Structures,magnetic properties,and XPS of cyanide-bridged NdIII/SmIII/GdIII–CrIII complexes

Synthesis, structural characterization, and spectroscopic and magnetic properties of three new cyano-bridged 3d–4f bimetallic complexes, Ln^III(DMF)₄(H₂O)₃Cr^III (CN)₆ · nH₂O (Ln = Nd, Sm, Gd), have been described. The Nd–Cr complex crystallizes in the monoclinic P2₁/n space group with the following unit cell parameters: a = 20.063(7) Å, b = 8.967(4) Å, c = 18.023(6) Å, b = 96.12(3)°, V = 3224(2) Å³, and Z = 4. The neodymium (III) ion, which adopts anti-prism eight-coordination environment, is linked to the [Cr^III(CN)₆]³⁻ moiety through a bridging cyanide ligand with Nd–N = 2.550(4) Å and Nd–N–C = 164.4(4)°. The variable-temperature (0.5 T at 2–300 K) and variable-field (0–5 T at 2 and 5 K) magnetic measurements reveal that the weak interaction of Gd–Cr complexes differs from that of Nd–Cr and Sm–Cr ones mainly because of the lack of orbital angular momentum. The XPS and diffuse reflectance electronic spectra were also measured to discuss charge transfer transitions concerning π-backdonation from the viewpoint of magneto-optical functions.     

Structural models for [M(CO)3(H2O)3]+ (M=Tc,Re): fully aqueous synthesis of technetium and rhenium tricarbonyl complexes of tripodal oxygen donor ligands

The reaction of [M(H₂O)₃(CO)₃]⁺ (M=Tc, Re) with Na[CpCo[PO(OR)₂]₃] (NaL_OR; R=Me, Et) in water produced the compounds M(CO)₃(L_OR), all of which were yellow solids, in yields varying from 55 to 89%. The two compounds M(CO)₃(L_OEt) were structurally characterized by single crystal X-ray crystallography. In both cases, the ligand L_OEt was bound to the metal center in a tridentate fashion utilizing an {OOO} donor set. The ligands L_OR can be used as models for facially coordinated triaqua groups owing to their position in the spectrochemical series. Therefore, these four compounds, M(CO)₃(L_OR), can be considered structural models for [M(H₂O)₃(CO)₃]⁺. Crystal data for Tc(CO)₃(L_OEt) are as follows: molecular formula C₂₀H₃₅CoO₁₂P₃Tc, MW=717.32, monoclinic, a=11.5661(11) Å, b=18.671(2) Å, c=13.7852(13) Å, β=92.770(2)°, V=2973.5(5) Å³, space group P2₁/n, Z=4, final R₁=0.0669, wR₂=0.1361. Crystal data for Re(CO)₃(L_OEt) are as follows: molecular formula C₂₀H₃₅CoO₁₂P₃Re, MW=805.52, monoclinic, a=11.5113(7) Å, b=18.6022(12) Å, c=13.7397(8) Å, β=92.7580(10)°, V=2938.7(3) Å³, space group P2₁/n, Z=4, final R₁=0.0384, wR₂=0.0760.     

The crystallographic structure of Panicum Mosaic Virus (PMV)

The structure of Panicum Mosaic Virus (PMV) was determined by X-ray diffraction analysis to 2.9 Å resolution. The crystals were of pseudo symmetry F23; the true crystallographic unit cell was of space group P2₁ with a = 411.7 Å, b = 403.9 Å and c = 412.5 Å, with β = 89.7°. The asymmetric unit was two entire T = 3 virus particles, or 360 protein subunits. The structure was solved by conventional molecular replacement from two distant homologues, Cocksfoot Mottle Virus (CfMV) and Tobacco Necrosis Virus (TNV), of ～20% sequence identity followed by phase extension. The model was initially refined with exact icosahedral constraints and then with icosahedral restraints. The virus has Ca⁺⁺ ions octahedrally coordinated by six aspartic acid residues on quasi threefold axes, which is completely different than for either CfMV or TNV. Amino terminal residues 1–53, 1–49 and 1–21 of the A, B and C subunits, respectively, and the four C-terminal residues (239–242) are not visible in electron density maps. The additional ordered residues of the C chain form a prominent “arm” that intertwines with symmetry equivalent “arms” at icosahedral threefold axes, as was seen in both CfMV and TNV. A 17 nucleotide hairpin segment of genomic RNA is icosahedrally ordered and bound at 60 equivalent sites at quasi twofold A–B subunit interfaces at the interior surface of the capsid. This segment of RNA may serve as a conformational switch for coat protein subunits, as has been proposed for similar RNA segments in other viruses.     

Structural insights into the dual substrate specificities of mammalian and Dictyostelium dihydropteridine reductases toward two stereoisomers of quinonoid dihydrobiopterin

Up to now, d-threo-tetrahydrobiopterin (DH₄, dictyopterin) was detected only in Dictyostelium discoideum, while the isomer l-erythro-tetrahydrobioterin (BH₄) is common in mammals. To elucidate the mechanism of DH₄ regeneration by D. discoideum dihydropteridine reductase (DicDHPR), we have determined the crystal structure of DicDHPR complexed with NAD⁺ at 2.16 Å resolution. Significant structural differences from mammalian DHPRs are found around the coenzyme binding site, resulting in a higher K_m value for NADH (K_m = 46.51 ± 0.4 μM) than mammals. In addition, we have found that rat DHPR as well as DicDHPR could bind to both substrates quinonoid-BH₂ and quinonoid-DH₂ by docking calculations and have confirmed their catalytic activity by in vitro assay.Structured summary of protein interactionsDHPR binds to DHPR by X-ray crystallography (View interaction)     

Isolation,spectroscopic characterization,X-ray,theoretical studies as well as in vitro cytotoxicity of Samarcandin

Samarcandin 1, a natural sesquiterpene-coumarin, was isolated as well as elucidated from F. assa-foetida which has significant effect in Iranian traditional medicine because of its medicinal attitudes. The crystal structure of samarcandin was determined by single-crystal X-ray structure analysis. It is orthorhombic, with unit cell parameters a = 10.8204 (5) Å, b = 12.9894 (7) Å, c = 15.2467 (9) Å, V = 2142.9 (2) Å³, space group P2₁2₁2₁ and four symmetry equivalent molecules in the unit cell. Samarcandin was isolated in order to study for its theoretical studies as well as its cellular toxicity as anti-cancer drug against two cancerous cells. In comparison with controls, our microscopic and MTT assay data showed that samarcandin suppresses cancer cell proliferation in a dose-dependent manner with IC₅₀ = 11 μM and 13 for AGS and WEHI-164 cell lines, respectively. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) of the structure was computed by three functional methods and 6-311++G⁷ standard basis set. The optimized molecular geometry and theoretical analysis agree closely to that obtained from the single crystal X-ray crystallography. To sum up, the good correlations between experimental and theoretical studies by UV, NMR, and IR spectra were found.     

Hydrothermal synthesis and structural characterization of an organic–inorganic hybrid material: (H2tptz)2[δ-Mo8O26]·2H2O (tptz=2,4,6-tripyridyltriazine)

The reaction of MoO₃ and 2,4,6-tripyridyltriazine (tptz) in water at 180°C for 48 h and pH 5.5 produces (H₂tptz)₂[Mo₈O₂₆]·2H₂O in 70% yield. The structure is constructed from δ-Mo₈O₂₆ ⁴⁻ clusters, H₂tptz²⁺ and H₃O⁺ cations linked through hydrogen bonding into a network. Crystal data: C₁₈H₁₆Mo₄N₆O₁₄; monoclinic P2₁/n; a=10.2225(5) Å, b=14.0072(6) Å, c=18.1154(8) Å, β=93.896(1)°, V=2587.9(2) Å³, Z=4, D_calc=2.372 g cm⁻³; R₁=0.0271 based on 3212 reflections.     

Energy metabolism and thermoregulation in pygmy lorises (Nycticebus pygmaeus) from Yunnan Daweishan Nature Reserve

The pygmy loris (Nycticebus pygmaeus) is a small prosimian living in Vietnam, Laos, eastern Cambodia and the south part of China. In China it is only found in Pingbian, Hekou, Jinping, Luchun of Yunnan. As N. pygmaeus is seriously threatened by hunting, trade and habitat destruction, it is listed in Appendix II of CITES, and in 2006 the IUCN classified it as “vulnerable”. In order to understand the characteristics of energy metabolism and thermoregulation of N. pygmaeus, the resting metabolic rate (RMR) and body temperature (T_b) at different ambient temperature (T_a) of pygmy lorises, as well as body mass, energy intake, digestable energy intake, digestability and the thermal conductance were measured in captivity. The results obtained mainly are as follows: (1) Pygmy loris feed dry food averaged 12.90 ± 1.02 g/d. They could gain 214.87 ± 16.65 kJ/d from food intake, and earned 200.15 ± 16.36 kJ digestable energy intake per day with 90.13 ± 1.34% of the digestability. (2) The T_b at room temperatures was a little low (35.23 ± 0.16 °C) and varied with T_a from 25 °C to 35 °C. There was a positive relationship between T_b and T_a, which was described as: T_b = 27.22 + 0.34T_a (r = 0.880). (3) The resting metabolic rate (RMR) of the pygmy loris was 0.3844 ± 0.0162 mlO₂/g/h, which was 51.91 ± 1.90% of the previous predicted rate by Kleiber (1961) [21]. (4) The average thermal conductance of the pygmy loris (N. pygmaeus) was 0.0449 ± 0.0031 mlO₂/g/h/°C. These characteristics of energy metabolism and thermoregulation of N. pygmaeus in Yunnan Daweishan Nature Reserve might be considered as the adaptive characteristics to their environment in tropical semi-evergreen forests and secondary forests.     

Root health evaluation of three alfalfa varieties in Kerquin sandy land

Without a robust and healthy root system, establishment, productivity, and persistence are compromised. Consequently, research on alfalfa root morphology and health is very important in development of technology for efficient improvement and production of alfalfa. The objectives of this study were to evaluate the root morphology and health of three alfalfa varieties, Algonquin, Golden Queen, and Yellow Flower and to determine relationships among root morphology traits and root health. Yields from these varieties ranged from 5.83 to 43.93 t/ha, total root length ranged from 215.17 to 708.89 mm, root surface area from 124.95 to 468.37 cm², volume from 3.24 to 57.72 cm³, and forks from 1.25 × 10³ to 10.54 × 10³, and tips from 0.65 × 10³ to 3.17 × 10³. Root infestation score was negatively correlated with yield (r = ?0.997, P < 0.01), and was positively correlated with all root morphology traits (r = 0.466–0.997, P < 0.01), and yield was negatively associated with root morphology traits (r = ?0.755 to ?0.998, p < 0.01) with the exception of root tips (r = 0.448, P < 0.01). Results from these analyses indicated that root infestation score was the lowest averaged over age of alfalfa stand in Algonquin. Yield in 2-year old stands was greater in Golden Queen compared to the other two cultivars.     

Effect of Metformin Therapy on Vitamin D and Vitamin B12 Levels in Patients with Type 2 Diabetes Mellitus

ObjectiveTo determine the effect of metformin on 25-hydroxyvitamin D [25(OH)D] and vitamin B₁₂ levels in patients with type 2 diabetes mellitus.MethodsWe performed a retrospective review of medical records of patients treated between 2003 and 2009 at Loyola University Medical Center, Maywood, Illinois, in both ambulatory primary care and endocrinology clinics. The study cohort consisted of 706 patients with type 2 diabetes mellitus who were 20 to 93 years old (mean age, 63 ± 13) and had a mean body mass index of 33.1 kg/m². Of these patients, 42% were treated with metformin, and 34% had been diagnosed with osteoporosis or osteopenia.ResultsPatients taking metformin had statistically significant lower vitamin B₁₂ levels than those not receiving metformin (P < .0001; 95% confidence interval [CI] = − 220 to − 84 pg/mL). No statistically significant difference was found between users and nonusers of metformin in regard to 25(OH)D levels when adjusted for variables (P = .297; 95% CI for mean difference = − 0.7 to 2.2 ng/mL). Metformin use did not adversely affect successful treatment of vitamin D deficiency in this patient population as a whole, nor did it affect the subgroup with osteoporosis (P = .956). The patients with osteoporosis had statistically significant lower baseline 25(OH)D levels in comparison with those without osteoporosis, when adjustments were made for all variables (P = .003; 95% CI = 0.7 to 3.5 ng/ mL).ConclusionThis study confirms the higher prevalence of vitamin B₁₂ deficiency in metformin-treated patients with type 2 diabetes than in those not treated with metformin. This study also suggests that vitamin D deficiency is not a clinical concern among metformin-treated patients with type 2 diabetes and that metformin does not negatively affect treatment of vitamin D deficiency in these patients. (Endocr Pract. 2012;18:179–184)     

N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: synthesis and biological evaluation

A group of N-1 and C-3 disubstituted-indole Schiff bases bearing an indole N-1 (R′ = H, CH₂Ph, COPh) substituent in conjunction with a C-3 –CHN–C₆H₄–4-X (X = F, Me, CF₃, Cl) substituent were synthesized and evaluated as inhibitors of cyclooxygenase (COX) isozymes (COX-1/COX-2). Within this group of Schiff bases, compounds 15 (R¹ = CH₂Ph, X = F), 17 (R¹ = CH₂Ph, X = CF₃), 18 (R¹ = COPh, X = F) and 20 (R¹ = COPh, X = CF₃) were identified as effective and selective COX-2 inhibitors (COX-2 IC₅₀’s = 0.32–0.84 μM range; COX-2 selectivity index (SI) = 113 to >312 range). 1-Benzoyl-3-[(4-trifluoromethylphenylimino)methyl]indole (20) emerged as the most potent (COX-1 IC₅₀ >100 μM; COX-2 IC₅₀ = 0.32 μM) and selective (SI >312) COX-2 inhibitor. Furthermore, compound 20 is a selective COX-2 inhibitor in contrast to the reference drug indomethacin that is a potent and selective COX-1 inhibitor (COX-1 IC₅₀ = 0.13 μM; COX-2 IC₅₀ = 6.9 μM, COX-2 SI = 0.02). Molecular modeling studies employing compound 20 showed that the phenyl CF₃ substituent attached to the CN spacer is positioned near the secondary pocket of the COX-2 active site, the CN nitrogen atom is hydrogen bonded (N?NH = 2.85 Å) to the H90 residue, and the indole N-1 benzoyl is positioned in a hydrophobic pocket of the COX-2 active site near W387.     

Exonuclease 1 (EXO1) gene variation and melanoma risk

ObjectiveDNA repair pathway genes play an important role in maintaining genomic integrity and protecting against cancer development. This study aimed to identify novel SNPs in the DNA repair-related genes associated with melanoma risk from a genome-wide association study (GWAS).MethodsA total of 8422 SNPs from the 165 DNA repair-related genes were extracted from a GWAS of melanoma risk, including 494 cases and 5628 controls from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). We further replicated the top SNPs in a GWAS of melanoma risk from the MD Anderson Cancer Center (1804 cases and 1026 controls).ResultsA total of 3 SNPs with P value <0.001 were selected for in silico replication. One SNP was replicated: rs3902093 [A] in EXO1 promoter region (P_discovery = 6.6 × 10^?4, P_replication = 0.039, P_joint = 2.5 × 10^?4; OR_joint = 0.80, 95% CI: 0.71, 0.90). This SNP was associated with the expression of the EXO1; carriers of the A allele showed lower expression (P = 0.002).ConclusionOur study found that a promoter region SNP in the editing and processing nucleases gene EXO1 was associated with decreased expression of EXO1 and decreased melanoma risk. Further studies are warranted to validate this association and to investigate the potential mechanisms.     

Elevated amniotic fluid F₂-isoprostane: a potential predictive marker for preeclampsia

In the complex mechanism of preeclampsia, oxidative stress is an important pathogenic factor, and F₂-isoprostane is a marker of oxidative stress and lipid peroxidation. The objective of this study was to identify if the amniotic fluid (AF) levels of F₂-isoprostanes were elevated in women who later developed preeclampsia. In this study, we analyzed AF F₂-isoprostane concentrations with enzyme immunoassay (EIA), and the EIA results could be validated by quantitative mass spectrometry. The mean AF concentration of F₂-isoprostanes was significantly higher in pregnancies with subsequent development of preeclampsia (123.1 ± 57.6 pg/ml, n = 85) than in controls (73.8 ± 36.6 pg/ml, n = 85). The AF elevation of F₂-isoprostanes was even higher in the preeclampsia with intrauterine growth restriction group (138.3 ± 65.2 pg/ml, n = 39). The area under the curve of the receiver operating characteristics analysis for AF F₂-isoprostanes assay was 0.81, supporting its potential as a biomarker for preeclampsia. These results indicate that oxidative stress existed before the onset of clinical preeclampsia, further suggesting that the elevation of AF F₂-isoprostanes may be used as a guide for antioxidant supplementation to reduce the risk and/or severity of preeclampsia.     

Structural changes that occur upon photolysis of the Fe(II)a3–CO complex in the cytochrome ba3-oxidase of Thermus thermophilus: A combined X-ray crystallographic and infrared spectral study demonstrates CO binding to CuB

The purpose of the work was to provide a crystallographic demonstration of the venerable idea that CO photolyzed from ferrous heme-a₃ moves to the nearby cuprous ion in the cytochrome c oxidases. Crystal structures of CO-bound cytochrome ba₃-oxidase from Thermus thermophilus, determined at ~ 2.8–3.2 Å resolution, reveal a Fe–C distance of ~ 2.0 Å, a Cu–O distance of 2.4 Å and a Fe–C–O angle of ~ 126°. Upon photodissociation at 100 K, X-ray structures indicate loss of Fe_a3–CO and appearance of Cu_B–CO having a Cu–C distance of ~ 1.9 Å and an O–Fe distance of ~ 2.3 Å. Absolute FTIR spectra recorded from single crystals of reduced ba₃–CO that had not been exposed to X-ray radiation, showed several peaks around 1975 cm^? 1; after photolysis at 100 K, the absolute FTIR spectra also showed a significant peak at 2050 cm^? 1. Analysis of the ‘light’ minus ‘dark’ difference spectra showed four very sharp CO stretching bands at 1970 cm^? 1, 1977 cm^? 1, 1981 cm^? 1, and 1985 cm^? 1, previously assigned to the Fe_a3–CO complex, and a significantly broader CO stretching band centered at ~ 2050 cm^? 1, previously assigned to the CO stretching frequency of Cu_B bound CO. As expected for light propagating along the tetragonal axis of the P4₃2₁2 space group, the single crystal spectra exhibit negligible dichroism. Absolute FTIR spectrometry of a CO-laden ba₃ crystal, exposed to an amount of X-ray radiation required to obtain structural data sets before FTIR characterization, showed a significant signal due to photogenerated CO₂ at 2337 cm^? 1 and one from traces of CO at 2133 cm^? 1; while bands associated with CO bound to either Fe_a3 or to Cu_B in “light” minus “dark” FTIR difference spectra shifted and broadened in response to X-ray exposure. In spite of considerable radiation damage to the crystals, both X-ray analysis at 2.8 and 3.2 Å and FTIR spectra support the long-held position that photolysis of Fe_a3–CO in cytochrome c oxidases leads to significant trapping of the CO on the Cu_B atom; Fe_a3 and Cu_B ligation, at the resolutions reported here, are otherwise unaltered. This article is part of a Special Issue entitled: Respiratory Oxidases.     

Purification,characterization, and crystallization of the adhesive domain of SdrD from Staphylococcus aureus

The adhesive domain of SdrD from Staphylococcus aureus was solubly expressed in Escherichia coli in high yield. After a series of purification steps, the purified protein was >95% pure, which was SdrD from S. aureus identified by SDS–PAGE and MALDI-TOF MS. Crystals were grown at 18 °C using 25% polyethylene glycol 3350 as precipitant. Diffraction by the crystal extends to 1.65 Å resolution, and the crystal belongs to the space group C2, with the unit cell parameters a = 133.3, b = 58.3, c = 112.3 Å, α = 90.00, β = 111.14, γ = 90.00.     

Low serum zinc levels in patients undergoing coronary angiography correlate with immune activation and inflammation

IntroductionLow serum zinc concentrations are associated with adverse outcomes. To explain this phenomenon we aimed to investigate whether low zinc levels are related to immune activation, renal function and coronary artery disease (CAD).MethodsSerum concentrations of zinc and the immune activation markers neopterin and C-reactive protein (CRP) were measured in 2048 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography.ResultsZinc concentrations did not differ between patients with CAD (mean ± SD: 13.3 ± 2.4 μmol/L) and controls (13.3 ± 2.2 μmol/L; Welch's t test: p = n.s.) but CAD patients had higher neopterin (8.6 ± 7.4 nmol/L) and CRP (9.7 ± 19.6 mg/L) concentrations compared to controls (neopterin: 7.5 ± 4.8 nmol/L, p = 0.0005; CRP: 5.5 ± 10.0 mg/L, p < 0.0001). There was an inverse correlation between serum zinc concentrations and neopterin (Spearman's rank correlation: r_s = ?0.222) and CRP (r_s = ?0.166; both p < 0.0001) concentrations.ConclusionsOur results indicate increased inflammatory processes in patients with low zinc levels. Further studies should clarify whether inflammation related processes such as renal wasting contribute to zinc deficiency and underlie the adverse health consequences of low serum zinc levels.     

Effects of shell morphological traits on the weight traits of Manila clam (Ruditapes philippinarum)

The shell length, height, and width, live body weight, and edible tissue weight of Manila clam of 1, 2, and 3 years of age were measured, and their correlation coefficients were calculated. The shell morphological traits were used as independent variables, and live body weight or edible tissue weigh used as a dependent variable for calculating the path coefficients, correlation index and determination coefficients. The results showed that the correlation coefficients between each shell morphological trait and the live body weight or edible tissue weight were all highly significant (P < 0. 01). The shell height at 1-year old clams was highly correlated with the live body weight and edible tissue weight. The shell width of 2- to 3-year-old clams was strongly associated with the live body weight, while the shell length was closely linked to the edible tissue weight. The results of coefficients of determination for the morphological traits against weight traits agreed well with the results of path analysis. The correlation indices for all morphological traits against weight traits were approximately the same as determination coefficients regardless of clam age. The correlation indices (R²) of morphological traits against the live body weight of clams of all ages and edible tissue weight of 1-year-old clams were larger than 0.85, but R² of morphological traits against the edible tissue weight of 2- and 3-year-old clams was smaller than 0.85, indicating that some other factors might be associated with the edible tissue weight of 2- and 3-year-old clams. Multiple regression equations were obtained to estimate shell length X₁ (cm), shell height X₂ (cm), shell width X₃ (cm) against live body weight Y (g), edible tissue weight Z (g): for 1-year-old clams: Y = ?4.317 + 0.18X₁ + 0.147X₂, (X₁ < 0.01, X₂ < 0.01), Z = ?1.011 + 0.095X₂, (X₂ < 0.01); for 2-year-old clams: Y = ?15.119 + 0.249X₁ + 0.176X₂ + 0.688X₃, (X₁ < 0.01, X₃ < 0.01), Z = ?4.248 + 0.198X₁, (X₁ < 0.05, X₃ < 0.01); and for 3-year-old clams: Y = ?25.013 + 0.415X₁ + 1.184X₃, (X₁ < 0.01, X₃ < 0.01), Z = ?7.082 + 0.119X₁ + 0.332X₃, (X₁ < 0.05, X₃ < 0.01).     

Combined effects of temperature and salinity on functional responses of haemocytes and survival in air of the clam Ruditapes philippinarum

The combined effects of temperature and salinity on both immune responses and survival in air of the clam, Ruditapes philippinarum, were evaluated for the first time. The animals were kept for 7 days at three differing temperature (5 °C, 15 °C, 30 °C) and salinity values (18 psu, 28 psu, 38 psu), and effects of the resulting 9 experimental conditions on total haemocyte count (THC), Neutral Red uptake (NRU), haemolymph protein concentration, and lysozyme activity in both haemocyte lysate (HL) and cell-free haemolymph (CFH) were evaluated. The survival-in-air test was also performed. Two-way ANOVA analysis revealed that temperature influenced significantly THC and NRU, whereas salinity and temperature/salinity interaction affected NRU only. Temperature and salinity did not influence significantly HL and CFH lysozyme activity, as well as haemolymph total protein content. Survival-in-air test is widely used to evaluate general stress conditions in clams. In the present study, temperature and salinity were shown to influence the resistance to air exposure of R. philippinarum. The highest LT₅₀ (air exposure time resulting in 50% mortality) value was recorded in clams kept at 18 psu and 15 °C, whereas the lowest value was observed in clams kept at 28 psu and 30 °C. Overall, results obtained demonstrated that temperature and salinity can affect some functional responses of haemocytes from R. philippinarum, and suggested a better physiological condition for animals kept at 15 °C temperature and 18 psu salinity.     

Insulin-like growth factor axis gene polymorphisms modify risk of pancreatic cancer

Objective: Insulin-like growth factor (IGF)-axis genes plays a critical role in cancer development and progression via their impact on the RAS/MAPK/ERK and PI3 K/AKT/mTOR signaling pathways. We hypothesized that IGF-axis genetic variants modify individual susceptibility to pancreatic cancer. Methods: We retrospectively genotyped 41 single-nucleotide polymorphisms of 10 IGF-axis genes (IGF1, IGF2, IGF1R, IGF2R, IGFBP1, IGFBP3, IGFBP5, IRS1, IRS2, and IRS4) in 706 pancreatic cancer patients and 706 cancer-free controls using Sequenom and TaqMan technology. The association between genotype and pancreatic cancer risk was evaluated using multivariate logistic regression. A P value ≤.007 at a false discovery rate of 10% was set as the significance level. Results: We observed that the IGF1 *10212C>A and Ex4+2776G>A and IGF1R IVS2?70184A>G and IVS2+46329T>C variant genotypes were significantly associated with decreased pancreatic cancer risk (odds ratio [OR] range, 0.60–0.75) and that IGFBP1 Ex4+111A>G (I253M) was significantly associated with increased pancreatic cancer risk (OR = 1.46) after adjusted for other risk factors and multiple comparisons (P ≤ .007). IGF2R and IGFBP3 variant haplotypes were associated with increased and decreased pancreatic cancer risk, respectively (P < .001). We also observed a weak interaction of the IGF1R IVS2+46329T>C and IGF2R Ex45+11C>T (L2222L) genotypes with diabetes (P_interaction = .05) and interaction of IGF2R and IRS1 genotypes with alcohol consumption (P_interaction = .03 and .019, respectively) on increased pancreatic cancer risk. Conclusion: These findings support our hypothesis that polymorphic variants of IGF-axis genes act alone or jointly with other risk factors to affect susceptibility to pancreatic cancer.     

Regulation of contractility and metabolic signaling by the β2-adrenergic receptor in rat ventricular muscle

AimsCardiac function is modulated by the sympathetic nervous system through β-adrenergic receptor (β-AR) activity and this represents the main regulatory mechanism for cardiac performance. To date, however, the metabolic and molecular responses to β₂-agonists are not well characterized. Therefore, we studied the inotropic effect and signaling response to selective β₂-AR activation by tulobuterol.Main methodsStrips of rat right ventricle were electrically stimulated (1 Hz) in standard Tyrode solution (95% O₂, 5% CO₂) in the presence of the β₁-antagonist CGP-20712A (1 μM). A cumulative dose–response curve for tulobuterol (0.1–10 μM), in the presence or absence of the phosphodiesterase (PDE) inhibitor IBMX (30 μM), or 10 min incubation (1 μM) with the β₂-agonist tulobuterol was performed.Key findingsβ₂-AR stimulation induced a positive inotropic effect (maximal effect = 33 ± 3.3%) and a decrease in the time required for half relaxation (from 45 ± 0.6 to 31 ± 1.8 ms, ? 30%, p < 0.001) after the inhibition of PDEs. After 10 min of β₂-AR stimulation, p-AMPKα^T172 (54%), p-PKB^T308 (38%), p-AS160^T642 (46%) and p-CREB^S133 (63%) increased, without any change in p-PKA^T197.SignificanceThese results suggest that the regulation of ventricular contractility is not the primary function of the β₂-AR. Rather, β₂-AR could function to activate PKB and AMPK signaling, thereby modulating muscle mass and energetic metabolism of rat ventricular muscle.