Iron overload and cofactors with special reference to alcohol,hepatitis C virus infection and steatosis/insulin resistance

There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In these conditions, iron is deposited in hepatocytes and Kupffer cells and reactive oxygen species （ROS） produced through Fenton reaction have key role to facilitate cellular uptake of transferrin-bound iron. Furthermore, hepcidin, antimicrobial peptide produced mainly in the liver is also responsible for intestinal iron absorption and reticuloendothelial iron release. In patients with ceruloplasmin deficiency, anemia and secondary iron overload in liver and neurodegeneration are reported. Furthermore, there is accumulating evidence that fatty acid accumulation without alcohol and obesity itself modifies iron overload states. Ineffective erythropoiesis is also an important factor to accelerate iron overload, which is associated with diseases such as thalassemia and myelodysplastic syndrome. When this condition persists, the dietary iron absorption is increased due to the increment of bone marrow erythropoiesis and tissue iron overload will thereafter occurs. In porphyria cutanea tarda, iron is secondarily accumulated in the liver.

The roles of tubulin-folding cofactors in neuronal morphogenesis and disease

Microtubules play important roles in neuronal morphogenesis, including cellular polarization, neurite growth, and branching. A microtubule is a polymer of a- and β-tubulin heterodimers that are formed by a multistep process assisted by at least five tubulin-fold- ing cofactors （TBCA-E） （Lopez-Fanarraga et al., 2001）. Newly syn- thesized α- and β-tubulins associate with the cytosolic chaperonin complex （CCT）, and then the quasi-native tubulins interact with five tubulin-folding cofactors. The α- and β-tubulins first interact with TBCB and TBCA, which are further transferred to TBCE and TBCD, respectively. The α- and β-tubulins, TBCC, TBCD, and TBCE form a supercomplex, and guanosine triphosphate （GTP） hydrolysis occurs within the supercomplex, releasing a tubulin heterodimer. In addition to their functions in tubulin folding and tubulin heterodimer formation, excess amounts of TBCD or TBCE may interact with tubulin heterodimers, leading to their degrada- tion. Thus, tubulin-folding cofactors may play a role in both the synthesis and degradation of tubulin heterodimers.

DECOMPOSITION THEOREM AND k-HYPERCONNECTION EXPRESSIONS FOR GENERAL k-ORDER COFACTORS

Two k-hyperconnection expressions of a general k-order cofactor Y（i,j） are presentedfor the indefinite parameter matrix Y of a linear system by applying directed hypergraph theory,and based on it a decomposition theorem of Y（i,j） is derived.By this theorem,the multi-leveltearing and analysis can be carried out easily for any linear large system.This is a new mul-tilevel topological analysis method.Using proposed method the scale of systems which can betopologically analysed by a computer will be enlarged.

Study of Cofactors Associated with Precancerous High-Grade Cervical Lesions at the Teaching Hospital Gabriel Touré, 2010 to 2015

Introduction: High grade dysplasia of the cervix has a high incidence and can progress to cervical cancer. The aim was to study cofactors associated with high-grade cervical dysplasia. Methodology: This was a retrospective case-control study without matching. Women with high grade dysplasia were the cases while those with a normal screening test represented the controls. The study took place at the Gabriel Touré University Hospital Center in Bamako. We included 351 cases and 420 controls. The capture and analysis were performed using the SPSS 20 software. A univariate and multivariate logistic regression analysis was performed for the analysis of risk cofactors. The statistical tests used were the odds ratio and its confidence interval and the statistical significance threshold was set at p Results: In univariate analysis, the co-factors statistically significantly associated with the occurrence of high-grade dysplasia were parity 0.6 (0.5 - 0.9), gestational 0.7 (0.5 - 0.9), smoking of the spouse 3.4 (1.1 - 11.3), the non-schooling 1.4 (1.2 - 2.1). In multivariate analysis after adjusting for confounding factors, two co-factors have significantly increased the risk of high-grade dysplasia: lack of schooling 1.4 (1.2 - 2.0) and polygamy 1.5 (1.4 - 2.5). Conclusion: At the end of this study, polygamy and lack of schooling were the main risk factors. The prevention of cervical cancer will go through the education of girls and women as well as communication for behavioral change and social change.

NEW PROOF OF DIMENSION FORMULA OF SPLINE SPACES OVER T-MESHES VIA SMOOTHING COFACTORS

A T-mesh is basically a rectangular grid that allows T-junctions. Recently, Deng etal introduced splines over T-meshes, which are generalizations of T-splines invented by Sederberg etal, and proposed a dimension formula based on the B-net method. In this paper, we derive an equivalent dimension formula in a different form with the smoothing cofactor method.

Targeting host cofactors to inhibit viral infection

The majority of FDA-approved drugs indicated for the treatment of viral infections are inhibitors of viral proteins, of which the emergence of resistant strains is a major concern. This issue is exacerbated as most developed antiviral therapies are indicated for the treatment of viruses with error-prone replication. These problems may be addressed by the development of drugs that modulate the function of host factors involved in various aspects of a viral life cycle. Targeting host factors uncouples the mutation of a druggable protein gene from the replication and survival selection pressure exerted on a virus. Currently, a host-targeting antiviral （HTA）, maraviroc, is approved for the treatment of human immunodeficiency virus （HIV） infection. In addition, several HTAs indicated for the treatment of hepatitis C virus （HCV） or HIV infection are at various stages of clinical evaluation. Targeting host factors is an attractive complement to therapies directly targeting a viral protein because of the expected higher genetic barrier for resistance and an overall increase in the diversity of treatment options. We examine how the integrated roles of emerging host cofactor screening approaches and drug development strategies may advance current treatment options.

Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

Hematopoiesis requires finely tuned regulation of gene expression at each stage of development.The regulation of gene transcription involves not only individual transcription factors(TFs)but also transcription complexes(TCs)composed of transcription factor(s)and multisubunit cofactors.In their normal compositions,TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis.The integration of posttranslational and conformational modifcations in the chromatin landscape,nucleosomes,histones and interacting components via the cofactor-TF interplay is critical to optimal TF activity.Mutations or translocations of cofactor genes are expected to alter cofactor-TF interactions,which may be causative for the pathogenesis of various hematologic disorders.Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy.In this review,we summarize the current knowledge regarding the models and functions of cofactor-TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies.This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

Creation of cytochrome P450 catalysis depending on a non-natural cofactor for fatty acid hydroxylation

Cytochrome P450 enzymes catalyze diverse oxidative transformations at the expense of reduced nicotinamide adenine dinucleotide phosphate(NADPH),however,their applications remain limited largely because NADPH is cost-prohibitive for biocatalysis at scale yet tightly regulated in host cells.A highly challenging task for P450 catalysis has been to develop an alternative and biocompatible electrondonating system.Here we engineered P450 BM3 to favor reduced nicotinamide cytosine dinucleotide(NCDH)and created non-natural cofactor-dependent P450 catalysis.Two outstanding mutants were identified with over 640-fold NCDH preference improvement and good catalytic efficiencies of over15,000 M^(-1)s^(-1)for the oxidation of the fatty acid probe 12-(para-nitrophenoxy)-dodecanoate.Molecular docking analysis indicated that these mutants bear a compacted cofactor entrance.Upon fusing with an NCD-dependent formate dehydrogenase,fused proteins functioned as NCDH-specific P450catalysts by using formate as the electron donor.Importantly,these mutants and fusions catalyzed NCDH-dependent hydroxylation of fatty acids with similar chain length preference to those by natural P450 BM3 in the presence of NADPH and also similar regioselectivity for subterminal hydroxylation of lauric acid.As P450 BM3 and its variants are catalytically powerful to take diverse substrates and convey different reaction paths,our results offer an exciting opportunity to devise advanced cell factories that convey oxidative biocatalysis with an orthogonal reducing power supply system.

牛蜘蛛腿综合征两个致病位点检测方法的建立

牛蜘蛛腿综合征(Arachnomelia syndrome,AS)是一种隐性遗传疾病,虽然在瑞士褐牛和西门塔尔牛中症状相同,然而却是由两个不同的基因突变引起的,分别是SUOX基因c.363-364insG突变和MOCS1基因c.1224_1225delCA突变。文章利用51头西门塔尔牛及80头与配母牛和106头杂交后代,以及55头新疆褐牛公牛为研究群体,通过荧光标记引物PCR扩增结合毛细管电泳技术,建立了一种荧光自动化检测方法,能够快速、准确、一次性实现对引起牛AS疾病的两个突变位点的同时检测,为今后我国牛群中AS致病位点的筛查工作奠定了基础。

PEO/Cofactor助留体系应用于ONP/OMG脱墨浆生产纸材料

介绍了PEO/Cofactor助留体系应用于ONP/OMG脱墨浆生产纸材料。实验结果表明:PEO/Cofactor助留体系对以ONP/OMG脱墨浆为主要纤维原料的助留作用效果良好,并可有效控制浆料中的树脂。脱墨浆中的水溶性杂质和非离子性表面活性剂不利于PEO/Cofactor助留体系的作用效果的发挥;PEO/Cofactor助留体系与阳离子壳聚糖共用时,效果更好。PEO/Cofactor助留体系对细小组分的留着没有选择性。

Recent advance of chemoenzymatic catalysis for the synthesis of chemicals: Scope and challenge

Chemoenzymatic catalysis can give full play to the advantages of versatile reactivity of chemocatalysis and excellent chemo-,regio-,and stereoselectivities of biocatalysis.These chemoenzymatic methods can not only save resource,cost,and operating time but also reduce the number of reaction steps,and avoid separating unstable intermediates,leading to the generation of more products under greener circumstances and thereby playing an indispensable role in the fields of medicine,materials and fine chemicals.Although incompatible challenges between chemocatalyst and biocatalyst remain,strategies such as biphasic system,artificial metalloenzymes,immobilization or supramolecular host,and protein engineering have been designed to overcome these issues.In this review,chemoenzymatic catalysis according to different chemocatalysis types was classifiably described,and in particular,the classic dynamic kinetic resolutions(DKR)and cofactor regeneration were summarized.Finally,the bottlenecks and development of chemoenzymatic catalysis were summarized,and future development was prospected.

A kind of bivariate spline space over rectangular partition and pure bending of thin plate

The mechanical background of the bivariate spline space of degree 2 and smoothness 1 on rectangular partition is presented constructively. Making use of mechanical analysis method, by acting couples along the interior edges with suitable evaluations, the deflection surface is divided into piecewise form, therefore, the relation between a class of bivariate splines on rectangular partition and the pure bending of thin plate is established. In addition, the interpretation of smoothing cofactor and conformality condition from the mechanical point of view is given. Furthermore, by introducing twisting moments, the mechanical background of any spline belong to the above space is set up.

The Insphere of a Tetrahedron

A contiguous derivation of radius and center of the insphere of a general tetrahedron is given. Therefore a linear system is derived. After a transformation of it the calculation of radius and center can be separated from each other. The remaining linear system for the center of the insphere can be solved after discovering the inverse of the corresponding coefficient matrix. This procedure can also be applied in the planar case to determine radius and center of the incircle of a triangle.

The theoretical study of one-carbon unit transfer with H_2O participation from imidazolidine to dUMP analogue

The ONIOM quantum mechanics method is used to study the reaction of one-carbon unit transfer from an imidazolidine to 6- aminouracil model with the participation of water molecules.The computation results show that in this reaction the participation of H_2O molecule makes the energy barrier lower because of the H-bond interaction.

Studies on Chem icalCom position ofIron-m olybdenum Cofactor fromNitrogenase by Fluorescence Analysis

The iron molybdenum cofactor(FeMoco) of nitrogenase MoFe protein from Azotobacter vinelandii OP was extracted by N methylformamide(NMF). The effects of FeMoco(in NMF) on electronic spectrum and fluorescence intensity of fluorescein dimercury acetate(FDMA)(in 1 mol/L NaOH) were investigated by fluorophotometric titrations and compared with those of (NH 4) 2MoS 4 and complexes of (NH 4) 2MoS 4 with Na 2S or Na 2S 2 or (NH 4) 2S x on the relative properties of FDMA. It was found that the electronic spectrum of FDMA displayed hypsochromic shift(17 nm) in the presence of FeMoco just like that in the presence of other inorganic sulfides and that the titration curve for the quench of FDMA with FeMoco is very similar to that for the quench of FDMA with complex of (NH 4) 2MoS 4 with Na 2S 2(mole ratio is 1∶3). The results showed that FeMoco(N) probably contained S—S bonds and its structure was found to be changed compared with Kim Rees structural model. This change should profit the formation of the polymer.

DFT Study on One-carbon Unit Transfer from 1,10-CH^+- tetrahydroquinoxaline to Methylamine

Density Functional Theory (DFT) method was used in this paper to study one-carbon transfer from 1,10-tetrahydroquinoxaline, an analogue of tetrahydrofolic acid, to methylamine. This reaction can be completed via two paths. From the computation result we can conclude that a general-acid catalysis exists in this reaction. By computation we find DFT has its limitation in describing a newly incorporated structure with a unit charge.

THE PROOF OF FERMAT'S LAST THEOREM

i) Instead of x￣n+ y￣n = z￣n ,we use as the general equation of Fermat's Last Theorem (FLT),where a and b are two arbitrary natural numbers .By means of binomial expansion ,(0.1) an be written as Because a￣r-(-b)￣r always contains a +b as its factor ,(0.2) can be written as where φ_r =[a￣r-(-b)￣r]/ (a+b ) are integers for r=1 . 2, 3. ...n (ii) Lets be a factor of a+b and let (a +b) = se. We can use x= sy to transform (0.3 ) to the following (0.4)(iii ) Dividing (0.4) by s￣2 we have On the left side of (0.5) there is a polynomial of y with integer coefficient and on the right side there is a constant cφ/s .If cφ/s is not an integer ,then we cannot find an integer y to satisfy (0.5), and then FLT is true for this case. If cφ_n/s is an integer ,we may change a and c such the cφ_n/s≠an integer .

A COMMENT ON THE PROOF OF FERMAT'S LAST THEOREM

In this paper, some conmments on the proof of Fermat’s last theorem are proposed.The main resuilt is thai the proof proposed by Wong Chiahe is only part of proof for fermat’s last theorem. That is to sqy ,the proof is not all-full proof to Fermat’s last theorem.

Factors Affecting Fines Flocculation Performance with Cofactor-Polyethylene Oxide

In literature, neutral polyethylene oxide (PEO) flocculated fines at low shear rates, while with cofactor (CF) addition, the formed CF-PEO complex showed larger ability to bridge fines, producing flocs. In this work, some process factors were found having significant effects on fines flocculation. Increases in CF to PEO ratio at constant PEO enhanced the bridging bonds, causing increases in flocculation initial rate (efficiency), amplitude (floc size), and fastness (a decrease in characteristic time). On the other hand, an increase in stirring rate (shear rate) in flocculation vessel caused decreases in initial rate and amplitude, and an increase in the fastness. All runs showed transient flocculation;the amplitude increased with time, reached maximum at equilibrium, and then started to decrease showing deflocculation. In brief, the CF to PEO ratio and the shear rate were found important parameters in mill operation, having significant effects on flocculation efficiency, fastness, and floc size.

Ultrafast Laser Energy Density and Retinal Absorption Cross-Section Determination by Saturable Absorption Measurements

Laser pulse nonlinear transmission measurements through saturable absorbers of known absorption parameters allow the measurement of their energy density. On the other hand, nonlinear transmission measurements of laser pulses of known energy density through absorbing media allow their absorption parameter determination. The peak energy density w0P of second harmonic pulses of a mode-locked titanium sapphire laser at wavelength λP = 400 nm is determined by nonlinear energy transmission measurement TE through the dye ADS084BE (1,4-bis(9-ethyl-3-car-bazovinylene)-2-methoxy-5-(2’-ethyl-hexyloxy)-benzene) in tetrahydrofuran. TE(w0P) calibration curves are calculated for laser pulse peak energy density reading w0P from measured pulse energy transmissions TE. The ground-state absorption cross-section σP and the excited-state absorption cross-section σex at λP, and the number density N0 of the retinal Schiff base isoform RetA in pH 7.4 buffer of the blue-light adapted recombinant rhodopsin fragment of the histidine kinase rhodopsin HKR1 from Chlamydomonas reinhardtii were determined by picosecond titanium sapphire second harmonic laser pulse energy transmission measurement TE through RetA as a function of laser input peak energy density w0P. The complete absorption cross-section spectrum