Novel bifunctional catalysts based on crystalline multi-oxide matrices containing iron ions for CO2 hydrogenation to liquid fuels and chemicals.

Seven solid mono-, bi- and tri-metallic oxide matrices where Fe(2+,3+) ions are distributed in different chemical/spatial environments were synthesized and characterized by XRD, N2-adsorption and EDAX methods. After basification with potassium, all matrices were activated by carburization or reduction-carburization under conditions selected based on the TPC/TPR spectra, tailoring the carburization extent of iron. The performances of the activated Fe-based catalysts with respect to CO2 conversion and C5+ selectivity were measured in a fixed-bed reactor under standard conditions in transient and continuous operation modes in units containing one or three reactors in series with water separations between the reactors. The catalysts were characterized by XRD, N2-adsorption, HRTEM-EELS and XPS before and after steady-state operation in the reactors. It was found that the rate of CO2 conversion is not limited by thermodynamic equilibrium but is strongly restricted by water inhibition and it depends on the nature of the Fe-oxide precursor. The ratio between the FTS and RWGS rates, which determines the C5+ hydrocarbons productivity, is strongly affected by the nature of the Fe-oxide matrix. The catalysts derived from the Fe-Al-O spinel and Fe-Ba-hexaaluminate precursors displayed the best balance of the two functions RFTS/RRWGS = 0.77-0.78. They were followed by magnetite, CuFe-delafossite, K-ferrite, Fe-La-hexaaluminate and LaFe-perovskite with a gradual lowering of RFTS/RRWGS from 0.60 to 0.15 and a gradual decrease in the C5+ productivity. The active sites that enhance the RWGS reaction are located on the surface of the Fe-oxide phases, while the FTS and methanation reactions occur on the surface of the Fe-carbide phases.

The molecular basis of low activity levels of coagulation factor VII: a Brazilian cohort.

Inherited factor VII (FVII) deficiency is the most common among the rare bleeding disorders. It is transmitted as an autosomal recessive inheritance, due to mutations in the FVII gene (F7). Molecular studies of FVII deficiency are rare in non-Caucasian populations. The aim of the study was to evaluate the molecular basis behind low levels of FVII activity (FVII:C) levels in a cohort of Brazilian patients. A total of 34 patients with low FVII levels were clinically evaluated and submitted to laboratory tests, among these, prothrombin time and FVII:C, with different thromboplastins. All exons and intron/exon boundaries of F7 were amplified and sequenced. A total of 14 genetic alterations were identified, of which six were described previously, c.1091G>A, c.1151C>T, c.-323_-313insCCTATATCCT, c.285G>A, c.525C>T, c.1238G>A and eight (54.0%) and eight were new, c.128G>A, c.252C>T, c.348G>A, c.417G>A, c.426G>A, c.745_747delGTG, c.843G>A and c.805+52C>T. In addition to the mutation c.1091G>A, known as FVII Padua, the mutation c.1151C>T also presented discrepant FVII:C levels when tested with human and rabbit brain thromboplastin. There was no association between phenotype and genotype. Most of the identified genetic alterations found were polymorphisms. Low levels of FVII:C in this population were mostly related to polymorphisms in F7 and associated with a mild clinical phenotype. Mutation c.1151C>T was associated with discrepant levels of FVII:C using different thromboplastins, such as reported with FVII Padua.

Reduced models for unidirectional block conduction and their geometrical setting.

This article revisits a reduced model of cardiac electro-physiology which was proposed to understand the genesis of unidirectional block pathology and of ectopic foci. We underline some specificities of the model from the viewpoint of dynamical systems and bifurcation theory. We point out that essentially the same properties are shared by a simpler system more accessible to analysis. With this simpler system, it becomes possible to give a new presentation of the phenomenon in a phase plane with time moving slow manifolds. This presentation can be of interest both for cardiac electro-physiologists and for mathematicians.

Three residues at the interface of factor XI (FXI) monomers augment covalent dimerization of FXI.

BACKGROUND: Human plasma factor XI is a homodimer, with each monomer comprising a catalytic domain and four homologous 'apple' domains. The monomers bind to each other through non-covalent bonds and through a disulfide bond between Cys321 residues in apple 4 domains. OBJECTIVE: To identify residues essential for dimerization in the FXI monomer interface. METHODS: Specificity-determining residues in apple 4 domains were sought by sequence alignment of FXI and prekallikrein apple domains in different species. Specific residues identified in apple 4 domains were mutagenized and expressed in baby hamster kidney (BHK) cells for evaluation of their effect on FXI dimerization, analyzed by non-reduced sodium dodecylsulfate polyacrylamide gel electrophoresis and size-exclusion chromatography. RESULTS: Among the 19 residues of the FXI monomer interface, Leu284, Ile290 and Tyr329 were defined as specificity-determining residues. Substitutions of these residues or pairs of residues did not affect FXI synthesis and secretion from transfected BHK cells, but did impair dimerization, despite the presence of cysteine at position 321. The double mutant 284A/290A yielded predominantly a monomer, whereas all other single or double mutants yielded monomers as well as disulfide-bonded dimers. CONCLUSIONS: The data suggest that Leu284, Ile290 and Tyr329 in the interface of FXI monomers are essential for forming non-covalently bonded dimers that facilitate formation of a disulfide-bonded stable FXI dimer.

Catalytic wet air oxidation of aniline with nanocasted Mn-Ce-oxide catalyst.

The catalytic wet air oxidation of aqueous solution containing 1000 ppm aniline was conducted in a trickle-bed reactor packed with a novel nanocasted Mn-Ce-oxide catalyst (surface area of 300 m2/g) prepared using SBA-15 silica as a hard template. A range of liquid hourly space velocities (5-20 h(-1)) and temperatures (110-140 degrees C) at 10 bar of oxygen were tested. The experiments were conducted to provide the intrinsic performance of the catalysts. Complete aniline conversion, 90% TOC conversion, and 80% nitrogen mineralization were achieved at 140 degrees C and 5 h(-1). Blank experiments yielded relatively low homogeneous aniline (<35%) and negligible TOC conversions. Fast deactivation of the catalysts was experienced due to leaching caused by complexation with aniline. Acidification of the solution with HCI (molar HCI to aniline ratio of 1.2) was necessary to avoid colloidization and leaching of the nanoparticulate catalyst components. The catalyst displayed stable performance for over 200 h on stream.

Trp207Gly in platelet glycoprotein Ibalpha is a novel mutation that disrupts the connection between the leucine-rich repeat domain and the disulfide loop structure and causes Bernard-Soulier syndrome.

BACKGROUND: Bernard-Soulier syndrome (BSS) is a severe inherited bleeding disorder that is caused by a defect in glycoprotein (GP)Ib-IX-V complex, the platelet membrane receptor for von Willebrand factor. PATIENTS: The diagnosis of BSS was made in two members of a Bukharian Jewish family who had life-long thrombocytopenia associated with mucocutaneous bleeding manifestations. METHODS AND RESULTS: Flow cytometry and Western blot analyses showed only trace amounts of GPIb and GPIX on the patients' platelets. Sequence analysis of the GPIbalpha gene revealed a homozygous T > G transversion at nucleotide 709 predicting Trp207Gly substitution in the mature protein. Introduction of the mutation into a mammalian expression construct abolished the surface expression of GPIbalpha in transfected baby hamster kidney cells. The crystal structure of the N-terminus of GPIbalpha (PDB: 1SQ0) indicates that Trp207 is completely buried and located in a disulfide loop structure that interacts with the leucine-rich repeat (LRR) domain. CONCLUSION: A novel mutation, Trp207Gly, causes BSS and predicts disruption of the interaction between a disulfide loop and the LRR domain that is essential for the integrity of GPIbalpha structure.

A 13-bp deletion in alpha(IIb) gene is a founder mutation that predominates in Palestinian-Arab patients with Glanzmann thrombasthenia.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder caused by lack or dysfunction of alpha(IIb)beta3 in platelets. GT is relatively frequent in highly inbred populations. We previously identified a 13-bp deletion in the alpha(IIb) gene that causes in-frame deletion of six amino acids in three Palestinian GT patients. In this study, we determined the molecular basis of GT in all known Palestinian patients, examined whether Jordanian patients harbor the same mutations, analyzed whether there is a founder effect for the 13-bp deletion, and determined the mechanism by which the 13-bp deletion abolishes alpha(IIb)beta3 surface expression. Of 11 unrelated Palestinian patients, eight were homozygous for the 13-bp deletion that displayed common ancestry by haplotype analysis, and was estimated to have occurred 300-600 years ago. Expression studies in baby hamster kidney cells showed that substitution of Cys107 or Trp110 located within the deletion caused defective alpha(IIb)beta3 maturation. Substitution of Trp110, but not of Cys107, prevented fibrinogen binding. The other Palestinian patients harbored three novel mutations: G2374 deletion in alpha(IIb) gene, TT1616-7 deletion in beta3 gene, and IVS14: -3C --> G in beta3 gene. The latter mutation caused cryptic splicing predicting an extended cytoplasmic tail of beta3 and was expressed as dysfunctional alpha(IIb)beta(3). None of 15 unrelated Jordanian patients carried any of the described mutations.

Combustion of chlorinated VOC on nanostructured chromia aerogel as catalyst and catalyst support.

The chromia-based catalysts have been reported to combine the high activity and resistance to deactivation in oxidative removal of chlorinated VOC. However, their activity is limited by the low amount of chromia that can be deposited on supports maintaining the optimal state of surface species and high surface area. The pure nanostructured chromia was used as a catalytically active support for noble metals and transition-metal oxide oxidation catalysts. High efficiency of Pt-promoted CrOOH aerogel with surface area of 500 m2*g(-1) was demonstrated in full combustion of 1,2-dichloroethane (DCE) and chlorobenzene (CB). At gas hour space velocity (GHSV) of 46 000 h(-1), the total conversion to CO2/H2O/HCl was achieved at 330 degrees C (DCE) and 380 degrees C (CB). The combustion rate constants measured at standard conditions with 0.5% Pt/CrOOH catalyst were 1 or 2 orders of magnitude higher than measured with 15%Cr2O3/Al2O3 or 0.5%Pt/Al2O3, respectively. The effects of Pt, Au, Mn, and Ce additives on the performance of CrOOH aerogel in combustion of chlorinated VOC were analyzed related to the materials structure.

Characterization of mutations causing factor VII deficiency in 61 unrelated Israeli patients.

Inherited factor (F)VII deficiency is rare in most populations but relatively common in Israel. The aim of this study was to characterize the molecular and functional defect in unrelated Israeli patients with FVII deficiency. Mutations were identified by direct sequencing of PCR-amplified genomic DNA fragments. Selected mutations were expressed in baby hamster kidney (BHK) cells and tested for binding to tissue factor (TF), activation by FXa and activation of FX. In 61 patients with FVII deficiency, the causative mutation in the FVII gene was discerned. The predominant mutation found in this and a previously reported cohort of 27 unrelated patients in Israel was Ala244Val substitution; of 121 independent mutant alleles defined in all 88 patients ascertained in Israel, 102 (84%) bore this alteration. Eleven additional mutations were identified of which one, Cys22Arg, is novel. Expression of the mutations in BHK cells revealed that four (Ala244Val, 11128delC, Leu300Pro and Cys22Arg) were cross-reacting material (CRM)- negative, and three (Ala294Val, Cys310Phe and Phe24del) were CRM-positive. As predicted by modeling, we observed no binding to TF of FVII Phe24del, diminished binding of FVII Cys310Phe and normal binding of FVII Ala294Val. The main defect of FVII Ala294Val was its inability to activate FX in the presence of TF. Coexpression of Ala294Val and Arg353Gln, a polymorphism known to affect FVII secretion, did not reveal an additive effect on FVII secretion, while coexpression of Ala244Val and Arg353Gln did yield an additive effect.

Severe factor XI deficiency caused by a Gly555 to Glu mutation (factor XI-Glu555): a cross-reactive material positive variant defective in factor IX activation.

During normal hemostasis, the coagulation protease factor (F)XIa activates FIX. Hereditary deficiency of the FXIa precursor, FXI, is usually associated with reduced FXI protein in plasma, and circulating dysfunctional FXI variants are rare. We identified a patient with < 1% normal plasma FXI activity and normal levels of FXI antigen, who is homozygous for a FXI Gly555 to Glu substitution. Gly555 is two amino acids N-terminal to the protease active site serine residue, and is highly conserved among serine proteases. Recombinant FXI-Glu555 is activated normally by FXIIa and thrombin, and FXIa-Glu555 binds activated factor IX similarly to wild type FXIa (FXIa(WT)). When compared with FXIa(WT), FXIa-Glu555 activates factor IX at a greatly reduced rate ( approximately 400-fold), and is resistant to inhibition by antithrombin. Interestingly, FXIa(WT) and FXIa-Glu555 cleave the small tripeptide substrate S-2366 with comparable k(cat)s. Modeling indicates that the side chain of Glu555 significantly alters the electrostatic charge around the active site, and would sterically interfere with the interaction between the FXIa S2' site and the P2' residues on factor IX and antithrombin. FXI-Glu555 is the first reported example of a naturally occurring FXI variant with a significant defect in FIX activation.

Seven novel mutations in the factor XIII A-subunit gene causing hereditary factor XIII deficiency in 10 unrelated families.

BACKGROUND: Hereditary factor (F)XIII deficiency is a rare bleeding disorder mostly due to mutations in FXIII A subunit. OBJECTIVES: We studied the molecular basis of FXIII deficiency in patients from 10 unrelated families originating from Israel, India and Tunisia. METHODS: Exons 2-15 of genomic DNA consisting of coding regions and intron/exon boundaries were amplified and sequenced. Structural analysis of the mutations was undertaken by computer modeling. RESULTS: Seven novel mutations were identified in the FXIIIA gene. The propositus from the Ethiopian-Jewish family was found to be a compound heterozygote for two novel mutations: a 10-bp deletion in exon 12 at nucleotides 1652-1661 (followed by 22 altered amino acids and termination codon) and Ala318Val mutation. The propositus of the Tunisian family was homozygous for C insertion after nucleotide 863 within a stretch of six cytosines of exon 7. This insertion results in generation of eight altered amino acids followed by a termination codon downstream. The propositus from Indian-Jewish origin was found to be homozygous for G to T substitution at IVS 11 [+1] resulting in skipping of exons 10 and 11. In addition to the Ala318Val mutation, three of the novel mutations identified are missense mutations: Arg260Leu, Thr398Asn and Gly210Arg each occurring in a homozygous state in an Israeli-Arab and two Indian families, respectively. CONCLUSIONS: Structure-function correlation analysis by computer modeling of the new missense mutations predicted that Gly210Arg will cause protein misfolding, Ala318Val and Thr398Asn will interfere with the catalytic process or protein stability, and Arg260Leu will impair dimerization.

A novel Phe171Cys mutation in integrin alpha causes Glanzmann thrombasthenia by abrogating alphabeta complex formation.

BACKGROUND: Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterized by lack of platelet aggregation induced by most agonists. The disease is caused by mutations in either alpha(IIb)[glycoprotein (GP) IIb] or beta(3) (GPIIIa) genes that lead to a lack or dysfunction of the integrin alpha(IIb)beta(3) which serves as a fibrinogen receptor. PATIENTS: Mucocutaneous bleeding manifestations and platelet dysfunction consistent with GT were observed in three members of a Cypriot family: a 3-year-old proband, her father and her paternal uncle. OBJECTIVE: To determine the molecular basis of GT in this family and to characterize possible biochemical and structural defects. RESULTS: Analysis of the patients' platelets by fluorescence-activated cell sorting demonstrated trace amounts of beta(3), no alpha(IIb) and no alpha(IIb)beta(3) on the membrane. Sequence analysis revealed a novel T607G transversion in exon 5 of the alpha(IIb) gene predicting a Phe171Cys alteration that created a PstI recognition site. All three patients were homozygous for the mutation, the mother and paternal grandparents of the proband were heterozygous, whereas 110 healthy subjects lacked this transversion. Chinese hamster ovary cells cotransfected with cDNAs of mutated alpha(IIb) and wild-type beta(3) failed to express alpha(IIb)beta(3) as shown by immunoprecipitation and immunohistochemistry experiments. Structural analysis of the alpha(IIb)beta(3) model, which was based on the crystal structure of alpha(v)beta(3), indicated that Phe171 plays an essential role in the interface between the beta-propeller domain of alpha(IIb) and the betaA domain of beta(3). CONCLUSIONS: A novel Phe171Cys mutation in the alpha(IIb) gene of patients with GT is associated with abrogation of alpha(IIb)beta(3) complex formation.

[Hypophysis metastasis of a hypernephroma tumor revealed by a chiasma syndrome]. / Métastase hypophysaire d'un hypernéphrome révélée par un syndrome chiasmatique.

In a 45-year-old man with a hypernephroma tumor of the right kidney, a metastasis in the pituitary gland of this neoplasm was diagnosed 9 years after removal of this kidney. He complained of bitemporal hemianopsia and slight impairment of vision. A hypernephroma metastasis in the pituitary gland is very rare and few have been reported to date. In general, these metastases occur in cases with multiple metastasis to many organs, which suggests that the appearance of pituitary metastasis represents extensive disease. Many of these patients present diabetes insipidus. Visual defects are frequently associated. The Goldmann perimeter is important to detect visual field anomalies. MRI is the key radiological exam to localize the tumor. Surgery is the preferred treatment and should be undertaken quickly if visual function is affected. The histological exam should be made to confirm the diagnosis.

Thermostable sulfated 2-4 nm tetragonal ZrO2 with high loading in nanotubes of SBA-15: a superior acidic catalytic material.

The high-loaded (48-60 wt.%) 2-4 nm tetragonal ZrO2 phase inserted in mesostructured silica SBA-15 by chemical solution decomposition (CSD) of Zr(n-PrO)4 and activated at 873 K displayed approximately 3 times higher capacity for surface sulfate ions and, respectively, 1.5-2.2 times higher catalytic activity per gram of SO4-ZrO2/SBA-15 composite in condensation of MeOH with t-BuOH and dehydration of isopropanol compared with the regular bulk sulfated zirconia material.

Sweet's syndrome in association with Crohn's disease: report of a case and review of the literature.

A 41-year-old woman developed a skin rash as part of Sweet's syndrome concurrent with the first episode of Crohn's disease of the colon. Sweet's syndrome, acute febrile neutrophilic dermatosis, may be associated with inflammatory, infectious, or neoplastic diseases. Its association with Crohn's disease is very rare, and when reported it has been mainly associated with Crohn's colitis. This association has been described in various stages of the disease. Sweet's syndrome may be considered one of the extraintestinal manifestations of Crohn's disease. Early diagnosis of this dermatosis may be important because of the prompt response to treatment with corticosteroids. The value of metronidazole should be considered because this medication may enhance response to treatment.

Adolescent-onset ichthyosiform-like erythroderma with lichenoid tissue reaction: a new entity?

A patient with severe ichthyosiform erythroderma and lichenoid histological changes is presented. We discuss the clinical and histological differential diagnosis, including lupus erythematosus, lichenoid drug eruption, lichen planus, graft-versus-host disease, lymphoma, keratosis lichenoides chronica, Netherton's syndrome and ichthyosiform erythroderma. None of these is consistent with the features in our case, which may represent either a hitherto unreported form of ichthyosiform erythroderma or possibly a new entity.