Abstract  Complement-dependent cytotoxicity (CDC) is a potent promoter of tumor clearance during monoclonal antibody therapy. Complement activation on antibody-bearing tumor cells results in formation of the membrane attack complex (MAC), which activates cell death. The complement activation cascade that bridges between antibody binding and MAC formation is regulated by complement inhibitors that are over-expressed on tumor cells. In order to bypass those complement regulators, we have designed an immunoconjugate composed of a humanized single chain Fv of an anti-Tac (CD25) monoclonal antibody fused at its C terminus either to complement protein C9 (scFv-C9) or to complement C7 (scFv-C7) and tagged with six histidines at the C terminal end. Recombinant scFv-C9 and scFv-C7 were expressed in 293T cells and purified. Both are shown to efficiently bind to CD25-positive tumor cells. In addition, scFv-C9, but not scFv-C7, increases MAC deposition on the cells and enhances complement-mediated cell death of target CD25-positive cells. Thus, scFv-C9 fusion protein is potentially a novel reagent for application in cancer immunotherapy.

Abstract  5-N-acetylneuraminic acid, commonly known as sialic acid (Sia), constitutes a family of N- and O-substituted 9-carbon monosaccharides. Frequent modification of O-acetylations at positions C-7, C-8, or C-9 of Sias generates a family of O-acetylated sialic acid (O-AcSia) and plays crucial roles in many cellular events like cell-cell adhesion, proliferation, migration, etc. Therefore, identification and analysis of O-acetylated sialoglycoproteins (O-AcSGPs) are important. In this chapter, we describe several approaches for successful identification of O-AcSGPs. We broadly divide them into two categories, i.e., invasive and noninvasive methods. Several O-AcSias-binding probes are used for this purpose. Detailed methodologies for step-by-step identification using these probes have been discussed. We have also included a few invasive analytical methods for identification and quantitation of O-AcSias. Several indirect methods are also elaborated for such purpose, in which O-acetyl group from sialic acids is initially removed followed by detection of Sias by several approaches. For molecular identification, we have described methods for affinity purification of O-AcSGPs using an O-AcSias-binding lectin as an affinity matrix followed by sequencing using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF-TOF) mass spectroscopy (MS). In spite of special attention, loss of O-acetyl groups due to its sensitivity towards alkaline pH and high temperature along with migration of labile O-acetyl groups from C7-C8-C9 during sample preparation is difficult to avoid. Therefore there is always a risk for underestimation of O-AcSias.

Abstract  Two new compounds, (2R,3R,4R)-3',5'-dimethoxy-3,4,7,4'-tetrahydroxy-flavan (1) and 2-(4-hydroxy-3-methoxybenzoyl)-4-methoxy-benzaldehyde (2), together with 35 known phenolic compounds were obtained from the fruits of Amomum tsao-ko. Structures of the new compounds were elucidated on the basis of spectroscopic means, including 2D NMR, a n d high-resolution M S analysis. The isolated compounds were tested in vitro for t heircomplement-inhibitory properties against the classical pathway (CP) and alternative pathway (AP). The results showed that 14 compounds exhibited anti-complementary activities against the CP and AP with CH50 values of 0.42 - 4.43 mM and AP50 values of 0.53 -1.51 mM. Preliminary mechanism studies showed that 1,7-bis(4-hydroxyphenyl)-4(E)-hepten-3-one (8) blocked C1q, C2, C3, C4, C5 and C9 components of the complement system, and hydroquinone (15) acted on C1q, C2, C3, C5 and C9 components.

Abstract  A highly efficient and green aerobic oxidation has been developed for selectively preparing a series of valuable 2,6-dialkyl-, dialkoxyl-, and alkoxylalkyl-substituted 4-hydroxybenzaldehydes from corresponding 4-cresols in good to excellent yields, using a catalytic system of Co(OAc)(2)center dot 4H(2)O (1.0mol%)-NaOH (1.0 equiv)-O-2 (1.0atm) in aqueous ethylene glycol (EG/H2O=20/1, v/v) at 50 degrees C. Furthermore, a plausible mechanism was proposed for the direct oxyfunctionalization of the aromatic methyl group into the aldehyde group.

Abstract  The reaction of OH radicals with a series of methylated benzenes was studied in a temperature range 300-350 K using a flash-photolysis resonance fluorescence technique. Reversible OH additions led to complex OH decays dependent on the number of distinguishable adducts. Except for hexamethylbenzene, triexponential OH decay curves were obtained, consistent with formation of at least two adduct species. For three compounds that can strictly form two adduct isomers for symmetry reasons (1,4-dimethyl-, 1,3,5-trimethyl-, and 1,2,4,5-tetramethylbenzene) with OH bound ortho or ipso with respect to the methyl groups, OH decay curves were analysed in terms of a reaction mechanism in which the two adducts can be formed directly by OH addition or indirectly by isomerization. In all cases one adduct (add(1)) is dominating the decomposition back to OH. The other (add(2)) is more elusive and only detectable at elevated temperatures, similar to the single OH adduct of hexamethylbenzene. Two limiting cases of the general reaction mechanism could be examined quantitatively: reversible formation of add2 exclusively in the OH reaction or by isomerization of add1. Total OH rate constants, adduct loss rate constants and products of forward and reverse rate constants of reversible reactions were determined. From these quantities, adduct yields, equilibrium constants, as well as reaction enthalpies and entropies were derived for the three aromatics. Adduct yields strongly depend on the selected reaction model but generally formation of add1 predominates. For both models equilibrium constants of OH reactions lie between those of OH + benzene from the literature and those obtained for OH + hexamethylbenzene. The corresponding reaction enthalpies of add1 and add(2) formations are in a range -87 +/- 20 kJ mol(-1), less exothermic than for hexamethylbenzene (-101 kJ mol(-1)). Reaction enthalpies of possible add(1) -> add(2) isomerizations are comparatively small. Because results for 1,3,5-trimethylbenzene are partly inconsistent with a direct formation of add(2), we promote the existence of isomerization reactions. Moreover, based on available theoretical work in the literature, add(1) and add(2) are tentatively identified as ortho and ipso adducts, respectively. Total OH rate constants were obtained for all title compounds. They can be described by Arrhenius equations: k(OH) = A x exp(-B/T). The parameters ln(A/(cm(3) s(-1))) = -25.6 + 0.3, -25.3 + 0.6, -27.3 + 0.3, -24.6 + 0.3, -26.2 + 0.4, -26.2 + 0.4 and -24.5 +/- 0.2, and B/K = -160 +/- 90, -550 +/- 180, -1120 +/- 90, -330 +/- 100, -820 +/- 100, -980 +/- 130, and -570 +/- 40 were determined for 1,4-dimethyl-, 1,3,5-trimethyl-, 1,2,4,5-, 1,2,3,5- and 1,2,3,4-tetramethyl-, pentamethyl-, and hexamethylbenzene.

Abstract  Ultraviolet electronic transitions of the linear carbon chains C6, C7, C8, and C9 were measured in the gas phase by a mass-resolved 1 + 1 resonant two-photon ionization technique using a picosecond laser. Broad absorptions with band maxima at 230.2 and 259.0 nm are identified as N(3)Σ(u)(-) - X(3)Σ(g)(-) (N > 3) transition of C6 and C8, respectively. Based on calculated Franck-Condon intensities, the band maxima are identified as origin bands. An upper limit of 30 ps is determined for the N(3)Σ(u)(-) excited state lifetime of C6. The (1)Σ(u)(+)- X(1)Σ(g)(+) transition with band maximum at 238.5 nm was observed for C7 and at 279.0 nm for C9. The proposition that intramolecular processes in the excited electronic states of carbon chains can lead to broadening as in the diffuse interstellar absorptions is experimentally demonstrated.

Abstract  Guided by anti-complementary activity, silica gel, Sephadex LH-20 and reversed-phase column chromatographies were used for fractionation and isolation of the ethyl acetate and n-butanol soluble fractions of Pogostemon cablin. Eighteen compounds were obtained, including 15 flavonoids: 5-hydroxy-3,7,3',4'-tetramethoxyflavone (1), 5-hydroxy-7,3',4'-trimethoxyflavanone (2), 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (3), 5-hydroxy-3,7,4'-trimethoxyflavone (4), 5,4'-dihydroxy-7,3'-dimethoxyflavone (5), luteolin (6), quercetin-7,3', 4'-trimethyl ether (7), ermanine (8), 3,5,7- trihydroxy-3', 4'-dimethoxyflavone (9), quercetin (10), apigenin (11), kaempferol (12), 5-hydroxy-7,3',4'-trimethoxyflavone (13), kaempferol-7-O-beta-D-glucopyranoside (14) and kaempferol-3-O-beta-D-glucopyranoside-7-O-alpha-L-rhamnoside (15); one triterpenoid: oleanic acid (16); and 2 phenolic acids: vanillic acid (17) and benzylalcohol (18). The isolation of 5, 7, 8, 12-15 and 18 from the Pogostemon genus is reported for the first time. All isolates were evaluated for their in vitro anti-complementary activities on the classical pathway and alternative pathway. And the targets of the most potent constituent in complement activation cascade were identified using complement-depleted sera. Compounds 3, 7, 10, 12 and 16 exhibited anti-complementary activities toward the classical pathway and alternative pathway (CH50 0.072-1.08 g x L(-1), AP50 0.39-0.49 g x L(-1)), while 5 and 6 showed inhibitory effect on the classical pathway only. Mechanism study indicated that 7 interacted with C1q, C2, C5 and C9 components.

Abstract  The kinetics of the irreversible phase conversion of covalent organic frameworks-1 (COF-1) has been investigated using time-resolved, in situ environmental X-ray diffraction (EXRD) and modeled with the Avrami-Erofe'ev model. Tightly fitting mesitylene solvent is found to be present in both the AB staggered and AA eclipsed polymorphs, which plays a key role in the phase change. Solid-state NMR (SSNMR) showed the presence of discrete dipolar coupling between residual mesitylene solvent and the framework in both polymorphs, indicative of a host-guest adsorptive interaction. Binding energy calculations indicate two different adsorbed mesitylene configurations in the AB and AA phases, both with short distances to the framework pore walls to generate the observed dipolar coupling. The mechanism of phase change has been illustrated using molecular dynamics simulations and was found to be a displacive transition from AB staggered to AA eclipsed COP-I structures, which was made possible due to low in-plane shear modulus of 2D COFs. Our findings highlight the polymorphic nature of COF-1 material mediated by the interactions with guest molecules and the irreversibility for polymorph formation and conversion.

Abstract  In the present work, two ultra-thin MFI membranes, prepared using hydroxide and fluoride ions as mineralizing agents, respectively, were carefully examined by permporometry. The amount of micropore defects, as determined by permporometry, differed significantly between the two different membranes. For the first time, it was demonstrated that the micropore defects determined by permporometry were most likely open grain boundaries. The results were verified by direct observation of the open grain boundaries by a state-of-the-art XHR-scanning electron microscopy instrument. In addition, the permporometry data were also consistent with permeation data using 1,3,5-trimethylbenzene (TMB) as a probe molecule, separation data using an equimolar mixture of n-hexane and TMB, and nitrogen adsorption data. (C) 2013 Elsevier Inc. All rights reserved.

Abstract  Transalkylation of toluene-tetramethylbenzene (TeMB) over MOR and BEA was investigated at 250-400 degrees C. Conversion of TeMB was higher than trimethylbenzene (TMB) and toluene. Xylene yield was in the following order: [toluene - TMB - TeMB) > [toluene - TeMB] > [toluene - TMB] [toluene]. Kinetic modeling for reaction network consisting of toluene-TeMB transalkylation; toluene disproportionation; and toluene-TMB transalkylation was carried out. Toluene-TeMB transalkylation rate was >50% higher than the toluene-TMB transalkylation while the toluene disproportionation was an order of magnitude slower than transallcylation reactions. An addition of 5-10 wt.% TeMBs to the heavy reformate caused minor impact on the xylene yield but an improvement in xylene selectivity. (C) 2014 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.

Abstract  Naphthalene diimides (NDIs) form emissive ground-state charge-transfer (CT) complexes with various electron rich aromatic solvents like benzene, o-xylene and mesitylene. TD-DFT calculation of the complexes suggests CT interaction and accounts for the observed ground-state changes.

Abstract  A comparison of activity and selectivity of external Bronsted acid sites in catalytic conversion of benzyl alcohol in mesitylene over unit-cell thick zeolite materials (MCM36 or pillared MWW, pillared MFI, and self-pillared pentasil (SPP)) showed that the external surface of MWW and MFI zeolites influences drastically the activity and selectivity of the parallel alkylation and etherification reactions. Pillared MWW, containing independent (not-interconnected) micropores and mesopores, catalyzed both of the parallel reactions only in the mesopores as evidenced by complete loss of the activity upon 2,6-di-tert-butylpyridine (DTBP) titration. Pillared MFI and SPP, consisting of highly interconnected micropores and mesopores, catalyzed both of the parallel reactions in the mesopores. Pillared MFI and SPP catalyzed only the etherification reaction in the micropores as illustrated by the complete suppression of alkylation and retention of residual etherification activity after DTBP titration. Moreover, it was found that the external surface of MWW zeolites favors the alkylation reaction, while the etherification reaction takes place with similar reaction rates on MFI and MWW external surfaces. The evidence shown here for the assessment of external acid sites in catalyzing parallel reactions extends the scope of observed catalytic performances in these materials beyond those reflecting transport effects and accessibility of acid sites and highlights the importance of external surface structure. (C) 2014 Elsevier Inc. All rights reserved.

Abstract  A very simple, fast and environmentally friendly sample extraction method was proposed for the analysis of phthalate esters (PAEs, di-isobutyl phthalate (DIBP), dibutylphthalate (DBP), butylbenzylphthalate (BBP) and bis(2-ethylhexyl)phthalate (DEHP)) in alcoholic beverages by using conventional ionic liquid dispersive liquid-liquid microextraction. The samples were extracted by 160μL 1-octyl-3-methylimidazolium hexafluorophosphate in the presence of appropriate amount of ethanol and 10% (w/v) sodium chloride solution; the enriched analytes in sedimented phases were analyzed by high performance liquid chromatography-diode array detector (HPLC-DAD). Under the optimum conditions, a satisfactory linearity (in the range of 0.02-1μgmL(-1) for white spirits and 0.01-0.5μgmL(-1) for red wines with the correlation coefficients (r) varying from 0.9983 to 1), acceptable recovery rates (88.5-103.5% for white spirits and 91.6-104.6% for red wines), good repeatability (RSD≤8.0%) and low detection limits (3.1-4.2ngmL(-1) for white spirits and 1.5-2.2ngmL(-1) for red wines) were obtained. The developed method was successfully applied for the determination of the four PAEs in 30 white spirits and 11 red wines collected locally, and the DBP content in 63% (19:30) white spirits exceeded the specific migration limit of 0.3mgkg(-1) established by international regulation.

Abstract  Two mesitylene based probes, having catechol/phenol units in conjunction to the Schiff base have been synthesized. The probe with a catechol unit can be used to sense and discriminate between F(-) and CN(-) through different colorimetric and fluorimetric responses using DMSO as solvent. However in DMSO:water (2:1) solution it responds selectively to CN(-) ion. The probe with a phenol unit is highly selective and sensitive for CN(-) and can be used for naked eye, semiquantitative sensing of CN(-) ion in DMSO:water (2:1) solution. The chemodosimetry has been attributed to the acid catalyzed Strecker's reaction of an imine bond and is being reported for the first time in a Schiff's base.

Abstract  Inverse gas chromatography (IGC) was used to characterize the thermodynamic properties of ionic liquid (IL) 1-hexyl-3-methylimidazolium tetrafluoroborate ([HMIM] BF4) in the temperature range from 343.15 K to 373. 15 K. A series of solvents with different chemical natures were used to determine the [HMIM] BF4-solvent interactions. The thermodynamic parameters including Flory-Huggins interaction parameter, partial molar heats of sorption, mixing and evaporation as well as the activity coefficient at infinite dilution were obtained to judge the interactions between [HMIM]BF4 and the selected solvents. In addition, the solubility parameters of [HMIM] BF4 at different temperatures were determined. The results showed that among the selected solvents, n-C6, n-C7, n-C8, n-C9, diethyl ether, tetrahydrofuran, benzene and cyclohexane were poor solvents for [HMIM] BF4, while toluene, m-xylene, methanol, ethanol, dichloromethane, tetrachloromethane, chloroform, acetone, ethyl acetate and methyl acetate were the favorite ones. The solubility parameter of [HMIM]BF4 at room temperature (298.15 K) was 23.70 (J x cm(-3)(0.5), which was obtained by the linear extrapolation method. The experiment proved that IGC is a simple and accurate method to obtain the thermodynamic properties of ionic liquids. The obtained thermodynamic parameters revealed the strength of the interactions between the selected solvents and the ionic liquid, which could be used as a reference to the further applications of the ionic liquid.

Abstract  Molecular and cellular luminescent biotests were used to reveal the effects of five alkylresorcinol homologues (C7-, C9-, C11-, C12-, and C18-AR) on the thermally induced denaturation and refolding ofbac- terial luciferases, as well as on the synthesis of heat shock proteins. The ARs activities were found to depend on their fine structure and concentration. Direct heat-protective effect of short-chain C7- and C9-AR on the chromatographically pure Photobactrium leiognathii luciferase/oxidoreductase was shown within broad range of concentration (10(-6)-10(-3) M). The long-chain ARs homologues exhibited a similar heat-protective effect at micromolar concentrations only, while their millimolarconcentrations have increased the sensitivity of the model proteins to thermal treatment. The recombinant strain Escherichia coli K12 MG1655 bearing constitutively expressed Vibrio fischieri luxAB genes was used to investigate theARs effect on the intracellular chaperone-independent refolding of bacterial luciferase. The functional activity of heat-inactivated enzyme was restored by micromolar concentrations of short-chain ARs, while long-chain homologues inhibited re- folding in the wide concentration range. The recombinant luminescent E. coli strain bearing the inducible ib- pA'::luxCDABE genetic construction was used to determine the effect of ARs on the synthesis of heat shock proteins (HSP). The preincubation mode of bacterial cells with long-chain alkylresorcinols led to dose-de- pendent stimulation of HSP synthesis (2.7 to 4 times) that confirmed some ARs function as "alarmones". Subsequent thermal treatment resulted in a 5-15-fold decrease of the following HSP induction compared to the control, while the number of viable cells opposite increased 1.5-4-fold. Thus, pretreatment of the bacte- rial cells with long-chain ARs resulted in their preadaptation to subsequent thermally induced stress. Short- chainARs caused less pronounced HSP suppression, although still was accompanied by increased heat resis- tance of the AR-pretreated bacterial cells.

Abstract  OBJECTIVE: To study the protective effect of Acai berries(Euterpe oleraceae) on chronic alcoholic hepatic injury in rats and their mechanism.

METHOD: Wistar rats were fed for 1 week and randomly divided into blank group, model group, Dongbao Gantai group, Acai 1.6, 0.8, 0.4 g . kg-1 groups. The blank group was given distilled water, and the other groups were orally given 56% white spirit (Erguotou) for eight weeks at the dosages of 8 mL . kg-1 in the 1st week, which increased by 0.1 mL week by week till to 15 mL . kg-1, in order to establish the chronic hepatic injury model, and observe the effect of Acai berry freeze-dried powder on hepatocyte membrane permeability, liver lipid peroxidation, changes in inflammatory cytokines and pathological changes in hepatocytes.

RESULT: Acai berries could significantly reduce serum ALT and AST(P<0.05), MDA(P<0.05), TG(P<0.05) and serum TNF-α and IL-6(P <0.05) and increase GSH and SOD(P <0.05). According to liver histopathological observation, livers in the model group were dominated by steatosis, some livers suffered spotty necrosis and inflammatory cell infiltration; The positive drug and Acai groups showed different changes in pathologic changes in rat livers.

CONCLUSION: Acai berries show s specific protective effect on alcoholic hepatic injury. Its mechanism may be correlated with the inhibition of such inflammatory factors as TNF-α and IL-6.

Abstract  BACKGROUND: Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) have been the leading cause of morbidity and mortality in intensive care units (ICU). Currently, there is no effective pharmacological treatment for acute lung injury. Curcumin, extracted from turmeric, exhibits broad anti-inflammatory properties through down-regulating inflammatory cytokines. However, the instability of curcumin limits its clinical application.

METHODS: A series of new curcumin analogs were synthesized and screened for their inhibitory effects on the production of TNF-α and IL-6 in mouse peritoneal macrophages by ELISA. The evaluation of stability and mechanism of active compounds was determined using UV-assay and Western Blot, respectively. In vivo, SD rats were pretreatment with c26 for seven days and then intratracheally injected with LPS to induce ALI. Pulmonary edema, protein concentration in BALF, injury of lung tissue, inflammatory cytokines in serum and BALF, inflammatory cell infiltration, inflammatory cytokines mRNA expression, and MAPKs phosphorylation were analyzed. We also measured the inflammatory gene expression in human pulmonary epithelial cells.

RESULTS: In the study, we synthesized 30 curcumin analogs. The bioscreeening assay showed that most compounds inhibited LPS-induced production of TNF-α and IL-6. The active compounds, a17, a18, c9 and c26, exhibited their anti-inflammatory activity in a dose-dependent manner and exhibited greater stability than curcumin in vitro. Furthermore, the active compound c26 dose-dependently inhibited ERK phosphorylation. In vivo, LPS significantly increased protein concentration and number of inflammatory cells in BALF, pulmonary edema, pathological changes of lung tissue, inflammatory cytokines in serum and BALF, macrophage infiltration, inflammatory gene expression, and MAPKs phosphorylation . However, pretreatment with c26 attenuated the LPS induced increase through ERK pathway in vivo. Meanwhile, compound c26 reduced the LPS-induced inflammatory gene expression in human pulmonary epithelial cells.

CONCLUSIONS: These results suggest that the novel curcumin analog c26 has remarkable protective effects on LPS-induced ALI in rat. These effects may be related to its ability to suppress production of inflammatory cytokines through ERK pathway. Compound c26, with improved chemical stability and bioactivity, may have the potential to be further developed into an anti-inflammatory candidate for the prevention and treatment of ALI.

Abstract  Dynamic mutation diseases are genetic diseases caused by unstable repeat expansions in coding region or noncoding region. The unstable repeat expansions located in the noncoding region usually perform as large expansions which the standard PCR assay is difficult to amplify. Traditional detection methods, including Southern blot, are supposed to be time-consuming and labor-wasting. A new method called fluorescent repeat-primed PCR assay was brought into genetic diagnosis. Here, we reviewed the advances in repeat-primed PCR assay for the genetic diagnoses of myotonic dystrophy, Friedreich's ataxia, SCA10, and amyotrophic lateral sclerosis or frontotemporal dementia caused by C9 or f72 mutations.

Abstract  Processes for the biotechnological production of kerosene and diesel blendstocks are often economically unattractive due to low yields and product titers. Recently, Clostridium acetobutylicum fermentation products acetone, butanol, and ethanol (ABE) were shown to serve as precursors for catalytic upgrading to higher chain-length molecules that can be used as fuel substitutes. To produce suitable kerosene and diesel blendstocks, the butanol:acetone ratio of fermentation products needs to be increased to 2-2.5:1, while ethanol production is minimized. Here we show that the overexpression of selected proteins changes the ratio of ABE products relative to the wild type ATCC 824 strain. Overexpression of the native alcohol/aldehyde dehydrogenase (AAD) has been reported to primarily increase ethanol formation in C. acetobutylicum. We found that overexpression of the AAD(D485G) variant increased ethanol titers by 294%. Catalytic upgrading of the 824(aad(D485G)) ABE products resulted in a blend with nearly 50wt%≤C9 products, which are unsuitable for diesel. To selectively increase butanol production, C. beijerinckii aldehyde dehydrogenase and C. ljungdhalii butanol dehydrogenase were co-expressed (strain designate 824(Cb ald-Cl bdh)), which increased butanol titers by 27% to 16.9gL(-1) while acetone and ethanol titers remained essentially unaffected. The solvent ratio from 824(Cb ald-Cl bdh) resulted in more than 80wt% of catalysis products having a carbon chain length≥C11 which amounts to 9.8gL(-1) of products suitable as kerosene or diesel blendstock based on fermentation volume. To further increase solvent production, we investigated expression of both native and heterologous chaperones in C. acetobutylicum. Expression of a heat shock protein (HSP33) from Bacillus psychrosaccharolyticus increased the total solvent titer by 22%. Co-expression of HSP33 and aldehyde/butanol dehydrogenases further increased ABE formation as well as acetone and butanol yields. HSP33 was identified as the first heterologous chaperone that significantly increases solvent titers above wild type C. acetobutylicum levels, which can be combined with metabolic engineering to further increase solvent production.

Abstract  Complement deficiencies comprise between 1 and 10% of all primary immunodeficiencies (PIDs) according to national and supranational registries. They are still considered rare and even of less clinical importance. This not only reflects (as in all PIDs) a great lack of awareness among clinicians and general practitioners but is also due to the fact that only few centers worldwide provide a comprehensive laboratory complement analysis. To enable early identification, our aim is to present warning signs for complement deficiencies and recommendations for diagnostic approach. The genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4) is often associated with autoimmune diseases whereas individuals, deficient of properdin or of the terminal pathway components (C5 to C9), are highly susceptible to meningococcal disease. Deficiency of C1 Inhibitor (hereditary angioedema, HAE) results in episodic angioedema, which in a considerable number of patients with identical symptoms also occurs in factor XII mutations. New clinical entities are now reported indicating disease association with partial complement defects or even certain polymorphisms (factor H, MBL, MASPs). Mutations affecting the regulators factor H, factor I, or CD46 and of C3 and factor B leading to severe dysregulation of the alternative pathway have been associated with renal disorders, such as atypical hemolytic uremic syndrome (aHUS) and - less frequent - with membranoproliferative glomerulonephritis (MPGN). We suggest a multi-stage diagnostic protocol starting based on the recognition of so called warning signs which should aid pediatricians and adult physicians in a timely identification followed by a step-wise complement analysis to characterize the defect at functional, protein and molecular level.

Abstract  A series of mesoporous titanosilicates (MTS-9x) are synthesized in an acidic media from titanosilicate precursors with a polymer surfactant (P123) under temperatures ranging from 100 to 180 degrees C. Characterization and analysis show that the hexagonal mesoporous titanosilicates (MTS-9x) contain both primary and secondary structural building units of TS-1 zeolite in their framework, in a manner similar to MTS-9. Furthermore, Si-29 NMR spectral analysis suggests that MTS-9(180) synthesized at 180 degrees C promotes a higher condensation of Ti-containing silica networks in the mesoporous walls compared to MTS-9(100) synthesized at 100 degrees C. The higher synthesis temperature may also be responsible for the increased thermal stability of the four-coordinated titanium species in MTS-9(180), which was verified by UV-vis spectral analysis. Catalytic experiments indicate that MTS-9(180) shows high hydroxylation activity, regardless of calcination, for both small organic molecules such as phenol and bulky organic molecules such as 2,3,6-trimethylphenol. Moreover, the recycled catalyst retains a high conversion, confirming the high thermal stability of the titanium species. (C) 2013 Elsevier Inc. All rights reserved.

Abstract  BACKGROUND: The transcription factor homeobox C9 (HOXC9) plays a crucial role in developmental regulatory systems, where it determines the specific positional identities of cells along the anteroposterior axis. The expression of HOXC9 has been found to be dysregulated in some cancers such as lung cancer, breast cancer, and neuroblastoma. Here, we report for the first time that HOXC9 is a novel autophagy regulator and reveal its oncogenic role in cell survival and its usefulness as a prognostic marker in glioblastoma patients.

METHODS: Kaplan-Meier analysis was performed to evaluate the possible prognostic value of HOXC9 in glioblastoma. Growth curve assays, subcutaneous, and orthotopic implantations were used to analyze cell viability and tumor formation, respectively. Luciferase and chromatin immunoprecipitation assays were employed to explore the mechanisms involved in the association between HOXC9 and its downstream effector, death-associated protein kinase 1 (DAPK1).

RESULTS: High expression of HOXC9 was found to be an indicator of a poor prognosis in glioblastoma. HOXC9 knockdown resulted in a significant reduction of cell viability, migration, invasion, and tumorigenicity and a marked increase in autophagy. During the autophagy process, HOXC9 inhibited DAPK1 transcription by directly binding to its promoter. The downregulation of HOXC9 releases its transcriptional inhibition of DAPK1, resulting in the activation of the DAPK1-Beclin1 pathway, which induces autophagy in glioblastoma cells.

CONCLUSIONS: Collectively, our data indicate that HOXC9 is an oncogene in glioblastoma. We have revealed its role in the control of autophagy, and we suggest that HOXC9 is a novel and promising therapeutic target.

Abstract  Systemic acquired resistance (SAR) is a form of broad-spectrum disease resistance that is induced in response to primary infection and that protects uninfected portions of the plant against secondary infections by related or unrelated pathogens. SAR is associated with an increase in chemical signals that operate in a collective manner to confer protection against secondary infections. These include, the phytohormone salicylic acid (SA), glycerol-3-phosphate (G3P), azelaic acid (AzA) and more recently identified signals nitric oxide (NO) and reactive oxygen species (ROS). NO, ROS, AzA and G3P function in the same branch of the SAR pathway, and in parallel to the SA-regulated branch. NO and ROS function upstream of AzA/G3P and different reactive oxygen species functions in an additive manner to mediate chemical cleavage of the C9 double bond on C18 unsaturated fatty acids to generate AzA. The parallel and additive functioning of various chemical signals provides important new insights in the overlapping pathways leading to SAR.