Substrate water exchange in photosystem II core complexes of the extremophilic red alga Cyanidioschyzon merolae

The binding affinity of the two substrate–water molecules to the water-oxidizing Mn₄CaO₅ catalyst in photosystem II core complexes of the extremophilic red alga Cyanidioschyzon merolae was studied in the S₂ and S₃ states by the exchange of bound ¹⁶O-substrate against ¹⁸O-labeled water. The rate of this exchange was detected via the membrane-inlet mass spectrometric analysis of flash-induced oxygen evolution. For both redox states a fast and slow phase of water-exchange was resolved at the mixed labeled m/z 34 mass peak: k_f = 52 ± 8 s^− 1 and k_s = 1.9 ± 0.3 s^− 1 in the S₂ state, and k_f = 42 ± 2 s^− 1 and k_slow = 1.2 ± 0.3 s^− 1 in S₃, respectively. Overall these exchange rates are similar to those observed previously with preparations of other organisms. The most remarkable finding is a significantly slower exchange at the fast substrate–water site in the S₂ state, which confirms beyond doubt that both substrate–water molecules are already bound in the S₂ state. This leads to a very small change of the affinity for both the fast and the slowly exchanging substrates during the S₂ → S₃ transition. Implications for recent models for water-oxidation are briefly discussed.     

Association of interleukin-13 SNP rs20541 with allergic rhinitis risk: A meta-analysis

Studies investigating the association between interleukin-13 (IL-13) single nucleotide polymorphism (SNP) rs20541 and allergic rhinitis (AR) risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible association of IL-13 SNP rs20541 with AR risk. Eight studies were included in the present meta-analysis (2153 cases and 3931 controls). The combined results based on all studies showed that IL-13 SNP rs20541 was associated with increased AR risk (Gln versus Arg: odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.08–1.30; Gln/Gln versus Arg/Arg: OR = 1.52, 95% CI = 1.20–1.92; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.19, 95% CI = 1.06–1.33; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.42, 95% CI = 1.13–1.79). When stratifying for race, IL-13 SNP rs20541 exhibited increased AR risk in Asians (Gln versus Arg: OR = 1.20, 95% CI = 1.06–1.36; Gln/Gln versus Arg/Arg: OR = 1.57, 95% CI = 1.17–2.12; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.22, 95% CI = 1.04–1.44; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.45, 95% CI = 1.09–1.93), while no significant association was detected in Caucasians (Gln versus Arg: OR = 1.28, 95% CI = 0.93 ~ 1.78; Gln/Gln versus Arg/Arg: OR = 1.42, 95% CI = 0.96–2.11; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.35, 95% CI = 0.89–2.05; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.37, 95% CI = 0.93–2.02). This meta-analysis supported that IL-13 SNP rs20541 was associated with AR, particularly in Asians.     

The use of small subcutaneous transponders for quantifying thermal biology and torpor in small mammals

Remote measurements of body temperature (T_b) in animals require implantation of relatively large temperature-sensitive radio-transmitters or data loggers, whereas rectal temperature (T_rec) measurements require handling and therefore may bias the results. We investigated whether ∼0.1 g temperature-sensitive subcutaneously implanted transponders can be reliably used to quantify thermal biology and torpor use in small mammals. We examined (i) the precision of transponder readings as a function of temperature and (ii) whether subcutaneous transponders can be used to remotely record subcutaneous temperature (T_sub). Five adult male dunnarts (Sminthopsis macroura, body mass 24 g) were implanted with subcutaneous transponders to determine T_sub as a function of time and ambient temperature (T_a), and in comparison to thermocouple readings of T_rec. Transponder temperature was highly correlated with water bath temperature (r²=0.96–0.99) over a range of approximately 10.0–40.0 °C. Transponders provided reliable data (±0.6 °C) over the T_sub of 21.4–36.9 °C and could be read from a distance of up to 5 cm. Below 21.4 °C, accuracy was reduced to ±2.8 °C, but individual transponder accuracy varied. Consequently, small subcutaneous transponders are useful to remotely quantify thermal physiology and torpor patterns without having to disturb the animal and disrupt torpor. Even at T_sub<21.4 °C where the accuracy of the temperature readings was reduced, transponders do provide reliable data on whether and when torpor is used.     

Higher frequency of septic shock in septic patients with the 47C allele (rs4880) of the SOD2 gene

Aim

To analyze the effect of the two different versions of the manganese superoxide dismutase gene (SOD2) on sepsis. The SOD2 gene presents the 47C > T single nucleotide polymorphism (SNP; ID: rs4880) which produces MnSOD with different activities. The − 9Val MnSOD (47T allele) is less efficient than the − 9Ala version (47C allele). During sepsis there are abundance of ROS, high SOD2 expression and excess of H₂O₂ synthesis. High concentrations of H₂O₂ could affect the sepsis scenario and/or the sepsis outcome.

Methods

We determined the 47C > T single nucleotide polymorphism (SNP) frequencies in 529 critically ill patients with or without sepsis, facing outcome. To collect information on population frequencies, we obtained a pilot 47C > T genotypic and allelic frequencies in a random group of 139 healthy subjects.

Results

We compared the 47C allele carriers (47CC + 47CT genotypes) with 47TT homozygotes and noticed a significant association between 47C allele carriers and septic shock in septic patients (P = 0.025). With an adjusted binary multivariate logistic regression, incorporating 47C > T SNP and the main clinical predictors, we showed high SOFA scores [P < 0.001, OR = 9.107 (95% CI = 5.319–15.592)] and 47C allele [P = 0.011, OR = 2.125 (95% CI = 1.190–3.794)] were significantly associated with septic shock outcome. With this information we presented a hypothesis suggesting that this negative outcome from sepsis is possibly explained by effects on cellular stress caused by 47C allele.

Conclusion

In our population there was a significant higher frequency of septic shock in septic patients with the 47C allele of the SOD2 gene. This higher 47C allele frequency in septic patients with negative outcome could be explained by effects of higher activity MnSOD on cellular stress during the sepsis.     

Simultaneous production of citric acid and invertase by Yarrowia lipolytica SUC+ transformants

Simultaneous production of citric acid (CA) and invertase by Yarrowia lipolytica A-101-B56-5 (SUC⁺ clone) growing from sucrose, mixture of glucose and fructose, glucose or glycerol was investigated. Among the tested substrates the highest concentration of CA was reached from glycerol (57.15 g/L) with high yield (Y_CA/S = 0.6 g/g). When sucrose was used, comparable amount of CA was secreted (45 g/L) with slightly higher yield (Y_CA/S = 0.643 g/g). In all cultures amount of isocitrate (ICA) was below 2% of total citrates. Considering invertase production, the best carbon source appeared to be sucrose (72 380 U/L). The highest yield of CA and invertase biosynthesis calculated for 1 g of biomass was obtained for cells growing from glycerol (9.9 g/g and 4325 U/g, respectively). Concentrates of extra- and intracellular invertase of the highest activity were obtained from sucrose as substrate (0.5 and 1.8 × 10⁶ U/L, respectively).     

Three single nucleotide variants of the HDAC gene are associated with type 2 diabetes mellitus in a Chinese population: A community-based case–control study

Objectives

There are no data regarding the possible role of the single nucleotide polymorphism (SNP) of class I histone deacetylases (HDACs) in type 2 diabetes mellitus (DM). We designed this study to examine whether polymorphisms of HDACs can be implicated in that disease.

Methods

A community-based, case–control study was conducted, with a total of 568 subjects (284 patients and 284 controls) enrolled. Four polymorphisms of HDAC1 (rs1741981) and HDAC3 (rs11741808, rs2547547, rs2530223) were examined by the use of TaqMan technology.

Results

We found a significant association with risk of type 2 DM for three SNPs of HDAC3, including rs11741808 [odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.35–0.81], rs2547547 [OR = 1.72, 95% CI: 1.13–2.64], and rs2530223 [OR = 1.39; 95% CI: 1.01–1.91]. Subgroup analysis showed that BMI ≥ 23 kg/m², high triglyceride and high blood pressure, together with the rs11741808AG genotype, were associated with a significantly decreased risk for type 2 DM, with ORs of 0.50 (95% CI: 0.27–0.91), 0.38 (95% CI: 0.20–0.71) and 0.43 (95% CI: 0.24–0.76) compared with the AA genotype, respectively. In a population with normal total cholesterol, the AG genotype yielded a significantly decreased risk of type 2 DM risk, with an OR of 0.42 (95% CI: 0.25–0.70) when compared with the persons of the AA genotype. For rs2547547, in a population with normal total cholesterol and triglyceride, the AG genotype was associated with a significantly increased risk of type 2 DM, with ORs of 1.92 (95% CI: 1.17–3.15) and 2.24 (95% CI: 1.28–3.94) when compared with the population carrying the AA genotype.

Conclusions

The results suggest that variants of HDAC3 contribute to an increased prevalence of type 2 DM in the Chinese Han population.     

Null genotypes of GSTM1 and GSTT1 contribute to increased risk of diabetes mellitus: A meta-analysis

Diabetes mellitus (DM) is a common disease which results from various causes including genetic and environmental factors. Glutathione S-Transferase M1 (GSTM1) and Glutathione S-Transferase T1 (GSTT1) genes are polymorphic in human and the null genotypes lead to the absence of enzyme function. Many studies assessed the associations between GSTM1/GSTT1 null genotypes and DM risk but reported conflicting results. In order to get a more precise estimate of the associations of GSTM1/GSTT1 null genotypes with DM risk, we performed this meta-analysis. Published literature from PubMed, Embase and China Biology Medicine (CBM) databases was searched for eligible studies. Pooled odds ratios (OR) and corresponding 95% confidence intervals (95%CI) were calculated using a fixed- or random-effects model. 11 publications (a total of 2577 cases and 4572 controls) were finally included into this meta-analysis. Meta-analyses indicated that null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 were all associated with increased risk of DM (GSTM1: OR _{random-effects} = 1.60, 95%CI 1.10–2.34, P_OR = 0.014; GSTT1: OR _{random-effects} = 1.47, 95%CI 1.12–1.92, P_OR = 0.005; GSTM1–GSTT1: OR _{fixed-effects} = 1.83, 95%CI 1.30–2.59, P_OR = 0.001). Subgroup by ethnicity suggested significant associations between null genotypes of GSTM1 and GSTT1 and DM risk among Asians (GSTM1: OR _{random-effects} = 1.77, 95%CI 1.24–2.53, P_OR = 0.002; GSTT1: OR _{random-effects} = 1.58, 95%CI 1.09–2.27, P_OR = 0.015). This meta-analysis suggests null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 are all associated with increased risk of DM, and null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 are potential biomarkers of DM.     

The human xenobiotic-metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1) is irreversibly inhibited by inorganic (Hg) and organic mercury (CH3Hg): Mechanism and kinetics

Human arylamine N-acetyltransferase 1 (NAT1) is a xenobiotic-metabolizing enzyme that biotransforms aromatic amine chemicals. We show here that biologically-relevant concentrations of inorganic (Hg²⁺) and organic (CH₃Hg⁺) mercury inhibit the biotransformation functions of NAT1. Both compounds react irreversibly with the active-site cysteine of NAT1 (half-maximal inhibitory concentration (IC₅₀) = 250 nM and k_inact = 1.4 × 10⁴ M⁻¹ s⁻¹ for Hg²⁺ and IC₅₀ = 1.4 μM and k_inact = 2 × 10² M⁻¹ s⁻¹ for CH₃Hg⁺). Exposure of lung epithelial cells led to the inhibition of cellular NAT1 (IC₅₀ = 3 and 20 μM for Hg²⁺ and CH₃Hg⁺, respectively). Our data suggest that exposure to mercury may affect the biotransformation of aromatic amines by NAT1.     

Magnetic and structural studies of novel tetranickel hydroxamates

The dinickel(II) compound [Ni₂(μ-OAc)₂(OAc)₂(μ-H₂O)(asy·dmen)₂]·2.5H₂O, 1; undergoes facile reaction in a 1:2 molar ratio with benzohydroxamic acid (BHA) in ethanol to give the novel nickel(II) tetranuclear hydroxamate complex [Ni₄(μ-OAc)₃(μ-BA)₃(asy·dmen)₃][OTf]₂·H₂O, 2, in which the bridging acetates, bridging two nickel atoms in 1, undergo a carboxylate shift from the μ₂-η¹:η¹ bridging mode of binding to the μ₃-η¹:η² bridging three nickel atoms in the tetramer. The structure of complex 2 was determined by single-crystal X-ray crystallography. The two monodentate acetates, water and two bidentate bridging acetates of two moles of complex 1 are replaced by three monodentate bridging acetates and three benzohydroxamates. Three nickel atoms in the tetramer, Ni(2), Ni(3) and Ni(4) are in a N₂O₄ octahedral environment, while the fourth nickel atom Ni(1) is in an O(6) octahedral environment. The Ni-Ni separations are Ni(1)-Ni(2) = 3.108 Å, Ni(1)-Ni(3) = 3.104 Å and Ni(1)-Ni(4) = 3.110 Å, which are longer than previously studied in dinuclear urease inhibited models but shorter than in the nickel(II) tetrameric glutarohydroxamate complex [Ni₄(μ-OAc)₂(μ-gluA₂)₂(tmen)₄][OTf]₂, isolated and characterized previously in this laboratory. Magnetic studies of the tetrameric complex show that the four Ni(II) ions are ferromagnetically coupled, leading to a total ground spin state S_T = 4. Three analogous tetranuclear nickel hydroxamates were prepared from AHA and BHA and the appropriate dinuclear complex with either sy·dmen or asy·dmen as capping ligands.     

A novel bifunctional peptidic aspartic protease inhibitor inhibits chitinase A from Serratia marcescens: Kinetic analysis of inhibition and binding affinity

Background

Chitinase inhibitors have chemotherapeutic potential as fungicides, pesticides and antiasthmatics. The majority of chitinase inhibitors reported are natural products like argifin, argifin linear fragments, argadin, allosamidin and disulfide-cyclized peptides. Here, we report a novel peptidic inhibitor API (Aspartic Protease Inhibitor), isolated from Bacillus licheniformis that inhibits chitinase A (ChiA) from Serratia marcescens.

Methods

The binding affinity of API with ChiA and type of inhibition was determined by the inhibition kinetics assays. Fluorescence and CD spectroscopic analysis and chemical modification of API with different affinity reagents elucidated the mechanism of binding of API with ChiA.

Results and conclusions

The peptide has an amino acid sequence N-Ile¹-Cys²-Glu³-Ala⁴-Glu⁵-His⁶-Lys⁷-Trp⁸-Gly⁹-Asp¹⁰-Tyr¹¹-Leu¹²-Asp¹³-C. The ChiA–API kinetic interactions reveal noncompetitive, irreversible and tight binding nature of API with I₅₀ = 600 nM and K_i = 510 nM in the presence of chromogenic substrate p-nitrophenyl-N,N′-diacetyl-β-chitobioside[p-NP-(GlcNAc)₂]. The inhibition progress curves show a two-step slow tight binding inhibition mechanism with the rate constant k₅ = 8.7 ± 1 × 10^− 3 s^− 1 and k₆ = 7.3 ± 0.6 × 10^− 5 s^− 1. CD-spectra and tryptophanyl fluorescence analysis of ChiA incubated with increasing API concentrations confirms conformational changes in enzyme structure which may be due to irreversible denaturation of enzyme upon binding of API. Chemical modifications by WRK abolished the anti-chitinase activity of API and revealed the involvement of carboxyl groups in the enzyme inactivation. Abolished isoindole fluorescence of OPTA-labeled ChiA demonstrates the irreversible denaturation of ChiA upon incubation with API for prolonged time and distortion of active site of the enzyme.

General significance

The data provide useful information that could lead to the generation of drug-like, natural product-based chitinase inhibitors.     

Inhibition of the calcium-activated chloride current in cardiac ventricular myocytes by N-(p-amylcinnamoyl)anthranilic acid (ACA)

N-(p-amylcinnamoyl)anthranilic acid (ACA), a phospholipase A₂ (PLA₂) inhibitor, is structurally-related to non-steroidal anti-inflammatory drugs (NSAIDs) of the fenamate group and may also modulate various ion channels. We used the whole-cell, patch-clamp technique at room temperature to investigate the effects of ACA on the Ca²⁺-activated chloride current (I_Cl(Ca)) and other chloride currents in isolated pig cardiac ventricular myocytes. ACA reversibly inhibited I_Cl(Ca) in a concentration-dependent manner (IC₅₀ = 4.2 μM, n_Hill = 1.1), without affecting the L-type Ca²⁺ current. Unlike ACA, the non-selective PLA₂ inhibitor bromophenacyl bromide (BPB; 50 μM) had no effect on I_Cl(Ca). In addition, the analgesic NSAID structurally-related to ACA, diclofenac (50 μM) also had no effect on I_Cl(Ca), whereas the current in the same cells could be suppressed by chloride channel blockers flufenamic acid (FFA; 100 μM) or 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS;100 μM). Besides I_Cl(Ca), ACA (50 μM) also suppressed the cAMP-activated chloride current, but to a lesser extent. It is proposed that the inhibitory effects of ACA on I_Cl(Ca) are PLA₂-independent and that the drug may serve as a useful tool in understanding the nature and function of cardiac anion channels.     

Association between a MYH9 polymorphism (rs3752462) and renal function in the Spanish RENASTUR cohort

The MYH9 gene encodes a protein that is expressed in the kidney glomerular podocytes. MYH9 single nucleotide polymorphisms (SNPs) have been linked to the risk for chronic kidney disease (CKD) and end stage renal disease. Our aim was to determine whether MYH9 SNPs were associated with renal disease in Spanish Caucasians. The RENASTUR cohort consisted of 592 Spanish Caucasians, aged 55–85 years. They were genotyped for SNPs rs3752462 and rs4821480, which tagged haplotype E. The main values between individuals with a glomerular filtration rate (eGFR) < 60 and ≥ 60 ml/min/1.73 m² were statistically compared. The next variables were significantly associated with the eGFR in the univariate analysis: age, gender, type 2 diabetes, total cholesterol, total LDL-cholesterol, and the MYH9 rs3752462 (TC + TT genotypes; p = 0.003). This SNP remained significantly associated with the eGFR in the multivariate analysis.     

In vitro and in vivo pharmacology of CP-945,598, a potent and selective cannabinoid CB1 receptor antagonist for the management of obesity

Cannabinoid CB₁ receptor antagonists exhibit pharmacologic properties favorable for the treatment of metabolic disease. CP-945,598 (1-[9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylamino piperidine-4-carboxylic acid amide hydrochloride) is a recently discovered selective, high affinity, competitive CB₁ receptor antagonist that inhibits both basal and cannabinoid agonist-mediated CB₁ receptor signaling in vitro and in vivo. CP-945,598 exhibits sub-nanomolar potency at human CB₁ receptors in both binding (K_i = 0.7 nM) and functional assays (K_i = 0.2 nM). The compound has low affinity (K_i = 7600 nM) for human CB₂ receptors. In vivo, CP-945,598 reverses four cannabinoid agonist-mediated CNS-driven responses (hypo-locomotion, hypothermia, analgesia, and catalepsy) to a synthetic cannabinoid receptor agonist. CP-945,598 exhibits dose and concentration-dependent anorectic activity in two models of acute food intake in rodents, fast-induced re-feeding and spontaneous, nocturnal feeding. CP-945,598 also acutely stimulates energy expenditure in rats and decreases the respiratory quotient indicating a metabolic switch to increased fat oxidation. CP-945,598 at 10 mg/kg promoted a 9%, vehicle adjusted weight loss in a 10 day weight loss study in diet-induced obese mice. Concentration/effect relationships combined with ex vivo brain CB₁ receptor occupancy data were used to evaluate efficacy in behavioral, food intake, and energy expenditure studies. Together, these in vitro, ex vivo, and in vivo data indicate that CP-945,598 is a novel CB₁ receptor competitive antagonist that may further our understanding of the endocannabinoid system.     

Development of cesium phosphotungstate salt and chitosan composite membrane for direct methanol fuel cells

A novel composite membrane has been developed by doping cesium phosphotungstate salt (Cs_xH_3−xPW₁₂O₄₀ (0 ≤ x ≤3), Cs_x-PTA) into chitosan (CTS/Cs_x-PTA) for application in direct methanol fuel cells (DMFCs). Uniform distribution of Cs_x-PTA nanoparticles has been achieved in the chitosan matrix. The proton conductivity of the composite membrane is significantly affected by the Cs_x-PTA content in the composite membrane as well as the Cs substitution in PTA. The highest proton conductivity for the CTS/Cs_x-PTA membranes was obtained with x = 2 and Cs₂-PTA content of 5 wt%. The value is 6 × 10⁻³ S cm⁻¹ and 1.75 × 10⁻² S cm⁻¹ at 298 K and 353 K, respectively. The methanol permeability of CTS/Cs₂-PTA membrane is about 5.6 × 10⁻⁷, 90% lower than that of Nafion-212 membrane. The highest selectivity factor (φ) was obtained on CTS/Cs₂-PTA-5 wt% composite membrane, 1.1 × 10⁴/S cm⁻³ s. The present study indicates the promising potential of CTS/Cs_x-PTA composite membrane as alternative proton exchange membranes in direct methanol fuel cells.     

Protein disulfide isomerase and glutathione are alternative substrates in the one Cys catalytic cycle of glutathione peroxidase 7

Background

Mammalian GPx7 is a monomeric glutathione peroxidase of the endoplasmic reticulum (ER), containing a Cys redox center (CysGPx). Although containing a peroxidatic Cys (C_P) it lacks the resolving Cys (C_R), that confers fast reactivity with thioredoxin (Trx) or related proteins to most other CysGPxs.

Methods

Reducing substrate specificity and mechanism were addressed by steady-state kinetic analysis of wild type or mutated mouse GPx7. The enzymes were heterologously expressed as a synuclein fusion to overcome limited expression. Phospholipid hydroperoxide was the oxidizing substrate. Enzyme–substrate and protein–protein interaction were analyzed by molecular docking and surface plasmon resonance analysis.

Results

Oxidation of the C_P is fast (k_+ 1 > 10³ M^− 1 s^− 1), however the rate of reduction by GSH is slow (k′_+ 2 = 12.6 M^− 1 s^− 1) even though molecular docking indicates a strong GSH–GPx7 interaction. Instead, the oxidized C_P can be reduced at a fast rate by human protein disulfide isomerase (HsPDI) (k_+ 1 > 10³ M^− 1 s^− 1), but not by Trx. By surface plasmon resonance analysis, a K_D = 5.2 μM was calculated for PDI–GPx7 complex. Participation of an alternative non-canonical C_R in the peroxidatic reaction was ruled out. Specific activity measurements in the presence of physiological reducing substrate concentration, suggest substrate competition in vivo.

Conclusions

GPx7 is an unusual CysGPx catalyzing the peroxidatic cycle by a one Cys mechanism in which GSH and PDI are alternative substrates.

General significance

In the ER, the emerging physiological role of GPx7 is oxidation of PDI, modulated by the amount of GSH.     

The sedimentation properties of ferritins. New insights and analysis of methods of nanoparticle preparation

Background

Ferritin exhibits complex behavior in the ultracentrifuge due to variability in iron core size among molecules. A comprehensive study was undertaken to develop procedures for obtaining more uniform cores and assessing their homogeneity.

Methods

Analytical ultracentrifugation was used to measure the mineral core size distributions obtained by adding iron under high- and low-flux conditions to horse spleen (apoHoSF) and human H-chain (apoHuHF) apoferritins.

Results

More uniform core sizes are obtained with the homopolymer human H-chain ferritin than with the heteropolymer horse spleen HoSF protein in which subpopulations of HoSF molecules with varying iron content are observed. A binomial probability distribution of H- and L-subunits among protein shells qualitatively accounts for the observed subpopulations. The addition of Fe²⁺ to apoHuHF produces iron core particle size diameters from 3.8 ± 0.3 to 6.2 ± 0.3 nm. Diameters from 3.4 ± 0.6 to 6.5 ± 0.6 nm are obtained with natural HoSF after sucrose gradient fractionation. The change in the sedimentation coefficient as iron accumulates in ferritin suggests that the protein shell contracts ∼ 10% to a more compact structure, a finding consistent with published electron micrographs. The physicochemical parameters for apoHoSF (15%/85% H/L subunits) are M = 484,120 g/mol, ν? = 0.735 mL/g, s_20,w = 17.0 S and D_20,w = 3.21 × 10⁻⁷ cm²/s; and for apoHuHF M = 506,266 g/mol, ν? = 0.724 mL/g, s_20,w = 18.3 S and D_20,w = 3.18 × 10⁻⁷ cm²/s.

Significance

The methods presented here should prove useful in the synthesis of size controlled nanoparticles of other minerals.     

The associations between the Val158Met in the catechol-O-methyltransferase (COMT) gene and the risk of uterine leiomyoma (ULM)

The Val158Met polymorphism of the COMT gene has been implicated in susceptibility to uterine leiomyoma (ULM), but the reported results were inconclusive. The aim of the study was to evaluate the Val158Met polymorphism of the COMT gene and the risk of ULM by meta-analysis. A comprehensive electronic search for relevant articles was conducted in Pubmed, Embase, CNKI, Wanfang, and Weipu databases. Statistical analysis was performed by using the Revman4.2 software and Stata10.0 software. A total of 7 articles including 12 case–control studies were identified in this meta-analysis. The results showed that the polymorphism was associated with decreased risk of ULM (Met/Met + Val/Met vs. Met/Met: OR = 0.84, 95% CI = 0.70–0.99, Z = 2.07, p = 0.04). In the subgroup analyses by ethnicity, significant decreased risk was found among the black populations (OR = 0.68, 95% CI = 0.48–0.97, Z = 2.15, p = 0.03). The current meta-analysis suggested that the Val158Met polymorphism in the COMT gene was associated with decreased risk of ULM, especially in the black population. Future studies are needed to validate our conclusions.     

Electron and nuclear dynamics in many-electron atoms, molecules and chlorophyll-protein complexes: A review

It has been shown [V.A. Shuvalov, Quantum dynamics of electrons in many-electron atoms of biologically important compounds, Biochemistry (Mosc.) 68 (2003) 1333-1354; V.A. Shuvalov, Quantum dynamics of electrons in atoms of biologically important molecules, Uspekhi biologicheskoi khimii, (Pushchino) 44 (2004) 79-108] that the orbit angular momentum L of each electron in many-electron atoms is L = mVr = n? and similar to L for one-electron atom suggested by N. Bohr. It has been found that for an atom with N electrons the total electron energy equation E = −(Z^eff)²e⁴m/(2n²?²N) is more appropriate for energy calculation than standard quantum mechanical expressions. It means that the value of L of each electron is independent of the presence of other electrons in an atom and correlates well to the properties of virtual photons emitted by the nucleus and creating a trap for electrons. The energies for elements of the 1st up to the 5th rows and their ions (total amount 240) of Mendeleev' Periodical table were calculated consistent with the experimental data (deviations in average were 5 × 10^− 3). The obtained equations can be used for electron dynamics calculations in molecules. For H₂ and H₂⁺ the interference of electron-photon orbits between the atoms determines the distances between the nuclei which are in agreement with the experimental values. The formation of resonance electron-photon orbit in molecules with the conjugated bonds, including chlorophyll-like molecules, appears to form a resonance trap for an electron with E values close to experimental data. Two mechanisms were suggested for non-barrier primary charge separation in reaction centers (RCs) of photosynthetic bacteria and green plants by using the idea of electron-photon orbit interference between the two molecules. Both mechanisms are connected to formation of the exciplexes of chlorophyll-like molecules. The first one includes some nuclear motion before exciplex formation, the second one is related to the optical transition to a charge transfer state.     

Identification of bovine NPC1 gene cSNPs and their effects on body size traits of Qinchuan cattle

NPC1 gene is an important gene closely related to the Niemann–Pick type C (NPC). Mutations in the NPC1 gene tend to cause Niemann–Pick type C, a lysosomal storage disorder. Previous studies have shown that NPC1 protein plays an important role in subcellular lipid transport, homeostasis, platelet function and formation, which are basic metabolic activities in the process of development. In this study, to explore the association between the NPC1 gene variation and body size traits in Qinchuan cattle, we detected four novel coding single nucleotide polymorphisms (cSNPs) in the bovine NPC1 gene, including one missense mutation (SNP1) and three synonymous mutations (SNP2, SNP3 and SNP4). Population genetic analyses of 518 individuals and association correlations between cSNPs and bovine body size traits were conducted in this research. A missense mutation at SNP1 locus was found to be significantly related to the heart girth, hip width and body weight (P < 0.01 or P < 0.05, 3.5-year-old). Two synonymous mutations at SNP2 and SNP3 loci also showed significant effects on hip width (P < 0.05, 3.5-year-old). One synonymous mutation at SNP4 locus showed significant effect on body weight (P < 0.05, 2.0-year-old). Combined haplotypes H₂H₆ and H₆H₆ showed significant effects on body size traits such as heart girth, hip width, and body weight (3.5-year-old, P < 0.01 or P < 0.05). This study provides evidence that the NPC1 gene might be involved in the regulation of bovine growth and body development, and may be considered as a candidate gene for marker assisted selection (MAS) in beef cattle breeding industry.