The dopamine D2 receptor mediates approach-avoidance tendencies in smokers

Dopamine D2 receptors (DRD2) have been strongly implicated in reward processing of natural stimuli and drugs. By using the Approach-Avoidance Task (AAT), we recently demonstrated that smokers show an increased approach bias toward smoking-related cues but not toward naturally-rewarding stimuli. Here we examined the contribution of the DRD2 Taq1B polymorphism to smokers’ and non-smokers’ responsivity toward smoking versus naturally-rewarding stimuli in the AAT. Smokers carrying the minor B1 allele of the DRD2 Taq1B polymorphism showed reduced approach behavior for food-related pictures compared to non-smokers with the same allele. In the group of smokers, a higher approach-bias toward smoking-related compared to food-related pictures was found in carriers of the B1 allele. This pattern was not evident in smokers homozygous for the B2 allele. Additionally, smokers with the B1 allele reported fewer attempts to quit smoking relative to smokers homozygous for the B2 allele. This is the first study demonstrating that behavioral shifts in response to smoking relative to natural rewards in smokers are mediated by the DRD2 Taq1B polymorphism. Our results indicate a reduced natural-reward brain reactivity in smokers with a genetically determined decrease in dopaminergic activity (i.e., reduction of DRD2 availability). It remains to be determined whether this pattern might be related to a different outcome after psychological cessation interventions, i.e. AAT modification paradigms, in smokers

Evaporative evolution of a Na–Cl–NO(3)–K–Ca–SO(4)–Mg–Si brine at 95°C: Experiments and modeling relevant to Yucca Mountain, Nevada

A synthetic Topopah Spring Tuff water representative of one type of pore water at Yucca Mountain, NV was evaporated at 95°C in a series of experiments to determine the geochemical controls for brines that may form on, and possibly impact upon the long-term integrity of waste containers and drip shields at the designated high-level, nuclear-waste repository. Solution chemistry, condensed vapor chemistry, and precipitate mineralogy were used to identify important chemical divides and to validate geochemical calculations of evaporating water chemistry using a high temperature Pitzer thermodynamic database. The water evolved toward a complex "sulfate type" brine that contained about 45 mol % Na, 40 mol % Cl, 9 mol % NO(3), 5 mol % K, and less than 1 mol % each of SO(4), Ca, Mg, ∑CO(2)(aq), F, and Si. All measured ions in the condensed vapor phase were below detection limits. The mineral precipitates identified were halite, anhydrite, bassanite, niter, and nitratine. Trends in the solution composition and identification of CaSO(4 )solids suggest that fluorite, carbonate, sulfate, and magnesium-silicate precipitation control the aqueous solution composition of sulfate type waters by removing fluoride, calcium, and magnesium during the early stages of evaporation. In most cases, the high temperature Pitzer database, used by EQ3/6 geochemical code, sufficiently predicts water composition and mineral precipitation during evaporation. Predicted solution compositions are generally within a factor of 2 of the experimental values. The model predicts that sepiolite, bassanite, amorphous silica, calcite, halite, and brucite are the solubility controlling mineral phases

Thermodynamic analysis of the Quantum Critical behavior of Ce-lattice compounds

A systematic analysis of low temperature magnetic phase diagrams of Ce compounds is performed in order to recognize the thermodynamic conditions to be fulfilled by those systems to reach a quantum critical regime and, alternatively, to identify other kinds of low temperature behaviors. Based on specific heat ($C_m$) and entropy ($S_m$) results, three different types of phase diagrams are recognized: i) with the entropy involved into the ordered phase ($S_{MO}$) decreasing proportionally to the ordering temperature ($T_{MO}$), ii) those showing a transference of degrees of freedom from the ordered phase to a non-magnetic component, with their $C_m(T_{MO})$ jump ($\Delta C_m$) vanishing at finite temperature, and iii) those ending in a critical point at finite temperature because their $\Delta C_m$ do not decrease with $T_{MO}$ producing an entropy accumulation at low temperature. Only those systems belonging to the first case, i.e. with $S_{MO}\to 0$ as $T_{MO}\to 0$, can be regarded as candidates for quantum critical behavior. Their magnetic phase boundaries deviate from the classical negative curvature below $T\approx 2.5$\,K, denouncing frequent misleading extrapolations down to T=0. Different characteristic concentrations are recognized and analyzed for Ce-ligand alloyed systems. Particularly, a pre-critical region is identified, where the nature of the magnetic transition undergoes significant modifications, with its $\partial C_m/\partial T$ discontinuity strongly affected by magnetic field and showing an increasing remnant entropy at $T\to 0$. Physical constraints arising from the third law at $T\to 0$ are discussed and recognized from experimental results

Constraint-based modeling analysis of the metabolism of two Pelobacter species

BACKGROUND: Pelobacter species are commonly found in a number of subsurface environments, and are unique members of the Geobacteraceae family. They are phylogenetically intertwined with both Geobacter and Desulfuromonas species. Pelobacter species likely play important roles in the fermentative degradation of unusual organic matters and syntrophic metabolism in the natural environments, and are of interest for applications in bioremediation and microbial fuel cells. RESULTS: In order to better understand the physiology of Pelobacter species, genome-scale metabolic models for Pelobacter carbinolicus and Pelobacter propionicus were developed. Model development was greatly aided by the availability of models of the closely related Geobacter sulfurreducens and G. metallireducens. The reconstructed P. carbinolicus model contains 741 genes and 708 reactions, whereas the reconstructed P. propionicus model contains 661 genes and 650 reactions. A total of 470 reactions are shared among the two Pelobacter models and the two Geobacter models. The different reactions between the Pelobacter and Geobacter models reflect some unique metabolic capabilities such as fermentative growth for both Pelobacter species. The reconstructed Pelobacter models were validated by simulating published growth conditions including fermentations, hydrogen production in syntrophic co-culture conditions, hydrogen utilization, and Fe(III) reduction. Simulation results matched well with experimental data and indicated the accuracy of the models. CONCLUSIONS: We have developed genome-scale metabolic models of P. carbinolicus and P. propionicus. These models of Pelobacter metabolism can now be incorporated into the growing repertoire of genome scale models of the Geobacteraceae family to aid in describing the growth and activity of these organisms in anoxic environments and in the study of their roles and interactions in the subsurface microbial community

Activation of mammalian skeletal-muscle carbonic anhydrase III by arginine modification

Purified carbonic anhydrase isozymes I, II, and III (CA I, CA II, CA III) from various sources were treated with 2,3-butanedione and their bicarbonate dehydration reactions followed. The specific activities of human and bovine CA I and CA II and chicken CA III were not affected by the butanedione treatment, whereas the activities of human, gorilla, and bovine CA III were rapidly activated. These findings suggest that one, or both, of the two arginyl residues which appear to be unique to the active sites of the mammalian CA III isozymes are modified by butanedione.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44191/1/10540_2005_Article_BF01121914.pd

Aspirin use and survival after the diagnosis of breast cancer:a population-based cohort study

Background: Aspirin use has been associated with a reduced cancer incidence and fewer deaths from cancer. This study examined whether women with breast cancer prescribed aspirin postdiagnosis had improved survival.Methods:An observational, population cohort study was undertaken using data linkage of cancer registry, dispensed prescriptions and death records in Tayside, Scotland. All community prescriptions for aspirin in women with breast cancer were extracted and use postdiagnosis for each individual examined using Cox's proportional hazard models. The main outcome measures were all-cause mortality and breast cancer-specific mortality.Results:Four thousand six hundred and twenty-seven patients diagnosed with breast cancer between 1 January 1998 and 31 December 2008 were followed up until 28 February 2010. Median age at diagnosis was 62 (IQR 52-74). One thousand eight hundred and two (39%) deaths were recorded, with 815 (18%) attributed to breast cancer. One thousand and thirty-five (22%) patients were prescribed aspirin postdiagnosis. Such aspirin use was associated with lower risk of all-cause mortality (HR=0.53, 95% CI=0.45-0.63, P<0.001) and breast cancer-specific mortality (HR=0.42, 95% CI=0.31-0.55, P<0.001) after adjusting for age, socioeconomic status, TNM stage, tumour grade, oestrogen receptor status, surgery, radiotherapy, chemotherapy, adjuvant endocrine therapy and aspirin use prediagnosis. Conclusions:Aspirin use postdiagnosis of breast cancer may reduce both all-cause and breast cancer-specific mortality. Further investigation seeking a causal relationship and which subgroups of patients benefit most await ongoing randomised controlled trials.Publisher PDFPeer reviewe

Biochemical and developmental characterization of carbonic anhydrase II from chicken erythrocytes

<p>Abstract</p> <p>Background</p> <p>Carbonic anhydrase (CA) of the chicken has attracted attention for a long time because it has an important role in the eggshell formation. The developmental profile of CA-II isozyme levels in chicken erythrocytes has not been determined or reported. Furthermore, the relations with CA-II in erythrocyte and egg production are not discussed. In the present study, we isolated CA-II from erythrocytes of chickens and determined age-related changes of CA-II levels in erythrocytes.</p> <p>Methods</p> <p>Chicken CA-II was purified by a combination of column chromatography. The levels of CA-II in the hemolysate of the chicken were determined using the ELISA system in blood samples from 279 female chickens, ages 1 to 93 weeks, 69 male chickens, ages 3 to 59 weeks and 52 weeks female Araucana-chickens.</p> <p>Results</p> <p>The mean concentration of CA-II in hemolysate from 1-week-old female was 50.8 ± 11.9 mg/g of Hb. The mean levels of CA-II in 25-week-old (188.1 ± 82.6 mg/g of Hb), 31-week-old (193.6 ± 69.7 mg/g of Hb) and 49-week-old (203.8 ± 123.5 mg/g of Hb) female-chickens showed the highest level of CA-II. The levels of CA-II in female WL-chickens significantly decreased at 63 week (139.0 ± 19.3 mg/g of Hb). The levels of CA-II in female WL-chicken did not change from week 63 until week 93.The mean level of CA-II in hemolysate of 3-week-old male WL-chickens was 78.3 ± 20.7 mg/g of Hb. The levels of CA-II in male WL-chickens did not show changes in the week 3 to week 59 timeframe. The mean level of CA-II in 53-week-old female Araucana-chickens was 23.4 ± 1.78 mg/g of Hb. These levels of CA-II were about 11% of those of 49-week-old female WL-chickens. Simple linear regression analysis showed significant associations between the level of CA-II and egg laying rate from 16 week-old at 63 week-old WL-chicken (p < 0.01).</p> <p>Conclusions</p> <p>Developmental changes and sexual differences of CA-II concentration in WL-chicken erythrocytes were observed. The concentration of CA-II in the erythrocyte of WL-chicken was much higher than that in Araucana-chicken (p < 0.01).</p

Association of Panton Valentine Leukocidin (PVL) genes with methicillin resistant Staphylococcus aureus (MRSA) in Western Nepal: a matter of concern for community infections (a hospital based prospective study)

BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) is a major human pathogen associated with nosocomial and community infections. Panton Valentine leukocidin (PVL) is considered one of the important virulence factors of S. aureus responsible for destruction of white blood cells, necrosis and apoptosis and as a marker of community acquired MRSA. This study was aimed to determine the prevalence of PVL genes among MRSA isolates and to check the reliability of PVL as marker of community acquired MRSA isolates from Western Nepal. METHODS: A total of 400 strains of S. aureus were collected from clinical specimens and various units (Operation Theater, Intensive Care Units) of the hospital and 139 of these had been confirmed as MRSA by previous study. Multiplex PCR was used to detect mecA and PVL genes. Clinical data as well as antimicrobial susceptibility data was analyzed and compared among PVL positive and negative MRSA isolates. RESULTS: Out of 139 MRSA isolates, 79 (56.8 %) were PVL positive. The majority of the community acquired MRSA (90.4 %) were PVL positive (Positive predictive value: 94.9 % and negative predictive value: 86.6 %), while PVL was detected only in 4 (7.1 %) hospital associated MRSA strains. None of the MRSA isolates from hospital environment was found positive for the PVL genes. The majority of the PVL positive strains (75.5 %) were isolated from pus samples. Antibiotic resistance among PVL negative MRSA isolates was found higher as compared to PVL positive MRSA. CONCLUSION: Our study showed high prevalence of PVL among community acquired MRSA isolates. Absence of PVL among MRSA isolates from hospital environment indicates its poor association with hospital acquired MRSA and therefore, PVL may be used a marker for community acquired MRSA. This is first study from Nepal, to test PVL among MRSA isolates from hospital environment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1531-1) contains supplementary material, which is available to authorized users

Associations of Insulin and Insulin-Like Growth Factors with Physical Performance in Old Age in the Boyd Orr and Caerphilly Studies

Objective Insulin and the insulin-like growth factor (IGF) system regulate growth and are involved in determining muscle mass, strength and body composition. We hypothesised that IGF-I and IGF-II are associated with improved, and insulin with worse, physical performance in old age. Methods Physical performance was measured using the get-up and go timed walk and flamingo balance test at 63–86 years. We examined prospective associations of insulin, IGF-I, IGF-II and IGFBP-3 with physical performance in the UK-based Caerphilly Prospective Study (CaPS; n = 739 men); and cross-sectional insulin, IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in the Boyd Orr cohort (n = 182 men, 223 women). Results In confounder-adjusted models, there was some evidence in CaPS that a standard deviation (SD) increase in IGF-I was associated with 1.5% faster get-up and go test times (95% CI: −0.2%, 3.2%; p = 0.08), but little association with poor balance, 19 years later. Coefficients in Boyd Orr were in the same direction as CaPS, but consistent with chance. Higher levels of insulin were weakly associated with worse physical performance (CaPS and Boyd Orr combined: get-up and go time = 1.3% slower per SD log-transformed insulin; 95% CI: 0.0%, 2.7%; p = 0.07; OR poor balance 1.13; 95% CI; 0.98, 1.29; p = 0.08), although associations were attenuated after controlling for body mass index (BMI) and co-morbidities. In Boyd Orr, a one SD increase in IGFBP-2 was associated with 2.6% slower get-up and go times (95% CI: 0.4%, 4.8% slower; p = 0.02), but this was only seen when controlling for BMI and co-morbidities. There was no consistent evidence of associations of IGF-II, or IGFBP-3 with physical performance. Conclusions There was some evidence that high IGF-I and low insulin levels in middle-age were associated with improved physical performance in old age, but estimates were imprecise. Larger cohorts are required to confirm or refute the findings