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Likely Mechanism (likely + mechanism)
Selected AbstractsCaffeine and theophylline block insulin-stimulated glucose uptake and PKB phosphorylation in rat skeletal musclesACTA PHYSIOLOGICA, Issue 1 2010A. J. Kolnes Abstract Aim:, Caffeine and theophylline inhibit phosphatidylinositol 3-kinase (PI3-kinase) activity and insulin-stimulated protein kinase B (PKB) phosphorylation. Insulin-stimulated glucose uptake involves PI3-kinase/PKB, and the aim of the present study was to test the hypothesis that caffeine and theophylline inhibit insulin-stimulated glucose uptake in skeletal muscles. Methods:, Rat epitrochlearis muscles and soleus strips were incubated with insulin and different concentrations of caffeine and theophylline for measurement of glucose uptake, force development and PKB phosphorylation. The effect of caffeine was also investigated in muscles stimulated electrically. Results:, Caffeine and theophylline completely blocked insulin-stimulated glucose uptake in both soleus and epitrochlearis muscles at 10 mm. Furthermore, insulin-stimulated PKB Ser473 and Thr308 and GSK-3, Ser9 phosphorylation were blocked by caffeine and theophylline. Caffeine reduced and theophylline blocked insulin-stimulated glycogen synthase activation. Caffeine stimulates Ca2+ release and force development increased rapidly to 10,20% of maximal tetanic contraction. Dantrolene (25 ,m), a well-known inhibitor of Ca2+ -release, prevented caffeine-induced force development, but caffeine inhibited insulin-stimulated glucose uptake in the presence of dantrolene. Contraction, like insulin, stimulates glucose uptake via translocation of glucose transporter-4 (GLUT4). Caffeine and theophylline reduced contraction-stimulated glucose uptake by about 50%, whereas contraction-stimulated glycogen breakdown was normal. Conclusion:, Caffeine and theophylline block insulin-stimulated glucose uptake independently of Ca2+ release, and the likely mechanism is via blockade of insulin-stimulated PI3-kinase/PKB activation. Caffeine and theophylline also reduced contraction-stimulated glucose uptake, which occurs independently of PI3-kinase/PKB, and we hypothesize that caffeine and theophylline also inhibit glucose uptake in skeletal muscles via an additional and hitherto unknown molecule involved in GLUT4 translocation. [source] Population genetics analysis of the origin of the Oriental fruit fly, Bactrocera dorsalis Hendel (Diptera: Tephritidae), in northern Yunnan Province, ChinaENTOMOLOGICAL SCIENCE, Issue 1 2007Jianhong LIU Abstract We examined genetic variation in the Oriental fruit fly, Bactrocera dorsalis (Hendel), using six populations in two regions of Yunnan Province, China, to determine the distribution and likely mechanism for the dispersal of this fly. A 501-bp portion of the mitochondrial cytochrome oxidase gene was sequenced from a minimum of eight individuals from each population, and 43 haplotypes were observed in the six Bactrocera dorsalis populations. When comparing the genetic diversity of populations in the northern and southern regions, which differ with respect to elevation, climate and plant phenology, we found a significantly greater haplotype diversity in the southern region (permutation test; P < 0.05), suggesting that the northern populations, those at Kunming and Qujing, probably originated from somewhere in the southern region. FST and number of pairwise differences revealed a high level of differentiation between the Panxi population and the other populations (permutation test; P < 0.05). Although the difference was marginally insignificant, the Shuitang population seemed to have differentiated from both northern populations. The Mantel test did not detect any isolation due to geographic distance. An amova analysis found that 2.56% of the variance was caused by the Panxi population. Haplotype network analysis showed that none of the six populations had a specific genetic lineage. Together, these analyses suggest that long-distance dispersal has occurred for this species, and the species most probably took advantage of both a mountain pass and prevailing air currents. The Panxi population was significantly isolated from the others, probably because of its distinguishing habitat features, host plants or the recent reduction of the population size. [source] Effects of adrenaline and potassium on QTc interval and QT dispersion in manEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2003S. Lee Abstract Background Hypoglycaemia alters cardiac repolarization acutely, with increases in rate-corrected QT (QTc) interval and QT dispersion (QTd) on the electrocardiogram (ECG); such changes are related to the counterregulatory sympatho-adrenal response. Adrenaline produces both QTc lengthening and a fall in plasma potassium (K+) when infused into healthy volunteers. Hypokalaemia prolongs cardiac repolarization independently however, and therefore our aim was to determine whether adrenaline-induced repolarization changes are mediated directly or through lowered plasma K+. Materials and methods Ten healthy males were studied on two occasions. At both visits they received similar l- adrenaline infusions but on one occasion potassium was also administered; infusion rates were adjusted to maintain circulating K+ at baseline. The QTc interval, QTd, peripheral physiological responses and plasma adrenaline and potassium concentrations were measured during both visits. Results The QTc interval and QTd increased both with and without potassium clamping. Without K+ replacement, mean (SE) QTc lengthened from 378 (5) ms to a final maximum value of 433 (10) ms, and QTd increased from 36 (5) ms to 69 (8) ms (both P < 0·001). During K+ replacement, QTc duration at baseline and study end was 385 (7) ms and 423 (11) ms, respectively (P < 0·001), and QTd 38 was (4) ms and 63 (5) ms (P = 0·001). Conclusions These data suggest that disturbed cardiac repolarization as a result of increases in circulating adrenaline occurs independently of extracellular potassium. A direct effect of adrenaline upon the myocardium appears the most likely mechanism. [source] Emerging model systems in evo-devo: cavefish and microevolution of developmentEVOLUTION AND DEVELOPMENT, Issue 3 2008William R. Jeffery SUMMARY Cavefish and their conspecific surface-dwelling ancestors (Astyanax mexicanus) are emerging as a model system to study the microevolution of development. Here we describe attributes that make this system highly promising for such studies. We review how the Astyanax system is being used to understand evolutionary forces underlying loss of eyes and pigmentation in cavefish. Pigment regression is probably explained by neutral mutations, whereas natural selection is a likely mechanism for loss of eyes. Finally, we discuss several research frontiers in which Astyanax is poised to make significant contributions in the future: evolution of constructive traits, the craniofacial skeleton, the central nervous system, and behavior. [source] Evidence for a single-step mechanism in the origin of hyperdiploid childhood acute lymphoblastic leukemiaGENES, CHROMOSOMES AND CANCER, Issue 2 2005Kajsa Paulsson High hyperdiploidy (>50 chromosomes) in childhood acute lymphoblastic leukemia (ALL) is characterized by nonrandom multiple trisomies and tetrasomies involving in particular chromosomes X, 4, 6, 8, 10, 14, 17, 18, and 21. This characteristic karyotypic pattern, the most common in pediatric ALL, may arise via a tetraploid state with subsequent loss of chromosomes, by sequential gains of chromosomes in consecutive cell divisions, or by simultaneous gain of chromosomes in a single mitosis. These alternatives may be distinguished by investigation of the allelic ratios of loci on the tetrasomic and disomic chromosomes. Previous studies of tetrasomy 21 and of the occurrence of uniparental disomies (UPDs) have suggested that the most likely mechanism is simultaneous gain. However, the other pathways have not been definitely excluded because complete analyses of all disomies and tetrasomies have never been performed. In the present study, we investigated 27 hyperdiploid ALLs by using 58 polymorphic microsatellite markers mapped to 23 of the 24 human chromosomes. Twenty-six tetrasomies were analyzed (involving chromosomes X, 8, 10, 14, 18, and 21), and the frequency of UPDs was determined in 10 cases. In total, 200 chromosomes were studied. Equal allele dosage was observed in 24 of 26 tetrasomies, and only 7 UPDs were found. These data strongly suggest that hyperdiploidy in childhood ALL generally arises by a simultaneous gain of all additional chromosomes in a single abnormal mitosis. © 2005 Wiley-Liss, Inc. [source] Modelling past and present geographical distribution of the marine gastropod Patella rustica as a tool for exploring responses to environmental changeGLOBAL CHANGE BIOLOGY, Issue 10 2007FERNANDO P. LIMA Abstract A climate envelope approach was used to model the distributions of the intertidal gastropod Patella rustica, to test the robustness of forecast responses to climate change. The model incorporated variables that were likely to determine the abundance and the northern range limit of this species in the NE Atlantic. The model was built using classification and regression tree analysis (CART) trained with historical distribution data from the mid 1950s and a set of corresponding climatic and oceanographic variables. Results indicated air and sea temperature, in particular during the reproductive and settlement periods, as the main determinants of the Atlantic distribution of P. rustica. The model was subsequently fed with contemporary climatic data and its output was compared with the current distribution and abundance of P. rustica, assessed during a 2002,2003 survey. The model correctly hindcasted the recent collapse of a distributional gap in northern Portugal, as well as an increase in abundance at locations within its range. The predicted northward expansion of the northern range limit did not occur because the absence of the species was confirmed in a survey encompassing the whole Atlantic French coast up to Brest. Stretches of unsuitable habitat too long to be overcome by dispersal are the likely mechanism controlling the northern limit of the distribution of this intertidal species. [source] Effects of Water Use on Arsenic Release to Well Water in a Confined AquiferGROUND WATER, Issue 4 2004Madeline B. Gotkowitz Field-based experiments were designed to investigate the release of naturally occurring, low to moderate (< 50 ug/L) arsenic concentrations to well water in a confined sandstone aquifer in northeastern Wisconsin. Geologic, geochemical, and hydrogeologic data collected from a 115 m2 site demonstrate that arsenic concentrations in ground water are heterogeneous at the scale of the field site, and that the distribution of arsenic in ground water correlates to solid-phase arsenic in aquifer materials. Arsenic concentrations in a test well varied from 1.8 to 22 ug/L during experiments conducted under no, low, and high pumping rates. The quality of ground water consumed from wells under typical domestic water use patterns differs from that of ground water in the aquifer because of reactions that occur within the well. Redox conditions in the well can change rapidly in response to ground water withdrawals. The well borehole is an environment conducive to microbiological growth, and biogeochemical reactions also affect borehole chemistry. While oxidation of sulfide minerals appears to release arsenic to ground water in zones within the aquifer, reduction of arsenic-bearing iron (hydr)oxides is a likely mechanism of arsenic release to water having a long residence time in the well borehole. [source] Clinically reported heterozygous mutations in the PINK1 kinase domain exert a gene dosage effect,HUMAN MUTATION, Issue 11 2009Eng-King Tan Abstract Mutations in the gene encoding phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) have been associated with the loss of dopaminergic neurons characteristic of familial and sporadic Parkinson disease. We developed an in vitro system of stable human dopaminergic neuronal cell lines coexpressing an equivalent copy of normal and mutant PINK1 to simulate "heterozygous" and "homozygous" states in patients. Mutants in the N-terminus, C-terminus, and kinase domain were generated and cloned into a two-gene mammalian expression vector to generate stable mammalian expression cell lines producing an equivalent copy number of wild-type/mutant PINK1. The cell lines were subjected to oxidative stress and the rate of apoptosis and change in mitochondrial membrane potential (,,m) were assessed. Cell lines expressing kinase and C-terminus mutants exhibited a greater rate of apoptosis and decrease in ,,m, and increased time-dependent cell loss when subjected to oxidative stress compared to the wild-type. Cell lines expressing two copies of kinase mutants exhibited a greater apoptosis rate and ,,m decrease than those expressing one copy of the mutant. In time-dependent experiments, there was a significant difference between "homozygous," "heterozygous," and wild-type cell lines, with decreasing cell survival in cell lines expressing mutant copies of PINK1 compared to the wild-type. We provided the first experimental evidence that clinically reported PINK1 heterozygous mutations exert a gene dosage effect, suggesting that haploinsufficiency of PINK1 is the most likely mechanism that increased the susceptibility to dopaminergic cellular loss. Hum Mutat 30:1551,1557, 2009. © 2009 Wiley-Liss, Inc. [source] Direct hydroxide attack is a plausible mechanism for amidase antibody 43C9,JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 12 2003Lillian T. Chong Abstract Direct hydroxide attack on the scissile carbonyl of the substrate has been suggested as a likely mechanism for esterase antibodies elicited by phosphonate haptens, which mimic the transition states for the alkaline hydrolysis of esters.1 The unique amidase activity of esterase antibody 43C9 has been attributed to nucleophilic attack by an active-site histidine residue.2 Yet, the active site of 43C9 is strikingly similar to those of other esterase antibodies, particularly 17E8. We have carried out quantum mechanical calculations, molecular dynamics simulations, and free energy calculations to assess the mechanism involving direct hydroxide attack for 43C9. Results support this mechanism and suggest that the mechanism is plausible for other antiphosphonate antibodies that catalyze the hydrolysis of (p -nitro)phenyl esters. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1371,1377, 2003 [source] Parthenogenesis in a large-bodied requiem shark, the blacktip Carcharhinus limbatusJOURNAL OF FISH BIOLOGY, Issue 6 2008D. D. Chapman Genetic evidence is provided for parthenogenesis in a large-bodied shark, the blacktip Carcharhinus limbatus, from the speciose and commercially important family Carcharhinidae, the first verified case of asexual development in this lineage and only the second for any chondrichthyan. The parthenogenetic embryo exhibited elevated homozygosity relative to its mother, indicating that automictic parthenogenesis is the most likely mechanism. Although this finding shows that parthenogenesis is more common and widespread in sharks than previously realized and supports the early existence of parthenogenetic abilities in vertebrates, the adaptive significance of automixis in these ancient fishes remains unclear. [source] Birds select conventional over organic wheat when given free choiceJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 11 2010Ailsa J McKenzie Abstract BACKGROUND: Global demand for organic produce is increasing by ,4 billion annually. One key reason why consumers buy organic food is because they consider it to be better for human and animal health. Reviews comparing organic and conventional food have stated that organic food is preferred by birds and mammals in choice tests. RESULTS: This study shows the opposite result,that captive birds in the laboratory and wild garden birds both consumed more conventional than organic wheat when given free choice. There was a lag in preference formation during which time birds learnt to distinguish between the two food types, which is likely to explain why the present results differ from those of previous studies. A further experiment confirmed that, of 16 potential causal factors, detection by birds of consistently higher levels of protein in conventional seeds (a common difference between many organic and conventional foodstuffs) is the likely mechanism behind this pattern. CONCLUSION: The results of this study suggest that the current dogma that organic food is preferred to conventional food may not always be true, which is of considerable importance for consumer perceptions of organically grown food. Copyright © 2010 Society of Chemical Industry [source] Acute Stress Hyperglycemia in Cats Is Associated with Struggling and Increased Concentrations of Lactate and NorepinephrineJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2002Jacqueline S. Rand We characterized the changes in blood glucose concentrations in healthy cats exposed to a short stressor and determined the associations between glucose concentrations, behavioral indicators of stress, and blood variables implicated in stress hyperglycemia (plasma glucose, lactate, insulin, glucagon, cortisol, epinephrine, and norepinephrine concentrations). Twenty healthy adult cats with normal glucose tolerance had a 5-minute spray bath. Struggling and vocalization were the most frequent behavioral responses. There was a strong relationship between struggling and concentrations of glucose and lactate. Glucose and lactate concentrations increased rapidly and significantly in all cats in response to bathing, with peak concentrations occurring at the end of the bath (glucose baseline 83 mg/dL, mean peak 162 mg/dL; lactate baseline 6.3 mg/dL, mean peak 64.0 mg/dL). Glucose response resolved within 90 minutes in 12 of the 20 cats. Changes in mean glucose concentrations were strongly correlated with changes in mean lactate (r= .84; P <.001) and mean norepinephrine concentrations (r= .81; P < .001). There was no significant correlation between changes in mean glucose concentrations and changes in mean insulin, glucagon, cortisol, or epinephrine concentrations. Struggling and lactate concentrations were predictive of hyperglycemia. Gluconeogenesis stimulated by lactate release is the likely mechanism for hyperglycemia in healthy cats in this model of acute stress. Careful handling techniques that minimize struggling associated with blood collection may reduce the incidence of stress hyperglycemia in cats. [source] Hybrid origin of a swordtail species (Teleostei: Xiphophorus clemenciae) driven by sexual selectionMOLECULAR ECOLOGY, Issue 3 2006AXEL MEYER Abstract The swordlike exaggerated caudal fin extensions of male swordtails are conspicuous traits that are selected for through female choice. Swords are one of only few examples where the hypothesis of a pre-existing bias is believed to apply for the evolution of a male trait. Previous laboratory experiments demonstrated that females prefer males with longer swords and even females from some swordless species show an affiliation for males of sworded species. Earlier phylogenetic studies based on maternally inherited mitochondrial DNA placed the sworded southern swordtail Xiphophorus clemenciae with swordless platies, contradicting its morphology-based evolutionary affinities. The analyses of new nuclear DNA markers now recover its traditional phylogenetic placement with other southern swordtails, suggesting that this species was formed by an ancient hybridization event. We propose that sexual selection through female choice was the likely process of hybrid speciation, by mating of platy females with males of an ancestral swordtail lineage. In artificial crosses of descendent species from the two potential ancestral lineages of X. clemenciae the hybrid and backcross males have swords of intermediate lengths. Additionally, mate choice experiments demonstrate that hybrid females prefer sworded males. These experimental lines of evidence make hybridization through xeno-specific sexual selection by female choice the likely mechanism of speciation. [source] Bone mineral density and urinary N -acetyl-,- d -glucosaminidase activity in paediatric patients with idiopathic hypercalciuriaNEPHROLOGY, Issue 2 2005SYLVA SKALOVA SUMMARY: Background: Idiopathic hypercalciuria (IH) is defined as hypercalciuria that persists after correction of dietary inbalances and has no detectable causes. Patients with IH have a higher prevalence of osteoporosis. Defective reabsorption of calcium by the renal tubule is considered a likely mechanism of IH. N -acetyl-beta- d -glucosaminidase (NAG) is a lysosomal enzyme that is a very sensitive marker of renal tubular impairment. Methods: Fifteen patients (nine boys and six girls, mean age 12.4 ± 4.0 years) with IH (urinary calcium excretion >0.1 mmol/kg per 24 h) had their bodyweight, height, body mass index (BMI), urinary NAG/creatinine ratio (U-NAG/Cr) and 24-h urinary calcium excretion (U-Ca/24 h) assessed. L1,L4 bone mineral density (BMD) was measured by dual energy X-ray absorptiometry and volumetric BMD (BMDvol) was calculated. The obtained results were expressed as Z-scores. Results: The values of basic anthropometric parameters did not differ significantly from the values of the reference population and there was a tendency to short stature, which did not reach statistical significance (P = 0.08). The values of calciuria and U-NAG/Cr were significantly higher while BMD was significantly lower when compared to the reference values (P < 0.0006, P < 0.006 and P < 0.001, respectively). Inverse and significant correlations were found between U-Ca/24 h and ,BMD, U-Ca/24 h and body height, and U-Ca/24 h and BMDvol (r = ,0.64 and ,0.70, respectively, P < 0.01; r = ,0.55, P < 0.05), while there was no correlation between U-NAG/Cr and U-Ca/24 h, nor between BMD and weight or BMD and BMI. Conclusion: Tubular impairment is highly probable in children with IH, but there is a poor relationship with the degree of calcium leakage. Idiopathic hypercalciuria should be considered as a risk factor for stunted growth and low bone mass. [source] Cardiac Effects of Electrical Stun Guns: Does Position of Barbs Contact Make a Difference?PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4 2008DHANUNJAYA LAKKIREDDY M.D. Background:The use of electrical stun guns has been rising among law enforcement authorities for subduing violent subjects. Multiple reports have raised concerns over their safety. The cardiovascular safety profile of these devices in relationship to the position of delivery on the torso has not been well studied. Methods:We tested 13 adult pigs using a custom device built to deliver neuromuscular incapacitating (NMI) discharge of increasing intensity that matched the waveform of a commercially available stun gun (TASER® X-26, TASER International, Scottsdale, AZ, USA). Discharges with increasing multiples of output capacitances were applied in a step-up and step-down fashion, using two-tethered barbs at five locations: (1) Sternal notch to cardiac apex (position-1), (2) sternal notch to supraumbilical area (position-2), (3) sternal notch to infraumbilical area (position-3), (4) side to side on the chest (position-4), and (5) upper to lower mid-posterior torso (position-5). Endpoints included determination of maximum safe multiple (MaxSM), ventricular fibrillation threshold (VFT), and minimum ventricular fibrillation induction multiple (MinVFIM). Results:Standard TASER discharges repeated three times did not cause ventricular fibrillation (VF) at any of the five locations. When the barbs were applied in the axis of the heart (position-1), MaxSM and MinVFIM were significantly lower than when applied away from the heart, on the dorsum (position-5) (4.31 ± 1.11 vs 40.77 ± 9.54, P< 0.001 and 8.31 ± 2.69 vs 50.77 ± 9.54, P< 0.001, respectively). The values of these endpoints at position-2, position-3, and position-4 were progressively higher and ranged in between those of position-1 and position-5. Presence of ventricular capture at a 2:1 ratio to the delivered TASER impulses correlated with induction of VF. No significant metabolic changes were seen after standard NMI TASER discharge. There was no evidence of myocardial damage based on serum cardiac markers, electrocardiography, echocardiography, and histopathologic findings confirming the absence of significant cardiac effects. Conclusions: Standard TASER discharges did not cause VF at any of the positions. Induction of VF at higher output multiples appear to be sensitive to electrode distance from the heart, giving highest ventricular fibrillation safety margin when the electrodes are placed on the dorsum. Rapid ventricular capture appears to be a likely mechanism of VF induction by higher output TASER discharges. [source] Photochemistry of Oxazolidinone Antibacterial Drugs,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2009Elisa Fasani The photochemistry of six N3-(3-fluoro-4-dialkylaminophenyl)-oxazolidinones known for their antimicrobial activity has been examined. All of these compounds are defluorinated in water (,dec , 0.25) and in methanol (,dec , 0.03), reasonably via the triplet. The chemical processes observed are reductive defluorination and solvolysis, depending on the structural variation introduced (thus, tethering the dialkylamino group to the aromatic ring and introducing a highly polar group in the oxazolidinone moiety have an effect). A likely mechanism involves the fragmentation of the C,F bond yielding the corresponding triplet phenyl cation. This intermediate either is reduced or, under appropriate conditions, intersystem crosses to the singlet state that adds the solvent. These data demonstrate a sizeable photodecomposition of these drugs that causes a decrease in the therapeutic activity. Furthermore, the likely formation of phenyl cations may cause a photogenotoxic effect. [source] Cortisol reactions in five-year-olds to parent,child interaction: the moderating role of ego-resiliencyTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 7 2007Sanny Smeekens Background:, This study with five-year-olds is the first to examine whether low-quality interactions with parents elicit physiological stress in children beyond toddlerhood, as evident from elevated cortisol levels in their saliva. It was hypothesised that particularly children with low levels of ego-resiliency ,a personality construct reflecting the capacity to cope with stress , would show cortisol increases during low-quality parent,child interactions. Method:, In a sample of 101 five-year-old children (62 boys), parent,child interaction was observed at home during parent,child discourse that involved the recollection and discussion of emotional events that happened to the child in the past. Saliva samples to assess cortisol levels were collected before and 20 minutes after the parent,child discourse task. The children's teacher rated child ego-resiliency using a Dutch translation of the California Child Q-set (CCQ; Block & Block, 1980). Results:, One of the two parent,child interaction factors that emerged from a principal component analysis, namely negative parent,child interactions, was significantly related to the children's cortisol reaction; more negative parent,child interactions elicited significantly stronger cortisol reactions. The other parent,child interaction factor that was found, i.e., effective guidance, was not significantly related to children's cortisol reaction. As predicted, children low on ego-resiliency showed increases in cortisol during negative interactions with their parents, whereas high ego-resilient children did not. Conclusions:, The association between negative parent,child interactions and cortisol elevations in children may point to a likely mechanism through which negative parent,child interactions contribute to negative developmental outcomes as the repeated exposure to high levels of cortisol have earlier been found to negatively affect children's development and functioning in various areas. [source] Inferolateral ST Elevation as a First Sign of Left Anterior Descending Artery OcclusionANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2010Po-Chao Hsu M.D. Combined anterior and inferior ST elevation due to occlusion of wrapped left anterior descending artery (LAD) is well reported in the literature. However, there is rare literature mentioned about inferolateral ST elevation in this patient group. Herein, we report a case of acute proximal wrapped LAD occlusion with initial electrocardiographic sign of inferolateral ST elevation. The most likely mechanism of this electrocardiographic finding might be related to old anteroseptal myocardial infarction, combination with other coronary abnormality, such as chronic total occlusion of left circumflex artery that caused larger injury current in inferolateral than anteroseptal myocardium, and made anteroseptal leads reveal isoelectric pattern. Ann Noninvasive Electrocardiol 2010;15(1):90,93 [source] A Proposed Mechanism for the Reductive Ring Opening of the Cyclodiphosphate MEcPP, a Crucial Transformation in the New DXP/MEP Pathway to Isoprenoids Based on Modeling Studies and Feeding ExperimentsCHEMBIOCHEM, Issue 3 2004Wolfgang Brandt Dr. Abstract Experimental and theoretical investigations concerning the second-to-last step of the DXP/MEP pathway in isoprenoid biosynthesis in plants are reported. The proposed intrinsic or late intermediates 4-oxo-DMAPP (12) and 4-hydroxy-DMAPP (11) were synthesized in deuterium- or tritium-labeled form according to new protocols especially adapted to work without protection of the diphosphate moiety. When the labeled compounds MEcPP (7), 11, and 12 were applied to chromoplast cultures, aldehyde 12 was not incorporated. This finding is in agreement with a mechanistic and structural model of the responsible enzyme family: a three-dimensional model of the fragment L271,A375 of the enzyme GcpE of Streptomyces coelicolor including NADPH, the Fe4S4cluster, and MEcPP (7) as ligand has been developed based on homology modeling techniques. The model has been accepted by the Protein Data Bank (entry code 1OX2). Supported by this model, semiempirical PM3 calculations were performed to analyze the likely catalysis mechanism of the reductive ring opening of MEcPP (7), hydroxyl abstraction, and formation of HMBPP (8). The mechanism is characterized by a proton transfer (presumably from a conserved arginine 286) to the substrate, accompanied by a ring opening without high energy barriers, followed by the transfer of two electrons delivered from the Fe4S4cluster, and finally proton transfer from a carboxylic acid side chain to the hydroxyl group to be removed from the ligand as water. The proposed mechanism is in agreement with all known experimental findings and the arrangement of the ligand within the enzyme. Thus, a very likely mechanism for the second to last step of the DXP/MEP pathway in isoprenoid biosynthesis in plants is presented. A principally similar mechanism is also expected for the reductive dehydroxylation of HMBPP (8) to IPP (9) and DMAPP (10) in the last step. [source] [8+2] and [8+3] Cyclization Reactions of Alkenyl Carbenes and 8-Azaheptafulvenes: Direct Access to Tetrahydro-1-azaazulene and Cyclohepta[b]pyridinone DerivativesCHEMISTRY - AN ASIAN JOURNAL, Issue 4 2008José Barluenga Prof. Abstract The reactivity of Fischer alkenyl carbenes toward 8-azaheptafulvenes is examined. Alkenyl carbenes react with 8-azaheptafulvenes with complete regio- and stereoselectivity through formal [8+3] and [8+2] heterocyclization reactions, which show an unprecedented dependence on the C, substituent at the alkenyl carbene complex. Thus, the formal [8+3] heterocyclization reaction is completely favored in carbene complexes that bear a coordinating moiety to give tetrahydrocyclohepta[b]pyridin-2-ones. Otherwise, alkenyl carbenes that lack appropriate coordinating groups undergo a formal [8+2] cyclization with 8-azaheptafulvenes to give compounds that bear a tetrahydroazaazulene structure. A likely mechanism for these reactions would follow well-established models and would involve a 1,4-addition/cyclization in the case of the [8+2] cyclization or a 1,2-addition/[1,2] shift,metal-promoted cyclization for the [8+3] reaction. The presence of a coordinating moiety in the carbene would favor the [1,2] metal shift through transition-state stabilization to lead to the [8+3] product. All these processes provide an entry into the tetrahydroazaazulene and cycloheptapyridone frameworks present in the structure of biologically active molecules. Se ha estudiado la reactividad de alquenilcarbenos de Fischer con 8-azaheptafulvenos. Los alquenilcarbenos reaccionan con 8-azaheptafulvenos a través de reacciones de heterociclación formales [8+3] y [8+2] con completa regioselectividad y estereoselectividad, mostrando una dependencia del sustituyente C, del complejo alquenilcarbeno sin precedentes. Así, en los complejos carbeno que contienen un resto coordinante la reacción de heterociclación formal [8+3] se favorece completamente para dar tetrahidrociclohepta[b]piridin-2-onas. Por otra parte, los alquenilcarbenos que carecen de grupos coordinantes apropiados, experimentan una ciclación formal [8+2] con los 8-azaheptafulvenos para dar compuestos con estructura de tetrahidroazuleno. Un mecanismo probable para estas reacciones se fundamenta en modelos bien establecidos e implica una adición 1,4/ciclación en el caso de la ciclación [8+2] o una adición 1,2/ciclación promovida por una migración 1,2 del metal en el caso de la reacción [8+3]. La presencia de un resto coordinante en el carbeno favorece la migración 1,2 del metal a través de una estabilización del estado de transición, conduciendo al producto [8+3]. Todos estos procesos representan una vía de acceso a los esqueletos de tetrahidroazuleno y cicloheptapiridona presentes en la estructura de moléculas biológicamente activas. [source] Controlling factors of gullying in the Maracujá Catchment, southeastern BrazilEARTH SURFACE PROCESSES AND LANDFORMS, Issue 11 2005L. de A. P. Bacellar Abstract Hundreds of gullies (,voçorocas') of huge dimensions (up to 400,500 m long, 150 m wide and 50 m deep) are very common in the small Maracujá Catchment in southeastern Brazil. These erosional features, which occur with an uneven intensity throughout the area, started due to bad soil management practices at the beginning of European settlement, at the end of the 17th century, and nowadays are still evolving, but at a slower rate. As surface soils are usually very resistant to erosion, the outcrop of the more erodible basement saprolites seems to be an essential condition for their beginning. An analysis of well known erosion controlling factors was performed, aiming to explain the beginning and evolution of these gullies and to understand the reasons for their spatial distribution. Data shows that geology and, mainly, geomorphology are the main controlling factors, since gullies tend to be concentrated in basement rock areas with lower relief (domain 2) of Maracujá Catchment, mainly at the fringes of broad and flat interfluves. At the detailed scale (1:10 000), gullies are more common in amphitheatre-like headwater hollows that frequently represent upper Quaternary gullies (paleogullies), which demonstrate the recurrence of channel erosion. So, gullies occur in areas of thicker saprolites (domain 2), in places with a natural concentration of surface and underground water (hollows). Saprolites of the preserved, non-eroded hollows are usually pressurized (confined aquifer) due to a thick seal of Quaternary clay layer, in a similar configuration to the ones found in hollows of mass movement (mudflow) sites in southeastern Brazil. Therefore, the erosion of the resistant soils by human activities, such as road cuts and trenches (,valos'), or their mobilization by mudflow movements, seem to be likely mechanisms of gullying initiation. Afterwards, gullies evolve by a combination of surface and underground processes, such as wash and tunnel erosion and falls and slumps of gully walls. Copyright © 2005 John Wiley & Sons, Ltd. [source] Developmental toxicity of in ovo exposure to polychlorinated biphenyls: I. Immediate and subsequent effects on first-generation nestling American kestrels (Falco sparverius)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2003Kim Fernie Abstract We determined that in ovo exposure to polychlorinated biphenyls (PCBs) alters growth off first-generation nestlings during and one year after parental exposure. Captive American kestrels (Falco sparverius) laid eggs with environmentally relevant total PCB levels (34.1 ,g/g whole-egg wet wt) when fed PCB-spiked (Aroclor® 1248, 1254, and 1260) food (7 mg/kg body wt/d) for 100 d in 1998. In 1999, the same adults laid eggs with estimated total PCBs of 29.0 ,g/g. Nonsurviving PCB-exposed chicks were small (mass, bones) in 1998. Survivors showed a strong sex-specific growth response (mass, bones) compared to respective sex controls: Only female hatchlings were larger, and only male nestlings had longer feathers (1998); maximal growth and bone growth rates also differed (males were advanced, faster; females delayed, slower) (1999); and male nestlings fledged earlier and were smaller, while females were larger (1998, 1999). However, regardless of sex, PCB-exposed nestlings generally grew at faster rates in both years. In 1998, greater contaminant burdens and toxic equivalent concentrations in sibling eggs were associated with nestlings being lighter, having longer bones and feathers, and growing at faster rates (mass, bone) for females but slower rates (mass) for males. Both physiological-biochemical and behavioral changes are likely mechanisms. This study supports and expands on the Great Lakes embryo mortality, edema, and deformities syndrome: While PCB exposure alters nestling size, maximal growth and growth rates also change immediately, are sustained, and are sex specific. [source] Stress and Headache ChronificationHEADACHE, Issue 1 2008Timothy Houle PhD In this special section, the concept of stress has been linked to the chronification of headache and is considered to be one of several likely mechanisms for the progression of an otherwise episodic disorder to a chronic daily phenomenon. The present review discusses the concept of stress and describes the mechanisms through which stress could influence headache progression. The hypothesized mechanisms include stress serving as a unique trigger for individual attacks, as a nociceptive activator, and as a moderator of other mechanisms. Finally, the techniques used in the screening and management of stress are mentioned in the context of employing strategies for the primary, secondary, or tertiary prevention of headache progression. [source] Neutrophils: key mediators of tumour angiogenesisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2009Simon Tazzyman Summary It is now well known that most malignant tumours contain a significant amount of leucocytic infiltrates the presence of which has, on many occasions, been linked to poor patient prognosis. These leucocyte populations are recruited to tumours by chemotactic factors released by either viable or necrotic tumour cells, or by cells within the tumour stroma. In recent times, most studies have analysed the role that tumour-associated macrophages (TAM) have on tumour progression. However, there is now increasing evidence to show that neutrophils also actively participate in this process. Whilst there are some data to suggest that neutrophil-derived factors can promote genetic mutations leading to tumourigenesis, or secrete factors that promote tumour cell proliferation; there is now substantial evidence to show that neutrophils, like TAM, significantly affect tumour angiogenesis. In this review, we discuss the likely mechanisms by which neutrophils are recruited into the tumour and then elaborate on how these cells may induce tumour vascularization by the secretion of powerful pro-angiogenic factors. We also discuss possible future chemotherapeutic strategies that are aimed at limiting tumour angiogenesis by inhibiting neutrophil recruitment. [source] Can paying for results help to achieve the Millennium Development Goals?JOURNAL OF EVIDENCE BASED MEDICINE, Issue 2 2009Overview of the effectiveness of results-based financing Abstract Objective Results-based financing and pay-for-performance refer to the transfer of money or material goods conditional on taking a measurable action or achieving a predetermined performance target. Results-based financing is widely advocated for achieving health goals, including the Millennium Development Goals. Methods We undertook an overview of systematic reviews of the effectiveness of RBF. We searched the Cochrane Library, EMBASE, and MEDLINE (up to August 2007). We also searched for related articles in PubMed, checked the reference lists of retrieved articles, and contacted key informants. We included reviews with a methods section that addressed the effects of any results-based financing in the health sector targeted at patients, providers, organizations, or governments. We summarized the characteristics and findings of each review using a structured format. Results We found 12 systematic reviews that met our inclusion criteria. Based on the findings of these reviews, financial incentives targeting recipients of health care and individual healthcare professionals are effective in the short run for simple and distinct, well-defined behavioral goals. There is less evidence that financial incentives can sustain long-term changes. Conditional cash transfers to poor and disadvantaged groups in Latin America are effective at increasing the uptake of some preventive services. There is otherwise very limited evidence of the effects of results-based financing in low- or middle-income countries. Results-based financing can have undesirable effects, including motivating unintended behaviors, distortions (ignoring important tasks that are not rewarded with incentives), gaming (improving or cheating on reporting rather than improving performance), widening the resource gap between rich and poor, and dependency on financial incentives. Conclusion There is limited evidence of the effectiveness of results-based financing and almost no evidence of the cost-effectiveness of results-based financing. Based on the available evidence and likely mechanisms through which financial incentives work, they are more likely to influence discrete individual behaviors in the short run and less likely to create sustained changes. [source] Systematic review: nutritional therapy in paediatric Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2008A. S. DAY Summary Background At least 25% of individuals diagnosed with Crohn's disease (CD) have onset of disease in childhood. Almost all children with CD have nutritional impairments, such as weight loss or stunting, at diagnosis or subsequently. Nutritional therapy (exclusive enteral nutrition) is established as a valid and effective treatment in paediatric CD. The advantages of this approach are induction of remission and control of inflammatory changes, mucosal healing, positive benefits to growth and overall nutritional status, and avoidance of other medical therapies. Aim To provide a comprehensive up-to-date review of the roles of nutritional therapy in CD and of the data supporting this therapy. Methods A search of PubMed was performed with search terms ,enteral nutrition', ,nutritional therapy', ,Crohn disease' and ,children'. Relevant articles were selected from this search. In addition, the reference lists of available articles were reviewed for further relevant articles. Results Nutritional therapy offers numerous benefits in the management of CD. Recent work has begun to elucidate the likely mechanisms of this therapy. These include direct mucosal anti-inflammatory effects and alteration of intestinal microflora. Conclusion Further studies are required to define longer-term effects of nutritional therapy in patients with CD. [source] Vibrio harveyi: a significant pathogen of marine vertebrates and invertebratesLETTERS IN APPLIED MICROBIOLOGY, Issue 2 2006B. Austin Abstract Vibrio harveyi, which now includes Vibrio carchariae as a junior synonym, is a serious pathogen of marine fish and invertebrates, particularly penaeid shrimp. In fish, the diseases include vasculitis, gastro-enteritis and eye lesions. With shrimp, the pathogen is associated with luminous vibriosis and Bolitas negricans. Yet, the pathogenicity mechanisms are imprecisely understood, with likely mechanisms involving the ability to attach and form biofilms, quorum sensing, various extracellular products including proteases and haemolysins, lipopolysaccharide, and interaction with bacteriophage and bacteriocin-like substances. [source] Mutation screening of the androgen receptor promoter and untranslated regions in prostate cancerTHE PROSTATE, Issue 15 2006Kati K. Waltering Abstract Background Mechanisms, other than gene amplification, leading to overexpression of AR in androgen ablation-resistant prostate cancer remain unknown and could include genetic alterations in the promoter or untranslated regions (UTR) of the AR gene. Materials and Methods DNAs from five prostate cancer cell lines, 19 LuCaP xenografts, 44 clinical tumors, and 36 non-malignant controls were used for screening mutations in the upstream regulatory region, promoter and the 5,- and 3,-UTRs of the AR gene with denaturating high performance liquid chromatography (DHPLC) and sequencing. Results Ten different sequence variations were found in prostate cancer cell lines and xenografts. However, none of them were recurrent or were found in clinical prostate cancer specimens or in normal controls. Conclusions Recurrent mutations in the promoter or UTRs of AR seem to be rare, and thus not likely mechanisms for the increased expression of the gene in the androgen ablation-resistant prostate cancer. Prostate 66: 1585,1591, 2006. © 2006 Wiley-Liss, Inc. [source] Induction of CD44 cleavage in articular chondrocytesARTHRITIS & RHEUMATISM, Issue 5 2010Nobunori Takahashi Objective The hyaluronan receptor CD44 provides chondrocytes with a mechanism for sensing and responding to changes in the extracellular matrix. The purpose of this study was to document the fragmentation and loss of CD44 and to determine the likely mechanisms involved. Methods A polyclonal anti-CD44 cytotail antibody was generated to detect CD44 fragmentation by Western blot analysis. Chondrocytes were isolated from human or bovine articular cartilage. Primary articular chondrocytes were treated with interleukin-1, (IL-1,), hyaluronan oligosaccharides, or phorbol myristate acetate or were passaged and subcultured in monolayer to induce dedifferentiation. Conditions that altered the capacity of CD44 to transit into lipid rafts, or pharmacologic inhibitors of metalloproteinase or ,-secretase activity were used to define the mechanism of fragmentation of CD44. Results Chondrocytes from osteoarthritic cartilage exhibited CD44 fragmentation as low molecular mass bands, corresponding to the CD44-EXT and CD44-ICD bands. Following dedifferentiation of chondrocytes or treatment of primary chondrocytes with hyaluronan oligosaccharides, IL-1,, or phorbol myristate acetate, CD44 fragmentation was enhanced. Subsequent culture of the dedifferentiated chondrocytes in 3-dimensional alginate beads rescued the chondrocyte phenotype and diminished the fragmentation of CD44. Fragmentation of CD44 in chondrocytes was blocked in the presence of the metalloproteinase inhibitor GM6001 and the ,-secretase inhibitor DAPT. Conclusion CD44 fragmentation, consistent with a signature pattern reported for sequential metalloproteinase/,-secretase cleavage of CD44, is a common metabolic feature of chondrocytes that have undergone dedifferentiation in vitro and osteoarthritic chondrocytes. Transit of CD44 into lipid rafts may be required for its fragmentation. 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