determination and Student Involvement in Functional Assessment: Innovative Practices
ERIC Educational Resources Information Center
Wehmeyer, Michael L.; Baker, Daniel J.; Blumberg, Richard; Harrison, Richard
2004-01-01
The fundamental feature that distinguishes positive behavior support (PBS) from previous generations of applied behavior analysis is its focus on the remediation of deficient contexts that are determined to be the source of the problem. Determining this source involves conducting a functional assessment. This innovative practices article presents…
Children on the Autism Spectrum: Grandmother Involvement and Family Functioning
ERIC Educational Resources Information Center
Sullivan, Alison; Winograd, Greta; Verkuilen, Jay; Fish, Marian C.
2012-01-01
Background: This study investigated associations between the presence of a child with autism or Asperger's disorder in the family, family functioning and grandmother experiences with the goal of better understanding grandparent involvement in the lives of grandchildren on the autism spectrum and their families. Methods: Mothers and grandmothers of…
Hansen, Jennifer A; Weissbrod, Carol; Schwartz, David D; Taylor, W Patrick
2012-03-01
Psychological functioning in fathers of children with Type 1 diabetes has received relatively little attention compared to mothers. This study examined fathers' perceived involvement in their children's diabetes care as it related to mothers' and fathers' pediatric parenting stress, depression, anxiety, marital satisfaction, and sleep, and to their children's diabetes regimen adherence and glycemic control. Eighty-two mothers and 43 fathers completed questionnaires. Multivariate linear regressions were conducted separately for mothers and fathers to determine the relationships between the perceived amount and the perceived helpfulness of father involvement in child diabetes care on parental psychosocial functioning and child diabetes control. Maternal perceptions of father helpfulness and amount of involvement in illness care were related to improved marital satisfaction and fewer depressive symptoms in mothers. In fathers, perception of their own amount of involvement was related to increased pediatric parenting stress and anxiety. Better child regimen adherence was associated with maternal perceptions of father helpfulness but not the amount of their involvement, while paternal perceptions of their own helpfulness were related to poorer glycemic control. These findings suggest that fathers and mothers may react differently to their roles in childhood illness and that perceptions of their involvement may be differently associated with children's glycemic control and regimen adherence.
Buddhist social networks and health in old age: A study in central Thailand.
Sasiwongsaroj, Kwanchit; Wada, Taizo; Okumiya, Kiyohito; Imai, Hissei; Ishimoto, Yasuko; Sakamoto, Ryota; Fujisawa, Michiko; Kimura, Yumi; Chen, Wen-ling; Fukutomi, Eriko; Matsubayashi, Kozo
2015-11-01
Religious social networks are well known for their capacity to improve individual health, yet the effects of friendship networks within the Buddhist context remain largely unknown. The present study aimed to compare health status and social support in community-dwelling older adults according to their level of Buddhist social network (BSN) involvement, and to examine the association between BSN involvement and functional health among older adults. A cross-sectional survey was carried out among 427 Buddhist community-dwelling older adults aged ≥60 years in Nakhon Pathom, Thailand. Data were collected from home-based personal interviews using a structured questionnaire. Health status was defined according to the measures of basic and advanced activities of daily living (ADL), the 15-item Geriatric Depression Scale and subjective quality of life. Perceived social support was assessed across the four dimensions of tangible, belonging, emotional and information support. Multiple logistic regression was used for analysis. Older adults with BSN involvement reported better functional, mental and social health status, and perceived greater social support than those without BSN involvement. In addition, BSN involvement was positively associated with independence in basic and advanced ADL. After adjusting for age, sex, education, income, morbidity and depressive symptoms, BSN showed a strong association with advanced ADL and a weak association with basic ADL. The results show that involvement in BSN could contribute positively to functional health, particularly with regard to advanced ADL. Addressing the need for involvement in these networks by older adults might help delay functional decline and save on healthcare costs. © 2014 Japan Geriatrics Society.
ERIC Educational Resources Information Center
Wilson, Damali M.; Gross, Deborah
2018-01-01
Background: Parents' involvement in their children's education is integral to academic success. Several education-based organizations have identified recommendations for how parents can best support their children's learning. However, executive functioning (EF), a high-ordered cognitive skill set, contributes to the extent to which parents can…
49 CFR 382.303 - Post-accident testing.
Code of Federal Regulations, 2013 CFR
2013-10-01
... functions with respect to the vehicle, if the accident involved the loss of human life; or (2) Who receives a citation within 8 hours of the occurrence under State or local law for a moving traffic violation... performing safety-sensitive functions with respect to the vehicle, if the accident involved the loss of human...
Calculus Limits Involving Infinity: The Role of Students' Informal Dynamic Reasoning
ERIC Educational Resources Information Center
Jones, Steven R.
2015-01-01
Few studies on calculus limits have centred their focus on student understanding of limits at infinity or infinite limits that involve continuous functions (as opposed to discrete sequences). This study examines student understanding of these types of limits using both pure mathematics and applied-science functions and formulas. Seven calculus…
ERIC Educational Resources Information Center
Brown, Jonathan D.; Riley, Anne W.; Walrath, Christine M.; Leaf, Philip J.; Valdez, Carmen
2008-01-01
The relationship between academic problems and delinquency is well documented among incarcerated populations but has not been examined among nonincarcerated youth involved with the juvenile justice system. This research examined the school functioning and academic achievement of 157 youth who had brief contact with a state department of juvenile…
NASA Astrophysics Data System (ADS)
Baricz, Árpád
2008-04-01
In this paper we study the monotonicity properties of some functions involving the Mills' ratio of the standard normal law. From these we deduce some new functional inequalities involving the Mills' ratio, and we show that the Mills' ratio is strictly completely monotonic. At the end of this paper we present some Turán-type inequalities for Mills' ratio.
49 CFR 382.303 - Post-accident testing.
Code of Federal Regulations, 2010 CFR
2010-10-01
... functions with respect to the vehicle, if the accident involved the loss of human life; or (2) Who receives... performing safety-sensitive functions with respect to the vehicle, if the accident involved the loss of human life; or (2) Who receives a citation within thirty-two hours of the occurrence under State or local law...
Proposal and Validation of an Entrepreneur Competency Profile: Implications for Education
ERIC Educational Resources Information Center
Alda-Varas, Rodrigo; Villardon-Gallego, Lourdes; Elexpuru-Albizuri, Itziar
2012-01-01
Introduction: This research presents the validated proposal of an entrepreneur competency profile. We analyzed the phases of the entrepreneurial process, and the functions involved in each of them, in order to identify the tasks involved in each function/role and consequently the specific competencies of entrepreneurs. Method: The proposal was…
Predicting the Academic Functioning of Youth Involved in Residential Care
ERIC Educational Resources Information Center
Griffith, Annette K.; Trout, Alexandra L.; Epstein, Michael H.; Garbin, Calvin P.; Pick, Robert; Wright, Tanya
2010-01-01
Youth involved in residential care programs present with significant difficulties across behavioral and mental health domains. Although this is a group that is also at considerable risk for academic failure, very little research has been done to understand the academic functioning of this population. The current study sought to expand what is…
Schlack, Robert; Ravens-Sieberer, Ulrike; Petermann, Franz
2013-06-01
This study investigates self-rated mental health in terms of psychological problems, protective factors and health-related quality of life (HRQOL) in a nationally representative sample of adolescents (n=6813) aged 11-17 involved in violence with varying frequency. Using MANCOVA and ANCOVA, youth with single and multiple histories of violent victimisation and violence perpetration were contrasted with non-involved comparisons. The results show that even low levels of violence involvement were associated with more problems, fewer protective factors and impaired HRQOL. Multiply victimised youth - not perpetrating victims - stood out with internalising, peer and hyperactivity/inattention problems. Discriminant function analysis separated non-involved from violence-affected youth, and multiply victimised from not multiply victimised youth. Externalising behaviours, family issues, male sex and school functioning predicted group separation on the first function (proportion variance explained 80.0%), while internalising and peer issues were predictive for the second function (PVE 14.2%). Implications for prevention, intervention and research are discussed. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.
The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology
Mallet, François; Bouton, Olivier; Prudhomme, Sarah; Cheynet, Valérie; Oriol, Guy; Bonnaud, Bertrand; Lucotte, Gérard; Duret, Laurent; Mandrand, Bernard
2004-01-01
The definitive demonstration of a role for a recently acquired gene is a difficult task, requiring exhaustive genetic investigations and functional analysis. The situation is indeed much more complicated when facing multicopy gene families, because most or portions of the gene are conserved among the hundred copies of the family. This is the case for the ERVWE1 locus of the human endogenous retrovirus W family (HERV-W), which encodes an envelope glycoprotein (syncytin) likely involved in trophoblast differentiation. Here we describe, in 155 individuals, the positional conservation of this locus and the preservation of the envelope ORF. Sequencing of the critical elements of the ERVWE1 provirus showed a striking conservation among the 48 alleles of 24 individuals, including the LTR elements involved in the transcriptional machinery, the splice sites involved in the maturation of subgenomic Env mRNA, and the Env ORF. The functionality and tissue specificity of the 5′ LTR were demonstrated, as well as the fusogenic activity of the envelope polymorphic variants. Such functions were also shown to be preserved in the orthologous loci isolated from chimpanzee, gorilla, orangutan, and gibbon. This functional preservation among humans and during evolution strongly argued for the involvement of this recently acquired retroviral envelope glycoprotein in hominoid placental physiology. PMID:14757826
Benefits of Simulation and Role-Playing to Teach Performance of Functional Assessments.
Trail Ross, Mary Ellen; Otto, Dorothy A; Stewart Helton, Anne
The use of simulation is an innovative teaching strategy that has proven to be valuable in nursing education. This article describes the benefits of a simulation lab involving faculty role-play to teach baccalaureate nursing students how to properly assess the functional status of older adults. Details about the simulation lab, which involved functional assessments of two elderly community-dwelling residents, are presented, along with student and faculty evaluations of this teaching modality.
Two distinct clinical courses of renal involvement in rheumatoid patients with AA amyloidosis.
Uda, Hiroshi; Yokota, Akira; Kobayashi, Kumiko; Miyake, Tadao; Fushimi, Hiroaki; Maeda, Akira; Saiki, Osamu
2006-08-01
We conducted a prospective study to investigate whether a correlation exists between the clinical course of renal involvement and the pathological findings of renal amyloidosis in patients with rheumatoid arthritis (RA). Patients with RA of more than 5 years' duration and who did not show renal manifestations were selected and received a duodenal biopsy for the diagnosis of amyloidosis. After the diagnosis of AA amyloidosis, patients received a renal biopsy, and patterns of amyloid deposition were examined. We followed the renal functions (serum levels of blood urea nitrogen and creatinine) of patients diagnosed with AA amyloidosis for 5 years. We diagnosed 53 patients with AA amyloidosis and monitored the renal function of 38 of them for > 5 years. The histological patterns were examined; in the 38 patients there were appreciable variations in the patterns of amyloid deposition. In 27 patients, amyloid deposits were found exclusively in the glomerulus (type 1). In the other 11 patients, however, amyloid deposits were found selectively around blood vessels and were totally absent in the glomerulus (type 2). In type 1 patients with glomerular involvement, renal function deteriorated rapidly regardless of disease state; most patients received hemodialysis. In type 2 patients with purely vascular involvement, however, renal function did not deteriorate significantly. In patients with RA and AA amyloidosis, 2 distinct clinical courses in terms of renal involvement were identified. It is suggested that renal function does not deteriorate when amyloid deposition is totally lacking in the glomerulus.
Task modulates functional connectivity networks in free viewing behavior.
Seidkhani, Hossein; Nikolaev, Andrey R; Meghanathan, Radha Nila; Pezeshk, Hamid; Masoudi-Nejad, Ali; van Leeuwen, Cees
2017-10-01
In free visual exploration, eye-movement is immediately followed by dynamic reconfiguration of brain functional connectivity. We studied the task-dependency of this process in a combined visual search-change detection experiment. Participants viewed two (nearly) same displays in succession. First time they had to find and remember multiple targets among distractors, so the ongoing task involved memory encoding. Second time they had to determine if a target had changed in orientation, so the ongoing task involved memory retrieval. From multichannel EEG recorded during 200 ms intervals time-locked to fixation onsets, we estimated the functional connectivity using a weighted phase lag index at the frequencies of theta, alpha, and beta bands, and derived global and local measures of the functional connectivity graphs. We found differences between both memory task conditions for several network measures, such as mean path length, radius, diameter, closeness and eccentricity, mainly in the alpha band. Both the local and the global measures indicated that encoding involved a more segregated mode of operation than retrieval. These differences arose immediately after fixation onset and persisted for the entire duration of the lambda complex, an evoked potential commonly associated with early visual perception. We concluded that encoding and retrieval differentially shape network configurations involved in early visual perception, affecting the way the visual input is processed at each fixation. These findings demonstrate that task requirements dynamically control the functional connectivity networks involved in early visual perception. Copyright © 2017 Elsevier Inc. All rights reserved.
Realistic simulated MRI and SPECT databases. Application to SPECT/MRI registration evaluation.
Aubert-Broche, Berengere; Grova, Christophe; Reilhac, Anthonin; Evans, Alan C; Collins, D Louis
2006-01-01
This paper describes the construction of simulated SPECT and MRI databases that account for realistic anatomical and functional variability. The data is used as a gold-standard to evaluate four SPECT/MRI similarity-based registration methods. Simulation realism was accounted for using accurate physical models of data generation and acquisition. MRI and SPECT simulations were generated from three subjects to take into account inter-subject anatomical variability. Functional SPECT data were computed from six functional models of brain perfusion. Previous models of normal perfusion and ictal perfusion observed in Mesial Temporal Lobe Epilepsy (MTLE) were considered to generate functional variability. We studied the impact noise and intensity non-uniformity in MRI simulations and SPECT scatter correction may have on registration accuracy. We quantified the amount of registration error caused by anatomical and functional variability. Registration involving ictal data was less accurate than registration involving normal data. MR intensity nonuniformity was the main factor decreasing registration accuracy. The proposed simulated database is promising to evaluate many functional neuroimaging methods, involving MRI and SPECT data.
Analysis of sequence repeats of proteins in the PDB.
Mary Rajathei, David; Selvaraj, Samuel
2013-12-01
Internal repeats in protein sequences play a significant role in the evolution of protein structure and function. Applications of different bioinformatics tools help in the identification and characterization of these repeats. In the present study, we analyzed sequence repeats in a non-redundant set of proteins available in the Protein Data Bank (PDB). We used RADAR for detecting internal repeats in a protein, PDBeFOLD for assessing structural similarity, PDBsum for finding functional involvement and Pfam for domain assignment of the repeats in a protein. Through the analysis of sequence repeats, we found that identity of the sequence repeats falls in the range of 20-40% and, the superimposed structures of the most of the sequence repeats maintain similar overall folding. Analysis sequence repeats at the functional level reveals that most of the sequence repeats are involved in the function of the protein through functionally involved residues in the repeat regions. We also found that sequence repeats in single and two domain proteins often contained conserved sequence motifs for the function of the domain. Copyright © 2013 Elsevier Ltd. All rights reserved.
Visual Learning Alters the Spontaneous Activity of the Resting Human Brain: An fNIRS Study
Niu, Haijing; Li, Hao; Sun, Li; Su, Yongming; Huang, Jing; Song, Yan
2014-01-01
Resting-state functional connectivity (RSFC) has been widely used to investigate spontaneous brain activity that exhibits correlated fluctuations. RSFC has been found to be changed along the developmental course and after learning. Here, we investigated whether and how visual learning modified the resting oxygenated hemoglobin (HbO) functional brain connectivity by using functional near-infrared spectroscopy (fNIRS). We demonstrate that after five days of training on an orientation discrimination task constrained to the right visual field, resting HbO functional connectivity and directed mutual interaction between high-level visual cortex and frontal/central areas involved in the top-down control were significantly modified. Moreover, these changes, which correlated with the degree of perceptual learning, were not limited to the trained left visual cortex. We conclude that the resting oxygenated hemoglobin functional connectivity could be used as a predictor of visual learning, supporting the involvement of high-level visual cortex and the involvement of frontal/central cortex during visual perceptual learning. PMID:25243168
Visual learning alters the spontaneous activity of the resting human brain: an fNIRS study.
Niu, Haijing; Li, Hao; Sun, Li; Su, Yongming; Huang, Jing; Song, Yan
2014-01-01
Resting-state functional connectivity (RSFC) has been widely used to investigate spontaneous brain activity that exhibits correlated fluctuations. RSFC has been found to be changed along the developmental course and after learning. Here, we investigated whether and how visual learning modified the resting oxygenated hemoglobin (HbO) functional brain connectivity by using functional near-infrared spectroscopy (fNIRS). We demonstrate that after five days of training on an orientation discrimination task constrained to the right visual field, resting HbO functional connectivity and directed mutual interaction between high-level visual cortex and frontal/central areas involved in the top-down control were significantly modified. Moreover, these changes, which correlated with the degree of perceptual learning, were not limited to the trained left visual cortex. We conclude that the resting oxygenated hemoglobin functional connectivity could be used as a predictor of visual learning, supporting the involvement of high-level visual cortex and the involvement of frontal/central cortex during visual perceptual learning.
Psychological commitment as a mediator of the relationship between involvement and loyalty
Joohyun Lee; Alan Graefe
2002-01-01
This study tested the ill-understood issues of involvement and loyalty relations. Even though many studies have indicated that loyalty is a function of involvement, only minimal agreement has been reached on the extent to which the constructs of involvement would predict repeat participation. A structural model is developed that relates members' involvement and...
Relationship between function of masticatory muscle in mouse and properties of muscle fibers.
Abe, Shinichi; Hiroki, Emi; Iwanuma, Osamu; Sakiyama, Koji; Shirakura, Yoshitaka; Hirose, Daiki; Shimoo, Yoshiaki; Suzuki, Masashi; Ikari, Yasutoyo; Kikuchi, Ryusuke; Ide, Yoshinobu; Yoshinari, Masao
2008-05-01
Mammals exhibit marked morphological differences in the muscles surrounding the jaw bone due to differences in eating habits. Furthermore, the myofiber properties of the muscles differ with function. Since the muscles in the oral region have various functions such as eating, swallowing, and speech, it is believed that the functional role of each muscle differs. Therefore, to clarify the functional role of each masticatory muscle, the myofiber properties of the adult mouse masticatory muscles were investigated at the transcriptional level. Expression of MyHC-2b with a fast contraction rate and strong force was frequently noted in the temporal and masseter muscles. This suggests that the temporal and masseter muscles are closely involved in rapid antero-posterior masticatory movement, which is characteristic in mice. Furthermore, expression of MyHC-1 with a low contraction rate and weak continuous force was frequently detected in the lateral pterygoid muscle. This suggests that, in contrast to other masticatory muscles, mouse lateral pterygoid muscle is not involved in fast masticatory movement, but is involved in functions requiring continuous force such as retention of jaw position. This study revealed that muscles with different roles function comprehensively during complicated masticatory movement.
Trust and Parents' Involvement in Schools of Choice
ERIC Educational Resources Information Center
Strier, Michal; Katz, Hagai
2016-01-01
Education researchers and policymakers have been focusing for the last three decades on increasing parental involvement in schools. Their work focused on the positive effects that parental involvement has on varied aspects of school quality and functioning. In this study we examined "trust," a known predictor of parental involvement in…
ERIC Educational Resources Information Center
Monti, Jennifer D.; Pomerantz, Eva M.; Roisman, Glenn I.
2014-01-01
Data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1,312) were analyzed to examine whether the adverse effects of early insensitive parenting on children's academic functioning can be offset by parents' later involvement in children's education. Observations of mothers' early…
ERIC Educational Resources Information Center
Grootscholten, Inge A. C.; van Wijngaarden, Bob; Kan, Cornelis C.
2018-01-01
Primary caregivers experience consequences from being in close contact to a person with autism spectrum disorder (ASD). This study used the Involvement Evaluation Questionnaire to explore the level of consequences of 104 caregivers involved with adults with High Functioning ASD (HF-ASD) and compared these with the consequences reported by…
ERIC Educational Resources Information Center
Schwartz, Seth J.; Finley, Gordon E.
2006-01-01
The present study was conducted to investigate differences in nurturant fathering, father involvement, and young adult psychosocial functioning among small samples of three nontraditional family forms. A total of 168 young-adult university students from three family forms (27 adoptive, 22 adoptive stepfather, 119 nonadoptive stepfather) completed…
ERIC Educational Resources Information Center
Tam, Vicky C. W.; Chan, Raymond M. C.
2011-01-01
This study examines the perceptions of Chinese students and parents in Hong Kong on homework involvement, assignment type and homework functions. The relationships of homework perceptions to student and parent attributes are also assessed. The sample includes 1393 pairs of students and their parents from 36 primary schools in Hong Kong. Findings…
ERIC Educational Resources Information Center
Perrachione, Tyler K.; Wong, Patrick C. M.
2007-01-01
Brain imaging studies of voice perception often contrast activation from vocal and verbal tasks to identify regions uniquely involved in processing voice. However, such a strategy precludes detection of the functional relationship between speech and voice perception. In a pair of experiments involving identifying voices from native and foreign…
Walker, Virginia L; Lyon, Kristin J; Loman, Sheldon L; Sennott, Samuel
2018-06-01
The purpose of this meta-analysis was to summarize single-case intervention studies in which Functional Communication Training (FCT) involving augmentative and alternative communication (AAC) was implemented in school settings. Overall, the findings suggest that FCT involving AAC was effective in reducing challenging behaviour and promoting aided or unaided AAC use among participants with disability. FCT was more effective for the participants who engaged in less severe forms of challenging behaviour prior to intervention. Additionally, FCT was more effective when informed by a descriptive functional behaviour assessment and delivered within inclusive school settings. Implications for practice and directions for future research related to FCT for students who use AAC are addressed.
A common network of functional areas for attention and eye movements
NASA Technical Reports Server (NTRS)
Corbetta, M.; Akbudak, E.; Conturo, T. E.; Snyder, A. Z.; Ollinger, J. M.; Drury, H. A.; Linenweber, M. R.; Petersen, S. E.; Raichle, M. E.; Van Essen, D. C.;
1998-01-01
Functional magnetic resonance imaging (fMRI) and surface-based representations of brain activity were used to compare the functional anatomy of two tasks, one involving covert shifts of attention to peripheral visual stimuli, the other involving both attentional and saccadic shifts to the same stimuli. Overlapping regional networks in parietal, frontal, and temporal lobes were active in both tasks. This anatomical overlap is consistent with the hypothesis that attentional and oculomotor processes are tightly integrated at the neural level.
A pilot study on factors involved with work participation in the early stages of multiple sclerosis.
Van der Hiele, Karin; Middelkoop, Huub A M; Ruimschotel, Rob; Kamminga, Noëlle G A; Visser, Leo H
2014-01-01
Up to 30% of recently diagnosed MS patients lose their jobs in the first four years after diagnosis. Taking into account the personal and socio-economic importance of sustaining employment, it is of the utmost importance to examine factors involved with work participation. To investigate differences in self-reported functioning in recently diagnosed MS patients with and without a paid job. Self-reports of physical and cognitive functioning, depression, anxiety and fatigue were gathered from 44 relapsing-remitting MS patients diagnosed within 3 years. Patients with a paid job (57%) reported better physical functioning (p<0.001), better memory functioning (p = 0.01) and a lower physical impact of fatigue (p = 0.018) than patients without a paid job. Physical functioning was the main predictor of employment status in a logistic regression model. In those with a paid job better memory functioning (r = 0.54, p = 0.005) and a lower social impact of fatigue (r = -0.46, p = 0.029) correlated with an increased number of working hours. Better physical functioning is the primary factor involved with increased work participation in early MS. Better self-reported memory functioning and less social fatigue were associated with increased working hours. These findings highlight the importance of battling these symptoms in the early stages of MS.
[Cognitive function in patients with systemic sclerosis].
Straszecka, J; Jonderko, G; Kucharz, E J; Brzezińska-Wcisło, L; Kotulska, A; Bogdanowski, T
1997-09-01
Central nervous system involvement is seldom reported in patients with systemic sclerosis (SSc). Cognitive functions were determined in 21 patients with definite SSc and 42 healthy controls. Thyroid function was also measured in order to eliminate the effect of hypothyroidism on cognitive functioning. It was found that the SSc patients with normal thyroid function showed defective long-term and recent memory, learning ability, criticism, perception and visuo-perceptual skills, their simple reaction time was prolonged. Similar but less advanced cognitive defects were shown in the SSc patients with overt or latent hypothyroidism. The obtained results indicate that the central nervous system involvement is more common in patients with SSc than it has been reported earlier.
Perry, Jennifer L.; Joseph, Jane E.; Jiang, Yang; Zimmerman, Rick S.; Kelly, Thomas H.; Darna, Mahesh; Huettl, Peter; Dwoskin, Linda P.; Bardo, Michael T.
2010-01-01
Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and primates. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences factors (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals. PMID:20837060
NASA Technical Reports Server (NTRS)
Fymat, A. L.; Kalaba, R. E.
1977-01-01
The original problem of anisotropic scattering in an atmosphere illuminated by a unidirectional source is replaced by an analogous formulation where the incident light is omnidirectional. A radiative-transfer equation for the omnidirectional case is obtained in which the direction of illumination plays no role and the source-function analog, Sobolev's (1972) source function Phi exponent m, contains only a single integral term. For radiation incident on the top or the bottom of the atmosphere, this equation involves the functions b exponent m and h exponent m, respectively, with m corresponding to the order of the harmonic component of the scattered radiation field; these two functions are shown to be only one through some simple reciprocity relations. The transfer problem is then reformulated for the function a exponent m, in which case the source-function analog (Sobolev's function D exponent m) involves incident direction.
Sex-related differences in amygdala functional connectivity during resting conditions.
Kilpatrick, L A; Zald, D H; Pardo, J V; Cahill, L F
2006-04-01
Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders.
Simple Test Functions in Meshless Local Petrov-Galerkin Methods
NASA Technical Reports Server (NTRS)
Raju, Ivatury S.
2016-01-01
Two meshless local Petrov-Galerkin (MLPG) methods based on two different trial functions but that use a simple linear test function were developed for beam and column problems. These methods used generalized moving least squares (GMLS) and radial basis (RB) interpolation functions as trial functions. These two methods were tested on various patch test problems. Both methods passed the patch tests successfully. Then the methods were applied to various beam vibration problems and problems involving Euler and Beck's columns. Both methods yielded accurate solutions for all problems studied. The simple linear test function offers considerable savings in computing efforts as the domain integrals involved in the weak form are avoided. The two methods based on this simple linear test function method produced accurate results for frequencies and buckling loads. Of the two methods studied, the method with radial basis trial functions is very attractive as the method is simple, accurate, and robust.
Religious involvement and health in dialysis patients in Saudi Arabia.
Al Zaben, Faten; Khalifa, Doaa Ahmed; Sehlo, Mohammad Gamal; Al Shohaib, Saad; Binzaqr, Salma Awad; Badreg, Alae Magdi; Alsaadi, Rawan Ali; Koenig, Harold G
2015-04-01
Patients on hemodialysis experience considerable psychological and physical stress due to the changes brought on by chronic kidney disease. Religion is often turned to in order to cope with illness and may buffer some of these stresses associated with illness. We describe here the religious activities of dialysis patients in Saudi Arabia and determined demographic, psychosocial, and physical health correlates. We administered an in-person questionnaire to 310 dialysis patients (99.4 % Muslim) in Jeddah, Saudi Arabia, that included the Muslim Religiosity Scale, Structured Clinical Interview for Depression, Hamilton Depression Rating Scale, Global Assessment of Functioning scale, and other established measures of psychosocial and physical health. Bivariate and multivariate analyses identified characteristics of patients who were more religiously involved. Religious practices and intrinsic religious beliefs were widespread. Religious involvement was more common among those who were older, better educated, had higher incomes, and were married. Overall psychological functioning was better and social support higher among those who were more religious. The religious also had better physical functioning, better cognitive functioning, and were less likely to smoke, despite having more severe overall illness and being on dialysis for longer than less religious patients. Religious involvement is correlated with better overall psychological functioning, greater social support, better physical and cognitive functioning, better health behavior, and longer duration of dialysis. Whether religion leads to or is a result of better mental and physical health will need to be determined by future longitudinal studies and clinical trials.
The FRAGILE FIBER8 gene was previously shown to be required for the biosynthesis of the reducing end tetrasaccharide sequence of glucuronoxylan (GX) in Arabidopsis thaliana. Here, we demonstrate that F8H, a close homolog of FRA8, is a functional ortholog of FRA8 involved in GX bi...
Son, Ji-Hye; Hwang, Eurim C; Kim, Joungmok
2016-03-01
Ultraviolet radiation resistance-associated gene product (UVRAG) was originally identified as a protein involved in cellular responses to UV irradiation. Subsequent studies have demonstrated that UVRAG plays as an important role in autophagy, a lysosome-dependent catabolic program, as a part of a pro-autophagy PIK3C3/VPS34 lipid kinase complex. Several recent studies have shown that UVRAG is also involved in autophagy-independent cellular functions, such as DNA repair/stability and vesicular trafficking/fusion. Here, we examined the UVRAG protein interactome to obtain information about its functional network. To this end, we screened UVRAG-interacting proteins using a tandem affinity purification method coupled with MALDI-TOF/MS analysis. Our results demonstrate that UVRAG interacts with various proteins involved in a wide spectrum of cellular functions, including genome stability, protein translational elongation, protein localization (trafficking), vacuole organization, transmembrane transport as well as autophagy. Notably, the interactome list of high-confidence UVRAG-interacting proteins is enriched for proteins involved in the regulation of genome stability. Our systematic UVRAG interactome analysis should provide important clues for understanding a variety of UVRAG functions.
Parker, J Alex; Metzler, Martina; Georgiou, John; Mage, Marilyne; Roder, John C; Rose, Ann M; Hayden, Michael R; Néri, Christian
2007-10-10
Huntingtin-interacting protein 1 (HIP1) was identified through its interaction with htt (huntingtin), the Huntington's disease (HD) protein. HIP1 is an endocytic protein that influences transport and function of AMPA and NMDA receptors in the brain. However, little is known about its contribution to neuronal dysfunction in HD. We report that the Caenorhabditis elegans HIP1 homolog hipr-1 modulates presynaptic activity and the abundance of synaptobrevin, a protein involved in synaptic vesicle fusion. Presynaptic function was also altered in hippocampal brain slices of HIP1-/- mice demonstrating delayed recovery from synaptic depression and a reduction in paired-pulse facilitation, a form of presynaptic plasticity. Interestingly, neuronal dysfunction in transgenic nematodes expressing mutant N-terminal huntingtin was specifically enhanced by hipr-1 loss of function. A similar effect was observed with several other mutant proteins that are expressed at the synapse and involved in endocytosis, such as unc-11/AP180, unc-26/synaptojanin, and unc-57/endophilin. Thus, HIP1 is involved in presynaptic nerve terminal activity and modulation of mutant polyglutamine-induced neuronal dysfunction. Moreover, synaptic proteins involved in endocytosis may protect neurons against amino acid homopolymer expansion.
Lee, Chang-Hun; Song, Juyoung
2012-08-01
This study uses an ecological systems theory to understand bullying behavior. Emphasis is given to overcome limitations found in the literature, such as very little empirical research on functions of parental involvement and the impacts of school climate on bullying as an outcome variable. Two functions of parental involvement investigated are (a) bridging the negative experiences within the family with bullying behaviors at schools, and (b) influencing school climate. Bullying behaviors were measured by a modified Korean version of Olweus' bully/victim questionnaire (reliability range: .78-.84) from 1,238 randomly selected Korean middle school students in 2007. Findings from structural equation modeling (SEM) analyses showed that (a) individual traits are one of the most important influence on bullying, (b) negative experiences in the family do not have direct influence on bullying behaviors at school, (c) parental involvement influences school climate, and (d) positive school climate was negatively related to bullying behaviors.
Cheng, Wei; Rolls, Edmund T; Gu, Huaguang; Zhang, Jie; Feng, Jianfeng
2015-05-01
Whole-brain voxel-based unbiased resting state functional connectivity was analysed in 418 subjects with autism and 509 matched typically developing individuals. We identified a key system in the middle temporal gyrus/superior temporal sulcus region that has reduced cortical functional connectivity (and increased with the medial thalamus), which is implicated in face expression processing involved in social behaviour. This system has reduced functional connectivity with the ventromedial prefrontal cortex, which is implicated in emotion and social communication. The middle temporal gyrus system is also implicated in theory of mind processing. We also identified in autism a second key system in the precuneus/superior parietal lobule region with reduced functional connectivity, which is implicated in spatial functions including of oneself, and of the spatial environment. It is proposed that these two types of functionality, face expression-related, and of one's self and the environment, are important components of the computations involved in theory of mind, whether of oneself or of others, and that reduced connectivity within and between these regions may make a major contribution to the symptoms of autism. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
Chen, Xiao-lei; Xu, Bai-nan; Wang, Fei; Meng, Xiang-hui; Zhang, Jun; Jiang, Jin-li; Yu, Xin-guang; Zhou, Ding-biao
2011-08-01
To explore the clinical value of functional neuro-navigation and high-field-strength intraoperative magnetic resonance imaging (iMRI) for the resection of intracerebral gliomas involving eloquent language structures. From April 2009 to April 2010, 48 patients with intracerebral gliomas involving eloquent language structures, were operated with functional neuro-navigation and iMRI. Blood oxygen level dependent functional MRI (BOLD-fMRI) was used to depict both Broca and Wernicke cortex, while diffusion tensor imaging (DTI) based fiber tracking was used to delineate arcuate fasciculus. The reconstructed language structures were integrated into a navigation system, so that intra-operative microscopic-based functional neuro-navigation could be achieved. iMRI was used to update the images for both language structures and residual tumors. All patients were evaluated for language function pre-operatively and post-operatively upon short-term and long-term follow-up. In all patients, functional neuro-navigation and iMRI were successfully achieved. In 38 cases (79.2%), gross total resection was accomplished, while in the rest 10 cases (20.8%), subtotal resection was achieved. Only 1 case (2.1%) developed long-term (more than 3 months) new language function deficits at post-operative follow-up. No peri-operative mortality was recorded. With functional neuro-navigation and iMRI, the eloquent structures for language can be precisely located, while the resection size can be accurately evaluated intra-operatively. This technique is safe and helpful for preservation of language function.
The relationship between attitude to disabled siblings and ratings of behavioural competency.
Wilson, C J; McGillivray, J A; Zetlin, A G
1992-08-01
The impact of maturation factors and functioning level on the relationship between disabled and non-disabled siblings was examined. Two groups of adults, distinguished by level of functioning of their mentally retarded sibling, completed a Schaefer Sibling Behavior Inventory (SBI) and participated in a semi-structured interview. The latter explored a number of dimensions of the relationship including degree of warmth, contact and involvement. Judgements about involvement and comfort as remembered from the past and judgements about the present were obtained to derive hypotheses about possible changes with time. Data from the SBI indicated that significantly more competent siblings tended to be involved in relationships with a higher degree of reciprocity. In contrast, measures of attitude derived from interview data did not appear to relate to the functioning level of the sibling in any systematic manner. The results suggest that level of discomfort with peers may decrease significantly over the years with neither level of functioning nor gender being important variables. The extent to which non-disabled individuals expressed a preparedness to participate in the life of their disabled sibling may relate to the life-stage of the two. Males in particular anticipated increased future involvement. Although higher-functioning siblings were described as more active in the relationship, this did not appear to influence perceived positiveness of regard. The implications of these results are discussed briefly.
Student Involvement Can Be Stressful: Implications and Interventions.
ERIC Educational Resources Information Center
Floerchinger, Debra S.
1988-01-01
Involvement on campus varies from involvement in student organization leadership positions to paid paraprofessional positions that also reflect strong leadership expectations. A minimum amount of student development knowledge is essential for advisers for a successful functioning and ethical interaction with students. (MLW)
Green's function of radial inhomogeneous spheres excited by internal sources.
Zouros, Grigorios P; Kokkorakis, Gerassimos C
2011-01-01
Green's function in the interior of penetrable bodies with inhomogeneous compressibility by sources placed inside them is evaluated through a Schwinger-Lippmann volume integral equation. In the case of a radial inhomogeneous sphere, the radial part of the unknown Green's function can be expanded in a double Dini's series, which allows analytical evaluation of the involved cumbersome integrals. The simple case treated here can be extended to more difficult situations involving inhomogeneous density as well as to the corresponding electromagnetic or elastic problem. Finally, numerical results are given for various inhomogeneous compressibility distributions.
ERIC Educational Resources Information Center
Curlew, Mary; Weber, Julie
2009-01-01
One of the most important factors in school performance is parental involvement. However, many parents do not have the flexibility in their work schedules or the leave policies necessary to attend school functions. As a result, legislators are creating policies to address this issue. School involvement leave policies provide parents with…
A Pilot Study on Factors Involved with Work Participation in the Early Stages of Multiple Sclerosis
Van der Hiele, Karin; Middelkoop, Huub A. M.; Ruimschotel, Rob; Kamminga, Noëlle G. A.; Visser, Leo H.
2014-01-01
Background Up to 30% of recently diagnosed MS patients lose their jobs in the first four years after diagnosis. Taking into account the personal and socio-economic importance of sustaining employment, it is of the utmost importance to examine factors involved with work participation. Objective To investigate differences in self-reported functioning in recently diagnosed MS patients with and without a paid job. Methods Self-reports of physical and cognitive functioning, depression, anxiety and fatigue were gathered from 44 relapsing-remitting MS patients diagnosed within 3 years. Results Patients with a paid job (57%) reported better physical functioning (p<0.001), better memory functioning (p = 0.01) and a lower physical impact of fatigue (p = 0.018) than patients without a paid job. Physical functioning was the main predictor of employment status in a logistic regression model. In those with a paid job better memory functioning (r = 0.54, p = 0.005) and a lower social impact of fatigue (r = −0.46, p = 0.029) correlated with an increased number of working hours. Conclusion Better physical functioning is the primary factor involved with increased work participation in early MS. Better self-reported memory functioning and less social fatigue were associated with increased working hours. These findings highlight the importance of battling these symptoms in the early stages of MS. PMID:25153710
Prosthodontic rehabilitation of completely edentulous patient with partial glossectomy.
Garg, Aditi
2016-01-01
Oral cancer accounts for about 40% of all cancers inflicting the human beings. Those involving the tongue results in mild to severe deficiencies of phonation, deglutition, mastication, and taste depending upon the degree and extent tissues involved. Often rehabilitation of such patient is a challenge for the prosthodontist and involves a careful observation and evaluation of the residual oral function and ways to restore them. This article presents a case report of prosthodontic rehabilitation completely edentulous patient, who underwent partial glossectomy following surgical resection of the squamous cell carcinoma involving left lateral borders of the tongue. An attempt was made to restore the comfort and function of the patient with the help of palatal augmentation prosthesis, with additional assistance through speech therapy and simple oral exercises.
Control of functional differential equations with function space boundary conditions
NASA Technical Reports Server (NTRS)
Banks, H. T.
1972-01-01
Problems involving functional differential equations with terminal conditions in function space are considered. Their application to mechanical and electrical systems is discussed. Investigations of controllability, existence of optimal controls, and necessary and sufficient conditions for optimality are reported.
Mitochondrial Ion Channels in Cancer Transformation
Madamba, Stephen M.; Damri, Kevin N.; Dejean, Laurent M.; Peixoto, Pablo M.
2015-01-01
Cancer transformation involves reprograming of mitochondrial function to avert cell death mechanisms, monopolize energy metabolism, accelerate mitotic proliferation, and promote metastasis. Mitochondrial ion channels have emerged as promising therapeutic targets because of their connection to metabolic and apoptotic functions. This mini review discusses how mitochondrial channels may be associated with cancer transformation and expands on the possible involvement of mitochondrial protein import complexes in pathophysiological process. PMID:26090338
Facilitating the Genesis of Functional Working Spaces in Guided Explorations
ERIC Educational Resources Information Center
Miranda, Vicente Carrión; Pluvinage, François; Adjiage, Robert
2016-01-01
Approximating given real-valued functions by affine functions is among the most basic activities with functions. In this study we examine two contexts in which two such approximations are performed. The first involves a microscopic representation of functions for the study of tangents; the second a macroscopic representation of functions for the…
Taghavi, Safiyh; Wu, Xiao; Ouyang, Liming; Stadler, Andrea; McCorkle, Sean; Zhu, Wei; Maslov, Sergei; van der Lelie, Daniel
2015-01-01
Growth in sucrose medium was previously found to trigger the expression of functions involved in the plant associated life style of the endophytic bacterium Enterobacter sp. 638. Therefore, comparative transcriptome analysis between cultures grown in sucrose or lactate medium was used to gain insights in the expression levels of bacterial functions involved in the endophytic life style of strain 638. Growth on sucrose as a carbon source resulted in major changes in cell physiology, including a shift from a planktonic life style to the formation of bacterial aggregates. This shift was accompanied by a decrease in transcription of genes involved in motility (e.g. flagella biosynthesis) and an increase in the transcription of genes involved in colonization, adhesion and biofilm formation. The transcription levels of functions previously suggested as being involved in endophytic behavior and functions responsible for plant growth promoting properties, including the synthesis of indole-acetic acid, acetoin and 2,3-butanediol, also increased significantly for cultures grown in sucrose medium. Interestingly, despite an abundance of essential nutrients transcription levels of functions related to uptake and processing of nitrogen and iron became increased for cultures grown on sucrose as sole carbon source. Transcriptome data were also used to analyze putative regulatory relationships. In addition to the small RNA csrABCD regulon, which seems to play a role in the physiological adaptation and possibly the shift between free-living and plant-associated endophytic life style of Enterobacter sp. 638, our results also pointed to the involvement of rcsAB in controlling responses by Enterobacter sp. 638 to a plant-associated life style. Targeted mutagenesis was used to confirm this role and showed that compared to wild-type Enterobacter sp. 638 a ΔrcsB mutant was affected in its plant growth promoting ability. PMID:25607953
Taghavi, Safiyh; Wu, Xiao; Ouyang, Liming; Zhang, Yian Biao; Stadler, Andrea; McCorkle, Sean; Zhu, Wei; Maslov, Sergei; van der Lelie, Daniel
2015-01-01
Growth in sucrose medium was previously found to trigger the expression of functions involved in the plant associated life style of the endophytic bacterium Enterobacter sp. 638. Therefore, comparative transcriptome analysis between cultures grown in sucrose or lactate medium was used to gain insights in the expression levels of bacterial functions involved in the endophytic life style of strain 638. Growth on sucrose as a carbon source resulted in major changes in cell physiology, including a shift from a planktonic life style to the formation of bacterial aggregates. This shift was accompanied by a decrease in transcription of genes involved in motility (e.g., flagella biosynthesis) and an increase in the transcription of genes involved in colonization, adhesion and biofilm formation. The transcription levels of functions previously suggested as being involved in endophytic behavior and functions responsible for plant growth promoting properties, including the synthesis of indole-acetic acid, acetoin and 2,3-butanediol, also increased significantly for cultures grown in sucrose medium. Interestingly, despite an abundance of essential nutrients transcription levels of functions related to uptake and processing of nitrogen and iron became increased for cultures grown on sucrose as sole carbon source. Transcriptome data were also used to analyze putative regulatory relationships. In addition to the small RNA csrABCD regulon, which seems to play a role in the physiological adaptation and possibly the shift between free-living and plant-associated endophytic life style of Enterobacter sp. 638, our results also pointed to the involvement of rcsAB in controlling responses by Enterobacter sp. 638 to a plant-associated life style. Targeted mutagenesis was used to confirm this role and showed that compared to wild-type Enterobacter sp. 638 a ΔrcsB mutant was affected in its plant growth promoting ability.
Jana, Subrata; Samal, Prasanjit
2017-06-29
Semilocal density functionals for the exchange-correlation energy of electrons are extensively used as they produce realistic and accurate results for finite and extended systems. The choice of techniques plays a crucial role in constructing such functionals of improved accuracy and efficiency. An accurate and efficient semilocal exchange energy functional in two dimensions is constructed by making use of the corresponding hole which is derived based on the density matrix expansion. The exchange hole involved is localized under the generalized coordinate transformation and satisfies all the relevant constraints. Comprehensive testing and excellent performance of the functional is demonstrated versus exact exchange results. The accuracy of results obtained by using the newly constructed functional is quite remarkable as it substantially reduces the errors present in the local and nonempirical exchange functionals proposed so far for two-dimensional quantum systems. The underlying principles involved in the functional construction are physically appealing and hold promise for developing range separated and nonlocal exchange functionals in two dimensions.
The Insula: A ‘Hub of Activity’ in Migraine
Borsook, David; Veggeberg, Rosanna; Erpelding, Nathalie; Borra, Ronald; Linnman, Clas; Burstein, Rami; Becerra, Lino
2017-01-01
The insula, a ‘cortical hub’ buried within the lateral sulcus, is involved in a number of processes including goal-directed cognition, conscious awareness, autonomic regulation, interoception and somatosensation. While some of these processes are well known in the clinical presentation of migraine (i.e., autonomic and somatosensory alterations), other more complex behaviors in migraine, such as conscious awareness and error detection, are less well described. Since the insula processes and relays afferent inputs from brain areas involved in these functions to areas involved in higher cortical function such as frontal, temporal and parietal regions, it may be implicated as a brain region that translates the signals of altered internal milieu in migraine, along with other chronic pain conditions, through the insula into complex behaviors. Here we review how the insula function and structure is altered in migraine. As a brain region of a number of brain functions, it may serve as a model to study new potential clinical perspectives for migraine treatment. PMID:26290446
Trait motivation moderates neural activation associated with goal pursuit
Miller, Gregory A.; Warren, Stacie L.; Engels, Anna S.; Crocker, Laura D.; Sutton, Bradley P.; Heller, Wendy
2012-01-01
Research has indicated that regions of left and right dorsolateral prefrontal cortex (DLPFC) are involved in integrating the motivational and executive function processes related to, respectively, approach and avoidance goals. Given that sensitivity to pleasant and unpleasant stimuli is an important feature of conceptualizations of approach and avoidance motivation, it is possible that these regions of DLPFC are preferentially activated by valenced stimuli. The present study tested this hypothesis by using a task in which goal pursuit was threatened by distraction from valenced stimuli while functional magnetic resonance imaging data were collected. The analyses examined whether the impact of trait approach and avoidance motivation on the neural processes associated with executive function differed depending on the valence or arousal level of the distractor stimuli. The present findings support the hypothesis that the regions of DLPFC under investigation are involved in integrating motivational and executive function processes, and they also indicate the involvement of a number of other brain areas in maintaining goal pursuit. However, DLPFC did not display differential sensitivity to valence. PMID:22460723
Trait motivation moderates neural activation associated with goal pursuit.
Spielberg, Jeffrey M; Miller, Gregory A; Warren, Stacie L; Engels, Anna S; Crocker, Laura D; Sutton, Bradley P; Heller, Wendy
2012-06-01
Research has indicated that regions of left and right dorsolateral prefrontal cortex (DLPFC) are involved in integrating the motivational and executive function processes related to, respectively, approach and avoidance goals. Given that sensitivity to pleasant and unpleasant stimuli is an important feature of conceptualizations of approach and avoidance motivation, it is possible that these regions of DLPFC are preferentially activated by valenced stimuli. The present study tested this hypothesis by using a task in which goal pursuit was threatened by distraction from valenced stimuli while functional magnetic resonance imaging data were collected. The analyses examined whether the impact of trait approach and avoidance motivation on the neural processes associated with executive function differed depending on the valence or arousal level of the distractor stimuli. The present findings support the hypothesis that the regions of DLPFC under investigation are involved in integrating motivational and executive function processes, and they also indicate the involvement of a number of other brain areas in maintaining goal pursuit. However, DLPFC did not display differential sensitivity to valence.
NASA Astrophysics Data System (ADS)
Ishkhanyan, Tigran A.; Krainov, Vladimir P.; Ishkhanyan, Artur M.
2018-05-01
We present a conditionally integrable potential, belonging to the bi-confluent Heun class, for which the Schrödinger equation is solved in terms of the confluent hypergeometric functions. The potential involves an attractive inverse square root term x-1/2 with arbitrary strength and a repulsive centrifugal barrier core x-2 with the strength fixed to a constant. This is a potential well defined on the half-axis. Each of the fundamental solutions composing the general solution of the Schrödinger equation is written as an irreducible linear combination, with non-constant coefficients, of two confluent hypergeometric functions. We present the explicit solution in terms of the non-integer order Hermite functions of scaled and shifted argument and discuss the bound states supported by the potential. We derive the exact equation for the energy spectrum and approximate that by a highly accurate transcendental equation involving trigonometric functions. Finally, we construct an accurate approximation for the bound-state energy levels.
Ergün, Recai; Evcik, Ender; Ergün, Dilek; Ergan, Begüm; Özkan, Esin; Gündüz, Özge
2017-05-05
The number of studies where non-malignant pulmonary diseases are evaluated after occupational arsenic exposure is very few. To investigate the effects of occupational arsenic exposure on the lung by high-resolution computed tomography and pulmonary function tests. Retrospective cross-sectional study. In this study, 256 workers with suspected respiratory occupational arsenic exposure were included, with an average age of 32.9±7.8 years and an average of 3.5±2.7 working years. Hair and urinary arsenic levels were analysed. High-resolution computed tomography and pulmonary function tests were done. In workers with occupational arsenic exposure, high-resolution computed tomography showed 18.8% pulmonary involvement. In pulmonary involvement, pulmonary nodule was the most frequently seen lesion (64.5%). The other findings of pulmonary involvement were 18.8% diffuse interstitial lung disease, 12.5% bronchiectasis, and 27.1% bullae-emphysema. The mean age of patients with pulmonary involvement was higher and as they smoked more. The pulmonary involvement was 5.2 times higher in patients with skin lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was significantly lower in patients with pulmonary involvement. Besides lung cancer, chronic occupational inhalation of arsenic exposure may cause non-malignant pulmonary findings such as bronchiectasis, pulmonary nodules and diffuse interstitial lung disease. So, in order to detect pulmonary involvement in the early stages, workers who experience occupational arsenic exposure should be followed by diffusion test and high-resolution computed tomography.
The Developmental Costs and Benefits of Children’s Involvement in Interparental Conflict
Davies, Patrick T.; Coe, Jesse L.; Martin, Meredith J.; Sturge-Apple, Melissa L.; Cummings, E. Mark
2015-01-01
Building on empirical documentation of children’s involvement in interparental conflicts as a weak predictor of psychopathology, we tested the hypothesis that involvement in conflict more consistently serves as a moderator of associations between children’s emotional reactivity to interparental conflict and their psychological problems. In Study 1, 263 early adolescents (M age = 12.62 years), mothers, and fathers completed surveys of family and child functioning at two measurement occasions spaced two years apart. In Study 2, 243 preschool children (M age = 4.60 years) participated in a multi-method (i.e., observations, structured interview, surveys) measurement battery to assess family functioning, children’s reactivity to interparental conflict, and their psychological adjustment. Across both studies, latent difference score (LDS) analyses revealed that involvement moderated associations between emotional reactivity and children’s increases in psychological (i.e., internalizing and externalizing) problems. Children’s emotional reactivity to interparental conflict was a significantly stronger predictor of their psychological maladjustment when they were highly involved in the conflicts. In addition, the developmental benefits and costs of involvement varied as a function of emotional reactivity. Involvement in interparental conflict predicted increases in psychological problems for children experiencing high emotional reactivity and decreases in psychological problems when they exhibited low emotional reactivity. We interpret the results in the context of the new formulation of emotional security theory (e.g. Davies & Martin, 2013) and family systems models of children’s parentification (e.g., Byng-Hall, 2002). PMID:26053147
The developmental costs and benefits of children's involvement in interparental conflict.
Davies, Patrick T; Coe, Jesse L; Martin, Meredith J; Sturge-Apple, Melissa L; Cummings, E Mark
2015-08-01
Building on empirical documentation of children's involvement in interparental conflicts as a weak predictor of psychopathology, we tested the hypothesis that involvement in conflict more consistently serves as a moderator of associations between children's emotional reactivity to interparental conflict and their psychological problems. In Study 1, 263 early adolescents (M age = 12.62 years), mothers, and fathers completed surveys of family and child functioning at 2 measurement occasions spaced 2 years apart. In Study 2, 243 preschool children (M age = 4.60 years) participated in a multimethod (i.e., observations, structured interview, surveys) measurement battery to assess family functioning, children's reactivity to interparental conflict, and their psychological adjustment. Across both studies, latent difference score analyses revealed that involvement moderated associations between emotional reactivity and children's increases in psychological (i.e., internalizing and externalizing) problems. Children's emotional reactivity to interparental conflict was a significantly stronger predictor of their psychological maladjustment when they were highly involved in the conflicts. In addition, the developmental benefits and costs of involvement varied as a function of emotional reactivity. Involvement in interparental conflict predicted increases in psychological problems for children experiencing high emotional reactivity and decreases in psychological problems when they exhibited low emotional reactivity. We interpret the results in the context of the new formulation of emotional security theory (e.g., Davies & Martin, 2013) and family systems models of children's parentification (e.g., Byng-Hall, 2002). (c) 2015 APA, all rights reserved).
Cheung, Cecilia Sin-Sze; Pomerantz, Eva M.
2014-01-01
This research examined whether the benefits of parents’ involvement in children’s learning are due in part to value development among children. Four times over the seventh and eighth grades, 825 American and Chinese children (mean age = 12.73 years) reported on their parents’ involvement in their learning and their perceptions of the value their parents place on school achievement as well as the value they themselves place on it. Children’s academic functioning was assessed via children’s reports and school records. Value development partially explained the effects of parents’ involvement on children’s academic functioning in the United States and China. For example, the more children reported their parents as involved, the more they perceived them as placing value on achievement six months later; such perceptions in turn predicted the subsequent value children placed on achievement, which foreshadowed enhanced grades. PMID:25937669
Woutersen, Karlijn; Guadron, Leslie; van den Berg, Albert V; Boonstra, F Nienke; Theelen, Thomas; Goossens, Jeroen
2017-12-01
The useful-field-of-view (UFOV) test measures the amount of information someone can extract from a visual scene in one glance. Its scores show relatively strong relationships with everyday activities. The UFOV test consists of three computer tests, suggested to measure processing speed and central vision, divided attention, and selective attention. However, other functions seem to be involved as well. In order to investigate the contribution of these suggested and other perceptual and cognitive functions, we performed a meta-analysis of 116 Pearson's correlation coefficients between UFOV scores and other test scores reported in 18 peer-reviewed articles. We divided these correlations into nine domains: attention, executive functioning, general cognition, memory, spatial ability, visual closure, contrast sensitivity, visual processing speed, and visual acuity. A multivariate mixed-effects model analysis revealed that each domain correlated significantly with each of the UFOV subtest scores. These correlations were stronger for Subtests 2 and 3 than for Subtest 1. Furthermore, some domains were more strongly correlated to the UFOV than others across subtests. We did not find interaction effects between subtest and domain, indicating that none of the UFOV subtests is more selectively sensitive to a particular domain than the others. Thus, none of the three UFOV subtests seem to measure one clear construct. Instead, a range of visual and cognitive functions is involved. Perhaps this is the reason for the UFOV's high ecological validity, as it involves many functions at once, making it harder to compensate if one of them fails.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hartmann, A.; Frenkel, J.; Hopf, R.
Amyloidosis is a systemic disease frequently involving the myocardium and leading to functional disturbances of the heart. Amyloidosis can mimic other cardiac diseases. A conclusive clinical diagnosis of cardiac involvement can only be made by a combination of different diagnostic methods. In 7 patients with myocardial amyloidosis we used a combined first-pass and static scintigraphy with technetium-99 m-pyrophosphate. There was only insignificant myocardial uptake of the tracer. The first-pass studies however revealed reduced systolic function in 4/7 patients and impaired diastolic function in 6/7 patients. Therefore, although cardiac amyloid could not be demonstrated in the static scintigraphy due to amyloidmore » fibril amount and composition, myocardial functional abnormalities were seen in the first-pass study.« less
A remark on fractional differential equation involving I-function
NASA Astrophysics Data System (ADS)
Mishra, Jyoti
2018-02-01
The present paper deals with the solution of the fractional differential equation using the Laplace transform operator and its corresponding properties in the fractional calculus; we derive an exact solution of a complex fractional differential equation involving a special function known as I-function. The analysis of the some fractional integral with two parameters is presented using the suggested Theorem 1. In addition, some very useful corollaries are established and their proofs presented in detail. Some obtained exact solutions are depicted to see the effect of each fractional order. Owing to the wider applicability of the I-function, we can conclude that, the obtained results in our work generalize numerous well-known results obtained by specializing the parameters.
Jung, Wi Hoon; Jang, Joon Hwan; Park, Jin Woo; Kim, Euitae; Goo, Eun-Hoe; Im, Oh-Soo; Kwon, Jun Soo
2014-01-01
As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were consistent with recent accounts of the functional distinctions of the striatum as well as with recent studies about its functional and anatomical connectivity. For example, we found functional connections between dorsal and ventral striatal clusters and the areas involved in cognitive and affective processes, respectively, and between rostral and caudal putamen clusters and the areas involved in cognitive and motor processes, respectively. This study confirms prior findings, showing similar striatal parcellation patterns between the present and prior studies. Given such striking similarity, it is suggested that striatal subregions are functionally linked to cortical networks involving specific functions rather than discrete portions of cortical regions. Our findings also demonstrate that the clustering of functional connectivity patterns is a reliable feature in parcellating the striatum into anatomically and functionally meaningful subdivisions. The striatal subdivisions identified here may have important implications for understanding the relationship between corticostriatal dysfunction and various neurodegenerative and psychiatric disorders. PMID:25203441
Buetefisch, Cathrin M; Pirog Revill, Kathleen; Haut, Marc W; Kowalski, Greg M; Wischnewski, Miles; Pifer, Marissa; Belagaje, Samir R; Nahab, Fadi; Cobia, Derin J; Hu, Xiaoping; Drake, Daniel; Hobbs, Gerald
2018-06-20
Stroke often involves primary motor cortex (M1) and its corticospinal projections (CST). As hand function is critically dependent on these structures, its recovery is often incomplete. The neuronal substrate supporting affected hand function is not well understood but likely involves reorganized M1 and CST of the lesioned hemisphere (M1 IL and CST IL ). We hypothesized that affected hand function in chronic stroke is related to structural and functional reorganization of M1 IL and CST IL . We tested 18 patients with chronic ischemic stroke involving M1 or CST. Their hand function was compared to 18 age matched healthy subjects. M1 IL thickness and CST IL fractional anisotropy (FA) were determined with MRI and compared to measures of the other hemisphere. Transcranial magnetic stimulation (TMS) was applied to M1 IL to determine its input output function (stimulus response curve, SRC). The plateau of the SRC (MEPmax), inflection point and slope parameters of the curve were extracted. Results were compared to measures in 12 age matched healthy controls. MEPmax of M1 IL was significantly smaller (p=0.02) in the patients, indicating reduced CST IL motor output, and was correlated with impaired hand function (p=0.02). M1 IL thickness (p<0.01) and CST IL -FA (p<0.01) were reduced but did not correlate with hand function. The results indicate that employed M1 IL or CST IL structural measures do not explain the extent of impairment in hand function once M1 and CST are sufficiently functional for TMS to evoke a motor potential. Instead, impairment of hand function is best explained by the abnormally low output from M1 IL .
Pandey, Shashank K; Nookaraju, Akula; Fujino, Takeshi; Pattathil, Sivakumar; Joshi, Chandrashekhar P
2016-11-01
Functional characterization of two tobacco genes, one involved in xylan synthesis and the other, a positive regulator of secondary cell wall formation, is reported. Lignocellulosic secondary cell walls (SCW) provide essential plant materials for the production of second-generation bioethanol. Therefore, thorough understanding of the process of SCW formation in plants is beneficial for efficient bioethanol production. Recently, we provided the first proof-of-concept for using virus-induced gene silencing (VIGS) approach for rapid functional characterization of nine genes involved in cellulose, hemicellulose and lignin synthesis during SCW formation. Here, we report VIGS-mediated functional characterization of two tobacco genes involved in SCW formation. Stems of VIGS plants silenced for both selected genes showed increased amount of xylem formation but thinner cell walls than controls. These results were further confirmed by production of stable transgenic tobacco plants manipulated in expression of these genes. Stems of stable transgenic tobacco plants silenced for these two genes showed increased xylem proliferation with thinner walls, whereas transgenic tobacco plants overexpressing these two genes showed increased fiber cell wall thickness but no change in xylem proliferation. These two selected genes were later identified as possible members of DUF579 family involved in xylan synthesis and KNAT7 transcription factor family involved in positive regulation of SCW formation, respectively. Glycome analyses of cell walls showed increased polysaccharide extractability in 1 M KOH extracts of both VIGS-NbDUF579 and VIGS-NbKNAT7 lines suggestive of cell wall loosening. Also, VIGS-NbDUF579 and VIGS-NbKNAT7 lines showed increased saccharification rates (74.5 and 40 % higher than controls, respectively). All these properties are highly desirable for producing higher quantities of bioethanol from lignocellulosic materials of bioenergy plants.
Bai, Feng; Zhang, Zhijun; Watson, David R; Yu, Hui; Shi, Yongmei; Yuan, Yonggui; Zang, Yufeng; Zhu, Chaozhe; Qian, Yun
2009-06-01
Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.
Signal Transduction Pathways of TNAP: Molecular Network Analyses.
Négyessy, László; Györffy, Balázs; Hanics, János; Bányai, Mihály; Fonta, Caroline; Bazsó, Fülöp
2015-01-01
Despite the growing body of evidence pointing on the involvement of tissue non-specific alkaline phosphatase (TNAP) in brain function and diseases like epilepsy and Alzheimer's disease, our understanding about the role of TNAP in the regulation of neurotransmission is severely limited. The aim of our study was to integrate the fragmented knowledge into a comprehensive view regarding neuronal functions of TNAP using objective tools. As a model we used the signal transduction molecular network of a pyramidal neuron after complementing with TNAP related data and performed the analysis using graph theoretic tools. The analyses show that TNAP is in the crossroad of numerous pathways and therefore is one of the key players of the neuronal signal transduction network. Through many of its connections, most notably with molecules of the purinergic system, TNAP serves as a controller by funnelling signal flow towards a subset of molecules. TNAP also appears as the source of signal to be spread via interactions with molecules involved among others in neurodegeneration. Cluster analyses identified TNAP as part of the second messenger signalling cascade. However, TNAP also forms connections with other functional groups involved in neuronal signal transduction. The results indicate the distinct ways of involvement of TNAP in multiple neuronal functions and diseases.
Functional Thinking Ways in Relation to Linear Function Tables of Elementary School Students
ERIC Educational Resources Information Center
Tanisli, Dilek
2011-01-01
One of the basic components of algebraic thinking is functional thinking. Functional thinking involves focusing on the relationship between two (or more) varying quantities and such thinking facilitates the studies on both algebra and the notion of function. The development of functional thinking of students should start in the early grades and it…
ERIC Educational Resources Information Center
Anderson, Deborah S.; Kristiansen, Connie M.
1990-01-01
Discusses the Attitude Functions Inventory (AFI), which assesses the extent to which a person's attitude fulfills each of four psychological functions. Reports findings of a study, involving 249 undergraduates, that tested the construct validity of the AFI. Suggests that the AFI provides conceptually meaningful measures of the functions of…
The interval testing procedure: A general framework for inference in functional data analysis.
Pini, Alessia; Vantini, Simone
2016-09-01
We introduce in this work the Interval Testing Procedure (ITP), a novel inferential technique for functional data. The procedure can be used to test different functional hypotheses, e.g., distributional equality between two or more functional populations, equality of mean function of a functional population to a reference. ITP involves three steps: (i) the representation of data on a (possibly high-dimensional) functional basis; (ii) the test of each possible set of consecutive basis coefficients; (iii) the computation of the adjusted p-values associated to each basis component, by means of a new strategy here proposed. We define a new type of error control, the interval-wise control of the family wise error rate, particularly suited for functional data. We show that ITP is provided with such a control. A simulation study comparing ITP with other testing procedures is reported. ITP is then applied to the analysis of hemodynamical features involved with cerebral aneurysm pathology. ITP is implemented in the fdatest R package. © 2016, The International Biometric Society.
Prosthodontic rehabilitation of completely edentulous patient with partial glossectomy
Garg, Aditi
2016-01-01
Oral cancer accounts for about 40% of all cancers inflicting the human beings. Those involving the tongue results in mild to severe deficiencies of phonation, deglutition, mastication, and taste depending upon the degree and extent tissues involved. Often rehabilitation of such patient is a challenge for the prosthodontist and involves a careful observation and evaluation of the residual oral function and ways to restore them. This article presents a case report of prosthodontic rehabilitation completely edentulous patient, who underwent partial glossectomy following surgical resection of the squamous cell carcinoma involving left lateral borders of the tongue. An attempt was made to restore the comfort and function of the patient with the help of palatal augmentation prosthesis, with additional assistance through speech therapy and simple oral exercises. PMID:27141173
Schmithorst, Vincent J
2005-04-01
Music perception is a quite complex cognitive task, involving the perception and integration of various elements including melody, harmony, pitch, rhythm, and timbre. A preliminary functional MRI investigation of music perception was performed, using a simplified passive listening task. Group independent component analysis (ICA) was used to separate out various components involved in music processing, as the hemodynamic responses are not known a priori. Various components consistent with auditory processing, expressive language, syntactic processing, and visual association were found. The results are discussed in light of various hypotheses regarding modularity of music processing and its overlap with language processing. The results suggest that, while some networks overlap with ones used for language processing, music processing may involve its own domain-specific processing subsystems.
Aldolase sequesters WASP and affects WASP/Arp2/3-stimulated actin dynamics.
Ritterson Lew, Carolyn; Tolan, Dean R
2013-08-01
In addition to its roles in sugar metabolism, fructose-1,6-bisphosphate aldolase (aldolase) has been implicated in cellular functions independent from these roles, termed "moonlighting functions." These moonlighting functions likely involve the known aldolase-actin interaction, as many proteins with which aldolase interacts are involved in actin-dependent processes. Specifically, aldolase interacts both in vitro and in cells with Wiskott-Aldrich Syndrome Protein (WASP), a protein involved in controlling actin dynamics, yet the function of this interaction remains unknown. Here, the effect of aldolase on WASP-dependent processes in vitro and in cells is investigated. Aldolase inhibits WASP/Arp2/3-dependent actin polymerization in vitro. In cells, knockdown of aldolase results in a decreased rate of cell motility and cell spreading, two WASP-dependent processes. Expression of exogenous aldolase rescues these defects. Whether these effects of aldolase on WASP-dependent processes were due to aldolase catalysis or moonlighting functions is tested using aldolase variants defective in either catalytic or actin-binding activity. While the actin-binding deficient aldolase variant is unable to inhibit actin polymerization in vitro and is unable to rescue cell motility defects in cells, the catalytically inactive aldolase is able to perform these functions, providing evidence that aldolase moonlighting plays a role in WASP-mediated processes. Copyright © 2013 Wiley Periodicals, Inc.
Illeghems, Koen; Weckx, Stefan; De Vuyst, Luc
2015-09-01
A high-resolution functional metagenomic analysis of a representative single sample of a Brazilian spontaneous cocoa bean fermentation process was carried out to gain insight into its bacterial community functioning. By reconstruction of microbial meta-pathways based on metagenomic data, the current knowledge about the metabolic capabilities of bacterial members involved in the cocoa bean fermentation ecosystem was extended. Functional meta-pathway analysis revealed the distribution of the metabolic pathways between the bacterial members involved. The metabolic capabilities of the lactic acid bacteria present were most associated with the heterolactic fermentation and citrate assimilation pathways. The role of Enterobacteriaceae in the conversion of substrates was shown through the use of the mixed-acid fermentation and methylglyoxal detoxification pathways. Furthermore, several other potential functional roles for Enterobacteriaceae were indicated, such as pectinolysis and citrate assimilation. Concerning acetic acid bacteria, metabolic pathways were partially reconstructed, in particular those related to responses toward stress, explaining their metabolic activities during cocoa bean fermentation processes. Further, the in-depth metagenomic analysis unveiled functionalities involved in bacterial competitiveness, such as the occurrence of CRISPRs and potential bacteriocin production. Finally, comparative analysis of the metagenomic data with bacterial genomes of cocoa bean fermentation isolates revealed the applicability of the selected strains as functional starter cultures. Copyright © 2015 Elsevier Ltd. All rights reserved.
Oil palm phenolics confer neuroprotective effects involving cognitive and motor functions in mice
Leow, Soon-Sen; Sekaran, Shamala Devi; Tan, YewAi; Sundram, Kalyana; Sambanthamurthi, Ravigadevi
2013-01-01
Objectives Phenolics are important phytochemicals which have positive effects on chronic diseases, including neurodegenerative ailments. The oil palm (Elaeis guineensis) is a rich source of water-soluble phenolics. This study was carried out to discover the effects of administering oil palm phenolics (OPP) to mice, with the aim of identifying whether these compounds possess significant neuroprotective properties. Methods OPP was given to BALB/c mice on a normal diet as fluids for 6 weeks while the controls were given distilled water. These animals were tested in a water maze and on a rotarod weekly to assess the effects of OPP on cognitive and motor functions, respectively. Using Illumina microarrays, we further explored the brain gene expression changes caused by OPP in order to determine the molecular mechanisms involved. Real-time quantitative reverse transcription-polymerase chain reaction experiments were then carried out to validate the microarray data. Results We found that mice given OPP showed better cognitive function and spatial learning when tested in a water maze, and their performance also improved when tested on a rotarod, possibly due to better motor function and balance. Microarray gene expression analysis showed that these compounds up-regulated genes involved in brain development and activity, such as those under the regulation of the brain-derived neurotrophic factor. OPP also down-regulated genes involved in inflammation. Discussion These results suggest that the improvement of mouse cognitive and motor functions by OPP is caused by the neuroprotective and anti-inflammatory effects of the extract. PMID:23433062
Functional Intersection Area -- Oregon Department of Transportation
DOT National Transportation Integrated Search
1996-01-01
This discussion paper addresses the concepts involved in defining the functional area of an intersection. The elements which comprise the upstream functional area are identified; dimensions of the upstream area exclusive of queue storage, are given f...
Learning a Foreign Language: A New Path to Enhancement of Cognitive Functions.
Shoghi Javan, Sara; Ghonsooly, Behzad
2018-02-01
The complicated cognitive processes involved in natural (primary) bilingualism lead to significant cognitive development. Executive functions as a fundamental component of human cognition are deemed to be affected by language learning. To date, a large number of studies have investigated how natural (primary) bilingualism influences executive functions; however, the way acquired (secondary) bilingualism manipulates executive functions is poorly understood. To fill this gap, controlling for age, gender, IQ, and socio-economic status, the researchers compared 60 advanced learners of English as a foreign language (EFL) to 60 beginners on measures of executive functions involving Stroop, Wisconsin Card Sorting Task (WCST) and Wechsler's digit span tasks. The results suggested that mastering English as a foreign language causes considerable enhancement in two components of executive functions, namely cognitive flexibility and working memory. However, no significant difference was observed in inhibitory control between the advanced EFL learners and beginners.
Rahman, Safikur; Rehman, Md Tabish; Singh, Laishram R; Warepam, Marina; Ahmad, Faizan; Dar, Tanveer Ali
2015-01-01
Cellular methylamines are osmolytes (low molecular weight organic compounds) believed to offset the urea's harmful effects on the stability and function of proteins in mammalian kidney and marine invertebrates. Although urea and methylamines are found at 2:1 molar ratio in tissues, their opposing effects on protein structure and function have been questioned on several grounds including failure to counteraction or partial counteraction. Here we investigated the possible involvement of cellular salt, NaCl, in urea-methylamine counteraction on protein stability and function. We found that NaCl mediates methylamine counteracting system from no or partial counteraction to complete counteraction of urea's effect on protein stability and function. These conclusions were drawn from the systematic thermodynamic stability and functional activity measurements of lysozyme and RNase-A. Our results revealed that salts might be involved in protein interaction with charged osmolytes and hence in the urea-methylamine counteraction.
Beneficial impact of exercise and obesity interventions on erectile function and its risk factors.
Hannan, Johanna L; Maio, M Tina; Komolova, Marina; Adams, Michael A
2009-03-01
Erectile dysfunction (ED) is a multifaceted disease involving cardiovascular, metabolic, and hormonal factors and affects over 100 million men worldwide. ED has been shown to be a harbinger of underlying cardiovascular diseases (CVD), as there are common risk factors (aging, hypertension, obesity) and mechanistic basis. To provide an update on clinical and experimental evidence regarding the impact of lifestyle modifications, such as exercise and diet, with respect to changes in erectile function. Published evidence regarding the impact of aging, hypertension, and obesity on ED and CVD, as well as new experimental data linking obesity and diminished erectile responses. We reviewed the literature regarding common risk factors of ED and CVD, particularly involving obesity, as well as performed new analysis on the findings of other experimental studies involving diet and exercise interventions. Physical inactivity negatively impacts on erectile function, and experimental and clinical exercise interventions have been shown to improve sexual responses and overall cardiovascular health. Mediterranean-style diets and a reduction in caloric intake have been found to improve erectile function in men with the aspects of the metabolic syndrome. In addition, both clinical and experimental studies have confirmed that combining the two interventions provides additional benefit to erectile function, likely via reduced metabolic disturbances (e.g., inflammatory markers, insulin resistance), decreased visceral adipose tissue, and improvement in vascular function (e.g., increased endothelial function). Lifestyle modifications provide significant benefits to vascular health and erectile function in a population that is increasingly aged and more obese.
Oliva, Carlos; Sierralta, Jimena
2010-08-15
The molecules and networks involved in the process of acquisition and maintenance of the form of a mature neuron are not completely known. Using a misexpression screen we identified the gene hindsight as a gene involved in the process of acquisition of the neuronal morphogenesis in the Drosophila adult nervous system. hindsight encodes a transcription factor known for its role in early developmental processes such as embryonic germ band retraction and dorsal closure, as well as in the establishment of cell morphology, planar cell polarity, and epithelial integrity during retinal development. We describe here a novel function for HNT by showing that both loss and gain of function of HNT affects the pathfinding of the photoreceptors axons. By manipulating the timing and level of HNT expression, together with the number of cells manipulated we show here that the function of HNT in axonal guidance is independent of the HNT functions previously reported in retinal cells. Based on genetic interaction experiments we show that part of HNT function in axonal development is exerted through the regulation of genes involved in the dynamics of the actin cytoskeleton. Copyright 2010 Elsevier Inc. All rights reserved.
Effects of NSAIDs on the Inner Ear: Possible Involvement in Cochlear Protection
Hoshino, Tomofumi; Tabuchi, Keiji; Hara, Akira
2010-01-01
Cyclooxygenase and lipoxygenase, two important enzymes involved in arachidonic acid metabolism, are major targets of non-steroidal anti-inflammatory drugs (NSAIDs). Recent investigations suggest that arachidonic cascades and their metabolites may be involved in maintaining inner ear functions. The excessive use of aspirin may cause tinnitus in humans and impairment of the outer hair cell functions in experimental animals. On the other hand, NSAIDs reportedly exhibit protective effects against various kinds of inner ear disorder. The present review summarizes the effects of NSAIDs on cochlear pathophysiology. NSAIDs are a useful ameliorative adjunct in the management of inner ear disorders. PMID:27713301
NASA Astrophysics Data System (ADS)
Set, Erhan; Özdemir, M. Emin; Alan, E. Aykan
2017-04-01
In this article, by using the Hölder's inequality and power mean inequality the authors establish several inequalities of Hermite-Hadamard type for n- time differentiable quasi-convex functions and P- functions involving Riemann-Liouville fractional integrals.
Muccioli, Giulio G.; Sia, Angela; Muchowski, Paul J.; Stella, Nephi
2009-01-01
Background Lipids can act as signaling molecules, activating intracellular and membrane-associated receptors to regulate physiological functions. To understand how a newly discovered signaling lipid functions, it is necessary to identify and characterize the enzymes involved in their production and inactivation. The signaling lipid N-palmitoylethanolamine (PEA) is known to activate intracellular and membrane-associated receptors and regulate physiological functions, but little is known about the enzymes involved in its production and inactivation. Principal Findings Here we show that Saccharomyces cerevisiae produce and inactivate PEA, suggesting that genetic manipulations of this lower eukaryote may be used to identify the enzymes involved in PEA metabolism. Accordingly, using single gene deletion mutants, we identified yeast genes that control PEA metabolism, including SPO14 (a yeast homologue of the mammalian phospholipase D) that controls PEA production and YJU3 (a yeast homologue of the mammalian monoacylglycerol lipase) that controls PEA inactivation. We also found that PEA metabolism is affected by heterologous expression of two mammalian proteins involved in neurodegenerative diseases, namely huntingtin and α-synuclein. Significance Together these findings show that forward and reverse genetics in S. cerevisiae can be used to identify proteins involved in PEA production and inactivation, and suggest that mutated proteins causing neurodegenerative diseases might affect the metabolism of this important signaling lipid. PMID:19529773
Reversing Anoikis Resistance in Triple-Negative Breast Cancer
2015-10-01
impaired function and therefore is not as efficient at inducing apoptosis. Supervillin is a protein involved in focal adhesions, and the shorter...splice variant archvillin is normally only expressed in muscle cells. GOLGA4 encodes a golgi protein involved in vesicle transport. It shuttles GPI...when miR-200c is induced and another more 3’ exon is retained, so we are still investigating the function of these regions. Figure 4. Alternative
An integrated optimum design approach for high speed prop-rotors including acoustic constraints
NASA Technical Reports Server (NTRS)
Chattopadhyay, Aditi; Wells, Valana; Mccarthy, Thomas; Han, Arris
1993-01-01
The objective of this research is to develop optimization procedures to provide design trends in high speed prop-rotors. The necessary disciplinary couplings are all considered within a closed loop multilevel decomposition optimization process. The procedures involve the consideration of blade-aeroelastic aerodynamic performance, structural-dynamic design requirements, and acoustics. Further, since the design involves consideration of several different objective functions, multiobjective function formulation techniques are developed.
HnRNP-like proteins as post-transcriptional regulators.
Yeap, Wan-Chin; Namasivayam, Parameswari; Ho, Chai-Ling
2014-10-01
Plant cells contain a diverse repertoire of RNA-binding proteins (RBPs) that coordinate a network of post-transcriptional regulation. RBPs govern diverse developmental processes by modulating the gene expression of specific transcripts. Recent gene annotation and RNA sequencing clearly showed that heterogeneous nuclear ribonucleoprotein (hnRNP)-like proteins which form a family of RBPs, are also expressed in higher plants and serve specific plant functions. In addition to their involvement in post-transcriptional regulation from mRNA capping to translation, they are also involved in telomere regulation, gene silencing and regulation in chloroplast. Here, we review the involvement of plant hnRNP-like proteins in post-transcription regulation of RNA processes and their functional roles in control of plant developmental processes especially plant-specific functions including flowering, chloroplastic-specific mRNA regulation, long-distance phloem transportation and plant responses to environmental stresses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Nesfatin-1 - More than a food intake regulatory peptide.
Stengel, Andreas
2015-10-01
Nesfatin-1 was discovered a decade ago and despite the fact that it represents just one of a multitude of food intake-inhibiting factors it received increasing attention. This led to a detailed characterization of NUCB2/nesfatin-1's physiological property to reduce food intake and also gave rise to an involvement in the long term regulation of body weight, especially under conditions of obesity. In addition, studies indicated the involvement of NUCB2/nesfatin-1 in other homeostatic functions as well: glucose homeostasis, water intake, gastrointestinal functions, temperature regulation, cardiovascular functions, puberty onset and sleep. These pleiotropic actions underline the physiological relevance of this peptide. Recently, the involvement of NUCB2/nesfatin-1 in psychiatric disorders such as anxiety has been investigated giving rise to the speculation that NUCB2/nesfatin-1 represents a peptidergic link between eating and anxiety/depression disorders. Copyright © 2015 Elsevier Inc. All rights reserved.
Zysset, S; Müller, K; Lehmann, C; Thöne-Otto, A I; von Cramon, D Y
2001-11-13
Previous studies have shown that reaction time in an item-recognition task with both short and long lists is a quadratic function of list length. This suggests that either different memory retrieval processes are implied for short and long lists or an adaptive process is involved. An event-related functional magnetic resonance imaging study with nine subjects and list lengths varying between 3 and 18 words was conducted to identify the underlying neuronal structures of retrieval from long and short lists. For the retrieval and processing of word-lists a single fronto-parietal network, including premotor, left prefrontal, left precuneal and left parietal regions, was activated. With increasing list length, no additional regions became involved in retrieving information from long-term memory, suggesting that not necessarily different, but highly adaptive retrieval processes are involved.
Linguistic attention control: attention shifting governed by grammaticized elements of language.
Taube-Schiff, Marlene; Segalowitz, Norman
2005-05-01
In 2 experiments, the authors investigated attention control for tasks involving the processing of grammaticized linguistic stimuli (function words) contextualized in sentence fragments. Attention control was operationalized as shift costs obtained with adult speakers of English in an alternating-runs experimental design (R. D. Rogers & S. Monsell, 1995). Experiment 1 yielded significant attention shift costs between tasks involving judgments about the meanings of grammatical function words. The authors used a 3-stage experimental design (G. Wylie & A. Allport, 2000), and the emerging pattern of results implicated task set reconfiguration and not task set inertia in these shift costs. Experiment 2 further demonstrated that shift costs were lower when the tasks involved shared attentional resources (processing the same grammatical dimension) versus unshared resources (different grammatical dimensions). The authors discuss the results from a cognitive linguistic perspective and for their implications for the view that language itself can serve a special attention-directing function.
Lupyan, Gary
2009-08-01
In addition to its communicative functions, language has been argued to have a variety of extracommunicative functions, as assessed by its causal involvement in putatively nonlinguistic tasks. In the present work, I argue that language may be critically involved in the ability of human adults to categorize objects on a specific dimension (e.g., color) while abstracting over other dimensions (e.g., size). This ability is frequently impaired in aphasic patients. The present work demonstrates that normal participants placed under conditions of verbal interference show a pattern of deficits strikingly similar to that of aphasic patients: impaired taxonomic categorization along perceptual dimensions, and preserved thematic categorization. A control experiment using a visuospatial-interference task failed to find this selective pattern of deficits. The present work has implications for understanding the online role of language in normal cognition and supports the claim that language is causally involved in nonverbal cognition.
Cambered Jet-Flapped Airfoil Theory with Tables and Computer Programs for Application.
1977-09-01
influence function which is a parametric function of the jet-momentum coefficient. In general, the integrals involved must be evaluated by numerical methods. Tables of the necessary influence functions are given in the report.
Todisco, T; de Benedictis, F M; Dottorini, M
1989-01-01
We studied the evolution of respiratory function during and for 3 years after the acute onset of viral and Mycoplasma pneumoniae pneumonias in 13 school-age children. A mixed type transient ventilatory defect (restrictive and obstructive, but mainly restrictive) with large and small airway involvement was observed during the acute phase of the pneumonias. Residual small airway involvement was found over the next 12 months, but no pulmonary function abnormalities were present after 3 years. At that time, one of the 13 subjects displayed bronchial hyperreactivity to distilled water mist challenge. The authors concluded that viral and Mycoplasma pneumoniae pneumonia in previously healthy school-age children does not cause impaired lung function in later childhood.
Neuroimaging studies of the striatum in cognition Part I: healthy individuals
Provost, Jean-Sebastien; Hanganu, Alexandru; Monchi, Oury
2015-01-01
The striatum has traditionally mainly been associated with playing a key role in the modulation of motor functions. Indeed, lesion studies in animals and studies of some neurological conditions in humans have brought further evidence to this idea. However, better methods of investigation have raised concerns about this notion, and it was proposed that the striatum could also be involved in different types of functions including cognitive ones. Although the notion was originally a matter of debate, it is now well-accepted that the caudate nucleus contributes to cognition, while the putamen could be involved in motor functions, and to some extent in cognitive functions as well. With the arrival of modern neuroimaging techniques in the early 1990, knowledge supporting the cognitive aspect of the striatum has greatly increased, and a substantial number of scientific papers were published studying the role of the striatum in healthy individuals. For the first time, it was possible to assess the contribution of specific areas of the brain during the execution of a cognitive task. Neuroanatomical studies have described functional loops involving the striatum and the prefrontal cortex suggesting a specific interaction between these two structures. This review examines the data up to date and provides strong evidence for a specific contribution of the fronto-striatal regions in different cognitive processes, such as set-shifting, self-initiated responses, rule learning, action-contingency, and planning. Finally, a new two-level functional model involving the prefrontal cortex and the dorsal striatum is proposed suggesting an essential role of the dorsal striatum in selecting between competing potential responses or actions, and in resolving a high level of ambiguity. PMID:26500513
Neuroimaging studies of the striatum in cognition Part I: healthy individuals.
Provost, Jean-Sebastien; Hanganu, Alexandru; Monchi, Oury
2015-01-01
The striatum has traditionally mainly been associated with playing a key role in the modulation of motor functions. Indeed, lesion studies in animals and studies of some neurological conditions in humans have brought further evidence to this idea. However, better methods of investigation have raised concerns about this notion, and it was proposed that the striatum could also be involved in different types of functions including cognitive ones. Although the notion was originally a matter of debate, it is now well-accepted that the caudate nucleus contributes to cognition, while the putamen could be involved in motor functions, and to some extent in cognitive functions as well. With the arrival of modern neuroimaging techniques in the early 1990, knowledge supporting the cognitive aspect of the striatum has greatly increased, and a substantial number of scientific papers were published studying the role of the striatum in healthy individuals. For the first time, it was possible to assess the contribution of specific areas of the brain during the execution of a cognitive task. Neuroanatomical studies have described functional loops involving the striatum and the prefrontal cortex suggesting a specific interaction between these two structures. This review examines the data up to date and provides strong evidence for a specific contribution of the fronto-striatal regions in different cognitive processes, such as set-shifting, self-initiated responses, rule learning, action-contingency, and planning. Finally, a new two-level functional model involving the prefrontal cortex and the dorsal striatum is proposed suggesting an essential role of the dorsal striatum in selecting between competing potential responses or actions, and in resolving a high level of ambiguity.
School Control--What, How and Why.
ERIC Educational Resources Information Center
Holmes, Mark
School administrators can get a better idea of what their purpose is by examining, first, what schools achieve; second, how schools function; and, third, why they function. A school's production function (what it achieves) involves many specific functions, but they all are a product of the relationship between school inputs and outputs. Inputs…
Functions and Mechanisms of Sleep
Zielinski, Mark R.; McKenna, James T.; McCarley, Robert W.
2017-01-01
Sleep is a complex physiological process that is regulated globally, regionally, and locally by both cellular and molecular mechanisms. It occurs to some extent in all animals, although sleep expression in lower animals may be co-extensive with rest. Sleep regulation plays an intrinsic part in many behavioral and physiological functions. Currently, all researchers agree there is no single physiological role sleep serves. Nevertheless, it is quite evident that sleep is essential for many vital functions including development, energy conservation, brain waste clearance, modulation of immune responses, cognition, performance, vigilance, disease, and psychological state. This review details the physiological processes involved in sleep regulation and the possible functions that sleep may serve. This description of the brain circuitry, cell types, and molecules involved in sleep regulation is intended to further the reader’s understanding of the functions of sleep. PMID:28413828
Berling, T; Bolze, P-A; Berthiller, J; Dubernard, G; Lamblin, G; Paparel, P; Golfier, F
2017-06-01
To assess postoperative complications, improvement of pain symptoms and residual urinary functional symptoms after surgery for deep infiltrative endometriosis affecting ureter or bladder. Retrospective study of complications (Clavien-Dindo classification), pain (visual analog scale [VAS]) and urinary functional symptoms (Urinary Symptom Profile questionnaire [USP]) of patients surgically treated between 2007 and 2015 in University Hospitals of Lyon. Among 31 patients with endometriosis involving the bladder, 83.9% had a partial cystectomy and 16.1% an extra-mucosal resection. Among patients (n=20) with ureteral involvement, 85% had ureterectomy with ureterocystoneostomy and 15% had only ureterolysis. Grade III postoperative complications occurred in 6% and 0% of patients with bladder or ureteral surgery, respectively and no grade IV or V complications were reported. Mean bladder VAS dropped from 5.3±4.2 to 0.3±0.9 after a follow-up of 42 months (P<0.0001). In patients with ureteral involvement, mean flank VAS dropped from 3.6 to 0.9 after a follow-up of 33 months (P<0.0005). Mean postoperative USP score for dysuria and detrusor overactivity were 1.35/9 and 2.48/21 in case of bladder involvement, and 1.10/9 and 2.15/21 in case of ureteral involvement. Multidisciplinary surgical management of deep infiltrative endometriosis affecting urinary tract was associated to a low risk of severe postoperative complications and to a long-term significant improvement of pain symptoms without significant residual functional urinary symptoms. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
ERIC Educational Resources Information Center
Richards, Margaret M.; Bowers, Mark J.; Lazicki, Tammy; Krall, Dan; Jacobs, Anne K.
2008-01-01
We examined behavioral markers of caregiver involvement and the ways in which family participation was related to treatment outcomes in 47 elementary school children with SED enrolled in a school-based intensive mental health program. Measures of caregiver involvement included therapeutic home visits, attendance at therapeutic meetings, completion…
Grandfather Involvement in Childrearing and the School Performance of Ojibwa Children.
ERIC Educational Resources Information Center
Williams, Edith; And Others
Nineteen Ojibwa families with 3- to 11-year-olds from Bay Mills reservation in Michigan were studied to identify: (1) the relationship between quantity and quality of grandfather involvement in their grandchild's rearing and the grandchild's academic and social functioning; and (2) antecedents to this involvement. Quantity of grandfather…
ERIC Educational Resources Information Center
Kaplan Toren, Nurit; Seginer, Rachel
2015-01-01
In this 2-year longitudinal study, we examine the effects of perceived classroom climate and two aspects of parental educational involvement (home-based and school-based) on junior high school students' self-evaluation and academic achievement. Our main hypothesis was that perceived parental educational involvement mediates students' perceived…
Thirunavukkarasu, Nepolean; Hossain, Firoz; Arora, Kanika; Sharma, Rinku; Shiriga, Kaliyugam; Mittal, Swati; Mohan, Sweta; Namratha, Pottekatt Mohanlal; Dogga, Sreelatha; Rani, Tikka Shobha; Katragadda, Sumalini; Rathore, Abhishek; Shah, Trushar; Mohapatra, Trilochan; Gupta, Hari Shankar
2014-12-24
Earlier studies were focused on the genetics of temperate and tropical maize under drought. We identified genetic loci and their association with functional mechanisms in 240 accessions of subtropical maize using a high-density marker set under water stress. Out of 61 significant SNPs (11 were false-discovery-rate-corrected associations), identified across agronomic traits, models, and locations by subjecting the accessions to water stress at flowering stage, 48% were associated with drought-tolerant genes. Maize gene models revealed that SNPs mapped for agronomic traits were in fact associated with number of functional traits as follows: stomatal closure, 28; flowering, 15; root development, 5; detoxification, 4; and reduced water potential, 2. Interactions of these SNPS through the functional traits could lead to drought tolerance. The SNPs associated with ABA-dependent signalling pathways played a major role in the plant's response to stress by regulating a series of functions including flowering, root development, auxin metabolism, guard cell functions, and scavenging reactive oxygen species (ROS). ABA signalling genes regulate flowering through epigenetic changes in stress-responsive genes. ROS generated by ABA signalling are reduced by the interplay between ethylene, ABA, and detoxification signalling transductions. Integration of ABA-signalling genes with auxin-inducible genes regulates root development which in turn, maintains the water balance by regulating electrochemical gradient in plant. Several genes are directly or indirectly involved in the functioning of agronomic traits related to water stress. Genes involved in these crucial biological functions interacted significantly in order to maintain the primary as well as exclusive functions related to coping with water stress. SNPs associated with drought-tolerant genes involved in strategic biological functions will be useful to understand the mechanisms of drought tolerance in subtropical maize.
The Videofluorographic Swallowing Study in Rheumatologic Diseases: A Comprehensive Review
Di Piazza, Ambra; Costanzo, Massimo; Scopelliti, Laura; Salvaggi, Francesco; Cupido, Francesco; Salerno, Sergio; Lo Casto, Antonio; Midiri, Massimo; Lo Re, Giuseppe; Lagalla, Roberto
2017-01-01
Autoimmune connective tissue diseases are a heterogeneous group of pathologies that affect about 10% of world population with chronic evolution in 20%–80%. Inflammation in autoimmune diseases may lead to serious damage to other organs including the gastrointestinal tract. Gastrointestinal tract involvement in these patients may also due to both a direct action of antibodies against organs and pharmacological therapies. Dysphagia is one of the most important symptom, and it is caused by failure of the swallowing function and may lead to aspiration pneumonia, malnutrition, dehydration, weight loss, and airway obstruction. The videofluorographic swallowing study is a key diagnostic tool in the detection of swallowing disorders, allowing to make an early diagnosis and to reduce the risk of gastrointestinal and pulmonary complications. This technique helps to identify both functional and structural anomalies of the anatomic chain involved in swallowing function. The aim of this review is to systematically analyze the basis of the pathological involvement of the swallowing function for each rheumatological disease and to show the main features of the videofluorographic study that may be encountered in these patients. PMID:28706536
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jia, Y.F.; Thomas, K.M.
Various types of oxygen functional groups were introduced onto the surface of coconut shell derived activated carbon by oxidation using nitric acid. Fourier-transform infrared spectroscopy (FTIR), temperature-programmed desorption (TPD), and selective neutralization were used to characterize the surface oxygen functional groups. The oxidized carbons were also heat treated to provide a suite of carbons where the oxygen functional groups of various thermal stabilities were varied progressively. The adsorption of cadmium ions was enhanced dramatically by oxidation of the carbon. The ratio of released protons to adsorbed cadmium ions on oxidized carbon was approximately 2, indicating cation exchange was involved inmore » the process of adsorption. Na{sup +} exchange studies with the oxidized carbon gave a similar ratio. After heat treatment of the oxidized carbons to remove oxygen functional groups, the ratio of H{sup +} released to Cd{sup 2+} adsorbed and the adsorption capacity decreased significantly. Both reversible and irreversible processes were involved in cadmium ion adsorption with reversible adsorption having higher enthalpy. The irreversible adsorption resulted from cation exchange with carboxylic acid groups, whereas the reversible adsorption probably involved physisorption of the partially hydrated cadmium ion.« less
Pejchal, Robert; Campbell, Elizabeth; Guenther, Brian D.; Lennon, Brett W.; Matthews, Rowena G.; Ludwig, Martha L.
2006-01-01
In human methylenetetrahydrofolate reductase (MTHFR) the Ala222Val (677C → T) polymorphism encodes a heat-labile gene product that is associated with elevated levels of homocysteine and possibly with risk for cardiovascular disease. Generation of the equivalent Ala to Val mutation in Escherichia coli MTHFR, which is 30% identical to the catalytic domain of the human enzyme, creates a protein with enhanced thermolability. In both human and E. coli MTHFR, the A → V mutation increases the rate of dissociation of FAD, and in both enzymes, loss of FAD is linked to changes in quaternary structure [Yamada, K., Chen, Z., Rozen, R., and Matthews, R. G. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 14853–14858; Guenther, B. D., Sheppard, C. A., Tran, P., Rozen, R., Matthews, R. G., and Ludwig, M. L. (1999) Nat. Struct. Biol. 6, 359–365]. Folates have been shown to protect both human and bacterial enzymes from loss of FAD. Despite its effect on affinity for FAD, the A → V mutation is located at the bottom of the (βα)8 barrel of the catalytic domain in a position that does not contact the bound FAD prosthetic group. Here we report the structures of the Ala177Val mutant of E. coli MTHFR and of its complex with the 5,10-dideazafolate analogue, LY309887, and suggest mechanisms by which the mutation may perturb FAD binding. Helix α5, which immediately precedes the loop bearing the mutation, carries several residues that interact with FAD, including Asn168, Arg171, and Lys172. In the structures of the mutant enzyme this helix is displaced, perturbing protein–FAD interactions. In the complex with LY309887, the pterin-like ring of the analogue stacks against the si face of the flavin and is secured by hydrogen bonds to residues Gln183 and Asp120 that adjoin this face. The direct interactions of bound folate with the cofactor provide one mechanism for linkage between binding of FAD and folate binding that could account in part for the protective action of folates. Conformation changes induced by folate binding may also suppress dissociation of FAD. PMID:16605249
Graentzdoerffer, Andrea; Rauh, David; Pich, Andreas; Andreesen, Jan R
2003-01-01
Two gene clusters encoding similar formate dehydrogenases (FDH) were identified in Eubacterium acidaminophilum. Each cluster is composed of one gene coding for a catalytic subunit ( fdhA-I, fdhA-II) and one for an electron-transferring subunit ( fdhB-I, fdhB-II). Both fdhA genes contain a TGA codon for selenocysteine incorporation and the encoded proteins harbor five putative iron-sulfur clusters in their N-terminal region. Both FdhB subunits resemble the N-terminal region of FdhA on the amino acid level and contain five putative iron-sulfur clusters. Four genes thought to encode the subunits of an iron-only hydrogenase are located upstream of the FDH gene cluster I. By sequence comparison, HymA and HymB are predicted to contain one and four iron-sulfur clusters, respectively, the latter protein also binding sites for FMN and NAD(P). Thus, HymA and HymB seem to represent electron-transferring subunits, and HymC the putative catalytic subunit containing motifs for four iron-sulfur clusters and one H-cluster specific for Fe-only hydrogenases. HymD has six predicted transmembrane helices and might be an integral membrane protein. Viologen-dependent FDH activity was purified from serine-grown cells of E. acidaminophilum and the purified protein complex contained four subunits, FdhA and FdhB, encoded by FDH gene cluster II, and HymA and HymB, identified after determination of their N-terminal sequences. Thus, this complex might represent the most simple type of a formate hydrogen lyase. The purified formate dehydrogenase fraction contained iron, tungsten, a pterin cofactor, and zinc, but no molybdenum. FDH-II had a two-fold higher K(m) for formate (0.37 mM) than FDH-I and also catalyzed CO(2) reduction to formate. Reverse transcription (RT)-PCR pointed to increased expression of FDH-II in serine-grown cells, supporting the isolation of this FDH isoform. The fdhA-I gene was expressed as inactive protein in Escherichia coli. The in-frame UGA codon for selenocysteine incorporation was read in the heterologous system only as stop codon, although its potential SECIS element exhibited a quite high similarity to that of E. coli FDH.
Gopalakrishna, Deepak; Pennington, Samantha; Karaa, Amel; Clemens, Mark G
2016-07-01
It has been shown that microcirculation is hypersensitized to endothelin1 (ET-1) following endotoxin (lipopolysaccharide [LPS]) treatment leading to an increased vasopressor response. This may be related in part to decreased activation of endothelial nitric oxide synthase (eNOS) by ET-1. eNOS can also be uncoupled to produce superoxide (O2). This aberrant eNOS activity could further contribute to the hyperconstriction and injury caused by ET-1 following LPS. We therefore tested whether LPS affects ROS production by vascular endothelial cells and whether and how this effect is altered by ET-1. Human umbilical vein endothelial cells (HUVEC) or human microvascular endothelial cells (HMEC) were subjected to a 6-h treatment with LPS (250 ng/mL) or LPS and sepiapterin (100 μM) followed by a 30-min treatment with 100 μM L-Iminoethyl Ornithine (L-NIO) an irreversible eNOS inhibitor and 30-min treatment with ET-1 (10 nM). Conversion of [H]L-arginine to [H]L-citrulline was used to measure eNOS activity. Superoxide dismutase (SOD) inhibitable reduction of Cytochrome-C, dihydro carboxy fluorescein (DCF), and Mitosox was used to estimate ROS. LT-SDS PAGE was used to assess the degree of monomerization of the eNOS homodimer. Stimulation of HUVECs with ET-1 significantly increased NO synthesis by 1.4-fold (P < 0.05). ET-1 stimulation of LPS-treated HUVECs failed to increase NO production. Western blot for eNOS protein showed no change in eNOS protein levels. LPS alone resulted in an insignificant increase in ROS production as measured by cytochrome C that was increased 4.6-fold by ET-1 stimulation (P < 0.05). L-NIO significantly decreased ET-1-induced ROS production (P < 0.05). Sepiapterin significantly decreased ROS production in both; unstimulated and ET-1-stimulated LPS-treated groups, but did not restore NO production. DCF experiments confirmed intracellular ROS while Mitosox suggested a non-mitochondrial source. ET-1 treatment following a chronic LPS stress significantly monomerized the eNOS homodimer that was inhibited by sepiapterin loading. The two concomitant phenomena of decreased NO production and increased ROS formation seem to be multifactorial in nature with ROS production dependent upon pterin availability.
Cytochemistry of the functional domains of the nucleus in normal and in pathologic conditions.
Maraldi, N M; Zini, N; Santi, S; Ognibene, A; Rizzoli, R; Mazzotti, G; Manzoli, F A
1998-01-01
By means of ultrastructural cytochemistry significant advances have been made in understanding the functional roles of many nuclear domains. This review gives schematic information about the main nuclear domains involved in replication, transcription, processing and transport of the transcripts in normal and in pathologic conditions. Particular attention is paid to a functional domain that appears to be involved in signal transduction. Data are reported on the intranuclear specific localization of key elements of the polyphosphoinositide signal transduction system in different cell types including human osteosarcoma cell lines. Compared with the compartmentalization of the cytoplasm, the nucleus has long been considered as relatively unstructured. On the other hand, fundamental nuclear functions, such as DNA replication and RNA transcription, can be molecularly characterized also in cell-free systems, suggesting that supramolecular organization is not so strictly required as for other cell functions occurring within intact cytoplasmic organelles. Nevertheless, a stringent organization is required for packing about 200 cm of DNA in the about 30 micron 3 of the nucleus. In the absence of membrane-delimited organelles, the nuclear organization is based on functional compartments, or domains, whose spatial localization involves the nuclear matrix, which shares many properties with the cytoskeleton. The nuclear domains are defined as structural compartments, not necessarily stable but dynamically variable, which perform specific metabolic functions through the partitioning of molecular complexes. Their identification has been made possible in the last few years by the development of specific nuclear probes for confocal and electron microscope immunocytochemistry. Therefore, the complex network of structures and enzymatic functions that make up the nucleus is in several cases yielding to molecular analysis, but a large part remains unknown (Strouboulis and Wolffe, 1996; Laemmli and Tjian, 1996). Rapid advances in understanding the functional role of the nuclear domains have been made recently: in particular, of the nuclear envelope, of the nucleolus, and of RNA splicing. In other cases, e.g. the precise localization of the nuclear domains involved in signal transduction, much remains to be clarified (Forbes and Johnson, 1997). It is conceivable that in the near future unexpected new nuclear domains will come to light and new nuclear functions may emerge, especially in field of post-transcriptional processing and transport of RNAs, and in the relationships between the nucleo-skeleton and enzymic fixed sites involved in replication, transcription and signal transduction. The aim of this review is to provide information about the morphological characteristics, the associated functions and the molecular composition of the main nuclear domains found to date. To simplify the exposition, the main data on each nuclear domain are reported in Tables, together with the principal references on the subject. Figures refer to original findings on some aspects of nuclear domain organization.
Arch-Tirado, Emilio; Lino-González, Ana Luisa; Alfaro-Rodríguez, Alfonso
2013-01-01
This paper aims to discuss and analyze the role of mathematics in neurodevelopment, for which discusses the historical, ontogenetic and physiological bases involved. The methodology of this paper is a deductive analysis, describing the use of mathematics in ancient cultures to the specialization of brain regions. Sensory perceptions are useful for the acquisition and development of cortical functions thus sensory stimulations is essential for the maturation of specialized neurologic functions.
Transition-Metal-Free Alkynylation of Aryl Chlorides
Truong, Thanh; Daugulis, Olafs
2011-01-01
Two sets of conditions have been developed for a base-mediated, transition-metal-free alkynylation of aryl chlorides that proceeds via benzyne intermediates. The first set of conditions involves the use of TMPLi base in a pentane/THF mixture at 25 °C. The second set involves use of a metal alkoxide base in dioxane at elevated temperature. Reasonable functional group tolerance has been observed. Fluoro, trifluoromethyl, silyl, cyano, and alcohol functionalities are compatible with the reaction conditions. PMID:21786825
Connectivity constraints on cortical reorganization of neural circuits involved in object naming.
Papagno, Costanza; Gallucci, Marcello; Casarotti, Alessandra; Castellano, Antonella; Falini, Andrea; Fava, Enrica; Giussani, Carlo; Carrabba, Giorgio; Bello, Lorenzo; Caramazza, Alfonso
2011-04-01
The brain's plasticity in response to sensory deprivation and other perturbations is well established. While the functional properties of the reorganized areas are under vigorous investigation, the factors that constrain cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions-reorganization attempts to preserve the functionality of subcortical connections. Here we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization of the networks involved in object naming following perturbation of normal function. We used direct electrical stimulation (DES) during surgical removal of gliomas to identify the sites that are involved in naming different categories of objects. The sites that were selectively inhibited in naming either living or non-living objects were displaced relative to those observed with other subject populations, possibly reflecting cortical reorganization due to slowly evolving brain damage. Subcortical DES applied to the white matter underlying these regions also led to category-specific naming deficits. The existence of these subcortical fiber pathways was confirmed using diffusion tensor tractography. These results constitute the first neurophysiological evidence for the critical role of subcortical pathways as part of the neural circuits that are involved in object naming; they also highlight the importance of subcortical connectivity in shaping cortical reorganization following perturbations of normal function. Copyright © 2011 Elsevier Inc. All rights reserved.
Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling
Diaz, Maira; Sanchez-Barrena, Maria Jose; Gonzalez-Rubio, Juana Maria; Rodriguez, Lesia; Fernandez, Daniel; Antoni, Regina; Yunta, Cristina; Belda-Palazon, Borja; Gonzalez-Guzman, Miguel; Peirats-Llobet, Marta; Menendez, Margarita; Boskovic, Jasminka; Marquez, Jose A.; Rodriguez, Pedro L.; Albert, Armando
2016-01-01
Regulation of ion transport in plants is essential for cell function. Abiotic stress unbalances cell ion homeostasis, and plants tend to readjust it, regulating membrane transporters and channels. The plant hormone abscisic acid (ABA) and the second messenger Ca2+ are central in such processes, as they are involved in the regulation of protein kinases and phosphatases that control ion transport activity in response to environmental stimuli. The identification and characterization of the molecular mechanisms underlying the effect of ABA and Ca2+ signaling pathways on membrane function are central and could provide opportunities for crop improvement. The C2-domain ABA-related (CAR) family of small proteins is involved in the Ca2+-dependent recruitment of the pyrabactin resistance 1/PYR1-like (PYR/PYL) ABA receptors to the membrane. However, to fully understand CAR function, it is necessary to define a molecular mechanism that integrates Ca2+ sensing, membrane interaction, and the recognition of the PYR/PYL interacting partners. We present structural and biochemical data showing that CARs are peripheral membrane proteins that functionally cluster on the membrane and generate strong positive membrane curvature in a Ca2+-dependent manner. These features represent a mechanism for the generation, stabilization, and/or specific recognition of membrane discontinuities. Such structures may act as signaling platforms involved in the recruitment of PYR/PYL receptors and other signaling components involved in cell responses to stress. PMID:26719420
Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling.
Diaz, Maira; Sanchez-Barrena, Maria Jose; Gonzalez-Rubio, Juana Maria; Rodriguez, Lesia; Fernandez, Daniel; Antoni, Regina; Yunta, Cristina; Belda-Palazon, Borja; Gonzalez-Guzman, Miguel; Peirats-Llobet, Marta; Menendez, Margarita; Boskovic, Jasminka; Marquez, Jose A; Rodriguez, Pedro L; Albert, Armando
2016-01-19
Regulation of ion transport in plants is essential for cell function. Abiotic stress unbalances cell ion homeostasis, and plants tend to readjust it, regulating membrane transporters and channels. The plant hormone abscisic acid (ABA) and the second messenger Ca(2+) are central in such processes, as they are involved in the regulation of protein kinases and phosphatases that control ion transport activity in response to environmental stimuli. The identification and characterization of the molecular mechanisms underlying the effect of ABA and Ca(2+) signaling pathways on membrane function are central and could provide opportunities for crop improvement. The C2-domain ABA-related (CAR) family of small proteins is involved in the Ca(2+)-dependent recruitment of the pyrabactin resistance 1/PYR1-like (PYR/PYL) ABA receptors to the membrane. However, to fully understand CAR function, it is necessary to define a molecular mechanism that integrates Ca(2+) sensing, membrane interaction, and the recognition of the PYR/PYL interacting partners. We present structural and biochemical data showing that CARs are peripheral membrane proteins that functionally cluster on the membrane and generate strong positive membrane curvature in a Ca(2+)-dependent manner. These features represent a mechanism for the generation, stabilization, and/or specific recognition of membrane discontinuities. Such structures may act as signaling platforms involved in the recruitment of PYR/PYL receptors and other signaling components involved in cell responses to stress.
Liu, Meng-Jung; Ma, Le-Yin; Chou, Wen-Jiun; Chen, Yu-Min; Liu, Tai-Ling; Hsiao, Ray C; Hu, Huei-Fan; Yen, Cheng-Fang
2018-01-01
Bullying involvement is prevalent among children and adolescents with autism spectrum disorder (ASD). This study examined the effects of theory of mind performance training (ToMPT) on reducing bullying involvement in children and adolescents with high-functioning ASD. Children and adolescents with high-functioning ASD completed ToMPT (n = 26) and social skills training (SST; n = 23) programs. Participants in both groups and their mothers rated the pretraining and posttraining bullying involvement of participants on the Chinese version of the School Bullying Experience Questionnaire. The paired t test was used to evaluate changes in bullying victimization and perpetration between the pretraining and posttraining assessments. Furthermore, the linear mixed-effect model was used to examine the difference in the training effect between the ToMPT and SST groups. The paired t test indicated that in the ToMPT group, the severities of both self-reported (p = .039) and mother-reported (p = .003) bullying victimization significantly decreased from the pretraining to posttraining assessments, whereas in the SST group, only self-reported bullying victimization significantly decreased (p = .027). The linear mixed-effect model indicated that compared with the SST program, the ToMPT program significantly reduced the severity of mother-reported bullying victimization (p = .041). The present study supports the effects of ToMPT on reducing mother-reported bullying victimization in children and adolescents with high-functioning ASD.
Major health service transformation and the public voice: conflict, challenge or complicity?
Martin, Graham P; Carter, Pam; Dent, Mike
2018-01-01
Objectives Calls for major reconfigurations of health services have been accompanied by recommendations that wide ranging stakeholders be involved. In particular, patients and the wider public are seen as critical contributors as both funders and beneficiaries of public health care. But public involvement is fraught with challenges, and little research has focused on involvement in the health service transformation initiatives. This paper examines the design and function of public involvement in reconfiguration of health services within the English NHS. Methods Qualitative data including interviews, observation and documents were collected in two health service 'transformation' programmes; interviews include involved public and professional participants. Data were analysed using parallel deductive and inductive approaches. Results Public involvement in the programmes was extensive but its terms of reference, and the individuals involved, were restricted by policy pressures and programme objectives. The degree to which participants descriptively or substantively represented the wider public was limited; participants sought to 'speak for' this public but their views on what was 'acceptable' and likely to influence decision-making led them to constrain their contributions. Conclusions Public involvement in two major service reconfiguration programmes in England was seen as important and functional, and could not be characterized as tokenistic. Yet involvement in these programmes fell short of normative ideals, and could inadvertently reduce, rather than enlarge, public influence on health service reconfiguration decisions.
Burger, Joanna; Gochfeld, Michael; Bunn, Amoret; Downs, Janelle; Jeitner, Christian; Pittfield, Taryn; Salisbury, Jennifer
2016-01-01
Governmental agencies, regulators, health professionals, tribal leaders, and the public are faced with understanding and evaluating the effects of cleanup activities on species, populations, and ecosystems. While engineers and managers understand the processes involved in different remediation types such as capping, pump and treat, and natural attenuation, there is often a disconnect between (1) how ecologists view the influence of different types of remediation, (2) how the public perceives them, and (3) how engineers understand them. The overall goal of the present investigation was to define the components of remediation types (= functional remediation). Objectives were to (1) define and describe functional components of remediation, regardless of the remediation type, (2) provide examples of each functional remediation component, and (3) explore potential effects of functional remediation components in the post-cleanup phase that may involve continued monitoring and assessment. Functional remediation components include types, numbers, and intensity of people, trucks, heavy equipment, pipes, and drill holes, among others. Several components may be involved in each remediation type, and each results in ecological effects, ranging from trampling of plants, to spreading invasive species, to disturbing rare species, and to creating fragmented habitats. In some cases remediation may exert a greater effect on ecological receptors than leaving the limited contamination in place. A goal of this conceptualization is to break down functional components of remediation such that managers, regulators, and the public might assess the effects of timing, extent, and duration of different remediation options on ecological systems.
Functional mechanisms involved in the internal inhibition of taboo words.
Severens, Els; Kühn, Simone; Hartsuiker, Robert J; Brass, Marcel
2012-04-01
The present study used functional magnetic resonance imaging to investigate brain processes associated with the inhibition of socially undesirable speech. It is tested whether the inhibition of undesirable speech is solely related to brain areas associated with classical stop signal tasks or rather also involves brain areas involved in endogenous self-control. During the experiment, subjects had to do a SLIP task, which was designed to elicit taboo or neutral spoonerisms. Here we show that the internal inhibition of taboo words activates the right inferior frontal gyrus, an area that has previously been associated with externally triggered inhibition. This finding strongly suggests that external social rules become internalized and act as a stop-signal.
Functional mechanisms involved in the internal inhibition of taboo words
Kühn, Simone; Hartsuiker, Robert J.; Brass, Marcel
2012-01-01
The present study used functional magnetic resonance imaging to investigate brain processes associated with the inhibition of socially undesirable speech. It is tested whether the inhibition of undesirable speech is solely related to brain areas associated with classical stop signal tasks or rather also involves brain areas involved in endogenous self-control. During the experiment, subjects had to do a SLIP task, which was designed to elicit taboo or neutral spoonerisms. Here we show that the internal inhibition of taboo words activates the right inferior frontal gyrus, an area that has previously been associated with externally triggered inhibition. This finding strongly suggests that external social rules become internalized and act as a stop-signal. PMID:21609970
Novel interactive partners of neuroligin 3: new aspects for pathogenesis of autism.
Shen, Chen; Huo, Li-rong; Zhao, Xin-liang; Wang, Pei-rong; Zhong, Nanbert
2015-05-01
Autism is a neurodevelopmental disorder with a strong genetic predisposition. Neurolign 3 (NLGN3) as a postsynaptic transmembrane protein, functions in both neuron synaptogenesis and glia-neuron communications. Previously, a gain of function mutation (R451C) in NLGN3 was identified in autistic patients, which illustrates the involvement of NLGN3 in autism pathogenesis. As proper synaptic targeting and functioning are controlled by intracellular protein interactions, in the current study, we tried to discover the intracellular regulation network in which NLGN3 might be involved by a yeast two-hybrid-based interactor identification. Fifty-one protein candidate partners were identified after screening a human fetal complementary DNA (cDNA) library with an intracellular fragment of NLGN3. The interactions of NLGN3 with a subset of candidates, including EEF1A1, FLNA, ITPRIP, CYP11A1, MT-CO2, GPR175, ACOT2, and QPRT, were further validated in human neuroblastoma cells or brain tissues. Furthermore, our study suggested that NLGN3 was functioning in cytosolic calcium balance and participating in calcium-regulated cellular processes. Our findings of novel NLGN3 binding partners provide evidences of involvement of NLGN3 in multiple biological pathways, especially calcium regulating and mitochondrial function, thus suggesting further significance. This new data not only leads to a better understanding of the physiological functions of NLGN3, but also provide new aspects for pathogenesis of autism.
Dittinger, Eva; Valizadeh, Seyed Abolfazl; Jäncke, Lutz; Besson, Mireille; Elmer, Stefan
2018-02-01
Current models of speech and language processing postulate the involvement of two parallel processing streams (the dual stream model): a ventral stream involved in mapping sensory and phonological representations onto lexical and conceptual representations and a dorsal stream contributing to sound-to-motor mapping, articulation, and to how verbal information is encoded and manipulated in memory. Based on previous evidence showing that music training has an influence on language processing, cognitive functions, and word learning, we examined EEG-based intracranial functional connectivity in the ventral and dorsal streams while musicians and nonmusicians learned the meaning of novel words through picture-word associations. In accordance with the dual stream model, word learning was generally associated with increased beta functional connectivity in the ventral stream compared to the dorsal stream. In addition, in the linguistically most demanding "semantic task," musicians outperformed nonmusicians, and this behavioral advantage was accompanied by increased left-hemispheric theta connectivity in both streams. Moreover, theta coherence in the left dorsal pathway was positively correlated with the number of years of music training. These results provide evidence for a complex interplay within a network of brain regions involved in semantic processing and verbal memory functions, and suggest that intensive music training can modify its functional architecture leading to advantages in novel word learning. © 2017 Wiley Periodicals, Inc.
Peradzyńska, Joanna; Krenke, Katarzyna; Szylling, Anna; Kołodziejczyk, Beata; Gazda, Agnieszka; Rutkowska-Sak, Lidia; Kulus, Marek
2016-01-01
Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. FEV₁, FEV₁/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.
Uddin, Lucina Q; Supekar, Kaustubh; Amin, Hitha; Rykhlevskaia, Elena; Nguyen, Daniel A; Greicius, Michael D; Menon, Vinod
2010-11-01
The inferior parietal lobule (IPL) of the human brain is a heterogeneous region involved in visuospatial attention, memory, and mathematical cognition. Detailed description of connectivity profiles of subdivisions within the IPL is critical for accurate interpretation of functional neuroimaging studies involving this region. We separately examined functional and structural connectivity of the angular gyrus (AG) and the intraparietal sulcus (IPS) using probabilistic cytoarchitectonic maps. Regions-of-interest (ROIs) included anterior and posterior AG subregions (PGa, PGp) and 3 IPS subregions (hIP2, hIP1, and hIP3). Resting-state functional connectivity analyses showed that PGa was more strongly linked to basal ganglia, ventral premotor areas, and ventrolateral prefrontal cortex, while PGp was more strongly connected with ventromedial prefrontal cortex, posterior cingulate, and hippocampus-regions comprising the default mode network. The anterior-most IPS ROIs, hIP2 and hIP1, were linked with ventral premotor and middle frontal gyrus, while the posterior-most IPS ROI, hIP3, showed connectivity with extrastriate visual areas. In addition, hIP1 was connected with the insula. Tractography using diffusion tensor imaging revealed structural connectivity between most of these functionally connected regions. Our findings provide evidence for functional heterogeneity of cytoarchitectonically defined subdivisions within IPL and offer a novel framework for synthesis and interpretation of the task-related activations and deactivations involving the IPL during cognition.
Supekar, Kaustubh; Amin, Hitha; Rykhlevskaia, Elena; Nguyen, Daniel A.; Greicius, Michael D.; Menon, Vinod
2010-01-01
The inferior parietal lobule (IPL) of the human brain is a heterogeneous region involved in visuospatial attention, memory, and mathematical cognition. Detailed description of connectivity profiles of subdivisions within the IPL is critical for accurate interpretation of functional neuroimaging studies involving this region. We separately examined functional and structural connectivity of the angular gyrus (AG) and the intraparietal sulcus (IPS) using probabilistic cytoarchitectonic maps. Regions-of-interest (ROIs) included anterior and posterior AG subregions (PGa, PGp) and 3 IPS subregions (hIP2, hIP1, and hIP3). Resting-state functional connectivity analyses showed that PGa was more strongly linked to basal ganglia, ventral premotor areas, and ventrolateral prefrontal cortex, while PGp was more strongly connected with ventromedial prefrontal cortex, posterior cingulate, and hippocampus—regions comprising the default mode network. The anterior-most IPS ROIs, hIP2 and hIP1, were linked with ventral premotor and middle frontal gyrus, while the posterior-most IPS ROI, hIP3, showed connectivity with extrastriate visual areas. In addition, hIP1 was connected with the insula. Tractography using diffusion tensor imaging revealed structural connectivity between most of these functionally connected regions. Our findings provide evidence for functional heterogeneity of cytoarchitectonically defined subdivisions within IPL and offer a novel framework for synthesis and interpretation of the task-related activations and deactivations involving the IPL during cognition. PMID:20154013
Understanding the Executive Functioning Heterogeneity in Schizophrenia
ERIC Educational Resources Information Center
Raffard, Stephane; Bayard, Sophie
2012-01-01
Schizophrenia is characterized by heterogeneous brain abnormalities involving cerebral regions implied in the executive functioning. The dysexecutive syndrome is one of the most prominent and functionally cognitive features of schizophrenia. Nevertheless, it is not clear to what extend executive deficits are heterogeneous in schizophrenia…
Functional Magnetic Resonance Imaging
ERIC Educational Resources Information Center
Voos, Avery; Pelphrey, Kevin
2013-01-01
Functional magnetic resonance imaging (fMRI), with its excellent spatial resolution and ability to visualize networks of neuroanatomical structures involved in complex information processing, has become the dominant technique for the study of brain function and its development. The accessibility of in-vivo pediatric brain-imaging techniques…
ERIC Educational Resources Information Center
Bornstein, Daniel B.; Pate, Russell R.; Beets, Michael W.; Saunders, Ruth P.; Blair, Steven N.
2015-01-01
Introduction: Coalitions are often composed of member organizations. Member involvement is thought to be associated with coalition success. No instrument currently exists for evaluating organizational member involvement in physical activity coalitions. This study aimed to develop a survey instrument for evaluating organizational member involvement…
The Function of Electronic Communication Devices in Assisting Parental Involvement in Middle Schools
ERIC Educational Resources Information Center
Koch, Cotton S.
2010-01-01
The importance of home-to-school and school-to-home communication and parental involvement is well documented by researchers and acknowledged by practitioners. A number of earlier studies argue that there is a positive association between two-way communication, parental involvement, and student achievement at all levels of K-12 education. However,…
ERIC Educational Resources Information Center
Jeynes, William H.
2010-01-01
Background/Context: For many years, educators, parents, and social scientists have conceptualized engaged parents as those who help their children with their homework, frequently attend school functions, and maintain household rules that dictate when their young engage in schoolwork and leisure. Recent meta-analyses on parental involvement confirm…
ERIC Educational Resources Information Center
Gaston, Sean Maurice
2013-01-01
The role of the "principal" in encouraging and supporting parent involvement has not received as much research attention as it would seem to merit. While the recent literature on parent involvement is extensive, virtually none are devoted to investigating the impact of school leadership, particularly the function of the principal on…
The cerebellum: its role in language and related cognitive and affective functions.
De Smet, Hyo Jung; Paquier, Philippe; Verhoeven, Jo; Mariën, Peter
2013-12-01
The traditional view on the cerebellum as the sole coordinator of motor function has been substantially redefined during the past decades. Neuroanatomical, neuroimaging and clinical studies have extended the role of the cerebellum to the modulation of cognitive and affective processing. Neuroanatomical studies have demonstrated cerebellar connectivity with the supratentorial association areas involved in higher cognitive and affective functioning, while functional neuroimaging and clinical studies have provided evidence of cerebellar involvement in a variety of cognitive and affective tasks. This paper reviews the recently acknowledged role of the cerebellum in linguistic and related cognitive and behavioral-affective functions. In addition, typical cerebellar syndromes such as the cerebellar cognitive affective syndrome (CCAS) and the posterior fossa syndrome (PFS) will be briefly discussed and the current hypotheses dealing with the presumed neurobiological mechanisms underlying the linguistic, cognitive and affective modulatory role of the cerebellum will be reviewed. Copyright © 2012 Elsevier Inc. All rights reserved.
Taghavi, Safiyh; Wu, Xiao; Ouyang, Liming; ...
2015-01-21
Growth in sucrose medium was previously found to trigger the expression of functions involved in the plant associated life style of the endophytic bacterium Enterobacter sp. 638. Therefore, comparative transcriptome analysis between cultures grown in sucrose or lactate medium was used to gain insights in the expression levels of bacterial functions involved in the endophytic life style of strain 638. Growth on sucrose as a carbon source resulted in major changes in cell physiology, including a shift from a planktonic life style to the formation of bacterial aggregates. This shift was accompanied by a decrease in transcription of genes involvedmore » in motility (e.g. flagella biosynthesis) and an increase in the transcription of genes involved in colonization, adhesion and biofilm formation. The transcription levels of functions previously suggested as being involved in endophytic behavior and functions responsible for plant growth promoting properties, including the synthesis of indole-acetic acid, acetoin and 2,3-butanediol, also increased significantly for cultures grown in sucrose medium. Interestingly, despite an abundance of essential nutrients transcription levels of functions related to uptake and processing of nitrogen and iron became increased for cultures grown on sucrose as sole carbon source. Transcriptome data were also used to analyze putative regulatory relationships. In addition to the small RNA csrABCD regulon, which seems to play a role in the physiological adaptation and possibly the shift between free-living and plant-associated endophytic life style of Enterobacter sp. 638, our results also pointed to the involvement of rcsAB in controlling responses by Enterobacter sp. 638 to a plant-associated life style. Lastly, targeted mutagenesis was used to confirm this role and showed that compared to wild-type Enterobacter sp. 638 a ΔrcsB mutant was affected in its plant growth promoting ability.« less
p53 suppresses hyper-recombination by modulating BRCA1 function
Dong, Chao; Zhang, Fengmei; Luo, Yue; Wang, Hui; Zhao, Xipeng; Guo, Gongshe; Powell, Simon N.; Feng, Zhihui
2015-01-01
Both p53 and BRCA1 are tumor suppressors and are involved in a number of cellular processes including cell cycle arrest, apoptosis, transcriptional regulation, and DNA damage repair. Some studies have suggested that the association of BRCA1 and p53 is required for transcriptional regulation of genes involved in cell replication and DNA repair pathways. However, the relationship between the two proteins in molecular mechanisms of DNA repair is still not clear. Therefore, we sought to determine whether there is a functional link between p53 and BRCA1 in DNA repair. Firstly, using a plasmid recombination substrate, pDR-GFP, integrated into the genome of breast cancer cell line MCF7, we have demonstrated that p53 suppressed Rad51-mediated hyper-recombinational repair by two independent cell models of HPV-E6 induced p53 inactivation and p53 knockdown assay. Our study further indicated that p53 mediated homologous recombination (HR) through inhibiting BRCA1 over-function via mechanism of transcription regulation in response to DNA repair. Since it was found p53 and BRCA1 existed in a protein complex, indicating both proteins may be associated at post-transcriptional level. Moreover, defective p53-induced hyper-recombination was associated with cell radioresistance and chromosomal stability, strongly supporting the involvement of p53 in the inhibition of hyper-recombination, which led to genetic stability and cellular function in response to DNA damage. In addition, it was found that p53 loss rescued BRCA1 deficiency via recovering HR and chromosomal stability, suggesting that p53 is also involved in the HR-inhibition independently of BRCA1. Thus, our data indicated that p53 was involved in inhibiting recombination by both BRCA1-dependent and -independent mechanisms, and there is a functional link between p53-suppression and BRCA1-promotion in regulation of HR activity at transcription level and possible post-transcription level. PMID:26162908
DOE Office of Scientific and Technical Information (OSTI.GOV)
Taghavi, Safiyh; Wu, Xiao; Ouyang, Liming
Growth in sucrose medium was previously found to trigger the expression of functions involved in the plant associated life style of the endophytic bacterium Enterobacter sp. 638. Therefore, comparative transcriptome analysis between cultures grown in sucrose or lactate medium was used to gain insights in the expression levels of bacterial functions involved in the endophytic life style of strain 638. Growth on sucrose as a carbon source resulted in major changes in cell physiology, including a shift from a planktonic life style to the formation of bacterial aggregates. This shift was accompanied by a decrease in transcription of genes involvedmore » in motility (e.g. flagella biosynthesis) and an increase in the transcription of genes involved in colonization, adhesion and biofilm formation. The transcription levels of functions previously suggested as being involved in endophytic behavior and functions responsible for plant growth promoting properties, including the synthesis of indole-acetic acid, acetoin and 2,3-butanediol, also increased significantly for cultures grown in sucrose medium. Interestingly, despite an abundance of essential nutrients transcription levels of functions related to uptake and processing of nitrogen and iron became increased for cultures grown on sucrose as sole carbon source. Transcriptome data were also used to analyze putative regulatory relationships. In addition to the small RNA csrABCD regulon, which seems to play a role in the physiological adaptation and possibly the shift between free-living and plant-associated endophytic life style of Enterobacter sp. 638, our results also pointed to the involvement of rcsAB in controlling responses by Enterobacter sp. 638 to a plant-associated life style. Lastly, targeted mutagenesis was used to confirm this role and showed that compared to wild-type Enterobacter sp. 638 a ΔrcsB mutant was affected in its plant growth promoting ability.« less
Atypical cross talk between mentalizing and mirror neuron networks in autism spectrum disorder.
Fishman, Inna; Keown, Christopher L; Lincoln, Alan J; Pineda, Jaime A; Müller, Ralph-Axel
2014-07-01
Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition. To investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS). Cross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ. Statistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures. Relative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction. Adolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect immature or aberrant developmental processes in 2 brain networks involved in understanding of others, a domain of impairment in ASD. Further, robust links with sociocommunicative symptoms of ASD implicate atypically increased ToM-MNS connectivity in social deficits observed in ASD.
Kakinuma, Yoshihiko; Katare, Rajesh G; Arikawa, Mikihiko; Muramoto, Kazuyo; Yamasaki, Fumiyasu; Sato, Takayuki
2008-01-23
Recently, we reported that acetylcholine-induced hypoxia-inducible factor-1alpha protects cardiomyocytes from hypoxia; however, the downstream factors reducing hypoxic stress are unknown. We identified apoptosis inhibitor (AI) gene as being differentially expressed between von Hippel Lindau (VHL) protein-positive cells with high levels of GRP78 expression and VHL-negative cells with lower GRP levels, using cDNA subtraction. AI decreased GRP78 level, suppressed mitochondrial function, reduced oxygen consumption and, ultimately, suppressed hypoxia-induced apoptosis. By contrast, knockdown of the AI gene increased mitochondrial function. Hypoxic cardiomyocytes and ischemic myocardium showed increased AI mRNA expression. These findings suggest that AI is involved in suppressing mitochondrial function, thereby leading to cellular stress eradication and consequently to protection during hypoxia.
Weiss, C A; White, E; Huang, H; Ma, H
1997-05-05
Towards the elucidation of the cellular function(s) of GP alpha1, we have characterized its subcellular localization using immunofluorescence and cell fractionation. GP alpha1 is not present in nuclei or chloroplasts. It is a membrane-bound protein, and analysis of isolated endoplasmic and plasma membranes indicates a good correlation between GP alpha1 in both the plasma membrane and the ER compartment. Interestingly, these results may suggest more different functions for GP alpha1: it might be involved in transmission of extracellular signals across the plasma membrane and in the cytoplasm, and/or it may also be involved in regulating some aspects of the ER functions or membrane trafficking between both membranes.
Lucas, James E; Siegel, Justin B
2015-01-01
Enzyme active site residues are often highly conserved, indicating a significant role in function. In this study we quantitate the functional contribution for all conserved molecular interactions occurring within a Michaelis complex for mannitol 2-dehydrogenase derived from Pseudomonas fluorescens (pfMDH). Through systematic mutagenesis of active site residues, we reveal that the molecular interactions in pfMDH mediated by highly conserved residues not directly involved in reaction chemistry can be as important to catalysis as those directly involved in the reaction chemistry. This quantitative analysis of the molecular interactions within the pfMDH active site provides direct insight into the functional role of each molecular interaction, several of which were unexpected based on canonical sequence conservation and structural analyses. PMID:25752240
Alkylation Damage by Lipid Electrophiles Targets Functional Protein Systems*
Codreanu, Simona G.; Ullery, Jody C.; Zhu, Jing; Tallman, Keri A.; Beavers, William N.; Porter, Ned A.; Marnett, Lawrence J.; Zhang, Bing; Liebler, Daniel C.
2014-01-01
Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells treated with lipid electrophile probes. Protein target profiles revealed three damage susceptibility classes, as well as proteins that were highly resistant to alkylation. Damage occurred selectively across functional protein interaction networks, with the most highly alkylation-susceptible proteins mapping to networks involved in cytoskeletal regulation. Proteins with lower damage susceptibility mapped to networks involved in protein synthesis and turnover and were alkylated only at electrophile concentrations that caused significant toxicity. Hierarchical susceptibility of proteome systems to alkylation may allow cells to survive sublethal damage while protecting critical cell functions. PMID:24429493
An Energy-Independent Pro-longevity Function of Triacylglycerol in Yeast
Hall, Kevin W.; Deng, Xiexiong; Li, Pan; Benning, Christoph; Williams, Barry L.; Kuo, Min-Hao
2016-01-01
Intracellular triacylglycerol (TAG) is a ubiquitous energy storage lipid also involved in lipid homeostasis and signaling. Comparatively, little is known about TAG’s role in other cellular functions. Here we show a pro-longevity function of TAG in the budding yeast Saccharomyces cerevisiae. In yeast strains derived from natural and laboratory environments a correlation between high levels of TAG and longer chronological lifespan was observed. Increased TAG abundance through the deletion of TAG lipases prolonged chronological lifespan of laboratory strains, while diminishing TAG biosynthesis shortened lifespan without apparently affecting vegetative growth. TAG-mediated lifespan extension was independent of several other known stress response factors involved in chronological aging. Because both lifespan regulation and TAG metabolism are conserved, this cellular pro-longevity function of TAG may extend to other organisms. PMID:26907989
Luo, Yonglun; Blechingberg, Jenny; Fernandes, Ana Miguel; Li, Shengting; Fryland, Tue; Børglum, Anders D; Bolund, Lars; Nielsen, Anders Lade
2015-11-14
FUS (TLS) and EWS (EWSR1) belong to the FET-protein family of RNA and DNA binding proteins. FUS and EWS are structurally and functionally related and participate in transcriptional regulation and RNA processing. FUS and EWS are identified in translocation generated cancer fusion proteins and involved in the human neurological diseases amyotrophic lateral sclerosis and fronto-temporal lobar degeneration. To determine the gene regulatory functions of FUS and EWS at the level of chromatin, we have performed chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Our results show that FUS and EWS bind to a subset of actively transcribed genes, that binding often is downstream the poly(A)-signal, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes identified that FUS and EWS can regulate gene expression at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level. The presented results yield new insights into gene interactions of EWS and FUS and have identified a set of FUS and EWS target genes involved in pathways at the RNA regulatory level with potential to mediate normal and disease-associated functions of the FUS and EWS proteins.
Maruyama, Tsukasa; Takeuchi, Hikaru; Taki, Yasuyuki; Motoki, Kosuke; Jeong, Hyeonjeong; Kotozaki, Yuka; Nakagawa, Seishu; Nouchi, Rui; Iizuka, Kunio; Yokoyama, Ryoichi; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Sakaki, Kohei; Sasaki, Yukako; Magistro, Daniele; Kawashima, Ryuta
2018-01-01
Time-compressed speech is an artificial form of rapidly presented speech. Training with time-compressed speech (TCSSL) in a second language leads to adaptation toward TCSSL. Here, we newly investigated the effects of 4 weeks of training with TCSSL on diverse cognitive functions and neural systems using the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), resting-state functional connectivity (RSFC) with the left superior temporal gyrus (STG), fractional anisotropy (FA), and regional gray matter volume (rGMV) of young adults by magnetic resonance imaging. There were no significant differences in change of performance of measures of cognitive functions or second language skills after training with TCSSL compared with that of the active control group. However, compared with the active control group, training with TCSSL was associated with increased fALFF, RSFC, and FA and decreased rGMV involving areas in the left STG. These results lacked evidence of a far transfer effect of time-compressed speech training on a wide range of cognitive functions and second language skills in young adults. However, these results demonstrated effects of time-compressed speech training on gray and white matter structures as well as on resting-state intrinsic activity and connectivity involving the left STG, which plays a key role in listening comprehension.
Functional sensorial complementation during host orientation in an Asilidae parasitoid larva.
Pueyrredon, J M; Crespo, J E; Castelo, M K
2017-10-01
Changes in environmental conditions influence the performance of organisms in every aspect of their life. Being capable of accurately sensing these changes allow organisms to better adapt. The detection of environmental conditions involves different sensory modalities. There are many studies on the morphology of different sensory structures but not so many studies showing their function. Here we studied the morphology of different sensory structures in the larva of a dipteran parasitoid. We occluded the putative sensory structures coupling the morphology with their function. First, we could develop a non-invasive method in which we occluded the putative sensorial structures annulling their function temporarily. Regarding their functionality, we found that larvae of Mallophora ruficauda require simultaneously of the sensilla found both in the antennae and those of the maxillary palps in order to orient to its host. When either both antennae or both maxillary palps were occluded, no orientation to the host was observed. We also found that these structures are not involved in the acceptance of the host because high and similar proportion of parasitized hosts was found in host acceptance experiments. We propose that other sensilla could be involved in host acceptance and discuss how the different sensilla in the antennae and maxillary palps complement each other to provide larvae with the information for locating its host.
The New Neurobiology of Autism
Minshew, Nancy J.; Williams, Diane L.
2008-01-01
This review covers a fraction of the new research developments in autism but establishes the basic elements of the new neurobiologic understanding of autism. Autism is a polygenetic developmental neurobiologic disorder with multiorgan system involvement, though it predominantly involves central nervous system dysfunction. The evidence supports autism as a disorder of the association cortex, both its neurons and their projections. In particular, it is a disorder of connectivity, which appears, from current evidence, to primarily involve intrahemispheric connectivity. The focus of connectivity studies thus far has been on white matter, but alterations in functional magnetic resonance imaging activation suggest that intracortical connectivity is also likely to be disturbed. Furthermore, the disorder has a broad impact on cognitive and neurologic functioning. Deficits in high-functioning individuals occur in processing that places high demands on integration of information and coordination of multiple neural systems. Intact or enhanced abilities share a dependence on low information-processing demands and local neural connections. This multidomain model with shared characteristics predicts an underlying pathophysiologic mechanism that impacts the brain broadly, according to a common neurobiologic principle. The multiorgan system involvement and diversity of central nervous system findings suggest an epigenetic mechanism. PMID:17620483
Quantum trajectory analysis of multimode subsystem-bath dynamics.
Wyatt, Robert E; Na, Kyungsun
2002-01-01
The dynamics of a swarm of quantum trajectories is investigated for systems involving the interaction of an active mode (the subsystem) with an M-mode harmonic reservoir (the bath). Equations of motion for the position, velocity, and action function for elements of the probability fluid are integrated in the Lagrangian (moving with the fluid) picture of quantum hydrodynamics. These fluid elements are coupled through the Bohm quantum potential and as a result evolve as a correlated ensemble. Wave function synthesis along the trajectories permits an exact description of the quantum dynamics for the evolving probability fluid. The approach is fully quantum mechanical and does not involve classical or semiclassical approximations. Computational results are presented for three systems involving the interaction on an active mode with M=1, 10, and 15 bath modes. These results include configuration space trajectory evolution, flux analysis of the evolving ensemble, wave function synthesis along trajectories, and energy partitioning along specific trajectories. These results demonstrate the feasibility of using a small number of quantum trajectories to obtain accurate quantum results on some types of open quantum systems that are not amenable to standard quantum approaches involving basis set expansions or Eulerian space-fixed grids.
Social Networks and Community-Based Natural Resource Management
NASA Astrophysics Data System (ADS)
Lauber, T. Bruce; Decker, Daniel J.; Knuth, Barbara A.
2008-10-01
We conducted case studies of three successful examples of collaborative, community-based natural resource conservation and development. Our purpose was to: (1) identify the functions served by interactions within the social networks of involved stakeholders; (2) describe key structural properties of these social networks; and (3) determine how these structural properties varied when the networks were serving different functions. The case studies relied on semi-structured, in-depth interviews of 8 to 11 key stakeholders at each site who had played a significant role in the collaborative projects. Interview questions focused on the roles played by key stakeholders and the functions of interactions between them. Interactions allowed the exchange of ideas, provided access to funding, and enabled some stakeholders to influence others. The exchange of ideas involved the largest number of stakeholders, the highest percentage of local stakeholders, and the highest density of interactions. Our findings demonstrated the value of tailoring strategies for involving stakeholders to meet different needs during a collaborative, community-based natural resource management project. Widespread involvement of local stakeholders may be most appropriate when ideas for a project are being developed. During efforts to exert influence to secure project approvals or funding, however, involving specific individuals with political connections or influence on possible sources of funds may be critical. Our findings are consistent with past work that has postulated that social networks may require specific characteristics to meet different needs in community-based environmental management.
The six-minute walk test in patients with AL amyloidosis: a single centre case series.
Pulido, Vina; Doros, Gheorghe; Berk, John L; Sanchorawala, Vaishali
2017-05-01
The six-minute walk test (6MWT) has been widely used as an objective evaluation of functional exercise capacity and response to medical intervention in cardiopulmonary diseases. However, little is known about the 6MWT in evaluating patients with AL amyloidosis. We performed a retrospective study of 120 adults with systemic AL amyloidosis (60 with cardiac involvement and 60 without cardiac involvement) who had their initial evaluation at the Amyloidosis Center between 2013 and 2015 and had undergone 6MWT as a measure of functional exercise capacity. Forty-seven patients with cardiac involvement and 41 patients without cardiac involvement were included in the final analysis. The six-minute walk distances (6MWD) were 368 ± 105 m and 420 ± 116 m (mean ± SD), respectively (P = 0·03). Among AL amyloidosis patients with cardiac involvement, the 6MWD was associated with New York Heart Association class (P < 0·001), B-type natriuretic peptide (P = 0·003) and overall survival (hazard ratio 0·381, 95% confidence interval 0·215-0·676, P = 0·001). In conclusion, the 6MWT is a valuable tool in assessing functional exercise capacity in patients with AL amyloidosis. © 2017 John Wiley & Sons Ltd.
Microbial diversity and their roles in the vinegar fermentation process.
Li, Sha; Li, Pan; Feng, Feng; Luo, Li-Xin
2015-06-01
Vinegar is one of the oldest acetic acid-diluted solution products in the world. It is produced from any fermentable sugary substrate by various fermentation methods. The final vinegar products possess unique functions, which are endowed with many kinds of compounds formed in the fermentation process. The quality of vinegar is determined by many factors, especially by the raw materials and microbial diversity involved in vinegar fermentation. Given that metabolic products from the fermenting strains are directly related to the quality of the final products of vinegar, the microbial diversity and features of the dominant strains involved in different fermentation stages should be analyzed to improve the strains and stabilize fermentation. Moreover, although numerous microbiological studies have been conducted to examine the process of vinegar fermentation, knowledge about microbial diversity and their roles involved in fermentation is still fragmentary and not systematic enough. Therefore, in this review, the dominant microorganism species involved in the stages of alcoholic fermentation and acetic acid fermentation of dissimilar vinegars were summarized. We also summarized various physicochemical properties and crucial compounds in disparate types of vinegar. Furthermore, the merits and drawbacks of vital fermentation methods were generalized. Finally, we described in detail the relationships among microbial diversity, raw materials, fermentation methods, physicochemical properties, compounds, functionality, and final quality of vinegar. The integration of this information can provide us a detailed map about the microbial diversity and function involved in vinegar fermentation.
Multi-Modal Traveler Information System - Gateway Functional Requirements
DOT National Transportation Integrated Search
1997-11-17
The Multi-Modal Traveler Information System (MMTIS) project involves a large number of Intelligent Transportation System (ITS) related tasks. It involves research of all ITS initiatives in the Gary-Chicago-Milwaukee (GCM) Corridor which are currently...
Low-Temperature Plasma Functionalization of Carbon Nanotubes
NASA Technical Reports Server (NTRS)
Khare, Bishun; Meyyappan, M.
2004-01-01
A low-temperature plasma process has been devised for attaching specified molecular groups to carbon nanotubes in order to impart desired chemical and/or physical properties to the nanotubes for specific applications. Unlike carbon-nanotube- functionalization processes reported heretofore, this process does not involve the use of wet chemicals, does not involve exposure of the nanotubes to high temperatures, and generates very little chemical residue. In addition, this process can be carried out in a relatively simple apparatus and can readily be scaled up to mass production.
Orthogonal Polynomials Associated with Complementary Chain Sequences
NASA Astrophysics Data System (ADS)
Behera, Kiran Kumar; Sri Ranga, A.; Swaminathan, A.
2016-07-01
Using the minimal parameter sequence of a given chain sequence, we introduce the concept of complementary chain sequences, which we view as perturbations of chain sequences. Using the relation between these complementary chain sequences and the corresponding Verblunsky coefficients, the para-orthogonal polynomials and the associated Szegő polynomials are analyzed. Two illustrations, one involving Gaussian hypergeometric functions and the other involving Carathéodory functions are also provided. A connection between these two illustrations by means of complementary chain sequences is also observed.
Functional Behavioral Assessment: A School Based Model.
ERIC Educational Resources Information Center
Asmus, Jennifer M.; Vollmer, Timothy R.; Borrero, John C.
2002-01-01
This article begins by discussing requirements for functional behavioral assessment under the Individuals with Disabilities Education Act and then describes a comprehensive model for the application of behavior analysis in the schools. The model includes descriptive assessment, functional analysis, and intervention and involves the participation…
Singh, Laishram R.; Warepam, Marina; Ahmad, Faizan; Dar, Tanveer Ali
2015-01-01
Cellular methylamines are osmolytes (low molecular weight organic compounds) believed to offset the urea’s harmful effects on the stability and function of proteins in mammalian kidney and marine invertebrates. Although urea and methylamines are found at 2:1 molar ratio in tissues, their opposing effects on protein structure and function have been questioned on several grounds including failure to counteraction or partial counteraction. Here we investigated the possible involvement of cellular salt, NaCl, in urea-methylamine counteraction on protein stability and function. We found that NaCl mediates methylamine counteracting system from no or partial counteraction to complete counteraction of urea’s effect on protein stability and function. These conclusions were drawn from the systematic thermodynamic stability and functional activity measurements of lysozyme and RNase-A. Our results revealed that salts might be involved in protein interaction with charged osmolytes and hence in the urea-methylamine counteraction. PMID:25793733
Hepatitis B virus pathogenesis: Fresh insights into hepatitis B virus RNA.
Sekiba, Kazuma; Otsuka, Motoyuki; Ohno, Motoko; Yamagami, Mari; Kishikawa, Takahiro; Suzuki, Tatsunori; Ishibashi, Rei; Seimiya, Takahiro; Tanaka, Eri; Koike, Kazuhiko
2018-06-07
Hepatitis B virus (HBV) is still a worldwide health concern. While divergent factors are involved in its pathogenesis, it is now clear that HBV RNAs, principally templates for viral proteins and viral DNAs, have diverse biological functions involved in HBV pathogenesis. These functions include viral replication, hepatic fibrosis and hepatocarcinogenesis. Depending on the sequence similarities, HBV RNAs may act as sponges for host miRNAs and may deregulate miRNA functions, possibly leading to pathological consequences. Some parts of the HBV RNA molecule may function as viral-derived miRNA, which regulates viral replication. HBV DNA can integrate into the host genomic DNA and produce novel viral-host fusion RNA, which may have pathological functions. To date, elimination of HBV-derived covalently closed circular DNA has not been achieved. However, RNA transcription silencing may be an alternative practical approach to treat HBV-induced pathogenesis. A full understanding of HBV RNA transcription and the biological functions of HBV RNA may open a new avenue for the development of novel HBV therapeutics.
Lee, Kirsty; Guy, Alexa; Dale, Jeremy; Wolke, Dieter
2017-03-24
Adolescent bullying is associated with a range of adversities for those who are bullied i.e., victims and bully-victims (e.g., those who bully others and get victimised), including reduced psychological functioning and eating disorder symptoms. Bullies are generally well-adjusted psychologically, but previous research suggests that bullies may also engage in problematic diet behaviours. This study investigates a) whether adolescents involved in bullying (bullies, victims, bully-victims) are at increased risk of weight loss preoccupation, b) whether psychological functioning mediates this relationship and c) whether sex is a key moderator. A two-stage design was used. In stage 1, adolescents (n = 2782) from five UK secondary schools were screened for bullying involvement using self and peer reports. In stage 2, a sample of bullies, victims, bully-victims and uninvolved adolescents (n = 767) completed a battery of assessments. The measures included the eating behaviours component of the Child and Adolescent Psychiatric Assessment, which was reduced to one factor (weight loss preoccupation) and used as the outcome variable. Measures of self-esteem, body-esteem and emotional problems were reduced to a latent (mediator) variable of psychological functioning. Multi-group analysis examined the effects of sex and all models were adjusted for covariates (BMI, pubertal stage, age, parental education and ethnicity). Bullies, victims and bully-victims were at increased risk of weight loss preoccupation compared to adolescents uninvolved in bullying. The mechanism by which bullying involvement related to increased weight loss preoccupation varied by bullying role: in bullies the effect was direct, in victims the effect was indirect (via reduced psychological functioning) and in bully-victims the effect was both direct and indirect. Sex significantly moderated the relationship in bullies: weight loss preoccupation was only statistically significant in bullies who were boys. Bullying involvement during adolescence is associated with weight loss preoccupation. Bullies are likely driven by a desire to increase attractiveness and social status; whereas weight loss preoccupation in bullied adolescents may have maladaptive influences on diet and exercise behaviours due to its association with reduced psychological functioning. Future research should consider peer victimisation as a potential modifiable risk factor for reduced psychological functioning and weight loss preoccupation, which if targeted, may help to prevent maladaptive diet and exercise behaviours.
Children's mental health and family functioning in Rhode Island.
Kim, Hyun Hanna K; Viner-Brown, Samara I; Garcia, Jorge
2007-02-01
Our objectives were to (a) estimate the prevalence of children's mental health problems, (b) assess family functioning, and (c) investigate the relationship between children's mental health and family functioning in Rhode Island. From the 2003 National Survey of Children's Health, Rhode Island data for children 6 to 17 years of age were used for the analyses (N = 1326). Two aspects of family functioning measures, parental stress and parental involvement, were constructed and were examined by children's mental health problems, as well as other child and family characteristics (child's age, gender, race/ethnicity, special needs, parent's education, income, employment, family structure, number of children, and mother's general and mental health). Bivariate analyses and multivariate logistic regression were used to investigate the relationship. Among Rhode Island children, nearly 1 (19.0%) in 5 had mental health problems, 1 (15.6%) in 6 lived with a highly stressed parent, and one third (32.7%) had parents with low involvement. Bivariate analyses showed that high parental stress and low parental involvement were higher among parents of children with mental health problems than parents of children without those problems (33.2% vs 11.0% and 41.0% vs 30.3%, respectively). In multivariate logistic regression, parents of children with mental health problems had nearly 4 times the odds of high stress compared with parents of children without those problems. When children's mental health problems were severe, the odds of high parental stress were elevated. However, children's mental health was not associated with parental involvement. Children's mental health was strongly associated with parental stress, but it was not associated with parental involvement. The findings indicate that when examining the mental health issues of children, parental mental health and stress must be considered.
Otte, Willem M; van der Marel, Kajo; van Meer, Maurits P A; van Rijen, Peter C; Gosselaar, Peter H; Braun, Kees P J; Dijkhuizen, Rick M
2015-08-01
Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions.
Roos, Leslie E; Kim, Hyoun K; Schnabler, Simone; Fisher, Philip A
2016-12-01
Prior research has identified the presence of executive function (EF) deficits in child protective service (CPS) involved (versus non-involved) children but minimal work has examined predictors that might explain individual differences within these CPS-involved children. Here, we sought to characterize EF in a large sample (N=694) of CPS-involved children and examine how specific adversities (physical abuse, neglect, caregiver domestic violence, and caregiver substance dependence) and cumulative adversity (at ages 0-3 and 3-6 years) predict EF (at approximately 5-6 years). It was expected that the sample would exhibit low EF overall based on previous research in maltreated children. Specific adversity and cumulative adversity analyses were largely exploratory given the limited previous work in this area. Results indicated poor EF overall, with 43.5% of children performing worse than chance. Amongst children who performed greater than chance, higher cumulative adversity, physical abuse, and caregiver substance use (at ages 3-6 years) predicted better EF. These findings join literature documenting that, within CPS-involved children, the presence of certain adversities predicts variable cognitive function. Findings highlight the potential relevance of evolutionary psychology to understanding how alterations in behavior linked to harsh and unpredictable early environments may cue accelerated brain development underlying relative cognitive advantages, within at-risk, low performing samples. Longitudinal studies are critical to determine if the relative EF advantages linked to higher adversity persist over time or result in lower EF later on, reflecting a more rapid, but overall limited, trajectory of cognitive development.
Reward loss and the basolateral amygdala: A function in reward comparisons.
Kawasaki, Katsuyoshi; Annicchiarico, Iván; Glueck, Amanda C; Morón, Ignacio; Papini, Mauricio R
2017-07-28
The neural circuitry underlying behavior in reward loss situations is poorly understood. We considered two such situations: reward devaluation (from large to small rewards) and reward omission (from large rewards to no rewards). There is evidence that the central nucleus of the amygdala (CeA) plays a role in the negative emotion accompanying reward loss. However, little is known about the function of the basolateral nucleus (BLA) in reward loss. Two hypotheses of BLA function in reward loss, negative emotion and reward comparisons, were tested in an experiment involving pretraining excitotoxic BLA lesions followed by training in four tasks: consummatory successive negative contrast (cSNC), autoshaping (AS) acquisition and extinction, anticipatory negative contrast (ANC), and open field testing (OF). Cell counts in the BLA (but not in the CeA) were significantly lower in animals with lesions vs. shams. BLA lesions eliminated cSNC and ANC, and accelerated extinction of lever pressing in AS. BLA lesions had no effect on OF testing: higher activity in the periphery than in the central area. This pattern of results provides support for the hypothesis that BLA neurons are important for reward comparison. The three affected tasks (cSNC, ANC, and AS extinction) involve reward comparisons. However, ANC does not seem to involve negative emotions and it was affected, whereas OF activity is known to involve negative emotion, but it was not affected. It is hypothesized that a circuit involving the thalamus, insular cortex, and BLA is critically involved in the mechanism comparing current and expected rewards. Copyright © 2017 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
He, Zhili; Xu, Meiying; Deng, Ye
2010-05-17
The global atmospheric concentration of CO2 has increased by more than 30percent since the industrial revolution. Although the stimulating effects of elevated CO2 (eCO2) on plant growth and primary productivity have been well studied, its influences on belowground microbial communities are poorly understood and controversial. In this study, we showed a significant change in the structure and functional potential of soil microbial communities at eCO2 in a grassland ecosystem, the BioCON (Biodiversity, CO2 and Nitrogen) experimental site (http://www.biocon.umn.edu/) using a comprehensive functional gene array, GeoChip 3.0, which contains about 28,0000 probes and covers approximately 57,000 gene variants from 292 functionalmore » gene families involved in carbon, nitrogen, phosphorus and sulfur cycles as well as other functional processes. GeoChip data indicated that the functional structure of microbial communities was markedly different between ambient CO2 (aCO2) and eCO2 by detrended correspondence analysis (DCA) of all 5001 detected functional gene probes although no significant differences were detected in the overall microbial diversity. A further analysis of 1503 detected functional genes involved in C, N, P, and S cycles showed that a considerable portion (39percent) of them were only detected under either aCO2 (14percent) or eCO2 (25percent), indicating that the functional characteristics of the microbial community were significantly altered by eCO2. Also, for those shared genes (61percent) detected, some significantly (p<0.05) changed their abundance at eCO2. Especially, genes involved in labile C degradation, such as amyA, egl, and ara for starch, cellulose, and hemicelluloses, respectively, C fixation (e.g., rbcL, pcc/acc), N fixation (nifH), and phosphorus utilization (ppx) were significantly increased under eCO2, while those involved in decomposing recalcitrant C, such as glx, lip, and mnp for lignin degradation remained unchanged. This study provides insights into our understanding of belowground microbial communities and their feedbacks to terrestrial ecosystems at eCO2.« less
Developing Mathematical Knowledge for Teaching in a Methods Course: The Case of Function
ERIC Educational Resources Information Center
Steele, Michael D.; Hillen, Amy F.; Smith, Margaret S.
2013-01-01
This study describes teacher learning in a teaching experiment consisting of a content-focused methods course involving the mathematical knowledge for teaching function. Prospective and practicing teachers in the course showed growth in their ability to define function, to provide examples of functions and link them to the definition, in the…
Multi-Modal Traveler Information System - GCM Corridor Architecture Functional Requirements
DOT National Transportation Integrated Search
1997-11-17
The Multi-Modal Traveler Information System (MMTIS) project involves a large number of Intelligent Transportation System (ITS) related tasks. It involves research of all ITS initiatives in the Gary-Chicago-Milwaukee (GCM) Corridor which are currently...
Functional Analysis in Virtual Environments
ERIC Educational Resources Information Center
Vasquez, Eleazar, III; Marino, Matthew T.; Donehower, Claire; Koch, Aaron
2017-01-01
Functional analysis (FA) is an assessment procedure involving the systematic manipulation of an individual's environment to determine why a target behavior is occurring. An analog FA provides practitioners the opportunity to manipulate variables in a controlled environment and formulate a hypothesis for the function of a behavior. In previous…
Traumatic Brain Injury Inpatient Rehabilitation
ERIC Educational Resources Information Center
Im, Brian; Schrer, Marcia J.; Gaeta, Raphael; Elias, Eileen
2010-01-01
Traumatic brain injuries (TBI) can cause multiple medical and functional problems. As the brain is involved in regulating nearly every bodily function, a TBI can affect any part of the body and aspect of cognitive, behavioral, and physical functioning. However, TBI affects each individual differently. Optimal management requires understanding the…
ERIC Educational Resources Information Center
Painter, Lynette Darleen Borjeson
2017-01-01
The college experience often includes activities outside the classroom that involve engaging with other students in a shared interest. These experiences often transform into alumni engaging in alumni functions, or participating through other means of identifying with the college, including wearing college logos. Online alumni involvement,…
Ghosh, Arijit; Kaur, Navneet; Kumar, Abhishek; Goswami, Chandan
2016-09-02
Every individual varies in character and so do their sensory functions and perceptions. The molecular mechanism and the molecular candidates involved in these processes are assumed to be similar if not same. So far several molecular factors have been identified which are fairly conserved across the phylogenetic tree and are involved in these complex sensory functions. Among all, members belonging to Transient Receptor Potential (TRP) channels have been widely characterized for their involvement in thermo-sensation. These include TRPV1 to TRPV4 channels which reveal complex thermo-gating behavior in response to changes in temperature. The molecular evolution of these channels is highly correlative with the thermal response of different species. However, recent 2504 human genome data suggest that these thermo-sensitive TRPV channels are highly variable and carry possible deleterious mutations in human population. These unexpected findings may explain the individual differences in terms of complex sensory functions.
Regulation of ROS Production and Vascular Function by Carbon Monoxide
Choi, Yoon Kyung; Por, Elaine D.; Kwon, Young-Guen; Kim, Young-Myeong
2012-01-01
Carbon monoxide (CO) is a gaseous molecule produced from heme by heme oxygenase (HO). CO interacts with reduced iron of heme-containing proteins, leading to its involvement in various cellular events via its production of mitochondrial reactive oxygen species (ROS). CO-mediated ROS production initiates intracellular signal events, which regulate the expression of adaptive genes implicated in oxidative stress and functions as signaling molecule for promoting vascular functions, including angiogenesis and mitochondrial biogenesis. Therefore, CO generated either by exogenous delivery or by HO activity can be fundamentally involved in regulating mitochondria-mediated redox cascades for adaptive gene expression and improving blood circulation (i.e., O2 delivery) via neovascularization, leading to the regulation of mitochondrial energy metabolism. This paper will highlight the biological effects of CO on ROS generation and cellular redox changes involved in mitochondrial metabolism and angiogenesis. Moreover, cellular mechanisms by which CO is exploited for disease prevention and therapeutic applications will also be discussed. PMID:22928087
Functional divergence of MYB-related genes, WEREWOLF and AtMYB23 in Arabidopsis.
Tominaga-Wada, Rumi; Nukumizu, Yuka; Sato, Shusei; Kato, Tomohiko; Tabata, Satoshi; Wada, Takuji
2012-01-01
Epidermal cell differentiation in Arabidopsis is studied as a model system to understand the mechanisms that determine the developmental end state of plant cells. MYB-related transcription factors are involved in cell fate determination. To examine the molecular basis of this process, we analyzed the functional relationship of two R2R3-type MYB genes, AtMYB23 (MYB23) and WEREWOLF (WER). MYB23 is involved in leaf trichome formation. WER represses root-hair formation. Swapping domains between MYB23 and WER, we found that a low homology region of MYB23 might be involved in ectopic trichome initiation on hypocotyls. MYB23 and all MYB23-WER (MW) chimeric transgenes rescued the increased root-hair phenotype of the wer-1 mutant. Although WER did not rescue the gl1-1 no-trichome phenotype, MYB23 and all MW chimeric transgenes rescued gl1-1. These results suggest that MYB23 acquired a specific function for trichome differentiation during evolution.
Visuomotor cerebellum in human and nonhuman primates.
Voogd, Jan; Schraa-Tam, Caroline K L; van der Geest, Jos N; De Zeeuw, Chris I
2012-06-01
In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula-nodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed.
Grilli, D J; Cerón, M E; Paez, S; Egea, V; Schnittger, L; Cravero, S; Escudero, M Sosa; Allegretti, L; Arenas, G N
2013-09-01
We isolated and identified functional groups of bacteria in the rumen of Creole goats involved in ruminal fermentation of native forage shrubs. The functional bacterial groups were evaluated by comparing the total viable, total anaerobic, cellulolytic, hemicellulolytic, and amylolytic bacterial counts in the samples taken from fistulated goats fed native forage diet (Atriplex lampa and Prosopis flexuosa). Alfalfa hay and corn were used as control diet. The roll tubes method increased the possibility of isolating and 16S rDNA gene sequencing allowed definitive identification of bacterial species involved in the ruminal fermentation. The starch and fiber contents of the diets influenced the number of total anaerobic bacteria and fibrolytic and amylolytic functional groups. Pseudobutyrivibrio ruminis and Pseudobutyrivibrio xylanivorans were the main species isolated and identified. The identification of bacterial strains involved in the rumen fermentation helps to explain the ability of these animals to digest fiber plant cell wall contained in native forage species.
Analysis of Nuclear Lamina Proteins in Myoblast Differentiation by Functional Complementation.
Tapia, Olga; Gerace, Larry
2016-01-01
We describe straightforward methodology for structure-function mapping of nuclear lamina proteins in myoblast differentiation, using populations of C2C12 myoblasts in which the endogenous lamina components are replaced with ectopically expressed mutant versions of the proteins. The procedure involves bulk isolation of C2C12 cell populations expressing the ectopic proteins by lentiviral transduction, followed by depletion of the endogenous proteins using siRNA, and incubation of cells under myoblast differentiation conditions. Similar methodology may be applied to mouse embryo fibroblasts or to other cell types as well, for the identification and characterization of sequences of lamina proteins involved in functions that can be measured biochemically or cytologically.
Target Discovery for Precision Medicine Using High-Throughput Genome Engineering.
Guo, Xinyi; Chitale, Poonam; Sanjana, Neville E
2017-01-01
Over the past few years, programmable RNA-guided nucleases such as the CRISPR/Cas9 system have ushered in a new era of precision genome editing in diverse model systems and in human cells. Functional screens using large libraries of RNA guides can interrogate a large hypothesis space to pinpoint particular genes and genetic elements involved in fundamental biological processes and disease-relevant phenotypes. Here, we review recent high-throughput CRISPR screens (e.g. loss-of-function, gain-of-function, and targeting noncoding elements) and highlight their potential for uncovering novel therapeutic targets, such as those involved in cancer resistance to small molecular drugs and immunotherapies, tumor evolution, infectious disease, inborn genetic disorders, and other therapeutic challenges.
Leach, J E; White, F F
1996-01-01
Although more than 30 bacterial avirulence genes have been cloned and characterized, the function of the gene products in the elictitation of resistance is unknown in all cases but one. The product of avrD from Pseudomonas syringae pv. glycinea likely functions indirectly to elicit resistance in soybean, that is, evidence suggests the gene product is an enzyme involved in elicitor production. In most if not all cases, bacterial avirulence gene function is dependent on interactions with the hypersensitive response and pathogenicity (hrp) genes. Many hrp genes are similar to genes involved in delivery of pathogenicity factors in mammalian bacterial pathogens. Thus, analogies between mammalian and plant pathogens may provide needed clues to elucidate how virulence gene products control induction of resistance.
[Clinical and neuropsychological characteristics in congenital central hypoventilation syndrome].
Seijas-Gomez, R; Esteso-Orduna, B; Melero-Llorente, J; Fournier-Del Castillo, M C
2018-05-01
Congenital central hypoventilation syndrome (CCHS) syndrome is a rare disease caused by mutations in the PHOX2B gene. Patients show a reduced response to hypercapnia and hypoxia accompanied by diffuse disturbances of the autonomic nervous system and occasionaly also disturbances in neuroimaging. A specific neuropsychological profile has not been described in children and adolescents with CCHS. We describe three cases (aged between 4 and 19 years) with different profiles of affectation in cognitive and functionality. These profiles are compared with the features described in the literature about neuropsychology in CCHS. The profile of functional impairment in the CCHS is variable: in case 1, a severe global developmental delay with autistic features and marked functional involvement is described. In case 2, bilateral atrophy of the hippocampus is associated with involvement in social cognition and in executive functions with moderate functional repercussion. Case 3 shows difficulties in some cognitive executive functions (planning and non-verbal fluency), but without functional repercussion. Neuropsychological assessment can help in the clinical management of these patients by determining and guiding the need for rehabilitation treatments.
Dynamics of polymers: A mean-field theory
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fredrickson, Glenn H.; Materials Research Laboratory, University of California, Santa Barbara, California 93106; Department of Materials, University of California, Santa Barbara, California 93106
2014-02-28
We derive a general mean-field theory of inhomogeneous polymer dynamics; a theory whose form has been speculated and widely applied, but not heretofore derived. Our approach involves a functional integral representation of a Martin-Siggia-Rose (MSR) type description of the exact many-chain dynamics. A saddle point approximation to the generating functional, involving conditions where the MSR action is stationary with respect to a collective density field ρ and a conjugate MSR response field ϕ, produces the desired dynamical mean-field theory. Besides clarifying the proper structure of mean-field theory out of equilibrium, our results have implications for numerical studies of polymer dynamicsmore » involving hybrid particle-field simulation techniques such as the single-chain in mean-field method.« less
Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications.
Goldstein, Rita Z; Volkow, Nora D
2011-10-20
The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.
Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications
Goldstein, Rita Z.; Volkow, Nora D.
2012-01-01
The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will. PMID:22011681
DOE Office of Scientific and Technical Information (OSTI.GOV)
Volkow N. D.; Wang G.; Volkow, N.D.
The ability to resist the urge to eat requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from eating the food and the desire to eat the food. Imaging studies show that obese subjects might have impairments in dopaminergic pathways that regulate neuronal systems associated with reward sensitivity, conditioning and control. It is known that the neuropeptides that regulate energy balance (homeostatic processes) through the hypothalamus also modulate the activity of dopamine cells and their projections into regions involved in the rewarding processes underlying food intake. It is postulated thatmore » this could also be a mechanism by which overeating and the resultant resistance to homoeostatic signals impairs the function of circuits involved in reward sensitivity, conditioning and cognitive control.« less
Standard Reference Specimens in Quality Control of Engineering Surfaces
Song, J. F.; Vorburger, T. V.
1991-01-01
In the quality control of engineering surfaces, we aim to understand and maintain a good relationship between the manufacturing process and surface function. This is achieved by controlling the surface texture. The control process involves: 1) learning the functional parameters and their control values through controlled experiments or through a long history of production and use; 2) maintaining high accuracy and reproducibility with measurements not only of roughness calibration specimens but also of real engineering parts. In this paper, the characteristics, utilizations, and limitations of different classes of precision roughness calibration specimens are described. A measuring procedure of engineering surfaces, based on the calibration procedure of roughness specimens at NIST, is proposed. This procedure involves utilization of check specimens with waveform, wavelength, and other roughness parameters similar to functioning engineering surfaces. These check specimens would be certified under standardized reference measuring conditions, or by a reference instrument, and could be used for overall checking of the measuring procedure and for maintaining accuracy and agreement in engineering surface measurement. The concept of “surface texture design” is also suggested, which involves designing the engineering surface texture, the manufacturing process, and the quality control procedure to meet the optimal functional needs. PMID:28184115
Hotta, Osamu; Tanaka, Ayaki; Torigoe, Akira; Imai, Kazuaki; Ieiri, Norio
2017-02-01
The epipharynx is an immunologically active site even under normal conditions, and enhanced immunologic activation is prone to occur in response to an upper respiratory infection, air pollution, and possibly to vaccine adjuvants. Due to the potential link between the central nervous system and immune function, a relationship between epipharyngitis and autonomic nervous disturbance as well as autoimmune disease has been suggested. Various functional somatic symptoms have been described after human papillomavirus (HPV) vaccination, although a causal relationship has not been established. We examined the epipharynx in young women showing functional somatic symptoms following HPV vaccination. Surprisingly, despite having minimal symptoms involving the pharynx, all patients were found to have severe epipharyngitis. In addition, significant improvement in symptoms was seen in most patients who underwent epipharyngeal treatment. Thus, we speculate that the chronic epipharyngitis potentially caused by the vaccine adjuvant may be involved in the pathogenesis of functional somatic syndrome (FSS) post-HPV vaccination. Further, we suggest that epipharyngeal treatment may be effective for various types of FSS regardless of the initial cause, as well as for some autoimmune diseases, and that this may be an important direction in future research.
Eng, Goi Khia; Sim, Kang; Chen, Shen-Hsing Annabel
2015-05-01
Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.
Eigensolutions of nonviscously damped systems based on the fixed-point iteration
NASA Astrophysics Data System (ADS)
Lázaro, Mario
2018-03-01
In this paper, nonviscous, nonproportional, symmetric vibrating structures are considered. Nonviscously damped systems present dissipative forces depending on the time history of the response via kernel hereditary functions. Solutions of the free motion equation leads to a nonlinear eigenvalue problem involving mass, stiffness and damping matrices, this latter as dependent on frequency. Viscous damping can be considered as a particular case, involving damping forces as function of the instantaneous velocity of the degrees of freedom. In this work, a new numerical procedure to compute eigensolutions is proposed. The method is based on the construction of certain recursive functions which, under a iterative scheme, allow to reach eigenvalues and eigenvectors simultaneously and avoiding computation of eigensensitivities. Eigenvalues can be read then as fixed-points of those functions. A deep analysis of the convergence is carried out, focusing specially on relating the convergence conditions and error-decay rate to the damping model features, such as the nonproportionality and the viscoelasticity. The method is validated using two 6 degrees of freedom numerical examples involving both nonviscous and viscous damping and a continuous system with a local nonviscous damper. The convergence and the sequences behavior are in agreement with the results foreseen by the theory.
Algorithms and physical parameters involved in the calculation of model stellar atmospheres
NASA Astrophysics Data System (ADS)
Merlo, D. C.
This contribution summarizes the Doctoral Thesis presented at Facultad de Matemática, Astronomía y Física, Universidad Nacional de Córdoba for the degree of PhD in Astronomy. We analyze some algorithms and physical parameters involved in the calculation of model stellar atmospheres, such as atomic partition functions, functional relations connecting gaseous and electronic pressure, molecular formation, temperature distribution, chemical compositions, Gaunt factors, atomic cross-sections and scattering sources, as well as computational codes for calculating models. Special attention is paid to the integration of hydrostatic equation. We compare our results with those obtained by other authors, finding reasonable agreement. We make efforts on the implementation of methods that modify the originally adopted temperature distribution in the atmosphere, in order to obtain constant energy flux throughout. We find limitations and we correct numerical instabilities. We integrate the transfer equation solving directly the integral equation involving the source function. As a by-product, we calculate updated atomic partition functions of the light elements. Also, we discuss and enumerate carefully selected formulae for the monochromatic absorption and dispersion of some atomic and molecular species. Finally, we obtain a flexible code to calculate model stellar atmospheres.
Highlighting the Need for Systems-Level Experimental Characterization of Plant Metabolic Enzymes.
Engqvist, Martin K M
2016-01-01
The biology of living organisms is determined by the action and interaction of a large number of individual gene products, each with specific functions. Discovering and annotating the function of gene products is key to our understanding of these organisms. Controlled experiments and bioinformatic predictions both contribute to functional gene annotation. For most species it is difficult to gain an overview of what portion of gene annotations are based on experiments and what portion represent predictions. Here, I survey the current state of experimental knowledge of enzymes and metabolism in Arabidopsis thaliana as well as eleven economically important crops and forestry trees - with a particular focus on reactions involving organic acids in central metabolism. I illustrate the limited availability of experimental data for functional annotation of enzymes in most of these species. Many enzymes involved in metabolism of citrate, malate, fumarate, lactate, and glycolate in crops and forestry trees have not been characterized. Furthermore, enzymes involved in key biosynthetic pathways which shape important traits in crops and forestry trees have not been characterized. I argue for the development of novel high-throughput platforms with which limited functional characterization of gene products can be performed quickly and relatively cheaply. I refer to this approach as systems-level experimental characterization. The data collected from such platforms would form a layer intermediate between bioinformatic gene function predictions and in-depth experimental studies of these functions. Such a data layer would greatly aid in the pursuit of understanding a multiplicity of biological processes in living organisms.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Burger, Joanna; Gochfeld, Michael; Bunn, Amoret
2016-08-30
Governmental agencies, regulators, health professionals, tribal leaders, and the public are faced with understanding and evaluating the effects of cleanup activities on species, populations, and ecosystems. While engineers and managers understand the processes involved in different remediation types such as capping, pump and treat, and natural attenuation, there is often a disconnect between (1) how ecologists view the influence of different types of remediation, (2) how the public perceives them, and (3) how engineers understand them. The overall goal of the present investigation was to define the components of remediation types (= functional remediation). Objectives were to (1) define andmore » describe functional components of remediation, regardless of the remediation type, (2) provide examples of each functional remediation component, and (3) explore potential effects of functional remediation components in the post-cleanup phase that may involve continued monitoring and assessment. Functional remediation components include types, numbers, and intensity of people, trucks, heavy equipment, pipes, and drill holes, among others. Several components may be involved in each remediation type, and each results in ecological effects, ranging from trampling of plants, to spreading invasive species, to disturbing rare species, and to creating fragmented habitats. In some cases remediation may exert a greater effect on ecological receptors than leaving the limited contamination in place. A goal of this conceptualization is to break down functional components of remediation such that managers, regulators, and the public might assess the effects of timing, extent, and duration of different remediation options on ecological systems.« less
Kim, Jaeik; Chey, Jeanyung; Kim, Sang-Eun; Kim, Hoyoung
2015-05-01
Education involves learning new information and acquiring cognitive skills. These require various cognitive processes including learning, memory, and language. Since cognitive processes activate associated brain areas, we proposed that the brains of elderly people with longer education periods would show traces of repeated activation as increased synaptic connectivity and capillary in brain areas involved in learning, memory, and language. Utilizing positron emission topography (PET), this study examined the effect of education in the human brain utilizing the regional cerebral glucose metabolism rates (rCMRglcs). 26 elderly women with high-level education (HEG) and 26 with low-level education (LEG) were compared with regard to their regional brain activation and association between the regions. Further, graphical theoretical analysis using rCMRglcs was applied to examine differences in the functional network properties of the brain. The results showed that the HEG had higher rCMRglc in the ventral cerebral regions that are mainly involved in memory, language, and neurogenesis, while the LEG had higher rCMRglc in apical areas of the cerebrum mainly involved in motor and somatosensory functions. Functional connectivity investigated with graph theoretical analysis illustrated that the brain of the HEG compared to those of the LEG were overall more efficient, more resilient, and characterized by small-worldness. This may be one of the brain's mechanisms mediating the reserve effects found in people with higher education. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
Lateral prefrontal cortex: architectonic and functional organization
Petrides, Michael
2005-01-01
A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral–caudal axis and a dorsal–ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal–ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information. PMID:15937012
Wu, Qiong; Chang, Chi-Fu; Xi, Sisi; Huang, I-Wen; Liu, Zuxiang; Juan, Chi-Hung; Wu, Yanhong; Fan, Jin
2015-01-01
Information processing can be biased toward behaviorally relevant and salient stimuli by top-down (goal-directed) and bottom-up (stimulus-driven) attentional control processes. However, the neural basis underlying the integration of these processes is not well understood. We employed functional magnetic resonance imaging and transcranial direct-current stimulation (tDCS) in humans to examine the brain mechanisms underlying the interaction between these two processes. We manipulated the cognitive load involved in top-down processing and stimulus surprise involved in bottom-up processing in a factorial design by combining a majority function task and an oddball paradigm. We found that high cognitive load and high surprise level were associated with prolonged reaction time compared to low cognitive load and low surprise level, with a synergistic interaction effect which was accompanied by a greater deactivation of bilateral temporoparietal junction (TPJ). In addition, the TPJ displayed negative functional connectivity with right middle occipital gyrus involved in bottom-up processing (modulated by the interaction effect) and the right frontal eye field (FEF) involved in top-down control. The enhanced negative functional connectivity between the TPJ and right FEF was accompanied by a larger behavioral interaction effect across subjects. Application of cathodal tDCS over the right TPJ eliminated the interaction effect. These results suggest that the TPJ plays a critical role in processing bottom-up information for top-down control of attention. PMID:26308973
Chen, Yu-Min; Liu, Tai-Ling; Hsiao, Ray C.; Hu, Huei-Fan
2018-01-01
Bullying involvement is prevalent among children and adolescents with autism spectrum disorder (ASD). This study examined the effects of theory of mind performance training (ToMPT) on reducing bullying involvement in children and adolescents with high-functioning ASD. Children and adolescents with high-functioning ASD completed ToMPT (n = 26) and social skills training (SST; n = 23) programs. Participants in both groups and their mothers rated the pretraining and posttraining bullying involvement of participants on the Chinese version of the School Bullying Experience Questionnaire. The paired t test was used to evaluate changes in bullying victimization and perpetration between the pretraining and posttraining assessments. Furthermore, the linear mixed-effect model was used to examine the difference in the training effect between the ToMPT and SST groups. The paired t test indicated that in the ToMPT group, the severities of both self-reported (p = .039) and mother-reported (p = .003) bullying victimization significantly decreased from the pretraining to posttraining assessments, whereas in the SST group, only self-reported bullying victimization significantly decreased (p = .027). The linear mixed-effect model indicated that compared with the SST program, the ToMPT program significantly reduced the severity of mother-reported bullying victimization (p = .041). The present study supports the effects of ToMPT on reducing mother-reported bullying victimization in children and adolescents with high-functioning ASD. PMID:29342210
Jiménez, Diego Javier; Andreote, Fernando Dini; Chaves, Diego; Montaña, José Salvador; Osorio-Forero, Cesar; Junca, Howard; Zambrano, María Mercedes; Baena, Sandra
2012-01-01
A taxonomic and annotated functional description of microbial life was deduced from 53 Mb of metagenomic sequence retrieved from a planktonic fraction of the Neotropical high Andean (3,973 meters above sea level) acidic hot spring El Coquito (EC). A classification of unassembled metagenomic reads using different databases showed a high proportion of Gammaproteobacteria and Alphaproteobacteria (in total read affiliation), and through taxonomic affiliation of 16S rRNA gene fragments we observed the presence of Proteobacteria, micro-algae chloroplast and Firmicutes. Reads mapped against the genomes Acidiphilium cryptum JF-5, Legionella pneumophila str. Corby and Acidithiobacillus caldus revealed the presence of transposase-like sequences, potentially involved in horizontal gene transfer. Functional annotation and hierarchical comparison with different datasets obtained by pyrosequencing in different ecosystems showed that the microbial community also contained extensive DNA repair systems, possibly to cope with ultraviolet radiation at such high altitudes. Analysis of genes involved in the nitrogen cycle indicated the presence of dissimilatory nitrate reduction to N2 (narGHI, nirS, norBCDQ and nosZ), associated with Proteobacteria-like sequences. Genes involved in the sulfur cycle (cysDN, cysNC and aprA) indicated adenylsulfate and sulfite production that were affiliated to several bacterial species. In summary, metagenomic sequence data provided insight regarding the structure and possible functions of this hot spring microbial community, describing some groups potentially involved in the nitrogen and sulfur cycling in this environment. PMID:23251687
Lesions causing freezing of gait localize to a cerebellar functional network
Fasano, Alfonso; Laganiere, Simon E.; Lam, Susy; Fox, Michael D.
2016-01-01
Objective Freezing of gait is a disabling symptom in Parkinson’s disease and related disorders, but the brain regions involved in symptom generation remain unclear. Here we analyze brain lesions causing acute onset freezing of gait to identify regions causally involved in symptom generation. Methods Fourteen cases of lesion-induced freezing of gait were identified from the literature and lesions were mapped to a common brain atlas. Because lesion-induced symptoms can come from sites connected to the lesion location, not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has been recently shown to identify regions involved in symptom generation across a variety of lesion-induced disorders. Results Lesion location was heterogeneous and no single region could be considered necessary for symptom generation. However, over 90% (13/14) of lesions were functionally connected to a focal area in the dorsal medial cerebellum. This cerebellar area overlapped previously recognized regions that are activated by locomotor tasks, termed the cerebellar locomotor region. Connectivity to this region was specific to lesions causing freezing of gait compared to lesions causing other movement disorders (hemichorea or asterixis). Interpretation Lesions causing freezing of gait are located within a common functional network characterized by connectivity to the cerebellar locomotor region. These results based on causal brain lesions complement prior neuroimaging studies in Parkinson’s disease patients, advancing our understanding of the brain regions involved in freezing of gait. PMID:28009063
Hornoy, Benjamin; Pavy, Nathalie; Gérardi, Sébastien; Beaulieu, Jean; Bousquet, Jean
2015-11-11
Understanding the genetic basis of adaptation to climate is of paramount importance for preserving and managing genetic diversity in plants in a context of climate change. Yet, this objective has been addressed mainly in short-lived model species. Thus, expanding knowledge to nonmodel species with contrasting life histories, such as forest trees, appears necessary. To uncover the genetic basis of adaptation to climate in the widely distributed boreal conifer white spruce (Picea glauca), an environmental association study was conducted using 11,085 single nucleotide polymorphisms representing 7,819 genes, that is, approximately a quarter of the transcriptome.Linear and quadratic regressions controlling for isolation-by-distance, and the Random Forest algorithm, identified several dozen genes putatively under selection, among which 43 showed strongest signals along temperature and precipitation gradients. Most of them were related to temperature. Small to moderate shifts in allele frequencies were observed. Genes involved encompassed a wide variety of functions and processes, some of them being likely important for plant survival under biotic and abiotic environmental stresses according to expression data. Literature mining and sequence comparison also highlighted conserved sequences and functions with angiosperm homologs.Our results are consistent with theoretical predictions that local adaptation involves genes with small frequency shifts when selection is recent and gene flow among populations is high. Accordingly, genetic adaptation to climate in P. glauca appears to be complex, involving many independent and interacting gene functions, biochemical pathways, and processes. From an applied perspective, these results shall lead to specific functional/association studies in conifers and to the development of markers useful for the conservation of genetic resources. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Hornoy, Benjamin; Pavy, Nathalie; Gérardi, Sébastien; Beaulieu, Jean; Bousquet, Jean
2015-01-01
Understanding the genetic basis of adaptation to climate is of paramount importance for preserving and managing genetic diversity in plants in a context of climate change. Yet, this objective has been addressed mainly in short-lived model species. Thus, expanding knowledge to nonmodel species with contrasting life histories, such as forest trees, appears necessary. To uncover the genetic basis of adaptation to climate in the widely distributed boreal conifer white spruce (Picea glauca), an environmental association study was conducted using 11,085 single nucleotide polymorphisms representing 7,819 genes, that is, approximately a quarter of the transcriptome. Linear and quadratic regressions controlling for isolation-by-distance, and the Random Forest algorithm, identified several dozen genes putatively under selection, among which 43 showed strongest signals along temperature and precipitation gradients. Most of them were related to temperature. Small to moderate shifts in allele frequencies were observed. Genes involved encompassed a wide variety of functions and processes, some of them being likely important for plant survival under biotic and abiotic environmental stresses according to expression data. Literature mining and sequence comparison also highlighted conserved sequences and functions with angiosperm homologs. Our results are consistent with theoretical predictions that local adaptation involves genes with small frequency shifts when selection is recent and gene flow among populations is high. Accordingly, genetic adaptation to climate in P. glauca appears to be complex, involving many independent and interacting gene functions, biochemical pathways, and processes. From an applied perspective, these results shall lead to specific functional/association studies in conifers and to the development of markers useful for the conservation of genetic resources. PMID:26560341
Song, Zhewei; Du, Hai; Zhang, Yan; Xu, Yan
2017-01-01
Fermentation microbiota is specific microorganisms that generate different types of metabolites in many productions. In traditional solid-state fermentation, the structural composition and functional capacity of the core microbiota determine the quality and quantity of products. As a typical example of food fermentation, Chinese Maotai-flavor liquor production involves a complex of various microorganisms and a wide variety of metabolites. However, the microbial succession and functional shift of the core microbiota in this traditional food fermentation remain unclear. Here, high-throughput amplicons (16S rRNA gene amplicon sequencing and internal transcribed space amplicon sequencing) and metatranscriptomics sequencing technologies were combined to reveal the structure and function of the core microbiota in Chinese soy sauce aroma type liquor production. In addition, ultra-performance liquid chromatography and headspace-solid phase microextraction-gas chromatography-mass spectrometry were employed to provide qualitative and quantitative analysis of the major flavor metabolites. A total of 10 fungal and 11 bacterial genera were identified as the core microbiota. In addition, metatranscriptomic analysis revealed pyruvate metabolism in yeasts (genera Pichia, Schizosaccharomyces, Saccharomyces , and Zygosaccharomyces ) and lactic acid bacteria (genus Lactobacillus ) classified into two stages in the production of flavor components. Stage I involved high-level alcohol (ethanol) production, with the genus Schizosaccharomyces serving as the core functional microorganism. Stage II involved high-level acid (lactic acid and acetic acid) production, with the genus Lactobacillus serving as the core functional microorganism. The functional shift from the genus Schizosaccharomyces to the genus Lactobacillus drives flavor component conversion from alcohol (ethanol) to acid (lactic acid and acetic acid) in Chinese Maotai-flavor liquor production. Our findings provide insight into the effects of the core functional microbiota in soy sauce aroma type liquor production and the characteristics of the fermentation microbiota under different environmental conditions.
Mass Media Functions, Knowledge and Social Control
ERIC Educational Resources Information Center
Donohue, G. A.; And Others
1973-01-01
Develops a macro-view of mass media as interdependent parts of a total social system including a series of interrelated subsystems with primary function involving the generation, dissemination, and assimilation of information. (RB)
Two distinct forms of functional lateralization in the human brain
Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex
2013-01-01
The hemispheric lateralization of certain faculties in the human brain has long been held to be beneficial for functioning. However, quantitative relationships between the degree of lateralization in particular brain regions and the level of functioning have yet to be established. Here we demonstrate that two distinct forms of functional lateralization are present in the left vs. the right cerebral hemisphere, with the left hemisphere showing a preference to interact more exclusively with itself, particularly for cortical regions involved in language and fine motor coordination. In contrast, right-hemisphere cortical regions involved in visuospatial and attentional processing interact in a more integrative fashion with both hemispheres. The degree of lateralization present in these distinct systems selectively predicted behavioral measures of verbal and visuospatial ability, providing direct evidence that lateralization is associated with enhanced cognitive ability. PMID:23959883
Exploring optimal topology of thermal cloaks by CMA-ES
NASA Astrophysics Data System (ADS)
Fujii, Garuda; Akimoto, Youhei; Takahashi, Masayuki
2018-02-01
This paper presents topology optimization for thermal cloaks expressed by level-set functions and explored using the covariance matrix adaptation evolution strategy (CMA-ES). Designed optimal configurations provide superior performances in thermal cloaks for the steady-state thermal conduction and succeed in realizing thermal invisibility, despite the structures being simply composed of iron and aluminum and without inhomogeneities caused by employing metamaterials. To design thermal cloaks, a prescribed objective function is used to evaluate the difference between the temperature field controlled by a thermal cloak and when no thermal insulator is present. The CMA-ES involves searches for optimal sets of level-set functions as design variables that minimize a regularized fitness involving a perimeter constraint. Through topology optimization subject to structural symmetries about four axes, we obtain a concept design of a thermal cloak that functions in an isotropic heat flux.
Adolescent Desire for Cosmetic Surgery: Associations with Bullying and Psychological Functioning.
Lee, Kirsty; Guy, Alexa; Dale, Jeremy; Wolke, Dieter
2017-05-01
Adolescent bullying may be a key driver of interest in cosmetic surgery. This study examined the extent of such interest and whether any effect was sex-specific, and examined psychological functioning as a potential mechanism through which bullying involvement may lead to a wish for cosmetic surgery. A two-stage design was used. In the first stage, 2782 adolescents (aged 11 to 16 years) were screened for bullying involvement using self-reports and peer nominations. In the second stage, 752 adolescents who were bullies, victims, bully-victims, or uninvolved in bullying reported their desire for cosmetic surgery. Psychological functioning was constructed as a composite of self-esteem and emotional problems (assessed at stage 1) and body-esteem scores (assessed at stage 2). Adolescents involved in bullying in any role were significantly more interested in cosmetic surgery than uninvolved adolescents. Desire for cosmetic surgery was greatest in adolescents who were bullied (victims and bully-victims) and girls. Desire for cosmetic surgery was highest in girls, but sex did not interact with bullying role. Being victimized by peers resulted in poor psychological functioning, which increased desire for cosmetic surgery. In contrast, desire for cosmetic surgery in bullies was not related to psychological functioning, which was in the normal range. Bullying victimization is related to poor psychological functioning, and both are related to a greater desire for cosmetic surgery in adolescents. Cosmetic surgeons should screen candidates for psychological vulnerability and may want to include a short screening questionnaire for a history of peer victimization.
Olivieri, Ivana; Bova, Stefania Maria; Urgesi, Cosimo; Ariaudo, Giada; Perotto, Eleonora; Fazzi, Elisa; Stronati, Mauro; Fabbro, Franco; Balottin, Umberto; Orcesi, Simona
2012-04-01
Extremely low birth weight (ELBW) infants, even those not presenting severe neuromotor sequelae, continue to be at risk of developing multiple, complex disorders involving the cognitive, emotional and behavioural domains. Follow-up protocols are able, in the short term, to identify subjects at risk of developing major sequelae, however they fail to identify all children at risk of developing disorders. To investigate the cognitive, neuropsychological and behavioural outcomes of a sample of ELBW children at the age of four years in order to identify characteristic profiles. Longitudinal study. 16 healthy ELBW children born in 2005 and followed up until the age of four. Performances on standardised tests evaluating intelligence, memory, cognitive visual functions, attention, and executive functions. General intelligence was within normal range. Cognitive profile showed mild or moderate deficits with different levels of involvement in many of the examined functions, in particular executive functions, attention and naming. There emerged a wide-ranging spectrum of weaknesses and deficits involving all the functions examined, which together give rise to a dysexecutive syndrome. Analysis of cognitive profiles showed that the sample could be divided into two subgroups of subjects that differ in the quality of their global cognitive and behavioural functioning. Our results confirm the need to continue follow up of ELBW children until school age, as this will allow early detection of at-risk children and the planning of timely preventive interventions. Copyright © 2011 Elsevier Ltd. All rights reserved.
Military fathers' perspectives on involvement.
Willerton, Elaine; Schwarz, Rona L; Wadsworth, Shelley M Macdermid; Oglesby, Mary Schultheis
2011-08-01
Military fathers endure repeated separations from their children. In this qualitative study we describe military fathers' range of involvement with their children, paying special attention to the implications of deployment separation and reintegration. We discuss father involvement using three overlapping major domains of functioning: cognitive, affective, and behavioral. Additionally, we consider how types of father involvement differ vis-à-vis child age. Data were gathered via focus groups conducted with 71 fathers at 14 U.S. military installations. Descriptions of involvement were rich and varied. Involvement with children was a major concern for fathers, despite or perhaps because of the challenges of military careers. We discuss factors that help explain variations in involvement and offer insights about the conceptualization of father involvement for occupations requiring prolonged absences from home.
Quadratic forms involving Green's and Robin functions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dubinin, Vladimir N
2009-10-31
General inequalities for quadratic forms with coefficients depending on the values of Green's and Robin functions are obtained. These inequalities cover also the reduced moduli of strips and half-strips. Some applications of the results obtained to extremal partitioning problems and related questions of geometric function theory are discussed. Bibliography: 29 titles.
Functional Neuroimaging Studies of Written Sentence Comprehension
ERIC Educational Resources Information Center
Caplan, David
2004-01-01
Sentences convey relationships between the meanings of words, such as who is accomplishing an action or receiving it. Functional neuroimaging based on positron-emission tomography and functional magnetic resonance imaging has been used to identify areas of the brain involved in structuring sentences and determining aspects of meaning associated…
ERIC Educational Resources Information Center
Pendry, Patricia; Adam, Emma K.
2007-01-01
Associations between family functioning and children's stress hormone levels are explored, by examining how aspects of the interparental relationship (parents' marital satisfaction and parent conflict styles), the mother-child relationship (maternal involvement and warmth) and maternal emotional functioning (depression, anxiety and self-esteem)…
ERIC Educational Resources Information Center
Austin, Jillian E.; Tiger, Jeffrey H.
2015-01-01
The earliest stages of functional communication training (FCT) involve providing immediate and continuous reinforcement for a communicative response (FCR) that is functionally equivalent to the targeted problem behavior. However, maintaining immediate reinforcement is not practical, and the introduction of delays is associated with increased…
Mapping Language Function in the Brain: A Review of the Recent Literature.
ERIC Educational Resources Information Center
Crafton, Robert E.; Kido, Elissa
2000-01-01
Considers the potential importance of brain study for composition instruction, briefly describes functional imaging techniques, and reviews the findings of recent brain-mapping studies investigating the neurocognitive systems involved in language function. Presents a review of the recent literature and considers the possible implications of this…
A Qualitative Approach to Sketch the Graph of a Function.
ERIC Educational Resources Information Center
Alson, Pedro
1992-01-01
Presents a qualitative and global method of graphing functions that involves transformations of the graph of a known function in the cartesian coordinate system referred to as graphic operators. Explains how the method has been taught to students and some comments about the results obtained. (MDH)
ERIC Educational Resources Information Center
Axelrod, Saul
1987-01-01
Emerging approaches for dealing with inappropriate behaviors of the disabled involve conducting a functional or structural behavior analysis to isolate the factors responsible for the aberrant behavior and implementing corrective procedures (often alternatives to punishment) relevant to the function of the inappropriate behavior. (Author/DB)
49 CFR 37.43 - Alteration of transportation facilities by public entities.
Code of Federal Regulations, 2011 CFR
2011-10-01
... of a facility containing a primary function, the entity shall make the alteration in such a manner... involve primary functions include, but are not necessarily limited to, ticket purchase and collection... primary function area (without regard to the costs of accessibility modifications). (2) Costs that may be...
49 CFR 37.43 - Alteration of transportation facilities by public entities.
Code of Federal Regulations, 2014 CFR
2014-10-01
... of a facility containing a primary function, the entity shall make the alteration in such a manner... involve primary functions include, but are not necessarily limited to, ticket purchase and collection... primary function area (without regard to the costs of accessibility modifications). (2) Costs that may be...
49 CFR 37.43 - Alteration of transportation facilities by public entities.
Code of Federal Regulations, 2012 CFR
2012-10-01
... of a facility containing a primary function, the entity shall make the alteration in such a manner... involve primary functions include, but are not necessarily limited to, ticket purchase and collection... primary function area (without regard to the costs of accessibility modifications). (2) Costs that may be...
49 CFR 37.43 - Alteration of transportation facilities by public entities.
Code of Federal Regulations, 2013 CFR
2013-10-01
... of a facility containing a primary function, the entity shall make the alteration in such a manner... involve primary functions include, but are not necessarily limited to, ticket purchase and collection... primary function area (without regard to the costs of accessibility modifications). (2) Costs that may be...
Kim, Unkyu; Siegel, Rachael; Ren, Xiaodi; Gunther, Cary S; Gaasterland, Terry; Roeder, Robert G
2003-07-22
The tissue-specific transcriptional coactivator OCA-B is required for antigen-dependent B cell differentiation events, including germinal center formation. However, the identity of OCA-B target genes involved in this process is unknown. This study has used large-scale cDNA arrays to monitor changes in gene expression patterns that accompany mature B cell differentiation. B cell receptor ligation alone induces many genes involved in B cell expansion, whereas B cell receptor and helper T cell costimulation induce genes associated with B cell effector function. OCA-B expression is induced by both B cell receptor ligation alone and helper T cell costimulation, suggesting that OCA-B is involved in B cell expansion as well as B cell function. Accordingly, several genes involved in cell proliferation and signaling, such as Lck, Kcnn4, Cdc37, cyclin D3, B4galt1, and Ms4a11, have been identified as OCA-B-dependent genes. Further studies on the roles played by these genes in B cells will contribute to an understanding of B cell differentiation.
Functional recovery in the avian ear after hair cell regeneration.
Smolders, J W
1999-01-01
Trauma to the inner ear in birds, due to acoustic overstimulation or ototoxic aminoglycosides, can lead to hair cell loss which is followed by regeneration of new hair cells. These processes are paralleled by hearing loss followed by significant functional recovery. After acoustic trauma, functional recovery is rapid and nearly complete. The early and major part of functional recovery after sound trauma occurs before regenerated hair cells become functional. Even very intense sound trauma causes loss of only a proportion of the hair cell population, mainly so-called short hair cells residing on the abneural mobile part of the avian basilar membrane. Uncoupling of the tectorial membrane from the hair cells during sound overexposure may serve as a protection mechanism. The rapid functional recovery after sound trauma appears not to be associated with regeneration of the lost hair cells, but with repair processes involving the surviving hair cells. Small residual functional deficits after recovery are most likely associated with the missing upper fibrous layer of the tectorial membrane which fails to regenerate after sound trauma. After aminoglycoside trauma, functional recovery is slower and parallels the structural regeneration more closely. Aminoglycosides cause damage to both types of hair cells, starting at the basal (high frequency) part of the basilar papilla. However, functional hearing loss and recovery also occur at lower frequencies, associated with areas of the papilla where hair cells survive. Functional recovery in these low frequency areas is complete, whereas functional recovery in high frequency areas with complete hair cell loss is incomplete, despite regeneration of the hair cells. Permanent residual functional deficits remain. This indicates that in low frequency regions functional recovery after aminoglycosides involves repair of nonlethal injury to hair cells and/or hair cell-neural synapses. In the high frequency regions functional recovery involves regenerated hair cells. The permanent functional deficits after the regeneration process in these areas are most likely associated with functional deficits in the regenerated hair cells or shortcomings in the synaptic reconnections of nerve fibers with the regenerated hair cells. In conclusion, the avian inner ear appears to be much more resistant to trauma than the mammalian ear and possesses a considerable capacity for functional recovery based on repair processes along with its capacity to regenerate hair cells. The functional recovery in areas with regenerated hair cells is considerable but incomplete.
Social relationships and health: the relative roles of family functioning and social support.
Franks, P; Campbell, T L; Shields, C G
1992-04-01
The associations between social relationships and health have been examined using two major research traditions. Using a social epidemiological approach, much research has shown the beneficial effect of social supports on health and health behaviors. Family interaction research, which has grown out of a more clinical tradition, has shown the complex effects of family functioning on health, particularly mental health. No studies have examined the relative power of these two approaches in explicating the connections between social relationships and health. We hypothesized that social relationships (social support and family functioning) would exert direct and indirect (through depressive symptoms) effects on health behaviors. We also hypothesized that the effects of social relationships on health would be more powerfully explicated by family functioning than by social support. We mailed a pilot survey to a random sample of patients attending a family practice center, including questions on depressive symptoms, cardiovascular health behaviors, demographics, social support using the ISEL scale, and family functioning using the FEICS scale. FEICS is a self-report questionnaire designed to assess family emotional involvement and criticism, the media elements of family expressed emotion. Eighty-three useable responses were obtained. Regression analyses and structural modelling showed both direct and indirect statistically significant paths from social relationships to health behaviors. Family criticism was directly associated (standardized coefficient = 0.29) with depressive symptoms, and family emotional involvement was directly associated with both depressive symptoms (coefficient = 0.35) and healthy cardiovascular behaviors (coefficient = 0.32). The results support the primacy of family functioning factors in understanding the associations among social relationships, mental health, and health behaviors. The contrasting relationships between emotional involvement and depressive symptoms on the one hand and emotional involvement and health behaviors on the other suggest the need for a more complex model to understand the connections between social relationships and health.
Hebscher, Melissa; Gilboa, Asaf
2016-09-01
The ventromedial prefrontal cortex (vmPFC) has been implicated in a wide array of functions across multiple domains. In this review, we focus on the vmPFC's involvement in mediating strategic aspects of memory retrieval, memory-related schema functions, and decision-making. We suggest that vmPFC generates a confidence signal that informs decisions and memory-guided behaviour. Confidence is central to these seemingly diverse functions: (1) Strategic retrieval: lesions to the vmPFC impair an early, automatic, and intuitive monitoring process ("feeling of rightness"; FOR) often associated with confabulation (spontaneous reporting of erroneous memories). Critically, confabulators typically demonstrate high levels of confidence in their false memories, suggesting that faulty monitoring following vmPFC damage may lead to indiscriminate confidence signals. (2) Memory schemas: the vmPFC is critically involved in instantiating and maintaining contextually relevant schemas, broadly defined as higher level knowledge structures that encapsulate lower level representational elements. The correspondence between memory retrieval cues and these activated schemas leads to FOR monitoring. Stronger, more elaborate schemas produce stronger FOR and influence confidence in the veracity of memory candidates. (3) Finally, we review evidence on the vmPFC's role in decision-making, extending this role to decision-making during memory retrieval. During non-mnemonic and mnemonic decision-making the vmPFC automatically encodes confidence. Confidence signal in the vmPFC is revealed as a non-linear relationship between a first-order monitoring assessment and second-order action or choice. Attempting to integrate the multiple functions of the vmPFC, we propose a posterior-anterior organizational principle for this region. More posterior vmPFC regions are involved in earlier, automatic, subjective, and contextually sensitive functions, while more anterior regions are involved in controlled actions based on these earlier functions. Confidence signals reflect the non-linear relationship between first-order, posterior-mediated and second-order, anterior-mediated processes and are represented along the entire axis. Copyright © 2016 Elsevier Ltd. All rights reserved.
Soliveres, Santiago; Maestre, Fernando T; Bowker, Matthew A; Torices, Rubén; Quero, José L; García-Gómez, Miguel; Cabrera, Omar; Cea, Alex; Coaguila, Daniel; Eldridge, David J; Espinosa, Carlos I; Hemmings, Frank; Monerris, Jorge J; Tighe, Matthew; Delgado-Baquerizo, Manuel; Escolar, Cristina; García-Palacios, Pablo; Gozalo, Beatriz; Ochoa, Victoria; Blones, Julio; Derak, Mchich; Ghiloufi, Wahida; Gutiérrez, Julio R; Hernández, Rosa M; Noumi, Zouhaier
2014-08-20
Plant-plant interactions are driven by environmental conditions, evolutionary relationships (ER) and the functional traits of the plants involved. However, studies addressing the relative importance of these drivers are rare, but crucial to improve our predictions of the effects of plant-plant interactions on plant communities and of how they respond to differing environmental conditions. To analyze the relative importance of -and interrelationships among- these factors as drivers of plant-plant interactions, we analyzed perennial plant co-occurrence at 106 dryland plant communities established across rainfall gradients in nine countries. We used structural equation modeling to disentangle the relationships between environmental conditions (aridity and soil fertility), functional traits extracted from the literature, and ER, and to assess their relative importance as drivers of the 929 pairwise plant-plant co-occurrence levels measured. Functional traits, specifically facilitated plants' height and nurse growth form, were of primary importance, and modulated the effect of the environment and ER on plant-plant interactions. Environmental conditions and ER were important mainly for those interactions involving woody and graminoid nurses, respectively. The relative importance of different plant-plant interaction drivers (ER, functional traits, and the environment) varied depending on the region considered, illustrating the difficulty of predicting the outcome of plant-plant interactions at broader spatial scales. In our global-scale study on drylands, plant-plant interactions were more strongly related to functional traits of the species involved than to the environmental variables considered. Thus, moving to a trait-based facilitation/competition approach help to predict that: 1) positive plant-plant interactions are more likely to occur for taller facilitated species in drylands, and 2) plant-plant interactions within woody-dominated ecosystems might be more sensitive to changing environmental conditions than those within grasslands. By providing insights on which species are likely to better perform beneath a given neighbour, our results will also help to succeed in restoration practices involving the use of nurse plants.
Soliveres, Santiago; Maestre, Fernando T.; Bowker, Matthew A.; Torices, Rubén; Quero, José L.; García-Gómez, Miguel; Cabrera, Omar; Cea, Alex; Coaguila, Daniel; Eldridge, David J.; Espinosa, Carlos I.; Hemmings, Frank; Monerris, Jorge J.; Tighe, Matthew; Delgado-Baquerizo, Manuel; Escolar, Cristina; García-Palacios, Pablo; Gozalo, Beatriz; Ochoa, Victoria; Blones, Julio; Derak, Mchich; Ghiloufi, Wahida; Gutiérrez, Julio R.; Hernández, Rosa M.; Noumi, Zouhaier
2015-01-01
Plant-plant interactions are driven by environmental conditions, evolutionary relationships (ER) and the functional traits of the plants involved. However, studies addressing the relative importance of these drivers are rare, but crucial to improve our predictions of the effects of plant-plant interactions on plant communities and of how they respond to differing environmental conditions. To analyze the relative importance of –and interrelationships among– these factors as drivers of plant-plant interactions, we analyzed perennial plant co-occurrence at 106 dryland plant communities established across rainfall gradients in nine countries. We used structural equation modeling to disentangle the relationships between environmental conditions (aridity and soil fertility), functional traits extracted from the literature, and ER, and to assess their relative importance as drivers of the 929 pairwise plant-plant co-occurrence levels measured. Functional traits, specifically facilitated plants’ height and nurse growth form, were of primary importance, and modulated the effect of the environment and ER on plant-plant interactions. Environmental conditions and ER were important mainly for those interactions involving woody and graminoid nurses, respectively. The relative importance of different plant-plant interaction drivers (ER, functional traits, and the environment) varied depending on the region considered, illustrating the difficulty of predicting the outcome of plant-plant interactions at broader spatial scales. In our global-scale study on drylands, plant-plant interactions were more strongly related to functional traits of the species involved than to the environmental variables considered. Thus, moving to a trait-based facilitation/competition approach help to predict that: 1) positive plant-plant interactions are more likely to occur for taller facilitated species in drylands, and 2) plant-plant interactions within woody-dominated ecosystems might be more sensitive to changing environmental conditions than those within grasslands. By providing insights on which species are likely to better perform beneath a given neighbour, our results will also help to succeed in restoration practices involving the use of nurse plants. PMID:25914604
NASA Technical Reports Server (NTRS)
1982-01-01
Tests to verify the as-designed performance of all circuits within the thematic mapper electronics module unit are described. Specifically, the tests involved the evaluation of the scan line corrector driver, shutter drivers function, cal lamp controller function, post amplifier function, command decoder verification unit, and the temperature and actuator controllers function.
Monotonicity and Logarithmic Concavity of Two Functions Involving Exponential Function
ERIC Educational Resources Information Center
Liu, Ai-Qi; Li, Guo-Fu; Guo, Bai-Ni; Qi, Feng
2008-01-01
The function 1 divided by "x"[superscript 2] minus "e"[superscript"-x"] divided by (1 minus "e"[superscript"-x"])[superscript 2] for "x" greater than 0 is proved to be strictly decreasing. As an application of this monotonicity, the logarithmic concavity of the function "t" divided by "e"[superscript "at"] minus "e"[superscript"(a-1)""t"] for "a"…
Control of functional differential equations with function space boundary conditions.
NASA Technical Reports Server (NTRS)
Banks, H. T.
1972-01-01
The results of various authors dealing with problems involving functional differential equations with terminal conditions in function space are reviewed. The review includes not only very recent results, but also some little known results of Soviet mathematicians prior to 1970. Particular attention is given to results concerning controllability, existence of optimal controls, and necessary and sufficient conditions for optimality.
ERIC Educational Resources Information Center
Tiger, Jeffrey H.; Hanley, Gregory P.; Bessette, Kimberly K.
2006-01-01
Functional analysis methodology has become the hallmark of behavioral assessment, yielding a determination of behavioral function in roughly 96% of the cases published (Hanley, Iwata, & McCord, 2003). Some authors have suggested that incorporating the results of a descriptive assessment into the design of a functional analysis may be useful in…
Schiebener, Johannes; García-Arias, María; García-Villamisar, Domingo; Cabanyes-Truffino, Javier; Brand, Matthias
2015-01-01
Previous studies have shown that children and adolescents often tend toward risky decisions despite explicit knowledge about the potential negative consequences. This phenomenon has been suggested to be associated with the immaturity of brain areas involved in cognitive control functions. Particularly, "frontal lobe functions," such as executive functions and reasoning, mature until young adulthood and are thought to be involved in age-related changes in decision making under explicit risk conditions. We investigated 112 participants, aged 8-19 years, with a frequently used task assessing decisions under risk, the Game of Dice Task (GDT). Additionally, we administered the Modified Card Sorting Test assessing executive functioning (categorization, cognitive flexibility, and strategy maintenance) as well as the Ravens Progressive Matrices assessing reasoning. The results showed that risk taking in the GDT decreased with increasing age and this effect was not moderated by reasoning but by executive functions: Particularly, young persons with weak executive functioning showed very risky decision making. Thus, the individual maturation of executive functions, associated with areas in the prefrontal cortex, seems to be an important factor in young peoples' behavior in risky decision-making situations.
Diurnal rhythmicity in biological processes involved in bioavailability of functional food factors.
Tsurusaki, Takashi; Sakakibara, Hiroyuki; Aoshima, Yoshiki; Yamazaki, Shunsuke; Sakono, Masanobu; Shimoi, Kayoko
2013-05-01
In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids.
Zhang, Jia-Shu; Qu, Ling; Wang, Qun; Jin, Wei; Hou, Yuan-Zheng; Sun, Guo-Chen; Li, Fang-Ye; Yu, Xin-Guang; Xu, Ban-Nan; Chen, Xiao-Lei
2017-12-20
For stereotactic brain biopsy involving motor eloquent regions, the surgical objective is to enhance diagnostic yield and preserve neurological function. To achieve this aim, we implemented functional neuro-navigation and intraoperative magnetic resonance imaging (iMRI) into the biopsy procedure. The impact of this integrated technique on the surgical outcome and postoperative neurological function was investigated and evaluated. Thirty nine patients with lesions involving motor eloquent structures underwent frameless stereotactic biopsy assisted by functional neuro-navigation and iMRI. Intraoperative visualisation was realised by integrating anatomical and functional information into a navigation framework to improve biopsy trajectories and preserve eloquent structures. iMRI was conducted to guarantee the biopsy accuracy and detect intraoperative complications. The perioperative change of motor function and biopsy error before and after iMRI were recorded, and the role of functional information in trajectory selection and the relationship between the distance from sampling site to nearby eloquent structures and the neurological deterioration were further analyzed. Functional neuro-navigation helped modify the original trajectories and sampling sites in 35.90% (16/39) of cases to avoid the damage of eloquent structures. Even though all the lesions were high-risk of causing neurological deficits, no significant difference was found between preoperative and postoperative muscle strength. After data analysis, 3mm was supposed to be the safe distance for avoiding transient neurological deterioration. During surgery, the use of iMRI significantly reduced the biopsy errors (p = 0.042) and potentially increased the diagnostic yield from 84.62% (33/39) to 94.87% (37/39). Moreover, iMRI detected intraoperative haemorrhage in 5.13% (2/39) of patients, all of them benefited from the intraoperative strategies based on iMRI findings. Intraoperative visualisation of functional structures could be a feasible, safe and effective technique. Combined with intraoperative high-field MRI, it contributed to enhance the biopsy accuracy and lower neurological complications in stereotactic brain biopsy involving motor eloquent areas.
Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia.
Li, Tao; Wang, Qiang; Zhang, Jie; Rolls, Edmund T; Yang, Wei; Palaniyappan, Lena; Zhang, Lu; Cheng, Wei; Yao, Ye; Liu, Zhaowen; Gong, Xiaohong; Luo, Qiang; Tang, Yanqing; Crow, Timothy J; Broome, Matthew R; Xu, Ke; Li, Chunbo; Wang, Jijun; Liu, Zhening; Lu, Guangming; Wang, Fei; Feng, Jianfeng
2017-03-01
Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components.
Pascarella, A; Ferrandino, G; Credendino, S C; Moccia, C; D'Angelo, F; Miranda, B; D'Ambrosio, C; Bielli, P; Spadaro, O; Ceccarelli, M; Scaloni, A; Sette, C; De Felice, M; De Vita, G; Amendola, E
2018-05-17
DNAJC17 is a heat shock protein (HSP40) family member, identified in mouse as susceptibility gene for congenital hypothyroidism. DNAJC17 knockout mouse embryos die prior to implantation. In humans, germline homozygous mutations in DNAJC17 have been found in syndromic retinal dystrophy patients, while heterozygous mutations represent candidate pathogenic events for myeloproliferative disorders. Despite widespread expression and involvement in human diseases, DNAJC17 function is still poorly understood. Herein, we have investigated its function through high-throughput transcriptomic and proteomic approaches. DNAJC17-depleted cells transcriptome highlighted genes involved in general functional categories, mainly related to gene expression. Conversely, DNAJC17 interactome can be classified in very specific functional networks, with the most enriched one including proteins involved in splicing. Furthermore, several splicing-related interactors, were independently validated by co-immunoprecipitation and in vivo co-localization. Accordingly, co-localization of DNAJC17 with SC35, a marker of nuclear speckles, further supported its interaction with spliceosomal components. Lastly, DNAJC17 up-regulation enhanced splicing efficiency of minigene reporter in live cells, while its knockdown induced perturbations of splicing efficiency at whole genome level, as demonstrated by specific analysis of RNAseq data. In conclusion, our study strongly suggests a role of DNAJC17 in splicing-related processes and provides support to its recognized essential function in early development.
Maruyama, Tsukasa; Taki, Yasuyuki; Motoki, Kosuke; Jeong, Hyeonjeong; Kotozaki, Yuka; Nakagawa, Seishu; Iizuka, Kunio; Yokoyama, Ryoichi; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Sakaki, Kohei; Sasaki, Yukako; Magistro, Daniele; Kawashima, Ryuta
2018-01-01
Time-compressed speech is an artificial form of rapidly presented speech. Training with time-compressed speech (TCSSL) in a second language leads to adaptation toward TCSSL. Here, we newly investigated the effects of 4 weeks of training with TCSSL on diverse cognitive functions and neural systems using the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), resting-state functional connectivity (RSFC) with the left superior temporal gyrus (STG), fractional anisotropy (FA), and regional gray matter volume (rGMV) of young adults by magnetic resonance imaging. There were no significant differences in change of performance of measures of cognitive functions or second language skills after training with TCSSL compared with that of the active control group. However, compared with the active control group, training with TCSSL was associated with increased fALFF, RSFC, and FA and decreased rGMV involving areas in the left STG. These results lacked evidence of a far transfer effect of time-compressed speech training on a wide range of cognitive functions and second language skills in young adults. However, these results demonstrated effects of time-compressed speech training on gray and white matter structures as well as on resting-state intrinsic activity and connectivity involving the left STG, which plays a key role in listening comprehension. PMID:29675038
Chassard, Christophe; Scott, Karen P; Marquet, Perrine; Martin, Jennifer C; Del'homme, Christophe; Dapoigny, Michel; Flint, Harry J; Bernalier-Donadille, Annick
2008-12-01
The human gut harbours a wide range of bacterial communities that play key roles in supplying nutrients and energy to the host through anaerobic fermentation of dietary components and host secretions. This fermentative process involves different functional groups of microorganisms linked in a trophic chain. Although the diversity of the intestinal microbiota has been studied extensively using molecular techniques, the functional aspects of this biodiversity remain mostly unexplored. The aim of the present work was to enumerate the principal metabolic groups of microorganisms involved in the fermentative process in the gut of healthy humans. These functional groups of microorganisms were quantified by a cultural approach, while the taxonomic composition of the microbiota was assessed by in situ hybridization on the same faecal samples. The functional groups of microorganisms that predominated in the gut were the polysaccharide-degrading populations involved in the breakdown of the most readily available exogenous and endogenous substrates and the predominant butyrate-producing species. Most of the functional groups of microorganisms studied appeared to be present at rather similar levels in all healthy volunteers, suggesting that optimal numbers of these various bacterial groups are crucial for efficient gut fermentation, as well as for host nutrition and health. Significant interindividual differences were, however, confirmed with respect to the numbers of methanogenic archaea, filter paper-degrading and acetogenic bacteria and the products formed by lactate-utilizing bacteria.
Nitric oxide signaling in the development and evolution of language and cognitive circuits.
Funk, Owen H; Kwan, Kenneth Y
2014-09-01
The neocortex underlies not only remarkable motor and sensory capabilities, but also some of our most distinctly human cognitive functions. The emergence of these higher functions during evolution was accompanied by structural changes in the neocortex, including the acquisition of areal specializations such as Broca's speech and language area. The study of these evolutionary mechanisms, which likely involve species-dependent gene expression and function, represents a substantial challenge. These species differences, however, may represent valuable opportunities to understand the molecular underpinnings of neocortical evolution. Here, we discuss nitric oxide signaling as a candidate mechanism in the assembly of neocortical circuits underlying language and higher cognitive functions. This hypothesis was based on the highly specific mid-fetal pattern of nitric oxide synthase 1 (NOS1, previously nNOS) expression in the pyramidal (projection) neurons of two human neocortical areas respectively involved in speech and language, and higher cognition; the frontal operculum (FOp) and the anterior cingulate cortex (ACC). This expression is transiently present during mid-gestation, suggesting that NOS1 may be involved in the development of these areas and the assembly of their neural circuits. As no other gene product is known to exhibit such exquisite spatiotemporal expression, NOS1 represents a remarkable candidate for these functions. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
NASA Astrophysics Data System (ADS)
Gifford, Brendan Joel
Single-walled carbon nanotubes (SWCNTs) are unique materials that exhibit chirality-specific properties due to their one-dimensional confinement. As a result, they are explored for a wide range of applications including single-photon sources in communications devices. Despite progress in this area, SWCNTs still suffer from a relatively narrow range of energies of emission features that fall short of the 1500 nm desired for long-distance lossless data transfer. One approach that is frequently used to resolve this involves chemical functionalization with aryl groups. However, this approach is met with a number of fundamental issues. First, chirality-specific SWCNTs must be acquired for subsequent functionalization. Synthesis of such samples has thus far eluded experimental efforts. As such, post-synthetic non-covalent functionalization is required to break bundles and create disperse SWCNTs that can undergo further separation, processing, and functionalization. Second, a number of low-energy emission features are introduced upon functionalization across a 200 nm range. The origin of such diverse emission features remains unknown. The research presented here focuses on computationally addressing these issues. A series of polyfluorene polymers possessing sidechains of varying length are explored using molecular mechanics to determine the impact of alkyl sidechains on SWCNT-conjugated polymer interaction strength and morphology. Additionally, density functional theory (DFT) and linear-response time-dependent DFT (TDDFT) are used to explore the effect of functionalization on emission features. A prerequisite to these calculations involves constructing finite-length SWCNT systems with similar electronic structure to their infinite counterparts: a methodological approach for the formation of such systems is presented. The optical features for aryl-functionalized SWCNTs are then explored. It is shown that the predominant effect on the energies of emission features involves the configuration of functionalization, with the identity of the functional group only playing a minor role. While the qualitative effect of such functionalization is determined, a quantitative comparison to experiment requires correction for several sources of computational error. A model to correct for such effects is also developed. This research not only explains the origin of the multiple emission features in functionalized SWCNTs for the first time but also lays the groundwork for their further computational exploration.
Rostral and caudal prefrontal contribution to creativity: a meta-analysis of functional imaging data
Gonen-Yaacovi, Gil; de Souza, Leonardo Cruz; Levy, Richard; Urbanski, Marika; Josse, Goulven; Volle, Emmanuelle
2013-01-01
Creativity is of central importance for human civilization, yet its neurocognitive bases are poorly understood. The aim of the present study was to integrate existing functional imaging data by using the meta-analysis approach. We reviewed 34 functional imaging studies that reported activation foci during tasks assumed to engage creative thinking in healthy adults. A coordinate-based meta-analysis using Activation Likelihood Estimation (ALE) first showed a set of predominantly left-hemispheric regions shared by the various creativity tasks examined. These regions included the caudal lateral prefrontal cortex (PFC), the medial and lateral rostral PFC, and the inferior parietal and posterior temporal cortices. Further analyses showed that tasks involving the combination of remote information (combination tasks) activated more anterior areas of the lateral PFC than tasks involving the free generation of unusual responses (unusual generation tasks), although both types of tasks shared caudal prefrontal areas. In addition, verbal and non-verbal tasks involved the same regions in the left caudal prefrontal, temporal, and parietal areas, but also distinct domain-oriented areas. Taken together, these findings suggest that several frontal and parieto-temporal regions may support cognitive processes shared by diverse creativity tasks, and that some regions may be specialized for distinct types of processes. In particular, the lateral PFC appeared to be organized along a rostro-caudal axis, with rostral regions involved in combining ideas creatively and more posterior regions involved in freely generating novel ideas. PMID:23966927
Gopinath, Pushparathinam; Nilaya, Surapaneni; Debi, Tripathy Ranjan; Ramkumar, Venkatachalam; Muraleedharan, Kannoth Manheri
2009-12-14
A novel reaction pathway involving 1,3-diketones and 2,2'-dithiodibenzoylchloride that gives access to benzothiophenes with spiroketal, lactone, carbonyl, hydroxyl and carboxylic acid functionalities is discussed.
ERIC Educational Resources Information Center
Selkoe, Dennis J.
1992-01-01
Discusses the aging process related to physical changes of the human neural structure involved in learning, memory, and reasoning. Presents evidence that indicates such alterations do not necessarily signal the decline in cognitive function. Vignettes provide images of brain structures involved in learning, memory, and reasoning; hippocampal…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cooks, Robert Graham; Li, Anyin; Luo, Qingjie
The invention generally relates to systems and methods for producing metal clusters; functionalized surfaces; and droplets including solvated metal ions. In certain aspects, the invention provides methods that involve providing a metal and a solvent. The methods additionally involve applying voltage to the solvated metal to thereby produce solvent droplets including ions of the metal containing compound, and directing the solvent droplets including the metal ions to a target. In certain embodiments, once at the target, the metal ions can react directly or catalyze reactions.
Cooks, Robert Graham; Li, Anyin; Luo, Qingjie
2017-01-24
The invention generally relates to systems and methods for producing metal clusters; functionalized surfaces; and droplets including solvated metal ions. In certain aspects, the invention provides methods that involve providing a metal and a solvent. The methods additionally involve applying voltage to the solvated metal to thereby produce solvent droplets including ions of the metal containing compound, and directing the solvent droplets including the metal ions to a target. In certain embodiments, once at the target, the metal ions can react directly or catalyze reactions.
Ma, Yanyan; Yang, Mingkun; Lin, Xiaohuang; Liu, Xin; Huang, Hui; Ge, Feng
2017-05-05
As a recently validated reversible post translational modification, lysine malonylation regulates diverse cellular processes from bacteria to mammals, but its existence and function in photosynthetic organisms remain unknown. Cyanobacteria are the most ancient group of photosynthetic prokaryotes and contribute about 50% of the total primary production on Earth. Previously, we reported the lysine acetylome in the model cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis). Here we performed the first proteomic survey of lysine malonylation in Synechocystis using highly accurate tandem mass spectrometry in combination with affinity purification. We identified 598 lysine malonylation sites on 339 proteins with high confidence in total. A bioinformatic analysis suggested that these malonylated proteins may play various functions and were distributed in diverse subcellular compartments. Among them, many malonylated proteins were involved in cellular metabolism. The functional significance of lysine malonylation in the metabolic enzyme activity of phosphoglycerate kinase (PGK) was determined by site-specific mutagenesis and biochemical studies. Interestingly, 27 proteins involved in photosynthesis were found to be malonylated for the first time, suggesting that lysine malonylation may be involved in photosynthesis. Thus our results provide the first lysine malonylome in a photosynthetic organism and suggest a previously unexplored role of lysine malonylation in the regulation of metabolic processes and photosynthesis in Synechocystis as well as in other photosynthetic organisms.
Jentsch, J D; Roth, R H; Taylor, J R
2000-01-01
We have discussed the role of dopamine in modulating the interactions between cortical and striatal regions that are involved in behavioral regulation. The evidence reviewed seems to suggest that dopamine acts, overall, to promote stimulus-induced responding for conditioned or reward-related stimuli by integrative actions at multiple forebrain sites. It is thus not surprising that dopaminergic dysfunction has been implicated in a number of neuropsychiatric disorders that involve abnormal cognitive and affective function. Future studies aimed at pinpointing the precise anatomical sites of action and molecular mechanisms involved in dopaminergic transmission within the corticolimbic circuit are critical for trying to disentangle the cellular mechanisms by which dopamine exerts its actions. Moreover, the afferent control of dopamine neurons from brainstem and forebrain sites need to be fully explored in order to begin to understand what mechanisms are involved in regulating the dopaminergic response to stimuli with incentive value. Finally, the post-synaptic consequences of prolonged and supranormal dopaminergic activation need to be investigated in order to understand what persistent neuroadaptations result from chronic activation of this neuromodulatory system (e.g. in drug addiction). Answers to these sorts of questions will undoubtedly provide important insights into the nature of dopaminergic function in the animal and human brain.
Distinct pathways of neural coupling for different basic emotions.
Tettamanti, Marco; Rognoni, Elena; Cafiero, Riccardo; Costa, Tommaso; Galati, Dario; Perani, Daniela
2012-01-16
Emotions are complex events recruiting distributed cortical and subcortical cerebral structures, where the functional integration dynamics within the involved neural circuits in relation to the nature of the different emotions are still unknown. Using fMRI, we measured the neural responses elicited by films representing basic emotions (fear, disgust, sadness, happiness). The amygdala and the associative cortex were conjointly activated by all basic emotions. Furthermore, distinct arrays of cortical and subcortical brain regions were additionally activated by each emotion, with the exception of sadness. Such findings informed the definition of three effective connectivity models, testing for the functional integration of visual cortex and amygdala, as regions processing all emotions, with domain-specific regions, namely: i) for fear, the frontoparietal system involved in preparing adaptive motor responses; ii) for disgust, the somatosensory system, reflecting protective responses against contaminating stimuli; iii) for happiness: medial prefrontal and temporoparietal cortices involved in understanding joyful interactions. Consistently with these domain-specific models, the results of the effective connectivity analysis indicate that the amygdala is involved in distinct functional integration effects with cortical networks processing sensorimotor, somatosensory, or cognitive aspects of basic emotions. The resulting effective connectivity networks may serve to regulate motor and cognitive behavior based on the quality of the induced emotional experience. Copyright © 2011. Published by Elsevier Inc.
Her versus his migraine: multiple sex differences in brain function and structure
Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David
2012-01-01
Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a ‘sex phenotype’ in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs. PMID:22843414
Not single brain areas but a network is involved in language: Applications in presurgical planning.
Alemi, Razieh; Batouli, Seyed Amir Hossein; Behzad, Ebrahim; Ebrahimpoor, Mitra; Oghabian, Mohammad Ali
2018-02-01
Language is an important human function, and is a determinant of the quality of life. In conditions such as brain lesions, disruption of the language function may occur, and lesion resection is a solution for that. Presurgical planning to determine the language-related brain areas would enhance the chances of language preservation after the operation; however, availability of a normative language template is essential. In this study, using data from 60 young individuals who were meticulously checked for mental and physical health, and using fMRI and robust imaging and data analysis methods, functional brain maps for the language production, perception and semantic were produced. The obtained templates showed that the language function should be considered as the product of the collaboration of a network of brain regions, instead of considering only few brain areas to be involved in that. This study has important clinical applications, and extends our knowledge on the neuroanatomy of the language function. Copyright © 2018 Elsevier B.V. All rights reserved.
Liu, Tai-Ling; Guo, Nai-Wen; Hsiao, Ray C; Hu, Huei-Fan; Yen, Cheng-Fang
2017-11-01
This study investigated the relationship of bullying victimization and perpetration with the levels of intelligence, attention, and executive function in children who had received a diagnosis of attention-deficit/hyperactivity disorder (ADHD). The experiences of bullying involvement in 105 children with ADHD were assessed using the Chinese version of the School Bullying Experience Questionnaire. Their scores for four intelligence indexes on the Wechsler Intelligence Scale for Children 4th Edition-Chinese version were determined. Their levels of attention and executive function were assessed using the Comprehensive Nonverbal Attention Test Battery. The results of logistic regression analyses indicated that a high Perceptual Reasoning Index was significantly associated with a decreased risk of being victims of bullying. A high level of executive function was significantly associated with a decreased risk of being victims and perpetrators of bullying. Bullying victimization and perpetration in children with ADHD having a low PRI and low executive function should be routinely surveyed. Copyright © 2017 Elsevier Ltd. All rights reserved.
Her versus his migraine: multiple sex differences in brain function and structure.
Maleki, Nasim; Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David
2012-08-01
Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs.
Computation of Standard Errors
Dowd, Bryan E; Greene, William H; Norton, Edward C
2014-01-01
Objectives We discuss the problem of computing the standard errors of functions involving estimated parameters and provide the relevant computer code for three different computational approaches using two popular computer packages. Study Design We show how to compute the standard errors of several functions of interest: the predicted value of the dependent variable for a particular subject, and the effect of a change in an explanatory variable on the predicted value of the dependent variable for an individual subject and average effect for a sample of subjects. Empirical Application Using a publicly available dataset, we explain three different methods of computing standard errors: the delta method, Krinsky–Robb, and bootstrapping. We provide computer code for Stata 12 and LIMDEP 10/NLOGIT 5. Conclusions In most applications, choice of the computational method for standard errors of functions of estimated parameters is a matter of convenience. However, when computing standard errors of the sample average of functions that involve both estimated parameters and nonstochastic explanatory variables, it is important to consider the sources of variation in the function's values. PMID:24800304
Designing Agent Collectives For Systems With Markovian Dynamics
NASA Technical Reports Server (NTRS)
Wolpert, David H.; Lawson, John W.
2004-01-01
The Collective Intelligence (COIN) framework concerns the design of collectives of agents so that as those agents strive to maximize their individual utility functions, their interaction causes a provided world utility function concerning the entire collective to be also maximized. Here we show how to extend that framework to scenarios having Markovian dynamics when no re-evolution of the system from counter-factual initial conditions (an often expensive calculation) is permitted. Our approach transforms the (time-extended) argument of each agent's utility function before evaluating that function. This transformation has benefits in scenarios not involving Markovian dynamics of an agent's utility function are observable. We investigate this transformation in simulations involving both hear and quadratic (nonlinear) dynamics. In addition, we find that a certain subset of these transformations, which result in utilities that have low opacity (analogous to having high signal to noise) but are not factored (analogous to not being incentive compatible), reliably improve performance over that arising with factored utilities. We also present a Taylor Series method for the fully general nonlinear case.
Plethystic vertex operators and boson-fermion correspondences
NASA Astrophysics Data System (ADS)
Fauser, Bertfried; Jarvis, Peter D.; King, Ronald C.
2016-10-01
We study the algebraic properties of plethystic vertex operators, introduced in (2010 J. Phys. A: Math. Theor. 43 405202), underlying the structure of symmetric functions associated with certain generalized universal character rings of subgroups of the general linear group, defined to stabilize tensors of Young symmetry type characterized by a partition of arbitrary shape π. Here we establish an extension of the well-known boson-fermion correspondence involving Schur functions and their associated (Bernstein) vertex operators: for each π, the modes generated by the plethystic vertex operators and their suitably constructed duals, satisfy the anticommutation relations of a complex Clifford algebra. The combinatorial manipulations underlying the results involve exchange identities exploiting the Hopf-algebraic structure of certain symmetric function series and their plethysms.
Tóth, Balázs I; Oláh, Attila; Szöllősi, Attila Gábor; Bíró, Tamás
2014-05-01
Emerging evidence suggests that transient receptor potential (TRP) ion channels not only act as 'polymodal cellular sensors' on sensory neurons but are also functionally expressed by a multitude of non-neuronal cell types. This is especially true in the skin, one of the largest organs of the body, where they appear to be critically involved in regulating various cutaneous functions both under physiological and pathophysiological conditions. In this review, we focus on introducing the roles of several cutaneous TRP channels in the regulation of the skin barrier, skin cell proliferation and differentiation, and immune functions. Moreover, we also describe the putative involvement of several TRP channels in the development of certain skin diseases and identify future TRP channel-targeted therapeutic opportunities. © 2013 The British Pharmacological Society.
Shuttle/payload communications and data systems interface analysis
NASA Technical Reports Server (NTRS)
Huth, G. K.
1980-01-01
The payload/orbiter functional command signal flow and telemetry signal flow are discussed. Functional descriptions of the various orbiter communication/avionic equipment involved in processing a command to a payload either from the ground through the orbiter by the payload specialist on the orbiter are included. Functional descriptions of the various orbiter communication/avionic equipment involved in processing telemetry data by the orbiter and transmitting the processed data to the ground are presented. The results of the attached payload/orbiter single processing and data handling system evaluation are described. The causes of the majority of attached payload/orbiter interface problems are delineated. A refined set of required flux density values for a detached payload to communicate with the orbiter is presented.
Emerging Functions for the Staphylococcus aureus RNome
Felden, Brice
2013-01-01
Staphylococcus aureus is a leading pathogen for animals and humans, not only being one of the most frequently isolated bacteria in hospital-associated infections but also causing diseases in the community. To coordinate the expression of its numerous virulence genes for growth and survival, S. aureus uses various signalling pathways that include two-component regulatory systems, transcription factors, and also around 250 regulatory RNAs. Biological roles have only been determined for a handful of these sRNAs, including cis, trans, and cis-trans acting RNAs, some internally encoding small, functional peptides and others possessing dual or multiple functions. Here we put forward an inventory of these fascinating sRNAs; the proteins involved in their activities; and those involved in stress response, metabolisms, and virulence. PMID:24348246
Brynsvold, Glen V.; Snyder, Jr., Harold J.
1976-06-22
An internal core tightener which is a linear actuated (vertical actuation motion) expanding device utilizing a minimum of moving parts to perform the lateral tightening function. The key features are: (1) large contact areas to transmit loads during reactor operation; (2) actuation cam surfaces loaded only during clamping and unclamping operation; (3) separation of the parts and internal operation involved in the holding function from those involved in the actuation function; and (4) preloaded pads with compliant travel at each face of the hexagonal assembly at the two clamping planes to accommodate thermal expansion and irradiation induced swelling. The latter feature enables use of a "fixed" outer core boundary, and thus eliminates the uncertainty in gross core dimensions, and potential for rapid core reactivity changes as a result of core dimensional change.
NASA Astrophysics Data System (ADS)
Zhang, G.; Yuan, Y.
2015-12-01
The use of fossil fuels and fertilizers has increased the amount of biologically reactive nitrogen in the atmosphere over the past century. Tibet is the one of the most threatened regions by nitrogen deposition, thus understanding how its microbial communities function maybe of high importance to predicting microbial responses to nitrogen deposition. Here we describe a short-time nitrogen addition conducted in an alpine steppe ecosystem to investigate the response of functional structure of soil microbial community to multi-level nitrogen addition. Using a GeoChip 4.0, we showed that functional diversities and richness of functional genes were unchanged at low level of nitrogen fertilizer inputs (<20 kg N ha-1 yr-1), but significantly decreased at higher nitrogen fertilizer inputs (>=40 kg N ha-1 yr-1). Detrended correspondence analysis indicated that the functional structure of microbial communities was markedly different across the nitrogen gradients. Most C degradation genes whose abundances significantly increased under elevated N fertilizer were those involved in the degradation of relatively labile C (starch, hemicellulose, cellulose), whereas the abundance of certain genes involved in the degradation of recalcitrant C (i.e. lignin) was largely decreased (such as manganese peroxidase, mnp). The results suggest that the elevated N fertilization rates might significantly accelerate the labile C degradation, but might not spur recalcitrant C degradation. The combined effect of gdh and ureC genes involved in N cycling appeared to shift the balance between ammonia and organic N toward organic N ammonification and hence increased the N mineralization potential. Moreover, Urease directly involved in urea mineralization significantly increased. Lastly, Canonical correspondence analysis showed that soil (TOC+NH4++NO3-+NO2-+pH) and plant (Aboveground plant productivity + Shannon Diversity) variables could explain 38.9% of the variation of soil microbial community composition. On the basis of above observations, we predict that increasing of nitrogen deposition on the Tibetan steppe ecosystem is very likely to change soil microbial community functional structure, with particular effects on microbial C and N-cycling genes and consequently microbe-mediated soil C and N dynamics.
Lingeswaran, Somiya; Ari, Geetha; Thyagarajan, Ramakrishnan; Logaranjani, Anitha
2016-01-01
The molar tooth of children and young adults is a common site for chronic hyperplastic pulpitis (pulp polyp). It rarely occurs in middle aged adults. This condition is usually characterized by extensive involvement of the pulp, dictating the extraction of involved tooth. Extraction of permanent molars can lead to transient or permanent malocclusion, aesthetic, phonetic and functional problems. Here we report a case of pulp polyp in mandibular first molar of a 33-year-old woman that grew into the carious cavity. The aim of this case report is to describe the diagnosis of a chronic hyperplastic pulpitis involving the permanent molar as well as to describe its management in order to preserve them as a functional unit of the dentition. PMID:26894192
Anilkumar, Kanakamedala; Lingeswaran, Somiya; Ari, Geetha; Thyagarajan, Ramakrishnan; Logaranjani, Anitha
2016-01-01
The molar tooth of children and young adults is a common site for chronic hyperplastic pulpitis (pulp polyp). It rarely occurs in middle aged adults. This condition is usually characterized by extensive involvement of the pulp, dictating the extraction of involved tooth. Extraction of permanent molars can lead to transient or permanent malocclusion, aesthetic, phonetic and functional problems. Here we report a case of pulp polyp in mandibular first molar of a 33-year-old woman that grew into the carious cavity. The aim of this case report is to describe the diagnosis of a chronic hyperplastic pulpitis involving the permanent molar as well as to describe its management in order to preserve them as a functional unit of the dentition.
Differentiation of Effector CD4 T Cell Populations*
Zhu, Jinfang; Yamane, Hidehiro; Paul, William E.
2012-01-01
CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, Th17, and iTreg, as defined by their pattern of cytokine production and function. In this review, we summarize the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation. PMID:20192806
Ipsilateral Closed Clavicle and Scapular spine Fracture with Acromioclavicular Joint Disruption.
Kembhavi, Raghavendra S; James, Boblee
2015-01-01
Injuries around shoulder and clavicle are quite common. Injuries involving lateral end of clavicle involving acromioclavicular joints are commoner injuries. In this rare injury, we report about a case involving clavicle and scapular spine fracture with acromioclavicular disruption which has never been described in English literature as per our knowledge. A patient with closed clavicle and scapular spine fracture with acromioclavicular joint disruption was treated with open reduction and internal fixation of clavicle and scapular spine as a staged procedures. Six months post operatively, patient had excellent functional recovery with near full range of movements. Though rare complex injury, clavicle fracture with scapular spine fracture with acromioclavicular disruption, when managed properly with good physiotherapy protocol post operatively will result in good clinical and functional outcome.
Kunz, C; Leiggener, C S; Fridrich, K; Schmuziger, N; Hammer, B
2003-07-01
For the temporomandibular joint (TMJ), functional disorders are common but tumors and tumor like lesions are rare, although these are often mistaken for functional ailments. Early examination by computed tomography or, as a method of choice, magnetic resonance imaging is recommended in case of persisting TMJ problems. Pigmented villonodular synovitis (PVNS) is a rare benign but locally destructive fibrohistiocytic lesion originating in synovial tissue. Involvement of the temporomandibular joint is extremely rare, with the average age of patients being 44.6 years. This paper reports on a 13-year-old patient with diffuse PVNS involving the middle ear and middle cranial fossa. The treatment of choice involves wide local excision and reconstruction of the temporomandibular joint with long-term follow-up. Pathogenesis and differential diagnosis are discussed.
ERIC Educational Resources Information Center
Han, Yvonne M. Y.; Leung, Winnie Wing-man; Wong, Chun Kwok; Lam, Joseph M. K.; Cheung, Mei-Chun; Chan, Agnes S.
2011-01-01
Increasing evidence suggests that immunological factors are involved in the pathogenesis of autism spectrum disorders (ASD). The present study examined whether immunological abnormalities are associated with cognitive deficits in children with ASD. Eighteen high-functioning (HFA) and 19 low-functioning (LFA) children with ASD, aged 8-17 years,…
ERIC Educational Resources Information Center
Moore, Crystal Dea
2010-01-01
A cross-sectional study of 76 family caregivers of older veterans with congestive heart failure utilized the McMaster model of family functioning to examine the impact of family functioning variables (problem solving, communication, roles, affective responsiveness, and affective involvement) on caregiver burden dimensions (relationship burden,…
ERIC Educational Resources Information Center
Ross, Samantha Mae; Case, Layne; Leung, Willie
2016-01-01
The introduction of the International Classification of Functioning, Disability and Health has placed emphasis on framing health behavior as a multidimensional construct. In relation to childhood physical activity, this encompasses dimensions of functional performance, activity attendance, and subjective perceptions of involvement and enjoyment…
Perception of Dialect Variation by Young Adults with High-Functioning Autism
ERIC Educational Resources Information Center
Clopper, Cynthia G.; Rohrbeck, Kristin L.; Wagner, Laura
2012-01-01
The linguistic profile of people with Autism spectrum disorders typically involves intact perceptual processing, accompanied by deficits in the social functions of language. In a series of three experiments, the impact of this profile on the perception of regional dialect was examined. Young adults with High-Functioning Autism exhibited similar…
Agnosia, apraxia, callosal disconnection and other specific cognitive disorders.
Acciarresi, Monica
2012-01-01
Cortical function deficits have long been studied by anatomoclinic correlations. Recent functional imaging studies have allowed scientists to better understand which cerebral areas and which networks are involved in cognitive function deficit. This chapter will review the current knowledge on agnosia, apraxia and callosal disconnection syndromes. Copyright © 2012 S. Karger AG, Basel.
Expectations for Visual Function: An Initial Evaluation of a New Clinical Instrument.
ERIC Educational Resources Information Center
Corn, Anne L.; Webne, Steve L.
2001-01-01
A study explored the internal consistency of items in a visual screening instrument developed by Project PAVE: Expectations for Visual Functioning (EVF). The test includes 20 items that evaluate a child's functional use of vision. A pilot test involving 129 teachers indicates the EFV is internally consistent. (Contains three references.) (CR)
Executive Functions in Young Adults with Autism Spectrum Disorder
ERIC Educational Resources Information Center
Brady, Danielle I.; Saklofske, Donald H.; Schwean, Vicki L.; Montgomery, Janine M.; Thorne, Keoma J.; McCrimmon, Adam W.
2017-01-01
Researchers have proposed that autism spectrum disorder (ASD) is characterized, at least in part, by executive function (EF) difficulties associated with the integrity of the frontal lobe. Given the paucity of research regarding EFs in young adults with high functioning ASD (HF-ASD), this research involves an examination of various indices of EF…
Photoreactive synthetic regulator of protein function and methods of use thereof
Trauner, Dirk; Isacoff, Ehud Y; Kramer, Richard H; Banghart, Matthew R; Fortin, Doris L; Mourot, Alexandre
2015-03-31
The present disclosure provides a photoreactive synthetic regulator of protein function. The present disclosure further provides a light-regulated polypeptide that includes a subject synthetic regulator. Also provided are cells and membranes comprising a subject light-regulated polypeptide. The present disclosure further provides methods of modulating protein function, involving use of light.
ERIC Educational Resources Information Center
Cartwright, Kelly B.
2012-01-01
Research Findings: Executive function begins to develop in infancy and involves an array of processes, such as attention, inhibition, working memory, and cognitive flexibility, which provide the means by which individuals control their own behavior, work toward goals, and manage complex cognitive processes. Thus, executive function plays a…
Regulation of antimicrobial resistance by extracytoplasmic function (ECF) sigma factors
Woods, Emily C.; McBride, Shonna M.
2017-01-01
Extracytoplasmic function (ECF) sigma factors are a subfamily of σ70 sigma factors that activate genes involved in stress-response functions. In many bacteria, ECF sigma factors regulate resistance to antimicrobial compounds. This review will summarize the ECF sigma factors that regulate antimicrobial resistance in model organisms and clinically relevant pathogens. PMID:28153747
ERIC Educational Resources Information Center
Wetterneck, Chad T.; Hart, John M.
2012-01-01
Problems with intimacy and interpersonal issues are exhibited across most psychiatric disorders. However, most of the targets in Cognitive Behavioral Therapy are primarily intrapersonal in nature, with few directly involved in interpersonal functioning and effective intimacy. Functional Analytic Psychotherapy (FAP) provides a behavioral basis for…
Cohesion and Discourse Deixis on English Articles.
ERIC Educational Resources Information Center
Mizuno, Mitsuharu
1993-01-01
The purpose of this paper is to describe the function of English articles in a functional-pragmatic perspective, to clarify how the functions of the articles are reflected in the discourse, and to give some pedagogical implications for teaching English as a foreign language (EFL). Deixis is a grammatical category involving reference to…
Function-selective domain architecture plasticity potentials in eukaryotic genome evolution
Linkeviciute, Viktorija; Rackham, Owen J.L.; Gough, Julian; Oates, Matt E.; Fang, Hai
2015-01-01
To help evaluate how protein function impacts on genome evolution, we introduce a new concept of ‘architecture plasticity potential’ – the capacity to form distinct domain architectures – both for an individual domain, or more generally for a set of domains grouped by shared function. We devise a scoring metric to measure the plasticity potential for these domain sets, and evaluate how function has changed over time for different species. Applying this metric to a phylogenetic tree of eukaryotic genomes, we find that the involvement of each function is not random but highly selective. For certain lineages there is strong bias for evolution to involve domains related to certain functions. In general eukaryotic genomes, particularly animals, expand complex functional activities such as signalling and regulation, but at the cost of reducing metabolic processes. We also observe differential evolution of transcriptional regulation and a unique evolutionary role of channel regulators; crucially this is only observable in terms of the architecture plasticity potential. Our findings provide a new layer of information to understand the significance of function in eukaryotic genome evolution. A web search tool, available at http://supfam.org/Pevo, offers a wide spectrum of options for exploring functional importance in eukaryotic genome evolution. PMID:25980317
Watermeyer, Tamlyn J; Brown, Richard G; Sidle, Katie C L; Oliver, David J; Allen, Christopher; Karlsson, Joanna; Ellis, Cathy; Shaw, Christopher E; Al-Chalabi, Ammar; Goldstein, Laura H
2015-01-01
Up to 50% of patients with amyotrophic lateral sclerosis (ALS) show mild to moderate cognitive-behavioural change alongside their progressive functional impairment. This study examines the relative impact of patients' disease symptoms, behavioural change and current executive function and social cognition abilities on psychosocial outcomes in spouse caregivers of people with ALS. Thirty-five spouse caregivers rated their own levels of depression and anxiety, subjective burden and marital satisfaction. Caregivers also rated their partner's everyday behaviour. The patients were assessed for disease severity and cognitive function, with composite scores derived for executive function and social cognition. Regression analyses revealed that caregiver burden was predicted by the severity of patients' limb involvement and behavioural problems. Depression was predicted by patients' limb involvement, while behavioural problems and patient age predicted caregiver anxiety. Current marital satisfaction was predicted by patient behavioural problems beyond the level of pre-illness marital satisfaction. In conclusion, the study highlights the potential impact of ALS patients' functional impairment and behavioural change on ALS caregivers' psychosocial functioning. Clinical communication with ALS families should emphasise both physical and psychological challenges presented by the disease.
DOE Office of Scientific and Technical Information (OSTI.GOV)
San Fabián, J.; Omar, S.; García de la Vega, J. M., E-mail: garcia.delavega@uam.es
The effect of a fraction of Hartree-Fock exchange on the calculated spin-spin coupling constants involving fluorine through a hydrogen bond is analyzed in detail. Coupling constants calculated using wavefunction methods are revisited in order to get high-level calculations using the same basis set. Accurate MCSCF results are obtained using an additive approach. These constants and their contributions are used as a reference for density functional calculations. Within the density functional theory, the Hartree-Fock exchange functional is split in short- and long-range using a modified version of the Coulomb-attenuating method with the SLYP functional as well as with the original B3LYP.more » Results support the difficulties for calculating hydrogen bond coupling constants using density functional methods when fluorine nuclei are involved. Coupling constants are very sensitive to the Hartree-Fock exchange and it seems that, contrary to other properties, it is important to include this exchange for short-range interactions. Best functionals are tested in two different groups of complexes: those related with anionic clusters of type [F(HF){sub n}]{sup −} and those formed by difluoroacetylene and either one or two hydrogen fluoride molecules.« less
Michigan urban trunkline segments safety performance functions (SPFs) : final report.
DOT National Transportation Integrated Search
2016-07-01
This study involves the development of safety performance functions (SPFs) for urban and suburban trunkline segments in the : state of Michigan. Extensive databases were developed through the integration of traffic crash information, traffic volumes,...
Safety performance functions for freeway merge zones.
DOT National Transportation Integrated Search
2013-12-01
This report documents the results of a research project to support CDOT in the area of Safety : Performance Function (SPF) development. The project involved collecting data and developing SPFs for : ramp-freeway merge zones categorized as isolated, n...
Railroad Classification Yard Technology : An Introductory Analysis of Functions and Operations
DOT National Transportation Integrated Search
1975-05-01
A review of the basic operating characteristics and functions of railroad classification yards is presented. Introductory descriptions of terms, concepts, and problems of railroad operations involving classification yards are included in an attempt t...
Hippocampal memory consolidation during sleep: a comparison of mammals and birds
Rattenborg, Niels C.; Martinez-Gonzalez, Dolores; Roth, Timothy C.; Pravosudov, Vladimir V.
2010-01-01
The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow-oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high-order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow-oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp-wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7–14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow-oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow-oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region – the caudolateral nidopallium (NCL) – involved in performing high-order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra-hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow-oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow-oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups. PMID:21070585
Hippocampal memory consolidation during sleep: a comparison of mammals and birds.
Rattenborg, Niels C; Martinez-Gonzalez, Dolores; Roth, Timothy C; Pravosudov, Vladimir V
2011-08-01
The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow-oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high-order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow-oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp-wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7-14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow-oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow-oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region--the caudolateral nidopallium (NCL)--involved in performing high-order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra-hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow-oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow-oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups. © 2010 The Authors. Biological Reviews © 2010 Cambridge Philosophical Society.
Involvement with Children and Low-Income Fathers’ Psychological Well-Being
Kotila, Letitia E.; Kamp Dush, Claire M.
2014-01-01
Low income men are at risk for depressive symptoms and reduced father involvement. Using the Fragile Families and Child Wellbeing Study (n = 2,703), we examined reciprocal associations between father involvement and depressive symptoms, and the moderating effect of relationship quality, for resident and nonresident fathers. Higher father involvement was associated with lower depressive symptoms two years later across the full sample of fathers. However, nonresidence functioned as a risk; higher nonresident father involvement with toddlers was associated with greater depressive symptoms two years later. Greater resident father involvement with toddlers was associated with fewer depressive symptoms two years later in low quality couple relationships. Across the full sample, the association between depressive symptoms and lower involvement was weak. PMID:25614731
Toward a Broader Role for Occupational Therapy in Supportive Oncology Care.
Sleight, Alix G; Duker, Leah I Stein
2016-01-01
Supportive care in oncology helps people cope with cancer and its psychological, physical, and emotional side effects. However, cancer survivors report dissatisfaction with supportive care and a need for more psychosocial and self-management services. Occupational therapy practitioners represent an integral part of the supportive care team because their scope of practice emphasizes function. Through a focus on function, practitioners address the full spectrum of physical and psychosocial care. Currently, conceptualizations of occupational therapy for cancer survivors often focus solely on physical interventions and, therefore, do not represent the unique involvement of the profession in supportive oncology care. We advocate for a focused framework for occupational therapy practitioners in oncology as experts in function and providers of both physical and psychosocial treatments. Barriers to a focus on function are identified, and strategies are suggested for expanding involvement for the profession in supportive oncology care. Copyright © 2016 by the American Occupational Therapy Association, Inc.
Toward a Broader Role for Occupational Therapy in Supportive Oncology Care
Duker, Leah I. Stein
2016-01-01
Supportive care in oncology helps people cope with cancer and its psychological, physical, and emotional side effects. However, cancer survivors report dissatisfaction with supportive care and a need for more psychosocial and self-management services. Occupational therapy practitioners represent an integral part of the supportive care team because their scope of practice emphasizes function. Through a focus on function, practitioners address the full spectrum of physical and psychosocial care. Currently, conceptualizations of occupational therapy for cancer survivors often focus solely on physical interventions and, therefore, do not represent the unique involvement of the profession in supportive oncology care. We advocate for a focused framework for occupational therapy practitioners in oncology as experts in function and providers of both physical and psychosocial treatments. Barriers to a focus on function are identified, and strategies are suggested for expanding involvement for the profession in supportive oncology care. PMID:27295001
Palmitoylation as a Functional Regulator of Neurotransmitter Receptors
Naumenko, Vladimir S.
2018-01-01
The majority of neuronal proteins involved in cellular signaling undergo different posttranslational modifications significantly affecting their functions. One of these modifications is a covalent attachment of a 16-C palmitic acid to one or more cysteine residues (S-palmitoylation) within the target protein. Palmitoylation is a reversible modification, and repeated cycles of palmitoylation/depalmitoylation might be critically involved in the regulation of multiple signaling processes. Palmitoylation also represents a common posttranslational modification of the neurotransmitter receptors, including G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LICs). From the functional point of view, palmitoylation affects a wide span of neurotransmitter receptors activities including their trafficking, sorting, stability, residence lifetime at the cell surface, endocytosis, recycling, and synaptic clustering. This review summarizes the current knowledge on the palmitoylation of neurotransmitter receptors and its role in the regulation of receptors functions as well as in the control of different kinds of physiological and pathological behavior. PMID:29849559
Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system.
Brüning, Ansgar; Blankenstein, Thomas; Jückstock, Julia; Mylonas, Ioannis
2014-12-01
The family of metastasis-associated (MTA) genes is a small group of transcriptional co-regulators which are involved in various physiological functions, ranging from lymphopoietic cell differentiation to the development and maintenance of epithelial cell adhesions. By recruiting histone-modifying enzymes to specific promoter sequences, MTA proteins can function both as transcriptional repressors and activators of a number of cancer-relevant proteins, including Snail, E-cadherin, signal transducer and activator of transcriptions (STATs), and the estrogen receptor. Their involvement in the epithelial-mesenchymal transition process and regulatory interactions with estrogen receptor activity has made MTA proteins highly interesting research candidates, especially in the field of hormone-sensitive breast cancer and malignancies of the female reproductive tract. This review focuses on the current knowledge about the function and regulation of MTA1 and MTA3 proteins in gynecological cancer, including ovarian, endometrial, and cervical tumors.
Poisson equation for the three-loop ladder diagram in string theory at genus one
NASA Astrophysics Data System (ADS)
Basu, Anirban
2016-11-01
The three-loop ladder diagram is a graph with six links and four cubic vertices that contributes to the D12ℛ4 amplitude at genus one in type II string theory. The vertices represent the insertion points of vertex operators on the toroidal worldsheet and the links represent scalar Green functions connecting them. By using the properties of the Green function and manipulating the various expressions, we obtain a modular invariant Poisson equation satisfied by this diagram, with source terms involving one-, two- and three-loop diagrams. Unlike the source terms in the Poisson equations for diagrams at lower orders in the momentum expansion or the Mercedes diagram, a particular source term involves a five-point function containing a holomorphic and a antiholomorphic worldsheet derivative acting on different Green functions. We also obtain simple equalities between topologically distinct diagrams, and consider some elementary examples.
A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue.
Elsayed, Maha; Magistretti, Pierre J
2015-01-01
Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment.
Koike, Takashi; Kanno, Takahiro; Karino, Masaaki; Sekine, Joji
2017-11-01
Surgery is generally indicated for the treatment of lower lip carcinoma. However, surgery can lead to esthetic as well as functional issues, with disturbances in eating and articulation. If the defect involves less than one-third of the width of the lower lip, primary closure is possible. If the defect is wider, reconstructive local flaps may be necessary for both esthetic and functional recovery. This report describes a case of lower lip verrucous carcinoma in which a tongue flap was used to treat a defect involving more than half the width of the lower lip following resection. The patient was a 91-year-old woman who complained of lower lip discomfort. A biopsy revealed verrucous carcinoma, and we performed resection. After a 3-week waiting period, we performed secondary tongue flap reconstruction. Satisfactory function and cosmetic results were achieved.
The TRPM2 channel: A thermo-sensitive metabolic sensor.
Kashio, Makiko; Tominaga, Makoto
2017-09-03
Living organisms continually experience changes in ambient temperature. To detect such temperature changes for adaptive behavioral responses, we evolved the ability to sense temperature. Thermosensitive transient receptor potential (TRP) channels, so-called thermo-TRPs, are involved in many physiologic functions in diverse organisms and constitute important temperature sensors. One of the important roles of thermo-TRPs is detecting ambient temperature in sensory neurons. Importantly, the functional expression of thermo-TRPs is observed not only in sensory neurons but also in tissues and cells that are not exposed to drastic temperature changes, indicating that thermo-TRPs are involved in many physiologic functions within the body's normal temperature range. Among such thermo-TRPs, this review focuses on one thermo-sensitive metabolic sensor in particular, TRPM2, and summarizes recent progress to clarify the regulatory mechanisms and physiologic functions of TRPM2 at body temperature under various metabolic states.
A New Outlook on Mental Illnesses: Glial Involvement Beyond the Glue
Elsayed, Maha; Magistretti, Pierre J.
2015-01-01
Mental illnesses have long been perceived as the exclusive consequence of abnormalities in neuronal functioning. Until recently, the role of glial cells in the pathophysiology of mental diseases has largely been overlooked. However recently, multiple lines of evidence suggest more diverse and significant functions of glia with behavior-altering effects. The newly ascribed roles of astrocytes, oligodendrocytes and microglia have led to their examination in brain pathology and mental illnesses. Indeed, abnormalities in glial function, structure and density have been observed in postmortem brain studies of subjects diagnosed with mental illnesses. In this review, we discuss the newly identified functions of glia and highlight the findings of glial abnormalities in psychiatric disorders. We discuss these preclinical and clinical findings implicating the involvement of glial cells in mental illnesses with the perspective that these cells may represent a new target for treatment. PMID:26733803
Jamin, Augusta; Wicklund, April; Wiebe, Matthew S
2014-05-01
Barrier-to-autointegration factor (BAF) is a DNA binding protein with multiple cellular functions, including the ability to act as a potent defense against vaccinia virus infection. This antiviral function involves BAF's ability to condense double-stranded DNA and subsequently prevent viral DNA replication. In recent years, it has become increasingly evident that dynamic phosphorylation involving the vaccinia virus B1 kinase and cellular enzymes is likely a key regulator of multiple BAF functions; however, the precise mechanisms are poorly understood. Here we analyzed how phosphorylation impacts BAF's DNA binding, subcellular localization, dimerization, and antipoxviral activity through the characterization of BAF phosphomimetic and unphosphorylatable mutants. Our studies demonstrate that increased phosphorylation enhances BAF's mobilization from the nucleus to the cytosol, while dephosphorylation restricts BAF to the nucleus. Phosphorylation also impairs both BAF's dimerization and its DNA binding activity. Furthermore, our studies of BAF's antiviral activity revealed that hyperphosphorylated BAF is unable to suppress viral DNA replication or virus production. Interestingly, the unphosphorylatable BAF mutant, which is capable of binding DNA but localizes predominantly to the nucleus, was also incapable of suppressing viral replication. Thus, both DNA binding and localization are important determinants of BAF's antiviral function. Finally, our examination of how phosphatases are involved in regulating BAF revealed that PP2A dephosphorylates BAF during vaccinia infection, thus counterbalancing the activity of the B1 kinase. Altogether, these data demonstrate that phosphoregulation of BAF by viral and cellular enzymes modulates this protein at multiple molecular levels, thus determining its effectiveness as an antiviral factor and likely other functions as well. The barrier-to-autointegration factor (BAF) contributes to cellular genomic integrity in multiple ways, the best characterized of which are as a host defense against cytoplasmic DNA and as a regulator of mitotic nuclear reassembly. Although dynamic phosphorylation involving both viral and cellular enzymes is likely a key regulator of multiple BAF functions, the precise mechanisms involved are poorly understood. Here we demonstrate that phosphorylation coordinately regulates BAF's DNA binding, subcellular localization, dimerization, and antipoxviral activity. Overall, our findings provide new insights into how phosphoregulation of BAF modulates this protein at multiple levels and governs its effectiveness as an antiviral factor against foreign DNA.
Handwriting Fluency and Visuospatial Generativity at Primary School
ERIC Educational Resources Information Center
Stievano, Paolo; Michetti, Silvia; McClintock, Shawn M.; Levi, Gabriel; Scalisi, Teresa Gloria
2016-01-01
Handwriting is a complex activity that involves continuous interaction between lowerlevel perceptual-motor and higher-level cognitive processes. All handwriting models describe involvement of executive functions (EF) in handwriting development. Particular EF domains associated with handwriting include maintenance of information in working memory,…
The involvement of audio-motor coupling in the music-supported therapy applied to stroke patients.
Rodriguez-Fornells, Antoni; Rojo, Nuria; Amengual, Julià L; Ripollés, Pablo; Altenmüller, Eckart; Münte, Thomas F
2012-04-01
Music-supported therapy (MST) has been developed recently to improve the use of the affected upper extremity after stroke. MST uses musical instruments, an electronic piano and an electronic drum set emitting piano sounds, to retrain fine and gross movements of the paretic upper extremity. In this paper, we first describe the rationale underlying MST, and we review the previous studies conducted on acute and chronic stroke patients using this new neurorehabilitation approach. Second, we address the neural mechanisms involved in the motor movement improvements observed in acute and chronic stroke patients. Third, we provide some recent studies on the involvement of auditory-motor coupling in the MST in chronic stroke patients using functional neuroimaging. Finally, these ideas are discussed and focused on understanding the dynamics involved in the neural circuit underlying audio-motor coupling and how functional connectivity could help to explain the neuroplastic changes observed after therapy in stroke patients. © 2012 New York Academy of Sciences.
Nitric Oxide and Mitochondrial Function in Neurological Diseases.
Ghasemi, Mehdi; Mayasi, Yunis; Hannoun, Anas; Eslami, Seyed Majid; Carandang, Raphael
2018-04-15
Mitochondria are key cellular organelles that play crucial roles in the energy production and regulation of cellular metabolism. Accumulating evidence suggests that mitochondrial activity can be modulated by nitric oxide (NO). As a key neurotransmitter in biologic systems, NO mediates the majority of its function through activation of the cyclic guanylyl cyclase (cGC) signaling pathway and S-nitrosylation of a variety of proteins involved in cellular functioning including those involved in mitochondrial biology. Moreover, excess NO or the formation of reactive NO species (RNS), e.g., peroxynitrite (ONOO - ), impairs mitochondrial functioning and this, in conjunction with nuclear events, eventually affects neuronal cell metabolism and survival, contributing to the pathogenesis of several neurodegenerative diseases. In this review we highlight the possible mechanisms underlying the noxious effects of excess NO and RNS on mitochondrial function including (i) negative effects on electron transport chain (ETC); (ii) ONOO - -mediated alteration in mitochondrial permeability transition; (iii) enhanced mitochondrial fragmentation and autophagy through S-nitrosylation of key proteins involved in this process such as dynamin-related protein 1 (DRP-1) and Parkin/PINK1 (protein phosphatase and tensin homolog-induced kinase 1) complex; (iv) alterations in the mitochondrial metabolic pathways including Krebs cycle, glycolysis, fatty acid metabolism, and urea cycle; and finally (v) mitochondrial ONOO - -induced nuclear toxicity and subsequent release of apoptosis-inducing factor (AIF) from mitochondria, causing neuronal cell death. These proposed mechanisms highlight the multidimensional nature of NO and its signaling in the mitochondrial function. Understanding the mechanisms by which NO mediates mitochondrial (dys)function can provide new insights into the treatment of neurodegenerative diseases. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
Age differences in the intrinsic functional connectivity of default network subsystems
Campbell, Karen L.; Grigg, Omer; Saverino, Cristina; Churchill, Nathan; Grady, Cheryl L.
2013-01-01
Recent work suggests that the default mode network (DMN) includes two core regions, the ventromedial prefrontal cortex and posterior cingulate cortex (PCC), and several unique subsystems that are functionally distinct. These include a medial temporal lobe (MTL) subsystem, active during remembering and future projection, and a dorsomedial prefrontal cortex (dmPFC) subsystem, active during self-reference. The PCC has been further subdivided into ventral (vPCC) and dorsal (dPCC) regions that are more strongly connected with the DMN and cognitive control networks, respectively. The goal of this study was to examine age differences in resting state functional connectivity within these subsystems. After applying a rigorous procedure to reduce the effects of head motion, we used a multivariate technique to identify both common and unique patterns of functional connectivity in the MTL vs. the dmPFC, and in vPCC vs. dPCC. All four areas had robust functional connectivity with other DMN regions, and each also showed distinct connectivity patterns in both age groups. Young and older adults had equivalent functional connectivity in the MTL subsystem. Older adults showed weaker connectivity in the vPCC and dmPFC subsystems, particularly with other DMN areas, but stronger connectivity than younger adults in the dPCC subsystem, which included areas involved in cognitive control. Our data provide evidence for distinct subsystems involving DMN nodes, which are maintained with age. Nevertheless, there are age differences in the strength of functional connectivity within these subsystems, supporting prior evidence that DMN connectivity is particularly vulnerable to age, whereas connectivity involving cognitive control regions is relatively maintained. These results suggest an age difference in the integrated activity among brain networks that can have implications for cognition in older adults. PMID:24294203
Age differences in the intrinsic functional connectivity of default network subsystems.
Campbell, Karen L; Grigg, Omer; Saverino, Cristina; Churchill, Nathan; Grady, Cheryl L
2013-01-01
Recent work suggests that the default mode network (DMN) includes two core regions, the ventromedial prefrontal cortex and posterior cingulate cortex (PCC), and several unique subsystems that are functionally distinct. These include a medial temporal lobe (MTL) subsystem, active during remembering and future projection, and a dorsomedial prefrontal cortex (dmPFC) subsystem, active during self-reference. The PCC has been further subdivided into ventral (vPCC) and dorsal (dPCC) regions that are more strongly connected with the DMN and cognitive control networks, respectively. The goal of this study was to examine age differences in resting state functional connectivity within these subsystems. After applying a rigorous procedure to reduce the effects of head motion, we used a multivariate technique to identify both common and unique patterns of functional connectivity in the MTL vs. the dmPFC, and in vPCC vs. dPCC. All four areas had robust functional connectivity with other DMN regions, and each also showed distinct connectivity patterns in both age groups. Young and older adults had equivalent functional connectivity in the MTL subsystem. Older adults showed weaker connectivity in the vPCC and dmPFC subsystems, particularly with other DMN areas, but stronger connectivity than younger adults in the dPCC subsystem, which included areas involved in cognitive control. Our data provide evidence for distinct subsystems involving DMN nodes, which are maintained with age. Nevertheless, there are age differences in the strength of functional connectivity within these subsystems, supporting prior evidence that DMN connectivity is particularly vulnerable to age, whereas connectivity involving cognitive control regions is relatively maintained. These results suggest an age difference in the integrated activity among brain networks that can have implications for cognition in older adults.
Fizke, Ella; Barthel, Dana; Peters, Thomas; Rakoczy, Hannes
2014-03-01
While developmental experiments with children and elderly subjects, work with neuropsychological patients and adult experimental studies have consistently found close relations between executive function and theory of mind, the foundation of this relation still remains somewhat unclear. One prominent account holds that executive function is specifically involved in ascribing such mental states, paradigmatically beliefs, that aim at representing the world truly because ascribing such states requires inhibition of normative defaults (beliefs being true) (e.g. Sabbagh, Moses, & Shiverick, 2006). The present studies systematically tested for the role of executive function in different forms of mental state ascription as a function of the type of state ascribed (beliefs or desires) and the first person involvement of the ascriber (whether she herself has an attitude conflicting with one to be ascribed to someone else) in young children. The results reveal that (i) executive function is related not only to belief ascription but equally to desire ascription when both are matched in terms of logical complexity (such that two subjective attitudes have to be ascribed to two agents that are incompatible with each other). (ii) Both for desires and for beliefs, these relations are strongest in such tasks where the ascriber herself is one of the two agents, i.e. has a belief or desire herself that stands in contrast to that to be ascribed to someone else. All in all, these findings suggest that executive function figures in coordinating perspectives more generally, not only epistemic ones, and in particular in coordinating others' and one's own conflicting perspectives. Copyright © 2013 Elsevier B.V. All rights reserved.
Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert
2014-08-01
Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.
ERIC Educational Resources Information Center
Lopez, Gerardo R.; Vazquez, Vanessa A.
2006-01-01
This qualitative research study aims to provide rich narratives of parental involvement in households of newcomer Latino immigrants in the Midwest. A total of 20 families participated in this 4-month research study. Findings suggest that parents do get involved in traditional ways but view "consejos" (the giving of sage advice) as a form of…
Hudson, Jennifer L; Kendall, Philip C; Chu, Brian C; Gosch, Elizabeth; Martin, Erin; Taylor, Alan; Knight, Ashleigh
2014-01-01
This study examined the relations between treatment process variables and child anxiety outcomes. Independent raters watched/listened to taped therapy sessions of 151 anxiety-disordered (6-14 yr-old; M = 10.71) children (43% boys) and assessed process variables (child alliance, therapist alliance, child involvement, therapist flexibility and therapist functionality) within a manual-based cognitive-behavioural treatment. Latent growth modelling examined three latent variables (intercept, slope, and quadratic) for each process variable. Child age, gender, family income and ethnicity were examined as potential antecedents. Outcome was analyzed using factorially derived clinician, mother, father, child and teacher scores from questionnaire and structured diagnostic interviews at pretreatment, posttreatment and 12-month follow-up. Latent growth models demonstrated a concave quadratic curve for child involvement and therapist flexibility over time. A predominantly linear, downward slope was observed for alliance, and functional flexibility remained consistent over time. Increased alliance, child involvement and therapist flexibility showed some albeit inconsistent, associations with positive treatment outcome. Findings support the notion that maintaining the initial high level of alliance or involvement is important for clinical improvement. There is some support that progressively increasing alliance/involvement also positively impacts on treatment outcome. These findings were not consistent across outcome measurement points or reporters. Copyright © 2013 Elsevier Ltd. All rights reserved.
Brach, Jennifer S; Perera, Subashan; Gilmore, Sandra; VanSwearingen, Jessie M; Brodine, Deborah; Wert, David; Nadkarni, Neelesh K; Ricci, Edmund
2016-09-01
Group exercise programs for older adults often exclude the timing and coordination of movement. Stakeholder involvement in the research process is strongly encouraged and improves the relevance and adoption of findings. We describe stakeholder involvement in the design of a clinical trial of a group-based exercise program that incorporates timing and coordination of movement into the exercises. The study was a cluster randomized, single-blind intervention trial to compare the effects on function, disability and mobility of a standard group exercise program and the "On the Move" group exercise program in older adults residing in independent living facilities and senior apartment buildings, and attending community centers. Exercise classes were twice weekly for 12weeks delivered by study exercise leaders and facility activity staff personnel. The primary outcomes function, disability and mobility were assessed at baseline and post-intervention. Function and disability were assessed using the Late Life Function and Disability Instrument, and mobility using the Six-Minute Walk Test and gait speed. Patient and provider stakeholders had significant input into the study aims, design, sample, intervention, outcomes and operational considerations. A community-based exercise program to improve walking can be developed to address both investigator identified missing components in current exercise to improve walking and stakeholder defined needs and interest for the activity program. Involvement of stakeholders substantially improves the relevance of research questions, increases the transparency of research activities and may accelerate the adoption of research into practice. Copyright © 2016 Elsevier Inc. All rights reserved.
Shapira-Lichter, Irit; Oren, Noga; Jacob, Yael; Gruberger, Michal; Hendler, Talma
2013-01-01
Numerous neuroimaging studies have implicated default mode network (DMN) involvement in both internally driven processes and memory. Nevertheless, it is unclear whether memory operations reflect a particular case of internally driven processing or alternatively involve the DMN in a distinct manner, possibly depending on memory type. This question is critical for refining neurocognitive memory theorem in the context of other endogenic processes and elucidating the functional significance of this key network. We used functional MRI to examine DMN activity and connectivity patterns while participants overtly generated words according to nonmnemonic (phonemic) or mnemonic (semantic or episodic) cues. Overall, mnemonic word fluency was found to elicit greater DMN activity and stronger within-network functional connectivity compared with nonmnemonic fluency. Furthermore, two levels of functional organization of memory retrieval were shown. First, across both mnemonic tasks, activity was greater mainly in the posterior cingulate cortex, implying selective contribution to generic aspects of memory beyond its general involvement in endogenous processes. Second, parts of the DMN showed distinct selectivity for each of the mnemonic conditions; greater recruitment of the anterior prefrontal cortex, retroesplenial cortex, and hippocampi and elevated connectivity between anterior and posterior medial DMN nodes characterized the semantic condition, whereas increased recruitment of posterior DMN components and elevated connectivity between them characterized the episodic condition. This finding emphasizes the involvement of DMN elements in discrete aspects of memory retrieval. Altogether, our results show a specific contribution of the DMN to memory processes, corresponding to the specific type of memory retrieval. PMID:23479650
Campanini, Emeline B.; Vandewege, Michael W.; Pillai, Nisha E.; Tay, Boon-Hui; Jones, Justin L.; Venkatesh, Byrappa; Hoffmann, Federico G.
2015-01-01
Abstract The genes in the Myb superfamily encode for three related transcription factors in most vertebrates, A-, B-, and c-Myb, with functionally distinct roles, whereas most invertebrates have a single Myb. B-Myb plays an essential role in cell division and cell cycle progression, c-Myb is involved in hematopoiesis, and A-Myb is involved in spermatogenesis and regulating expression of pachytene PIWI interacting RNAs, a class of small RNAs involved in posttranscriptional gene regulation and the maintenance of reproductive tissues. Comparisons between teleost fish and tetrapods suggest that the emergence and functional divergence of the Myb genes were linked to the two rounds of whole-genome duplication early in vertebrate evolution. We combined phylogenetic, synteny, structural, and gene expression analyses of the Myb paralogs from elephant shark and lampreys with data from 12 bony vertebrates to reconstruct the early evolution of vertebrate Mybs. Phylogenetic and synteny analyses suggest that the elephant shark and Japanese lamprey have copies of the A-, B-, and c-Myb genes, implying their origin could be traced back to the common ancestor of lampreys and gnathostomes. However, structural and gene expression analyses suggest that their functional roles diverged between gnathostomes and cyclostomes. In particular, we did not detect A-Myb expression in testis suggesting that the involvement of A-Myb in the pachytene PIWI interacting RNA pathway is probably a gnathostome-specific innovation. We speculate that the secondary loss of a central domain in lamprey A-Myb underlies the functional differences between the cyclostome and gnathostome A-Myb proteins. PMID:26475318
Brach, Jennifer S.; Perera, Subashan; Gilmore, Sandra; VanSwearingen, Jessie M.; Brodine, Deborah; Wert, David; Nadkarni, Neelesh K.; Ricci, Edmund
2016-01-01
Background Group exercise programs for older adults often exclude the timing and coordination of movement. Stakeholder involvement in the research process is strongly encouraged and improves the relevance and adoption of findings. We describe stakeholder involvement in the design of a clinical trial of a group-based exercise program that incorporates timing and coordination of movement into the exercises. Methods The study was a cluster randomized, single-blind intervention trial to compare the effects on function, disability and mobility of a standard group exercise program and the “On the Move” group exercise program in older adults residing in independent living facilities and senior apartment buildings, and attending community centers. Exercise classes were twice weekly for 12 weeks delivered by study exercise leaders and facility activity staff personnel. Outcomes The primary outcomes function, disability and mobility were assessed at baseline and post-intervention. Function and disability were assessed using the Late Life Function and Disability Instrument, and mobility using the Six-Minute Walk Test and gait speed. Stakeholders Patient and provider stakeholders had significant input into the study aims, design, sample, intervention, outcomes and operational considerations. Summary A community-based exercise program to improve walking can be developed to address both investigator identified missing components in current exercise to improve walking and stakeholder defined needs and interest for the activity program. Involvement of stakeholders substantially improves the relevance of research questions, increases the transparency of research activities and may accelerate the adoption of research into practice. PMID:27521806
Kollner, B.; Fisher, U.; Rombout, J.H.W.M.; Taverne-Thiele, J.J.; Hansen, J.D.
2004-01-01
The functional relationship between fish and mammalian thrombocytes is relatively unknown. In this study, a panel of monoclonal antibodies (mAbs) was used to investigate the functional properties of rainbow trout thrombocytes. The mAbs recognize cell-surface molecules on thrombocytes with molecular weights ranging from 17 to 160 kDa. Flow cytometric and immuno-electron microscopic analyses demonstrate that these molecules are expressed at different levels and that surface expression increased upon activation with bovine collagen. Two of these cell-surface molecules (17 and 21 kDa) were directly involved in collagen-induced aggregation of thrombocytes since aggregation was blocked upon pre-treatment with mAbs that recognize the two surface markers. Interestingly, the percentage of thrombocytes in blood increased after stimulation using different antigens. The transcriptional profile of trout thrombocytes was then examined after immuno-magnetic enrichment using the described mAbs to assess potential roles of trout thrombocytes in immune functions. Trout thrombocytes express components of the MHC class Ia pathway, IL1β, TNFα, TGFβ, the interleukin receptor common γ chain as well as CXC and CC chemokines. MHC class IIB and TNFα were expressed at low levels in resting thrombocytes. No evidence was found for the expression of TCRαβ, Ig heavy chain, CD8α or CK1 mRNA. Taken together, these results suggest that rainbow trout thrombocytes express molecules involved in activation, aggregation and genes encoding proteins, that are involved in antigen presentation and immune regulation.
Thundathil, J C; Rajamanickam, G D; Kastelic, J P; Newton, L D
2012-08-01
Impaired testicular thermoregulation is commonly implicated in abnormal spermatogenesis and impaired sperm function in animals and humans, with outcomes ranging from subclinical infertility to sterility. Bovine testes must be maintained 4-5 °C below body-core temperature for normal spermatogenesis. The effects of elevated testicular temperature have been extensively studied in cattle using a scrotal insulation model, which results in abnormal spermatogenesis and impaired sperm morphology and function. Using this model and proteomic approaches, we compared normal and abnormal sperm (from the same bulls) to elucidate the molecular basis of impaired function. We identified a cohort of sperm functional proteins differentially expressed between normal vs abnormal sperm, including a testis-specific isoform of Na(+) /K(+) -ATPase. In addition to its role as a sodium pump regulating sperm motility, Na(+) /K(+) -ATPase is also involved as a signalling molecule during sperm capacitation. In conclusion, because of its involvement in regulation of sperm function, this protein has potential as a fertility marker. Furthermore, comparing normal vs abnormal sperm (induced by scrotal insulation) is a useful model for identifying proteins regulating sperm function. © 2012 Blackwell Verlag GmbH.
How Can a Ketogenic Diet Improve Motor Function?
Veyrat-Durebex, Charlotte; Reynier, Pascal; Procaccio, Vincent; Hergesheimer, Rudolf; Corcia, Philippe; Andres, Christian R.; Blasco, Hélène
2018-01-01
A ketogenic diet (KD) is a normocaloric diet composed by high fat (80–90%), low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs) production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production. KD is a therapy that has been used for almost a century to treat medically intractable epilepsy and has been increasingly explored in a number of neurological diseases. Motor function has also been shown to be improved by KD and/or medium-chain triglyceride diets in rodent models of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinal cord injury. These studies have proposed that KD may induce a modification in synaptic morphology and function, involving ionic channels, glutamatergic transmission, or synaptic vesicular cycling machinery. However, little is understood about the molecular mechanisms underlying the impact of KD on motor function and the perspectives of its use to acquire the neuromuscular effects. The aim of this review is to explore the conditions through which KD might improve motor function. First, we will describe the main consequences of KD exposure in tissues involved in motor function. Second, we will report and discuss the relevance of KD in pre-clinical and clinical trials in the major diseases presenting motor dysfunction. PMID:29434537
Divergent functions of the left and right central amygdala in visceral nociception
Sadler, Katelyn E.; McQuaid, Neal A.; Cox, Abigail C.; Behun, Marissa N.; Trouten, Allison M.; Kolber, Benedict J.
2017-01-01
The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2–mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase–activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2–mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain–like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries. PMID:28225716
Chrzanowski, Stephen M; Baligand, Celine; Willcocks, Rebecca J; Deol, Jasjit; Schmalfuss, Ilona; Lott, Donovan J; Daniels, Michael J; Senesac, Claudia; Walter, Glenn A; Vandenborne, Krista
2017-09-01
Duchenne muscular dystrophy (DMD) causes progressive pathologic changes to muscle secondary to a cascade of inflammation, lipid deposition, and fibrosis. Clinically, this manifests as progressive weakness, functional loss, and premature mortality. Though insult to whole muscle groups is well established, less is known about the relationship between intramuscular pathology and function. Differences of intramuscular heterogeneity across muscle length were assessed using an ordinal MRI grading scale in lower leg muscles of boys with DMD and correlated to patient's functional status. Cross sectional T 1 weighted MRI images with fat suppression were obtained from ambulatory boys with DMD. Six muscles (tibialis anterior, extensor digitorum longus, peroneus, soleus, medial and lateral gastrocnemii) were graded using an ordinal grading scale over 5 slice sections along the lower leg length. The scores from each slice were combined and results were compared to global motor function and age. Statistically greater differences of involvement were observed at the proximal ends of muscle compared to the midbellies. Multi-slice assessment correlated significantly to age and the Vignos functional scale, whereas single-slice assessment correlated to the Vignos functional scale only. Lastly, differential disease involvement of whole muscle groups and intramuscular heterogeneity were observed amongst similar age subjects. A multi-slice ordinal MRI grading scale revealed that muscles are not uniformly affected, with more advanced disease visible near the tendons in a primarily ambulatory population with DMD. A geographically comprehensive evaluation of the heterogeneously affected muscle in boys with DMD may more accurately assess disease involvement.
The zinc pool is involved in the immune-reconstituting effect of melatonin in pinealectomized mice.
Mocchegiani, E; Bulian, D; Santarelli, L; Tibaldi, A; Muzzioli, M; Lesnikov, V; Pierpaoli, W; Fabris, N
1996-06-01
Melatonin (MEL) affects the immune system by direct or indirect mechanisms. An involvement of the zinc pool in the immune-reconstituting effect of MEL in old mice has recently been documented. An altered zinc turnover and impaired immune functions are also evident in pinealectomized (px) mice. The present work investigates further the effect of "physiological" doses of MEL on the zinc pool and on thymic and peripheral immune functions in px mice. Daily injections of MEL (100 micrograms/mouse) for 1 month in px mice restored the crude zinc balance from negative to positive values. Thymic and peripheral immune functions, including plasma levels of interleukin-2, also recovered. The nontoxic effect of MEL on immune functions was observed in sham-operated mice. Because the half-life of MEL is very short (12 min), interruption of MEL treatment in px mice resulted, after 1 month, in a renewed negative crude zinc balance and a regression of immune functions. Both the zinc pool and immunological parameters were restored by 30 further days of MEL treatment. The existence of a significant correlation between zinc and thymic hormone after both cycles of MEL treatment clearly shows an involvement of the zinc pool in the immunoenhancing effects of MEL and thus suggests an inter-relationship between zinc and MEL in px mice. Moreover, the existence of significant positive correlations between zinc or thymulin and interleukin-2 suggests that interleukin-2 may participate in the action of MEL, via zinc, on thymic functions in px MEL-treated mice.
Divergent functions of the left and right central amygdala in visceral nociception.
Sadler, Katelyn E; McQuaid, Neal A; Cox, Abigail C; Behun, Marissa N; Trouten, Allison M; Kolber, Benedict J
2017-04-01
The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2-mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase-activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2-mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain-like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.
Solomon, Marjorie; Yoon, Jong; Ragland, J. Daniel; Niendam, Tara; Lesh, Tyler A.; Fairbrother, Wonja; Carter, Cameron S.
2013-01-01
Background Autism spectrum disorders (ASD) involve impairments in cognitive control. In typical development (TYP), neural systems underlying cognitive control undergo substantial maturation during adolescence. Development is delayed in adolescents with ASD. Little is known about the neural substrates of this delay. Method We used event-related functional magnetic resonance imaging (fMRI) and a cognitive control task involving overcoming a prepotent response tendency to examine the development of cognitive control in young (ages 12–15; n = 13 with ASD and n = 13 with TYP) and older (ages 16–18; n= 14 with ASD and n = 14 with TYP) adolescents with whole-brain voxel-wise univariate and task-related functional connectivity analyses. Results Older ASD and TYP showed reduced activation in sensory and premotor areas relative to younger ones. The older ASD group showed reduced left parietal activation relative to TYP. Functional connectivity analyses showed a significant age by group interaction with the older ASD group exhibiting increased functional connectivity strength between the ventrolateral prefrontal cortex (VLPFC) and the anterior cingulate cortex (ACC), bilaterally. This functional connectivity strength was related to task performance in ASD, whereas that between DLPFC and parietal cortex (BA 9 and BA 40) was related to task performance in TYP. Conclusions Adolescents with ASD rely more on “reactive” cognitive control, involving last minute conflict detection and control implementation by the ACC and VLPFC, versus “proactive” cognitive control requiring processing by DLPFC and parietal cortex. Findings await replication in larger longitudinal studies that examine their functional consequences and amenability to intervention. PMID:24209777
Raschpichler, Matthias; Straatman, Kees; Schroeter, Matthias Leopold; Arelin, Katrin; Schlögl, Haiko; Fritzsch, Dominik; Mende, Meinhard; Pampel, André; Böttcher, Yvonne; Stumvoll, Michael; Villringer, Arno; Mueller, Karsten
2013-01-01
Objectives To investigate whether the metabolically important visceral adipose tissue (VAT) relates differently to structural and functional brain changes in comparison with body weight measured as body mass index (BMI). Moreover, we aimed to investigate whether these effects change with age. Design Cross-sectional, exploratory. Setting University Clinic, Integrative Research and Treatment Centre. Participants We included 100 (mean BMI=26.0 kg/m², 42 women) out of 202 volunteers randomly invited by the city's registration office, subdivided into two age groups: young-to-mid-age (n=51, 20–45 years of age, mean BMI=24.9, 24 women) versus old (n=49, 65–70 years of age, mean BMI=27.0, 18 women). Main outcome measures VAT, BMI, subcutaneous abdominal adipose tissue, brain structure (grey matter density), functional brain architecture (eigenvector centrality, EC). Results We discovered a loss of cerebellar structure with increasing VAT in the younger participants, most significantly in regions involved in motor processing. This negative correlation disappeared in the elderly. Investigating functional brain architecture showed again inverse VAT–cerebellum correlations, whereas now regions involved in cognitive and emotional processing were significant. Although we detected similar results for EC using BMI, significant age interaction for both brain structure and functional architecture was only found using VAT. Conclusions Visceral adiposity is associated with cerebellar changes of both structure and function, whereas the regions involved contribute to motor, cognitive and emotional processes. Furthermore, these associations seem to be age dependent, with younger adults’ brains being adversely affected. PMID:23355665
Qiu, Jia-jun; Ren, Zhao-rui; Yan, Jing-bin
2016-01-01
Epigenetics regulations have an important role in fertilization and proper embryonic development, and several human diseases are associated with epigenetic modification disorders, such as Rett syndrome, Beckwith-Wiedemann syndrome and Angelman syndrome. However, the dynamics and functions of long non-coding RNAs (lncRNAs), one type of epigenetic regulators, in human pre-implantation development have not yet been demonstrated. In this study, a comprehensive analysis of human and mouse early-stage embryonic lncRNAs was performed based on public single-cell RNA sequencing data. Expression profile analysis revealed that lncRNAs are expressed in a developmental stage–specific manner during human early-stage embryonic development, whereas a more temporal-specific expression pattern was identified in mouse embryos. Weighted gene co-expression network analysis suggested that lncRNAs involved in human early-stage embryonic development are associated with several important functions and processes, such as oocyte maturation, zygotic genome activation and mitochondrial functions. We also found that the network of lncRNAs involved in zygotic genome activation was highly preservative between human and mouse embryos, whereas in other stages no strong correlation between human and mouse embryo was observed. This study provides insight into the molecular mechanism underlying lncRNA involvement in human pre-implantation embryonic development. PMID:27542205
Hahn, Alexander; Stevanovic, Mara; Mirus, Oliver; Schleiff, Enrico
2012-11-30
The role of TolC has largely been explored in proteobacteria, where it functions as a metabolite and protein exporter. In contrast, little research has been carried out on the function of cyanobacterial homologues, and as a consequence, not much is known about the mechanism of cyanobacterial antibiotic uptake and metabolite secretion in general. It has been suggested that the TolC-like homologue of the filamentous, heterocyst-forming cyanobacterium Anabaena sp. PCC 7120, termed heterocyst glycolipid deposition protein D (HgdD), is involved in both protein and lipid secretion. To describe its function in secondary metabolite secretion, we established a system to measure the uptake of antibiotics based on the fluorescent molecule ethidium bromide. We analyzed the rate of porin-dependent metabolite uptake and confirmed the functional relation between detoxification and the action of HgdD. Moreover, we identified two major facilitator superfamily proteins that are involved in this process. It appears that anaOmp85 (Alr2269) is not required for insertion or assembly of HgdD, because an alr2269 mutant does not exhibit a phenotype similar to the hgdD mutant. Thus, we could assign components of the metabolite efflux system and describe parameters of detoxification by Anabaena sp. PCC 7120.
Raivio, Tracy L; Leblanc, Shannon K D; Price, Nancy L
2013-06-01
The Cpx envelope stress response mediates adaptation to stresses that cause envelope protein misfolding. Adaptation is partly conferred through increased expression of protein folding and degradation factors. The Cpx response also plays a conserved role in the regulation of virulence determinant expression and impacts antibiotic resistance. We sought to identify adaptive mechanisms that may be involved in these important functions by characterizing changes in the transcriptome of two different Escherichia coli strains when the Cpx response is induced. We show that, while there is considerable strain- and condition-specific variability in the Cpx response, the regulon is enriched for proteins and functions that are inner membrane associated under all conditions. Genes that were changed by Cpx pathway induction under all conditions were involved in a number of cellular functions and included several intergenic regions, suggesting that posttranscriptional regulation is important during Cpx-mediated adaptation. Some Cpx-regulated genes are centrally involved in energetics and play a role in antibiotic resistance. We show that a number of small, uncharacterized envelope proteins are Cpx regulated and at least two of these affect phenotypes associated with membrane integrity. Altogether, our work suggests new mechanisms of Cpx-mediated envelope stress adaptation and antibiotic resistance.
Investigations of the Effects of Altered Vestibular System Function on Hindlimb Anti-Gravity Muscles
NASA Technical Reports Server (NTRS)
Lowery, Mary Sue
1998-01-01
Exposure to different gravitational environments, both the microgravity of spaceflight and the hypergravity of centrifugation, result in altered vestibulo-spinal function which can be reversed by reacclimation to earth gravity (2). Control of orientation, posture, and locomotion are functions of the vestibular system which are altered by changes in gravitational environment. Not only is the vestibular system involved with coordination and proprioception, but the gravity sensing portion of the vestibular system also plays a major role in maintaining muscle tone through projections to spinal cord motoneurons that control anti-gravity muscles. I have been involved with investigations of several aspects of the link between vestibular inputs and muscle morphology and function during my work with Dr. Nancy Daunton this summer and the previous summer. We have prepared a manuscript for submission (4) to Aviation, Space, and Environmental Medicine based on work that I performed last summer in Dr. Daunton's lab. Techniques developed for that project will be utilized in subsequent experiments begun in the summer of 1998. I have been involved with the development of a pilot project to test the effects of vestibular galvanic stimulation (VGS) on anti-gravity muscles and in another project testing the effects of the ototoxic drug streptomycin on the otolith-spinal reflex and anti-gravity muscle morphology.
Kim, Bong-Soo; Han, Dong-Hun; Lee, Ho; Oh, Bumjo
2018-03-28
Salivary microbiota alterations can correlate with dental caries development in children, and mechanisms mediating this association need to be studied in further detail. Our study explored salivary microbiota shifts in children and their association with the incidence of dental caries with dentine involvement. Salivary samples were collected from children with caries and their subsequently matched caries-free controls before and after caries development. The microbiota was analyzed by 16S rRNA gene-based high-throughput sequencing. The salivary microbiota was more diverse in caries-free subjects than in those with dental caries with dentine involvement (DC). Although both groups exhibited similar shifts in microbiota composition, an association with caries was found by function prediction. Analysis of potential microbiome functions revealed that Granulicatella, Streptococcus, Bulleidia , and Staphylococcus in the DC group could be associated with the bacterial invasion of epithelial cells, phosphotransferase system, and D -alanine metabolism, whereas Neisseria, Lautropia , and Leptotrichia in caries-free subjects could be associated with bacterial motility protein genes, linoleic acid metabolism, and flavonoid biosynthesis, suggesting that functional differences in the salivary microbiota may be associated with caries formation. These results expand the current understanding of the functional significance of the salivary microbiome in caries development, and may facilitate the identification of novel biomarkers and treatment targets.
Safety performance functions for ramp terminals at diamond interchanges.
DOT National Transportation Integrated Search
2011-07-01
This report documents two efforts to support CDOT in the area of Safety Performance Function (SPF) : development. The first involved the data collection and development of SPFs for five categories of ramp : terminals at diamond interchanges. For each...
[Functional tear production indices in thyroid eye disease].
Safonova, T N; Likhvantseva, V G; Gontiurova, O A; Rudenko, E I; Vygodin, V A
2013-01-01
Analysis of functional tear production indices in patients with Grave's disease and thyroid eye disease confirmed lacrimal gland involvement in inflammatory autoimmune process. Close direct correlation was found between tear production and main disease characteristics - severity and activity.
Michigan urban trunkline intersections safety performance functions (SPFs) development and support.
DOT National Transportation Integrated Search
2015-06-01
This study involves the development of safety performance functions (SPFs) for signalized and stop-controlled intersections : located along urban and suburban arterials in the state of Michigan. Extensive databases were developed that resulted in the...
Quantum identities for the action
NASA Astrophysics Data System (ADS)
Gozzi, E.
2018-04-01
In this paper we derive various identities involving the action functional which enters the path-integral formulation of quantum mechanics. They provide some kind of generalisations of the Ehrenfest theorem giving correlations between powers of the action and its functional derivatives.
Evaluation of pulmonary function and respiratory symptoms in pyrochlore mine workers
Borges, Ritta de Cássia Canedo Oliveira; Barros, José Cerqueira; Oliveira, Fabrício Borges; Brunherotti, Marisa Andrade; Quemelo, Paulo Roberto Veiga
2016-01-01
ABSTRACT Objective: To identify respiratory symptoms and evaluate lung function in mine workers. Methods: This was a cross-sectional observational study involving production sector workers of a pyrochlore mining company. The subjects completed the British Medical Research Council questionnaire, which is designed to evaluate respiratory symptoms, occupational exposure factors, and smoking status. In addition, they underwent pulmonary function tests with a portable spirometer. Results: The study involved 147 workers (all male). The mean age was 41.37 ± 8.71 years, and the mean duration of occupational exposure was 12.26 ± 7.09 years. We found that 33 (22.44%) of the workers had respiratory symptoms and that 26 (17.69%) showed abnormalities in the spirometry results. However, we found that the spirometry results did not correlate significantly with the presence of respiratory symptoms or with the duration of occupational exposure. Conclusions: The frequencies of respiratory symptoms and spirometric changes were low when compared with those reported in other studies involving occupational exposure to dust. No significant associations were observed between respiratory symptoms and spirometry results. PMID:27832236
Kobayakawa, Mutsutaka; Kawamura, Mitsuru
2011-12-01
Social cognition includes various components of information processing related to communication with other individuals. In this review, we have discussed 3 components of social cognitive function: face recognition, empathy, and decision making. Our social behavior involves recognition based on facial features and also involves empathizing with others; while making decisions, it is important to consider the social consequences of the course of action followed. Face recognition is divided into 2 routes for information processing: a route responsible for overt recognition of the face's identity and a route for emotional and orienting responses based on the face's personal affective significance. Two systems are possibly involved in empathy: a basic emotional contagion "mirroring" system and a more advanced "theory of mind" system that considers the cognitive perspective. Decision making is mediated by a widespread system that includes several cortical and subcortical components. Numerous lesion and neuroimaging studies have contributed to clarifying the neural correlates of social cognitive function, and greater information can be obtained on social cognitive function by combining these 2 approaches.
Díaz, Estrella; Vargas, Juan Pedro; Quintero, Esperanza; Gonzalo de la Casa, Luis; O'Donnell, Patricio; Lopez, Juan Carlos
2014-05-01
The dorsal striatum has been ascribed to different behavioral roles. While the lateral area (dls) is implicated in habitual actions, its medial part (dms) is linked to goal expectancy. According to this model, dls function includes representation of stimulus-response associations, but not of goals. Dls function has been typically analyzed with regard to movement, and there is no data indicating whether this region could processes specific stimulus-outcome associations. To test this possibility, we analyzed the effects of dls and dms inactivation on the retrieval phase, and dms lesion on the acquisition phase of a latent inhibition procedure using two conditions, long and short presentations of the future conditioned stimulus. Contrary to current theories of basal ganglia function, we report evidence in favor of the dls involvement in cognitive processes of learning and retrieval. Moreover, we provide data about the sequential relationship between dms and dls, in which the dms could be involved, but it would not be critical, in new learning and the dls could be subsequently involved in consolidating cognitive routines. Copyright © 2014 Elsevier Inc. All rights reserved.
Dopamine receptors – IUPHAR Review 13
Beaulieu, Jean-Martin; Espinoza, Stefano; Gainetdinov, Raul R
2015-01-01
The variety of physiological functions controlled by dopamine in the brain and periphery is mediated by the D1, D2, D3, D4 and D5 dopamine GPCRs. Drugs acting on dopamine receptors are significant tools for the management of several neuropsychiatric disorders including schizophrenia, bipolar disorder, depression and Parkinson's disease. Recent investigations of dopamine receptor signalling have shown that dopamine receptors, apart from their canonical action on cAMP-mediated signalling, can regulate a myriad of cellular responses to fine-tune the expression of dopamine-associated behaviours and functions. Such signalling mechanisms may involve alternate G protein coupling or non-G protein mechanisms involving ion channels, receptor tyrosine kinases or proteins such as β-arrestins that are classically involved in GPCR desensitization. Another level of complexity is the growing appreciation of the physiological roles played by dopamine receptor heteromers. Applications of new in vivo techniques have significantly furthered the understanding of the physiological functions played by dopamine receptors. Here we provide an update of the current knowledge regarding the complex biology, signalling, physiology and pharmacology of dopamine receptors. PMID:25671228
Optimal Robust Motion Controller Design Using Multiobjective Genetic Algorithm
Svečko, Rajko
2014-01-01
This paper describes the use of a multiobjective genetic algorithm for robust motion controller design. Motion controller structure is based on a disturbance observer in an RIC framework. The RIC approach is presented in the form with internal and external feedback loops, in which an internal disturbance rejection controller and an external performance controller must be synthesised. This paper involves novel objectives for robustness and performance assessments for such an approach. Objective functions for the robustness property of RIC are based on simple even polynomials with nonnegativity conditions. Regional pole placement method is presented with the aims of controllers' structures simplification and their additional arbitrary selection. Regional pole placement involves arbitrary selection of central polynomials for both loops, with additional admissible region of the optimized pole location. Polynomial deviation between selected and optimized polynomials is measured with derived performance objective functions. A multiobjective function is composed of different unrelated criteria such as robust stability, controllers' stability, and time-performance indexes of closed loops. The design of controllers and multiobjective optimization procedure involve a set of the objectives, which are optimized simultaneously with a genetic algorithm—differential evolution. PMID:24987749
Bartha-Doering, Lisa; Novak, Astrid; Kollndorfer, Kathrin; Kasprian, Gregor; Schuler, Anna-Lisa; Berl, Madison M; Fischmeister, Florian Ph S; Gaillard, William D; Alexopoulos, Johanna; Prayer, Daniela; Seidl, Rainer
2018-06-15
This study considered the involvement of the mesial temporal lobe (MTL) in language and verbal memory functions in healthy children and adolescents. We investigated 30 healthy, right-handed children and adolescents, aged 7-16, with a fMRI language paradigm and a comprehensive cognitive test battery. We found significant MTL activations during language fMRI in all participants; 63% of them had left lateralized MTL activations, 20% exhibited right MTL lateralization, and 17% showed bilateral MTL involvement during the fMRI language paradigm. Group analyses demonstrated a strong negative correlation between the lateralization of MTL activations and language functions. Specifically, children with less lateralized MTL activation showed significantly better vocabulary skills. These findings suggest that the mesial temporal lobes of both hemispheres play an important role in language functioning, even in right-handers. Our results furthermore show that bilateral mesial temporal lobe involvement is advantageous for vocabulary skills in healthy, right-handed children and adolescents. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
March, N. H.; Nagy, Á.
A fonnally exact integral equation theory for the exchange-only potential Vx(r) in density functional theory was recently set up by Howard and March [I.A. Howard, N.H. March, J. Chem. Phys. 119 (2003) 5789]. It involved a `closure' function P(r) satisfying the exact sum rule ∫ P(r) dr = 0. The simplest choice P(r) = 0 recovers then the approximation proposed by Della Sala and Görling [F. Della Sala, A. Görling, J. Chem. Phys. 115 (2001) 5718] and by Gritsenko and Baerends [O.V. Gritsenko, E.J. Baerends, Phys. Rev. A 64 (2001) 042506]. Here, refined choices of P(r) are proposed, the most direct being based on the KLI (Krieger-Li-Iafrate) approximation. A further choice given some attention is where P(r) involves frontier orbital properties. In particular, the introduction of the LUMO (lowest unoccupied molecular) orbital, along with the energy separation between HOMO (highest occupied molecular orbital) and LUMO levels, should prove a significant step beyond current approximations to the optimized potential method, all of which involve only single-particle occupied orbitals.
New Hydrocarbon Degradation Pathways in the Microbial Metagenome from Brazilian Petroleum Reservoirs
Sierra-García, Isabel Natalia; Correa Alvarez, Javier; Pantaroto de Vasconcellos, Suzan; Pereira de Souza, Anete; dos Santos Neto, Eugenio Vaz; de Oliveira, Valéria Maia
2014-01-01
Current knowledge of the microbial diversity and metabolic pathways involved in hydrocarbon degradation in petroleum reservoirs is still limited, mostly due to the difficulty in recovering the complex community from such an extreme environment. Metagenomics is a valuable tool to investigate the genetic and functional diversity of previously uncultured microorganisms in natural environments. Using a function-driven metagenomic approach, we investigated the metabolic abilities of microbial communities in oil reservoirs. Here, we describe novel functional metabolic pathways involved in the biodegradation of aromatic compounds in a metagenomic library obtained from an oil reservoir. Although many of the deduced proteins shared homology with known enzymes of different well-described aerobic and anaerobic catabolic pathways, the metagenomic fragments did not contain the complete clusters known to be involved in hydrocarbon degradation. Instead, the metagenomic fragments comprised genes belonging to different pathways, showing novel gene arrangements. These results reinforce the potential of the metagenomic approach for the identification and elucidation of new genes and pathways in poorly studied environments and contribute to a broader perspective on the hydrocarbon degradation processes in petroleum reservoirs. PMID:24587220
Dynamic functional brain networks involved in simple visual discrimination learning.
Fidalgo, Camino; Conejo, Nélida María; González-Pardo, Héctor; Arias, Jorge Luis
2014-10-01
Visual discrimination tasks have been widely used to evaluate many types of learning and memory processes. However, little is known about the brain regions involved at different stages of visual discrimination learning. We used cytochrome c oxidase histochemistry to evaluate changes in regional brain oxidative metabolism during visual discrimination learning in a water-T maze at different time points during training. As compared with control groups, the results of the present study reveal the gradual activation of cortical (prefrontal and temporal cortices) and subcortical brain regions (including the striatum and the hippocampus) associated to the mastery of a simple visual discrimination task. On the other hand, the brain regions involved and their functional interactions changed progressively over days of training. Regions associated with novelty, emotion, visuo-spatial orientation and motor aspects of the behavioral task seem to be relevant during the earlier phase of training, whereas a brain network comprising the prefrontal cortex was found along the whole learning process. This study highlights the relevance of functional interactions among brain regions to investigate learning and memory processes. Copyright © 2014 Elsevier Inc. All rights reserved.
Function and expression pattern of nonsyndromic deafness genes
Hilgert, Nele; Smith, Richard J.H.; Van Camp, Guy
2010-01-01
Hearing loss is the most common sensory disorder, present in 1 of every 500 newborns. To date, 46 genes have been identified that cause nonsyndromic hearing loss, making it an extremely heterogeneous trait. This review provides a comprehensive overview of the inner ear function and expression pattern of these genes. In general, they are involved in hair bundle morphogenesis, form constituents of the extracellular matrix, play a role in cochlear ion homeostasis or serve as transcription factors. During the past few years, our knowledge of genes involved in hair bundle morphogenesis has increased substantially. We give an up-to-date overview of both the nonsyndromic and Usher syndrome genes involved in this process, highlighting proteins that interact to form macromolecular complexes. For every gene, we also summarize its expression pattern and impact on hearing at the functional level. Gene-specific cochlear expression is summarized in a unique table by structure/cell type and is illustrated on a cochlear cross-section, which is available online via the Hereditary Hearing Loss Homepage. This review should provide auditory scientists the most relevant information for all identified nonsyndromic deafness genes. PMID:19601806
Walter C. Shortle; Rakesh Minocha
1999-01-01
Cancer is one of the most feared diseases. It involves the rapid and uncontrolled proliferation of "abnormal" cells in the body. The cancerous cell mass disrupts normal functioning of the organ or tissue in which it is found. Current treatments involve surgery, radiotherapy, and chemotherapy often applied in some combination. Naturally occurring...
Neuroanatomical Correlates of Oral Reading in Acute Left Hemispheric Stroke
ERIC Educational Resources Information Center
Cloutman, Lauren L.; Newhart, Melisssa; Davis, Cameron L.; Heidler-Gary, Jennifer; Hillis, Argye E.
2011-01-01
Oral reading is a complex skill involving the interaction of orthographic, phonological, and semantic processes. Functional imaging studies with nonimpaired adult readers have identified a widely distributed network of frontal, inferior parietal, posterior temporal, and occipital brain regions involved in the task. However, while functional…
Catholic Schools and Volunteers: A Planned Involvement.
ERIC Educational Resources Information Center
Tedesco, Janis E.
Policies and procedures for developing a successful school volunteer program within Catholic schools are presented in this booklet. Chapter 1 describes the philosophy of a volunteer support program, which stresses the importance of volunteer involvement for developing schools as functional communities. Chapter 2 presents reasons why volunteers are…
36 CFR 2.32 - Interfering with agency functions.
Code of Federal Regulations, 2010 CFR
2010-07-01
... and rescue operations, wildlife management operations involving animals that pose a threat to public safety, law enforcement actions, and emergency operations that involve a threat to public safety or park... order and public safety. (3) False information. Knowingly giving a false or fictitious report or other...
36 CFR 1002.32 - Interfering with agency functions.
Code of Federal Regulations, 2010 CFR
2010-07-01
... operations, wildlife management operations involving animals that pose a threat to public safety, law enforcement actions, and emergency operations that involve a threat to public safety or resources of the area... necessary to maintain order and public safety. (3) False information. Knowingly giving a false or fictitious...
Relative risk of fatal crash involvement by BAC, age, and gender
DOT National Transportation Integrated Search
2000-04-01
The objective of this study was to re-examine and refine estimates for alcohol-related relative risk of driver involvement in fatal crashes by age and gender as a function of blood alcohol concentration (BAC) using recent data. The method of study wa...
Leadership through Instructional Design in Higher Education
ERIC Educational Resources Information Center
Shaw, Kristi
2012-01-01
The function of leadership is to create a vision for the future, establish strategic priorities, and develop an environment of trust within and between organizations. Great leadership is a process; leadership involves motivational influence, leadership occurs in groups, and involves a shared vision (Northouse, 2010). Instructional designers are…
Stanley T. Asah; Dale J. Blahna
2012-01-01
Conservation in urban areas faces growing financial challenges and inadequate stakeholder involvement. Conservation psychology can mitigate these challenges in many ways. One way is through conservation volunteerism, if we attend to and capitalize on volunteers' motivations. Conservation volunteerism significantly contributes to ecological knowledge acquisition,...
The Human Thalamus Is an Integrative Hub for Functional Brain Networks
Bertolero, Maxwell A.
2017-01-01
The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks. SIGNIFICANCE STATEMENT The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks. PMID:28450543
Wang, Yu; Zhang, Rui; He, Zhili; Van Nostrand, Joy D.; Zheng, Qiang; Zhou, Jizhong; Jiao, Nianzhi
2017-01-01
Microbes play crucial roles in various biogeochemical processes in the ocean, including carbon (C), nitrogen (N), and phosphorus (P) cycling. Functional gene diversity and the structure of the microbial community determines its metabolic potential and therefore its ecological function in the marine ecosystem. However, little is known about the functional gene composition and metabolic potential of bacterioplankton in estuary areas. The East China Sea (ECS) is a dynamic marginal ecosystem in the western Pacific Ocean that is mainly affected by input from the Changjiang River and the Kuroshio Current. Here, using a high-throughput functional gene microarray (GeoChip), we analyzed the functional gene diversity, composition, structure, and metabolic potential of microbial assemblages in different ECS water masses. Four water masses determined by temperature and salinity relationship showed different patterns of functional gene diversity and composition. Generally, functional gene diversity [Shannon–Weaner’s H and reciprocal of Simpson’s 1/(1-D)] in the surface water masses was higher than that in the bottom water masses. The different presence and proportion of functional genes involved in C, N, and P cycling among the bacteria of the different water masses showed different metabolic preferences of the microbial populations in the ECS. Genes involved in starch metabolism (amyA and nplT) showed higher proportion in microbial communities of the surface water masses than of the bottom water masses. In contrast, a higher proportion of genes involved in chitin degradation was observed in microorganisms of the bottom water masses. Moreover, we found a higher proportion of nitrogen fixation (nifH), transformation of hydroxylamine to nitrite (hao) and ammonification (gdh) genes in the microbial communities of the bottom water masses compared with those of the surface water masses. The spatial variation of microbial functional genes was significantly correlated with salinity, temperature, and chlorophyll based on canonical correspondence analysis, suggesting a significant influence of hydrologic conditions on water microbial communities. Our data provide new insights into better understanding of the functional potential of microbial communities in the complex estuarine-coastal environmental gradient of the ECS. PMID:28680420
Rengaraj, Deivendran; Lee, Bo Ram; Jang, Hyun-Jun; Kim, Young Min; Han, Jae Yong
2013-01-01
Metabolism provides energy and nutrients required for the cellular growth, maintenance, and reproduction. When compared with genomics and proteomics, metabolism studies provide novel findings in terms of cellular functions. In this study, we examined significant and differentially expressed genes in primordial germ cells (PGCs), gonadal stromal cells, and chicken embryonic fibroblasts compared with blastoderms using microarray. All upregulated genes (1001, 1118, and 974, respectively) and downregulated genes (504, 627, and 1317, respectively) in three test samples were categorized into functional groups according to gene ontology. Then all selected genes were tested to examine their involvement in metabolic pathways through Kyoto Encyclopedia of Genes and Genomes pathway database using overrepresentation analysis. In our results, most of the upregulated and downregulated genes were involved in at least one subcategory of seven major metabolic pathways. The main objective of this study is to compare the PGC expressed genes and their metabolic pathways with blastoderms, gonadal stromal cells, and chicken embryonic fibroblasts. Among the genes involved in metabolic pathways, a higher number of PGC upregulated genes were identified in retinol metabolism, and a higher number of PGC downregulated genes were identified in sphingolipid metabolism. In terms of the fold change, acyl-CoA synthetase medium-chain family member 3 (ACSM3), which is involved in butanoate metabolism, and N-acetyltransferase, pineal gland isozyme NAT-10 (PNAT10), which is involved in energy metabolism, showed higher expression in PGCs. To validate these gene changes, the expression of 12 nucleotide metabolism-related genes in chicken PGCs was examined by real-time polymerase chain reaction. The results of this study provide new information on the expression of genes associated with metabolism function of PGCs and will facilitate more basic research on animal PGC differentiation and function. Copyright © 2013 Elsevier Inc. All rights reserved.
The Limits of Functional Analysis in the Study of Mass Communication.
ERIC Educational Resources Information Center
Anderson, James A.; Meyer, Timothy P.
The fundamental limits of the functional approach to the study of mass communication are embodied in two of its criticisms. The first weakness is in its logical structure and the second involves the limits that are set by known methods. Functional analysis has difficulties as a meaningful research perspective because the process of mass…
ERIC Educational Resources Information Center
Matta, Cherif F.; Massa, Lou; Gubskaya, Anna V.; Knoll, Eva
2011-01-01
The fate of dimensions of dimensioned quantities that are inserted into the argument of transcendental functions such as logarithms, exponentiation, trigonometric, and hyperbolic functions is discussed. Emphasis is placed on common misconceptions that are not often systematically examined in undergraduate courses of physical sciences. The argument…
ERIC Educational Resources Information Center
Xu, Tuo; Zhang, Beili
2015-01-01
This article discusses the importance of functional grammar and demonstrates its application to the teaching of reading among graded college students. Functional grammar holds that a discourse is composed of two levels: the interior level and the exterior level. Therefore, reading activities involve both linguistic elements and contexts.…
ERIC Educational Resources Information Center
Wilkie, Karina J,; Clarke, Doug
2014-01-01
This design-based research project investigated the development of functional thinking in algebra for the upper primary years of schooling. Ten teachers and their students were involved in a sequence of five cycles of collaborative planning, team-teaching, evaluating and revising five lessons on functional thinking for their students over one…
Brain Structure-function Couplings (FY11)
2012-01-01
influence time-evolving models of global brain function and dynamic changes in cognitive performance. Both structural and functional connections change on...Artifact Resistant Measure to Detect Cognitive EEG Activity During Locomotion. Journal of NeuroEngineering and Rehabilitation, submitted. 10...Specifically, identifying the communication between brain regions that occurs during tasks may provide information regarding the cognitive processes involved in
An update on gain-of-function mutations in primary immunodeficiency diseases.
Jhamnani, Rekha D; Rosenzweig, Sergio D
2017-12-01
Most primary immunodeficiencies described since 1952 were associated with loss-of-function defects. With the advent and popularization of unbiased next-generation sequencing diagnostic approaches followed by functional validation techniques, many gain-of-function mutations leading to immunodeficiency have also been identified. This review highlights the updates on pathophysiology mechanisms and new therapeutic approaches involving primary immunodeficiencies because of gain-of-function mutations. The more recent developments related to gain-of-function primary immunodeficiencies mostly involving increased infection susceptibility but also immune dysregulation and autoimmunity, were reviewed. Updates regarding pathophysiology mechanisms, different mutation types, clinical features, laboratory markers, current and potential new treatments on patients with caspase recruitment domain family member 11, signal transducer and activator of transcription 1, signal transducer and activator of transcription 3, phosphatidylinositol-4,5-biphosphate 3-kinase catalytic 110, phosphatidylinositol-4,5-biphosphate 3-kinase regulatory subunit 1, chemokine C-X-C motif receptor 4, sterile α motif domain containing 9-like, and nuclear factor κ-B subunit 2 gain-of-function mutations are reviewed for each disease. With the identification of gain-of-function mutations as a cause of immunodeficiency, new genetic pathophysiology mechanisms unveiled and new-targeted therapeutic approaches can be explored as potential rescue treatments for these diseases.
Decreased Functional Brain Connectivity in Adolescents with Internet Addiction
Hong, Soon-Beom; Zalesky, Andrew; Cocchi, Luca; Fornito, Alex; Choi, Eun-Jung; Kim, Ho-Hyun; Suh, Jeong-Eun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung
2013-01-01
Background Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry. Methods Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures. Results Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio. Conclusions Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology. PMID:23451272
Independent component model for cognitive functions of multiple subjects using [15O]H2O PET images.
Park, Hae-Jeong; Kim, Jae-Jin; Youn, Tak; Lee, Dong Soo; Lee, Myung Chul; Kwon, Jun Soo
2003-04-01
An independent component model of multiple subjects' positron emission tomography (PET) images is proposed to explore the overall functional components involved in a task and to explain subject specific variations of metabolic activities under altered experimental conditions utilizing the Independent component analysis (ICA) concept. As PET images represent time-compressed activities of several cognitive components, we derived a mathematical model to decompose functional components from cross-sectional images based on two fundamental hypotheses: (1) all subjects share basic functional components that are common to subjects and spatially independent of each other in relation to the given experimental task, and (2) all subjects share common functional components throughout tasks which are also spatially independent. The variations of hemodynamic activities according to subjects or tasks can be explained by the variations in the usage weight of the functional components. We investigated the plausibility of the model using serial cognitive experiments of simple object perception, object recognition, two-back working memory, and divided attention of a syntactic process. We found that the independent component model satisfactorily explained the functional components involved in the task and discuss here the application of ICA in multiple subjects' PET images to explore the functional association of brain activations. Copyright 2003 Wiley-Liss, Inc.
Material specific lateralization of medial temporal lobe function: An fMRI investigation.
Dalton, Marshall A; Hornberger, Michael; Piguet, Olivier
2016-03-01
The theory of material specific lateralization of memory function posits that left and right MTL regions are asymmetrically involved in mnemonic processing of verbal and nonverbal material respectively. Lesion and functional imaging (fMRI) studies provide robust evidence for a left MTL asymmetry in the verbal memory domain. Evidence for a right MTL/nonverbal asymmetry is not as robust. A handful of fMRI studies have investigated this issue but have generally utilised nonverbal stimuli which are amenable to semantic elaboration. This fMRI study aimed to investigate the neural correlates of recognition memory processing in 20 healthy young adults (mean age = 26 years) for verbal stimuli and nonverbal stimuli that were specifically designed to minimize verbalisation. Analyses revealed that the neural correlates of recognition memory processing for verbal and nonverbal stimuli were differentiable and asymmetrically recruited the left and right MTL respectively. The right perirhinal cortex and hippocampus were preferentially involved in successful recognition memory of items devoid of semantic information. In contrast, the left anterior hippocampus was preferentially involved in successful recognition memory of stimuli which contained semantic meaning. These results suggest that the left MTL is preferentially involved in mnemonic processing of verbal/semantic information. In contrast, the right MTL is preferentially involved in visual/non-semantic mnemonic processing. We propose that during development, the left MTL becomes specialised for verbal mnemonic processing due to its proximity with left lateralised cortical language processing areas while visual/non-semantic mnemonic processing gets 'crowded out' to become predominantly, but not completely, the domain of the right MTL. © 2015 Wiley Periodicals, Inc.
The role of the putamen in language: a meta-analytic connectivity modeling study.
Viñas-Guasch, Nestor; Wu, Yan Jing
2017-12-01
The putamen is a subcortical structure that forms part of the dorsal striatum of basal ganglia, and has traditionally been associated with reinforcement learning and motor control, including speech articulation. However, recent studies have shown involvement of the left putamen in other language functions such as bilingual language processing (Abutalebi et al. 2012) and production, with some authors arguing for functional segregation of anterior and posterior putamen (Oberhuber et al. 2013). A further step in exploring the role of putamen in language would involve identifying the network of coactivations of not only the left, but also the right putamen, given the involvement of right hemisphere in high order language functions (Vigneau et al. 2011). Here, a meta-analytic connectivity modeling technique was used to determine the patterns of coactivation of anterior and bilateral putamen in the language domain. Based on previous evidence, we hypothesized that left putamen coactivations would include brain regions directly associated with language processing, whereas right putamen coactivations would encompass regions involved in broader semantic processes, such as memory and visual imagery. The results showed that left anterior putamen coactivated with clusters predominantly in left hemisphere, encompassing regions directly associated with language processing, a left posterior putamen network spanning both hemispheres, and cerebellum. In right hemisphere, coactivations were in both hemispheres, in regions associated with visual and orthographic processing. These results confirm the differential involvement of right and left putamen in different language components, thus highlighting the need for further research into the role of putamen in language.
Bardoni, Barbara; Abekhoukh, Sabiha; Zongaro, Samantha; Melko, Mireille
2012-01-01
Intellectual disability (ID) is the most frequent cause of serious handicap in children and young adults and interests 2-3% of worldwide population, representing a serious problem from the medical, social, and economic points of view. The causes are very heterogeneous. Genes involved in ID have various functions altering different pathways important in neuronal function. Regulation of mRNA metabolism is particularly important in neurons for synaptic structure and function. Here, we review ID due to alteration of mRNA metabolism. Functional absence of some RNA-binding proteins--namely, FMRP, FMR2P, PQBP1, UFP3B, VCX-A--causes different forms of ID. These proteins are involved in different steps of RNA metabolism and, even if a detailed analysis of their RNA targets has been performed so far only for FMRP, it appears clear that they modulate some aspects (translation, stability, transport, and sublocalization) of a subset of RNAs coding for proteins, whose function must be relevant for neurons. Two other proteins, DYRK1A and CDKL5, involved in Down syndrome and Rett syndrome, respectively, have been shown to have an impact on splicing efficiency of specific mRNAs. Both proteins are kinases and their effect is indirect. Interestingly, both are localized in nuclear speckles, the nuclear domains where splicing factors are assembled, stocked, and recycled and influence their biogenesis and/or their organization. Copyright © 2012 Elsevier B.V. All rights reserved.
BOLD signal and functional connectivity associated with loving kindness meditation
Garrison, Kathleen A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A
2014-01-01
Loving kindness is a form of meditation involving directed well-wishing, typically supported by the silent repetition of phrases such as “may all beings be happy,” to foster a feeling of selfless love. Here we used functional magnetic resonance imaging to assess the neural substrate of loving kindness meditation in experienced meditators and novices. We first assessed group differences in blood oxygen level-dependent (BOLD) signal during loving kindness meditation. We next used a relatively novel approach, the intrinsic connectivity distribution of functional connectivity, to identify regions that differ in intrinsic connectivity between groups, and then used a data-driven approach to seed-based connectivity analysis to identify which connections differ between groups. Our findings suggest group differences in brain regions involved in self-related processing and mind wandering, emotional processing, inner speech, and memory. Meditators showed overall reduced BOLD signal and intrinsic connectivity during loving kindness as compared to novices, more specifically in the posterior cingulate cortex/precuneus (PCC/PCu), a finding that is consistent with our prior work and other recent neuroimaging studies of meditation. Furthermore, meditators showed greater functional connectivity during loving kindness between the PCC/PCu and the left inferior frontal gyrus, whereas novices showed greater functional connectivity during loving kindness between the PCC/PCu and other cortical midline regions of the default mode network, the bilateral posterior insula lobe, and the bilateral parahippocampus/hippocampus. These novel findings suggest that loving kindness meditation involves a present-centered, selfless focus for meditators as compared to novices. PMID:24944863
Higo, Noriyuki; Hayashi, Takuya; Nishimura, Yukio; Sugiyama, Yoko; Oishi, Takao; Tsukada, Hideo; Isa, Tadashi; Onoe, Hirotaka
2015-01-01
The question of how intensive motor training restores motor function after brain damage or stroke remains unresolved. Here we show that the ipsilesional ventral premotor cortex (PMv) and perilesional primary motor cortex (M1) of rhesus macaque monkeys are involved in the recovery of manual dexterity after a lesion of M1. A focal lesion of the hand digit area in M1 was made by means of ibotenic acid injection. This lesion initially caused flaccid paralysis in the contralateral hand but was followed by functional recovery of hand movements, including precision grip, during the course of daily postlesion motor training. Brain imaging of regional cerebral blood flow by means of H215O-positron emission tomography revealed enhanced activity of the PMv during the early postrecovery period and increased functional connectivity within M1 during the late postrecovery period. The causal role of these areas in motor recovery was confirmed by means of pharmacological inactivation by muscimol during the different recovery periods. These findings indicate that, in both the remaining primary motor and premotor cortical areas, time-dependent plastic changes in neural activity and connectivity are involved in functional recovery from the motor deficit caused by the M1 lesion. Therefore, it is likely that the PMv, an area distant from the core of the lesion, plays an important role during the early postrecovery period, whereas the perilesional M1 contributes to functional recovery especially during the late postrecovery period. PMID:25568105
Singh, Brijendra; Kasam, Rajesh K; Sontake, Vishwaraj; Wynn, Thomas A; Madala, Satish K
2017-11-01
IL-4 and IL-13 are major T-helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared with saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline were attenuated in mice deficient in either IL-13 or IL-4Rα-driven signaling compared with wild-type mice treated with bleomycin. Furthermore, our results demonstrated that IL-13 and IL-4Rα-driven signaling are involved in excessive migration of macrophages and fibroblasts. Notably, our findings demonstrated that IL-13-driven migration involves increased phospho-focal adhesion kinase signaling and F-actin polymerization. Importantly, in vivo findings demonstrated that IL-13 augments matrix metalloproteinase (MMP)-2 and MMP9 activity that has also been shown to increase migration and invasiveness of fibroblasts in the lungs during bleomycin-induced pulmonary fibrosis. Together, our findings demonstrate a pathogenic role for Th2-cytokine signaling that includes excessive migration and protease activity involved in severe fibrotic lung disease.
Genome-Wide Protein Interaction Screens Reveal Functional Networks Involving Sm-Like Proteins
Fromont-Racine, Micheline; Mayes, Andrew E.; Brunet-Simon, Adeline; Rain, Jean-Christophe; Colley, Alan; Dix, Ian; Decourty, Laurence; Joly, Nicolas; Ricard, Florence; Beggs, Jean D.
2000-01-01
A set of seven structurally related Sm proteins forms the core of the snRNP particles containing the spliceosomal U1, U2, U4 and U5 snRNAs. A search of the genomic sequence of Saccharomyces cerevisiae has identified a number of open reading frames that potentially encode structurally similar proteins termed Lsm (Like Sm) proteins. With the aim of analysing all possible interactions between the Lsm proteins and any protein encoded in the yeast genome, we performed exhaustive and iterative genomic two-hybrid screens, starting with the Lsm proteins as baits. Indeed, extensive interactions amongst eight Lsm proteins were found that suggest the existence of a Lsm complex or complexes. These Lsm interactions apparently involve the conserved Sm domain that also mediates interactions between the Sm proteins. The screens also reveal functionally significant interactions with splicing factors, in particular with Prp4 and Prp24, compatible with genetic studies and with the reported association of Lsm proteins with spliceosomal U6 and U4/U6 particles. In addition, interactions with proteins involved in mRNA turnover, such as Mrt1, Dcp1, Dcp2 and Xrn1, point to roles for Lsm complexes in distinct RNA metabolic processes, that are confirmed in independent functional studies. These results provide compelling evidence that two-hybrid screens yield functionally meaningful information about protein–protein interactions and can suggest functions for uncharacterized proteins, especially when they are performed on a genome-wide scale. PMID:10900456
Continuation of probability density functions using a generalized Lyapunov approach
DOE Office of Scientific and Technical Information (OSTI.GOV)
Baars, S., E-mail: s.baars@rug.nl; Viebahn, J.P., E-mail: viebahn@cwi.nl; Mulder, T.E., E-mail: t.e.mulder@uu.nl
Techniques from numerical bifurcation theory are very useful to study transitions between steady fluid flow patterns and the instabilities involved. Here, we provide computational methodology to use parameter continuation in determining probability density functions of systems of stochastic partial differential equations near fixed points, under a small noise approximation. Key innovation is the efficient solution of a generalized Lyapunov equation using an iterative method involving low-rank approximations. We apply and illustrate the capabilities of the method using a problem in physical oceanography, i.e. the occurrence of multiple steady states of the Atlantic Ocean circulation.
Galectin-3 as a Potential Target to Prevent Cancer Metastasis
Ahmed, Hafiz; AlSadek, Dina M. M.
2015-01-01
Interactions between two cells or between cell and extracellular matrix mediated by protein–carbohydrate interactions play pivotal roles in modulating various biological processes such as growth regulation, immune function, cancer metastasis, and apoptosis. Galectin-3, a member of the β-galactoside-binding lectin family, is involved in fibrosis as well as cancer progression and metastasis, but the detailed mechanisms of its functions remain elusive. This review discusses its structure, carbohydrate-binding properties, and involvement in various aspects of tumorigenesis and some potential carbohydrate ligands that are currently investigated to block galectin-3 activity. PMID:26640395
A real time spectrum to dose conversion system
NASA Technical Reports Server (NTRS)
Farmer, B. J.; Johnson, J. H.; Bagwell, R. G.
1972-01-01
A system has been developed which permits the determination of dose in real time or near real time directly from the pulse-height output of a radiation spectrometer. The technique involves the use of the resolution matrix of a spectrometer, the radiation energy-to-dose conversion function, and the geometrical factors, although the order of matrix operations is reversed. The new technique yields a result which is mathematically identical to the standard method while requiring no matrix manipulations or resolution matrix storage in the remote computer. It utilizes only a single function for each type dose required and each geometric factor involved.
Polychronidou, Eleftheria; Vlachakis, Dimitrios; Vlamos, Panayiotis; Baumann, Marc; Kossida, Sophia
2015-01-01
Notch signaling is a master controller of the neural stem cell and neural development maintaining a significant role in the normal brain function. Notch genes are involved in embryogenesis, nervous system, and cardiovascular and endocrine function. On the other side, there are studies representing the involvement of Notch mutations in sporadic Alzheimer disease, other neurodegenerative diseases such as Down syndrome, Pick's and Prion's disease, and CADASIL. This manuscript attempts to present a holistic view of the positive or negative contribution of Notch signaling in the adult brain, and at the same time to present and promote the promising research fields of study.
2013-01-01
Background Reproductive health and Family Planning (FP) services have been of global concern especially in developing countries where fertility rates are high. Traditionally FP services had always targeted females with little or no attention given to males. To ensure equitable distribution of health services, Ministry of Health (MOH), Ghana adopted the Community-Based Health Planning and Services (CHPS) as a nationwide health policy with the aim of reducing obstacles to physical and geographical access to health care delivery including FP services. However, not much is known about the extent to which this policy has contributed to male involvement in FP services. This qualitative descriptive study was therefore designed to explore male involvement in FP services in communities with well functioning CHPS and those with less or no functioning CHPS structures. The study further solicited views of the community on the health status of children. Methods This was a qualitative descriptive study and adapted the design of an ongoing study to assess the impact of male involvement in FP referred to as the Navrongo experiment in Northern Ghana. Twelve focus group discussions were held with both male and female community members, six in communities with functional CHPS and six for communities with less/no-functional CHPS. In addition, fifty- nine (59) in-depth interviews were held with Community Health Officers (CHOs), Community Health Volunteers (CHVs) and Health Managers at both the districts and regional levels. The interviews and discussions were tape recorded digitally, transcribed and entered into QSR Nvivo 10© for analysis. Results The results revealed a general high perception of an improved health status of children in the last ten years in the communities. These improvements were attributed to immunization of children, exclusive breastfeeding, health education given to mothers on childcare, growth monitoring of children and accessible health care. Despite these achievements in the health of children, participants reported that malnutrition was still rife in the community. The results also revealed that spousal approval was still relevant for women in the use of contraceptives; however, the matrilineal system appears to give more autonomy to women in decision-making. The CHPS strategy was perceived as very helpful with full community participation at all levels of the implementation process. Males were more involved in FP services in communities with functioning CHPS than those without functioning CHPS. Conclusion The CHPS strategy has increased access to FP services but spousal consent was very important in the use of FP services. Involving males in reproductive health issues including FP is important to attain reproductive health targets. PMID:23890362
Two Methods for Teaching Simple Visual Discriminations to Learners with Severe Disabilities
ERIC Educational Resources Information Center
Graff, Richard B.; Green, Gina
2004-01-01
Simple discriminations are involved in many functional skills; additionally, they are components of conditional discriminations (identity and arbitrary matching-to-sample), which are involved in a wide array of other important performances. Many individuals with severe disabilities have difficulty acquiring simple discriminations with standard…
The Citizen/Teacher Curriculum Council: A Curriculum Development Involvement Strategy.
ERIC Educational Resources Information Center
Peters, Richard O.
In most school systems today, curriculum development is the work of specialists who function as consultants to classroom teachers, administrators, and school boards. An alternative is the Citizen/Teacher Curriculum Council (C/TCC) approach, which calls for direct involvement of community members and classroom teachers in curriculum development.…
Trauma among Street-Involved Youth
ERIC Educational Resources Information Center
Bender, Kimberly A.; Thompson, Sanna J.; Ferguson, Kristin M.; Yoder, Jamie R.; Kern, Leah
2014-01-01
Previous research documents that street-involved youth experience rates of trauma and posttraumatic stress disorder (PTSD) that are significantly higher than their housed counterparts. Trauma and PTSD are of particular concern for homeless youth as they can negatively affect youths' ability to function adaptively and to transition off the streets.…
Public Relations Manager Involvement in Strategic Issue Diagnosis.
ERIC Educational Resources Information Center
Lauzen, Martha M.
1995-01-01
Reports on an exploratory study that seeks to build theoretical understanding of how public relations practitioner involvement in one type of strategic organizational decision making--strategic issue diagnosis--is related to shared values with top management, diagnosis accuracy, strategy pursued, and the power of the public relations function. (TB)
ERIC Educational Resources Information Center
Slotnik, William J.; And Others
Methods for encouraging community involvement and training community volunteers for decision making positions in community schools are described. The functions of community schools are to provide a broad diversity of learning opportunities and to involve citizens in assessing community needs, evaluating services, and advocating…
ERIC Educational Resources Information Center
Shatshat, Hussein M.
1980-01-01
Examines the role of communication directors involved in internal communication activities in business organizations. Indicates that directors perform a variety of roles ranging from journalistic to advisory/support work. Proposes a functional role involved in determining major policies for communications systems. (JMF)
USDA-ARS?s Scientific Manuscript database
Trichoderma species produce trichothecenes, most notably trichodermin and harzianum A (HA), by a biosynthetic pathway in which several of the involved proteins have significant differences in functionality, compared to their Fusarium orthologues. In addition, the genes encoding these proteins show a...
ERIC Educational Resources Information Center
Mashal, N.; Vishne, T.; Laor, N.; Titone, D.
2013-01-01
The neural basis involved in novel metaphor comprehension in schizophrenia is relatively unknown. Fourteen people with schizophrenia and fourteen controls were scanned while they silently read novel metaphors, conventional metaphors, literal expressions, and meaningless word-pairs. People with schizophrenia showed reduced comprehension of both…
USDA-ARS?s Scientific Manuscript database
While lipid droplets have traditionally been considered as inert sites for the storage of triacylglycerols and sterol esters, they are now recognized as dynamic and functionally diverse organelles involved in energy homeostasis, lipid signaling, and stress responses. Unlike most other organelles, li...
Age-Dependent Glutamate Induction of Synaptic Plasticity in Cultured Hippocampal Neurons
ERIC Educational Resources Information Center
Ivenshitz, Miriam; Segal, Menahem; Sapoznik, Stav
2006-01-01
A common denominator for the induction of morphological and functional plasticity in cultured hippocampal neurons involves the activation of excitatory synapses. We now demonstrate massive morphological plasticity in mature cultured hippocampal neurons caused by a brief exposure to glutamate. This plasticity involves a slow, 70%-80% increase in…
Community-Referenced Math Activities for Moderately and Severely Handicapped Individuals.
ERIC Educational Resources Information Center
Schoen, Sharon F.
Community-referenced activities, which involve combinations of skills used in routine tasks of daily living, are critical for the independent functioning of moderately and severely handicapped persons. The paper examines the characteristics of these activities in order to extract implications for enhancing instruction. The tasks involved in such…
Evolution of Protein Synthesis from an RNA World
Noller, Harry F.
2012-01-01
SUMMARY Because of the molecular complexity of the ribosome and protein synthesis, it is a challenge to imagine how translation could have evolved from a primitive RNA World. Two specific suggestions are made here to help to address this, involving separate evolution of the peptidyl transferase and decoding functions. First, it is proposed that translation originally arose not to synthesize functional proteins, but to provide simple (perhaps random) peptides that bound to RNA, increasing its available structure space, and therefore its functional capabilities. Second, it is proposed that the decoding site of the ribosome evolved from a mechanism for duplication of RNA. This process involved homodimeric “duplicator RNAs,” resembling the anticodon arms of tRNAs, which directed ligation of trinucleotides in response to an RNA template. PMID:20610545
The Functional Theory of Counterfactual Thinking
Epstude, Kai; Roese, Neal J.
2008-01-01
Counterfactuals are thoughts about alternatives to past events, that is, thoughts of what might have been. This article provides an updated account of the functional theory of counterfactual thinking, suggesting that such thoughts are best explained in terms of their role in behavior regulation and performance improvement. The article reviews a wide range of cognitive experiments indicating that counterfactual thoughts may influence behavior by either of two routes: a content-specific pathway (which involves specific informational effects on behavioral intentions, which then influence behavior) and a content-neutral pathway (which involves indirect effects via affect, mind-sets, or motivation). The functional theory is particularly useful in organizing recent findings regarding counterfactual thinking and mental health. The article concludes by considering the connections to other theoretical conceptions, especially recent advances in goal cognition. PMID:18453477
The functional theory of counterfactual thinking.
Epstude, Kai; Roese, Neal J
2008-05-01
Counterfactuals are thoughts about alternatives to past events, that is, thoughts of what might have been. This article provides an updated account of the functional theory of counterfactual thinking, suggesting that such thoughts are best explained in terms of their role in behavior regulation and performance improvement. The article reviews a wide range of cognitive experiments indicating that counterfactual thoughts may influence behavior by either of two routes: a content-specific pathway (which involves specific informational effects on behavioral intentions, which then influence behavior) and a content-neutral pathway (which involves indirect effects via affect, mind-sets, or motivation). The functional theory is particularly useful in organizing recent findings regarding counterfactual thinking and mental health. The article concludes by considering the connections to other theoretical conceptions, especially recent advances in goal cognition.