Charging of Macroparticles in a Corona Discharge in an Air Flow

The charging of Al₂O₃ macroparticles with dimensions ranging from 20 to 40 μm in a gas flow passing through a multielectrode corona discharge is investigated. The corona discharge is produced by a system of wire electrodes arranged across the gas flow. The particle charge and mass are measured using a linear electrodynamic trap. For a corona voltage of 18 kV, the average charge-to-mass ratio is found to be 1.69 × 10¹³e/g for particles charged in the positive corona and 1.35 × 10¹³e/g for particles charged in the negative corona.     

Heterobifunctional Poly(ethylene glycol) Derivatives for the Surface Modification of Gold Nanoparticles Toward Bone Mineral Targeting

Heterobifunctional poly(ethylene glycol)s can be used for many biomedical applications ranging from solubility enhancement of hardly soluble compounds to surface modification of medical devices. In order to modify gold nanoparticles as model particles for drug targeting applications, PEG derivatives are synthesized that possess a high affinity for gold surfaces, namely a thioalkyl function, known to form stable monolayers on gold. Additionally a bisphosphonate function is introduced in the PEG molecule to allow targeting of hydroxyapatite rich tissues, like bone. Gold nanoparticles are modified using the synthesized bifunctional PEG and investigated for their stability in biological fluids and their ability to bind to hydroxyapatite granules in these fluids.     

Modification of Plasma Membrane Organization in Tobacco Cells Elicited by Cryptogein

Lipid mixtures within artificial membranes undergo a separation into liquid-disordered and liquid-ordered phases. However, the existence of this segregation into microscopic liquid-ordered phases has been difficult to prove in living cells, and the precise organization of the plasma membrane into such phases has not been elucidated in plant cells. We developed a multispectral confocal microscopy approach to generate ratiometric images of the plasma membrane surface of Bright Yellow 2 tobacco (Nicotiana tabacum) suspension cells labeled with an environment sensitive fluorescent probe. This allowed the in vivo characterization of the global level of order of this membrane, by which we could demonstrate that an increase in its proportion of ordered phases transiently occurred in the early steps of the signaling triggered by cryptogein and flagellin, two elicitors of plant defense reactions. The use of fluorescence recovery after photobleaching revealed an increase in plasma membrane fluidity induced by cryptogein, but not by flagellin. Moreover, we characterized the spatial distribution of liquid-ordered phases on the membrane of living plant cells and monitored their variations induced by cryptogein elicitation. We analyze these results in the context of plant defense signaling, discuss their meaning within the framework of the “membrane raft” hypothesis, and propose a new mechanism of signaling platform formation in response to elicitor treatment.The adaptive capacity of biological membranes is a primary determinant of cell survival in fluctuating conditions. In particular, membrane physical properties are adjusted in the perception of and response to environmental modifications (including temperature, mechanical, and osmotic stresses) in various organisms (Los and Murata, 2004; Vígh et al., 2007; Verstraeten et al., 2010), including plants (Vaultier et al., 2006; Königshofer et al., 2008). Moreover, it has been shown that modifications of plasma membrane (PM) physical properties induced by pharmacological treatments can trigger signaling events in tobacco (Nicotiana tabacum) suspension cells (Bonneau et al., 2010). This reinforces the need to analyze the relationships between membrane organization and signaling in greater detail.Fluidity, a physical property of the PM, is a measure of the rotational and translational motions of molecules within the membrane, and consequently this reflects the level of lipid order in the bilayer. Lipid order is comprised of structure, microviscosity, and membrane phase; the latter feature includes lipid shape, packing, and curvature (Rilfors et al., 1984; van der Meer et al., 1984; Bloom et al., 1991). Lipid self-association induces a physical segregation into lipid bilayers, wherein a liquid-ordered (Lo) phase coexists with a liquid-disordered (Ld) phase (Veatch and Keller, 2005; Gaus et al., 2006; Klymchenko et al., 2009; Heberle et al., 2010). The Lo phase couples a high rotational mobility with a high conformational order in the lipid acyl chain, two physical properties that could be spatially resolved by fluorescence microscopy (Kubiak et al., 2011). Moreover, some observations indicate that Lo size or proportion could be controlled by temperature or cholesterol content (Roche et al., 2008; Orth et al., 2011).This preferential association of some lipids in complex mixtures has resulted in the “membrane raft” hypothesis within the cell biology field. This theory postulates the existence of small (20–200 nm), short-lived, sterol-, and sphingolipid-enriched Lo assemblies within the membrane. An important feature is that these aggregations are believed to coalesce, upon a biological stimulus, into larger structures whose dynamics can regulate many cellular processes (Simons and Ikonen, 1997; Pike, 2006; Lingwood and Simons, 2010; Simons and Gerl, 2010). An increased resistance to solubilization by detergents of Lo versus Ld phases has led researchers to consider that membrane fractions insoluble to nonionic detergents at low temperatures could contain the putative “raft” fractions. One caveat of this theory is that recovered detergent-insoluble membrane fractions (DIMs) only exist after detergent treatment and do not correspond to the native membrane structure (Lichtenberg et al., 2005). Nevertheless, their significant enrichment in sterols, sphingolipids, and specific subsets of proteins, some of which displaying a clustered distribution within the PM (Simons and Gerl, 2010), has encouraged their use as a biochemical counterpart of Lo microdomains existing in biological membranes.Plant DIMs with a lipid content similar to animal DIMs have been isolated from several species, including tobacco cells, and are enriched in proteins involved in signaling and stress responses (Mongrand et al., 2004; Borner et al., 2005; Morel et al., 2006; Lefebvre et al., 2007; Kierszniowska et al., 2009). Moreover, immunoelectron microscopy experiments have revealed that lateral segregation of lipids and proteins occurs at the nanoscale level at the tobacco PM, thus correlating detergent insolubility with membrane domain localization of presumptive raft proteins (Raffaele et al., 2009; Furt et al., 2010; Demir et al., 2013). Together, these data point to the existence of specialized lipid domains in plants. Concomitantly, the presence of sterol-rich Lo membrane domains was observed in vivo at the tip of the growing pollen tube in Picea meyeri, using both filipin and the fluorescent probe 1-[2-hydroxy-3-(N,N-dimethyl-N-hydroxyethyl)ammoniopropyl]-4-[β-[2-(di-n-butylamino)-6-napthyl]vinyl] pyridinium dibromide (di-4-ANEPPDHQ; Liu et al., 2009). This observation argues in favor of a sterol-dependent organization of ordered domains at the plant PM surface. In addition, the combined use of fluorescent lipid analogs and the environmental dye laurdan has revealed different lipid phases that emerge in the PM of Arabidopsis (Arabidopsis thaliana) protoplasts during restoration of the cell wall (Blachutzik et al., 2012). Despite these details, necessary data concerning the presence and in vivo characterization of Lo domains at a micrometer to nanometer scale are still lacking.The importance of a more refined resolution for observing Lo domains was proposed in several recent reviews (Bagatolli, 2006; Duggan et al., 2008; García-Sáez and Schwille, 2010; Owen et al., 2010a; Stöckl and Herrmann, 2010; Klenerman et al., 2011). Although the physical properties of biological membranes have been studied in situ by various techniques, including two-channel ratiometric microscopy (Owen et al., 2010c) and microscopy imaging of partitioning of fluorescent lipids and proteins (Rosetti et al., 2010) or environmentally sensitive probes (Parasassi et al., 1990; Jin et al., 2006), membrane segregation into microscopic Lo- and Ld-like phases has been difficult to observe in living cells. Furthermore, only a few studies have demonstrated that a microscopic phase separation involving an ordered phase similar to the Lo domain of model membranes could occur in biomembranes using PM giant vesicles (Baumgart et al., 2007; Lingwood et al., 2008; Sengupta et al., 2008). A potentially powerful approach for imaging small ordered membrane domains relies on environment-sensitive probes coupled with fluorescence spectroscopy (Gaus et al., 2003, 2006; Oncul et al., 2010). In particular, analysis of the fluorescence of the di-4-ANEPPDHQ probe, which exhibits an emission shift independent of local chemical composition under different lipid packing conditions (Jin et al., 2005; Demchenko et al., 2009; Dinic et al., 2011), recently enabled the imaging of plant membrane domains at the micrometer scale (Liu et al., 2009). The relevance of this approach has been confirmed by mapping membrane domains using generalized anisotropy-based images of di-4-ANEPPDHQ-stained T cell immunological synapses (Owen et al., 2010c), together with the characterization of membrane organization of nonadherent cells (such as living zebrafish embryo tissues) labeled with this dye (Owen et al., 2012a).The function of dynamic PM compartmentalization in the detection and transduction of environmental signals in plant cells has only recently begun to emerge, along with a crucial role for sterols in this organization (for review, see Zappel and Panstruga, 2008; Mongrand et al., 2010; Simon-Plas et al., 2011). These observations make it indispensable to align how the surface membrane of living cells might reorganize during signaling with the membrane raft hypothesis. To investigate possible modifications of membrane organization during the initial steps of plant defense signaling, tobacco cells were treated with two well-described elicitors of defense reaction, cryptogein, a small protein able to trigger an hypersensitive reaction (HR) and an acquired resistance in tobacco plants (Ponchet et al., 1999; Garcia Brugger et al., 2006) together with a widely described signaling cascade in tobacco suspension cells, and flg22 (a 22-amino acid peptide corresponding to a conserved domain of bacterial flagellin). The latter peptide is also a potent elicitor in plants, yet it does not induce an HR type of necrosis (Gomez-Gomez and Boller, 2002; Chinchilla et al., 2007). The study of cryptogein response reveals that the earliest steps of the signal transduction pathway mainly involve PM activities (Ponchet et al., 1999; Garcia-Brugger et al., 2006). How the PM is laterally organized and possibly reorganized in response to this stress so it can efficiently trigger a signaling cascade remains unknown.Here, we have developed a confocal multispectral microscopy approach to generate in vivo ratiometric pictures of large areas of the tobacco cell PM labeled with di-4-ANEPPDHQ, allowing the in vivo characterization of the global level of order of this membrane. Although an increase in the proportion of ordered phase within the membrane transiently occurred in the early steps of the cryptogein and flg22 signaling cascades, the fluorescence recovery after photobleaching (FRAP) technique revealed an increase in PM fluidity induced by cryptogein, but not by flagellin. Moreover, we characterized the spatial distribution of Lo phases on the membrane of living plant cells and monitored the variations induced by cryptogein elicitation. The results are discussed within the framework of the “membrane raft” hypothesis, in which we propose a new mechanism of signaling platform formation in the context of plant defense.     

Modification of proteins by mono(ADP-ribosylation) in vivo

We have pursued the detection of in vivo modified, ADP-ribosylated proteins containing N-glycosylic linkages to arginine. ADP-ribosylated histone, elongation factor 2, and transducin, containing the different known ADP-ribosylated amino acids (arginine, diphthamide, and cysteine, respectively), were employed as model conjugates to establish conditions for the selective detection of adenosine(5')diphosphoribose (ADP-ribose) residues bound to arginine. We report here the detection and quantification of protein-bound ADP-ribose residues in adult rat liver with linkages characteristic of arginine. These mono(ADP-ribose) residues were present in vivo at a level of 31.8 pmol/mg of protein which is 400-fold higher than polymeric ADP-ribose residues. A minor fraction (23%) of the ADP-ribose residues detected were bound via a second, more labile linkage with chemical properties very similar to those described for carboxylate ester linked ADP-ribose.     

Inhibition and Ultraviolet-Induced Chemical Modification of UDP-Glucose:(1,3)-beta-Glucan (Callose) Synthase by Chlorpromazine : Mechanism of Chlorpromazine Binding to the Plant Plasma Membrane

UDP-glucose:(1,3)-β-glucan (callose) synthase (CS) from storage tissue of red beet (Beta vulgaris L.) was strongly inhibited by the phenothiazine drug chlorpromazine (CPZ). In the absence of ultraviolet irradiation, CPZ was a noncompetitive inhibitor with 50% inhibitory concentration values for plasma membrane and solubilized CS of 100 and 90 μm, respectively. Both the Ca²⁺- and Mg²⁺- stimulated components of CS activity were affected. CPZ inhibition was partially alleviated at saturating levels of Ca²⁺, but not Mg²⁺, suggesting that CPZ interferes with the Ca²⁺-binding site of CS. Binding experiments with [¹⁴C]CPZ, however, showed strong non-specific partitioning of CPZ into the plasma membrane, providing evidence that perturbation of the membrane environment is probably the predominant mode of inhibition. Ultraviolet irradiation at 254 nm markedly enhanced CPZ inhibition, with complete activity loss following exposure to 4 μm CPZ for 2 min. Inhibition followed a pseudo-first order mechanism with at least three CPZ binding sites per CS complex. Under these conditions, [³H]CPZ was covalently incorporated into plasma membrane preparations by a free radical mechanism; however, polypeptide labeling profiles showed labeling to be largely nonspecific, with many polypeptides labeled even at [³H]CPZ levels as low as 1 μm, and with boiled membranes. Although CPZ is one of the most potent known inhibitors of CS, its use as a photolabel will require a homogeneous CS complex or establishment of conditions that protect against the interaction of CPZ with specific binding sites located on various polypeptide components of the CS complex.     

植物中的小类泛素修饰因子(SUMO)修饰系统

小类泛素修饰因子(SUMO)是一种可以通过异肽键修饰其他蛋白质的小分子多肽,是在动物中发现的类似于泛素的蛋白质修饰方式。它参与调节了植物对逆境反应、病源防御、脱落酸信号传递以及成花诱导等许多过程,是植物正常生长发育中必不可少的蛋白质修饰方式。文章就其研究进展作一简要介绍。     

Plasma platelet activating factor-acetylhydrolase (PAF-AH)

The platelet-activating factor-acetylhydrolase (PAF-AH) is an enzyme which catalyzes the hydrolysis of acetyl ester at the sn-2 position of PAF. The family of PAF-AHs consists of two intracellular isoforms (Ib and II), and one secreted isoform (plasma). These PAF-AHs show different biochemical characteristics and molecular structures. Plasma PAF-AH and intracellular isoform, II degrade not only PAF but also oxidatively fragmented phospholipids with potent biological activities. Among these PAF-AHs, plasma PAF-AH has been the target of many clinical studies in inflammatory diseases, such as asthma, sepsis, and vascular diseases, because the plasma PAF-AH activity in the patients with these diseases is altered when compared with normal individuals. Finding a genetic deficiency in the plasma PAF-AH opened the gate in elucidating the protecting role of this enzyme in inflammatory diseases. The most common loss-of-function mutation, V279F, is found in more than 30% of Japanese subjects (4% homozygous, 27% heterozygous). This single nucleotide polymorphism in plasma PAF-AH and the resulting enzymatic deficiency is thought to be a genetic risk factor in various inflammatory diseases in Japanese subjects. Administration of recombinant plasma PAF-AH or transfer of the plasma PAF-AH gene improves pathology in animal models. Therefore, substitution of plasma PAF-AH would be an effective in the treatment of the patients with the inflammatory diseases and a novel clinical approach. In addition, the detection of polymorphisms in the plasma PAF-AH gene and abnormalities in enzyme activity would be beneficial in the diagnosis of the inflammatory diseases.     

Laccase-Catalyzed Surface Modification of Thermo-Mechanical Pulp (TMP) for the Production of Wood Fiber Insulation Boards Using Industrial Process Water

Low-density wood fiber insulation boards are traditionally manufactured in a wet process using a closed water circuit (process water). The water of these industrial processes contains natural phenolic extractives, aside from small amounts of admixtures (e.g., binders and paraffin). The suitability of two fungal laccases and one bacterial laccase was determined by biochemical characterization considering stability and substrate spectra. In a series of laboratory scale experiments, the selected commercial laccase from Myceliophtora thermophila was used to catalyze the surface modification of thermo-mechanical pulp (TMP) using process water. The laccase catalyzed the covalent binding of the phenolic compounds of the process water onto the wood fiber surface and led to change of the surface chemistry directly via crosslinking of lignin moieties. Although a complete substitution of the binder was not accomplished by laccase, the combined use of laccase and latex significantly improved the mechanical strength properties of wood fiber boards. The enzymatically-treated TMP showed better interactions with the synthetic binder, as shown by FTIR-analysis. Moreover, the enzyme is extensively stable in the process water and the approach requires no fresh water as well as no cost-intensive mediator. By applying a second-order polynomial model in combination with the genetic algorithm (GA), the required amount of laccase and synthetic latex could be optimized enabling the reduction of the binder by 40%.     

Modification of the Red Beet Plasma Membrane H-ATPase by Diethylpyrocarbonate

Incubation of the red beet (Beta vulgaris L.) plasma membrane H⁺-ATPase with micromolar concentrations of diethylpyrocarbonate (DEPC) resulted in inhibition of both ATP hydrolytic and proton pumping activity. Enzyme activity was restored when DEPC-modified protein was incubated with hydroxylamine, suggesting specific modification of histidine residues. Kinetic analyses of DEPC inhibition performed on both membrane-bound and solubilized enzyme preparations suggested the presence of at least one essential histidine moiety per active site. Inclusion of either ATP (substrate) or ADP (product and competitive inhibitor) in the modification medium reduced the amount of inhibition observed in the presence of DEPC. However, protection was not entirely effective in returning activity to noninhibited control values. These results suggest that the modified histidine does not reside directly in the ATP binding region of the enzyme, but is more likely involved in enzyme regulation through subtle conformational effects.     

Modification of arginine residues in pyruvate kinase (author's transl)

Pyruvate kinase from pig heart is inactivated by the specific arginyl reagent phenylglyoxal. The loss of activity is caused by the reaction of a single molecule of phenylglyoxal per subunit of enzyme. During inactivation 3 - 6 arginyl residues are modified dependent on the concentration of phenylglyoxal used for modification. The solubility of the protein is reduced by the modification. ATP or phosphoenolpyruvate protect against inactivation. A single arginine is less subject to chemical modification in their presence. Therefore we assume that an arginine is essential at the substrate binding site. The activating ion K does not affectinactivation, where as Mg2 diminishes inactivation. Pyruvate kinase from rabbit muscle is modified by phenylglyoxal in a similar manner.     

Plasma Effects in Dust Devils near the Martian Surface

Plasma?dust effects in the martian atmosphere are discussed. A specific feature of the martian atmosphere is the presence of dust grains in a wide range of altitudes. Taking into account the presence of the martian ionosphere and the high conductivity of the medium at lower altitudes, the appearance of plasma systems in the martian atmosphere can be considered quite a common phenomenon. Special attention is paid to dust devils that frequently form in the martian atmosphere and can efficiently lift dust grains. The processes of dust grain charging as a result of triboelectric effect and generation of electric fields in a dust devil are discussed. The dynamics of dust grains in such a vortex is simulated with allowance for their charging and the generated electric field.     

Theory of Electromagnetic Surface Waves in Plasma with Smooth Boundaries

A theory of nonpotential surface waves in plasma with smooth boundaries is developed. The complex frequencies of surface waves for plasma systems of different geometries and different profiles of the plasma density are calculated. Expressions for the rates of collisionless damping of surface waves due to their resonance interaction with local plasma waves of continuous spectrum are obtained. The influence of collisions in plasma is also considered.     

Surface behavior of prostaglandins (PGs)

This study establishes some correlations between molecular structure and surface function of six prostaglandins in a model membrane system. Using spread films at the air/water interface, we determined surface pressure and surface potential of PGs A₁, A₂, E₁, E₂, F_1α and F_2α. All the PGs formed films with low pressure (0 to 9 dyne/cm) and relatively low surface potentials (ΔV = 10 to 250 mV). On 0.15 M NaCl, the π and ΔV values were in the order E₁ > F_1α > A₁ > F_1α > A₁ > F₂α = A₂ > E₂ and F_1α > E₁ > A₁ > A₂ > F_2α > E₂ respectively. Clearly, the cis unsaturation in the carboxylic chain of the PG₂ series conferred greater instability to the films, as indicated by the lowest π and ΔV values. Also, members of the PG₁ series penetrated films of dipalmitoyl phosphatidyl choline (DPPC) better than PG₂ did, the ablest being E₁ (Δπ = 12 dyne/cm) and the poorest F₂α (Δπ = 2 dyne/cm); penetration of E₁ and F₂α was independent of the initial pressure (π_i) of the DPPC film, whereas with A₁ and F_1α Δπ decreased as π_i increased. The PGs expressed marked discriminating capacities for the electrolyte, as indicated by differences in their π and ΔV responses to Na⁺ and Ca⁺⁺ as well as for the lipid, as indicated by different penetration (Δπ values) into DPPC films.     

Complex estrogenic regulation of catechol-O-methyltransferase (COMT) in rats

Catechol-O-methyltransferase (COMT) activity depends on gender, age and physiological status suggesting that estrogen may regulate COMT activity. In fact, estrogens down-regulate the function of COMT promoters in cell cultures. On the other hand, COMT may play an important role in estrogen-induced cancers due to its ability to inactivate estrogen metabolites and thereby lowering the levels of these potential carcinogens. In this study, we explored the effect of estrogen on COMT activity in vivo in rats. Male and female Wistar rats received 14-day treatments with either estradiol (100 μg/kg/day; s.c.) or tamoxifen (500 μg/kg/day; s.c.), respectively; in addition ovariectomized rats were studied. COMT activity and COMT protein expression were measured from various brain- and peripheral tissues. Although we found a regulatory function of estrogen, its effects were sex and tissue dependent. Antagonizing the effects of estrogen via tamoxifen increased COMT protein expression in several central and peripheral tissues. However, amounts of COMT protein and COMT activities did not always match. Generally, COMT activities were quite resistant to the effects of tamoxifen and estradiol. Estradiol, unexpectedly, doubled the amount of COMT protein in the prostate but exhibited down-regulatory function in the prefrontal cortex and kidneys. Ovariectomy by itself, however, had only minor effects on COMT activity and expression. It is noteworthy that the estrogen down-regulation and tamoxifen up-regulation of COMT were best substantiated in the prefrontal cortex and kidneys where COMT is physiologically important for dopamine metabolism.     

人血浆载脂蛋白（a）的分离及纯化

本文报道从人血浆脂蛋白Ｌｐ（ａ）中,分离纯化载脂蛋白（ａ）。收集富含Ｌｐ（ａ）的混合血浆,超离心,获密度１．０５ｇ／ｍｌ至１．０８ｇ／ｍｌ的粗制Ｌｐ（ａ）,经过Ｂｉｏ－Ｇｅｌ Ａ５ｍ层析后,证明纯化后的Ｌｐ（ａ）仅与ａｐｏ（ａ）抗血清反应,经ＤＴＴ处理过的Ｌｐ（ａ）,在琼脂糖电泳中的泳动率由胶β位移到β位,在印迹免疫反应中,对ａｐｏ（ａ）的抗血清反应依然显示在前β位,ＳＤＳ聚丙烯凝胶电脉的迁移率慢     

Plasma semicarbazide-sensitive amine oxidase in human (patho)physiology

Semicarbazide-sensitive amine oxidases (SSAO) are widely distributed enzymes, with as yet not fully elucidated functions and roles, present in many tissues but also circulating in plasma. The enzyme also functions as an adhesion molecule, the vascular adhesion protein-1. In healthy humans, plasma SSAO activity is constant from birth until 16 years of age, when it drops to lower values, gradually increasing again at advanced ages. When measuring SSAO activity, care should be taken to ensure proper preparation and storage conditions, and it should be realized that quite a few drugs unintentionally are good inhibitors, and sometimes even substrates, of SSAO. Under normal conditions SSAO activity is constant and inter-individual variation is small. In various pathophysiological conditions plasma SSAO activities are increased, most notably in diabetes mellitus (both type I and type II), in congestive heart failure and in cirrhotic liver inflammation. In patients with other vascular and inflammatory diseases plasma SSAO is normal, while it is low in children with congenital lung diseases. Interpretation of these changes is speculative, since source and regulation of plasma SSAO are as yet unknown. However, in two situations where the disease-causing process was ended (transplantation, delivery), plasma SSAO returned to normal. Many questions remain to be answered.     

Modification of Oligo (Poly) Nucleotide Phosphomonoester Groups in Aqueous Solutions

Abstract

Selective modification of oligo (poly) nucleotide phosphomonoester groups in an aqueous medium by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide in the presence of various nucleophilic agents has been investigated. Optimal conditions of the modification by amino- and hydroxycompounds have been found. Based on these studies a general efficient method for preparation of oligo (poly) nucleotide phosphoamidates and phosphodiesters in an aqueous solution has been developed. The method allows to prepare both oligodeoxyribonucleotide derivatives at 3′- and 5′-terminal phosphate groups and oligoribonucleotide derivatives at 5′-terminal phosphate groups with 80–100% yields.     

Modification of cap group in delta-lactam-based histone deacetylase (HDAC) inhibitors

Novel delta-lactam-based HDAC inhibitors which have various substituted benzyl, bi-aromatic cap groups were prepared using ring closure metathesis reaction, and evaluated their HDAC inhibitory activities and anti-proliferative effects. Among prepared analogues, 11m and 11o have very strong HDAC enzymatic inhibition and showed the most potent growth inhibitory activity to five human tumor cell lines including PC-3, ACHN, NUGC-3, HCT-15, and MBA-MB-231 tumor cell lines. Compounds 11m and 11o also showed good tumor growth inhibition of MDA-MB-231 cells in in vivo xenograft model. Structure-activity relationship study using docking model explained the significance of hydrophobic aromatic cap groups for their in vitro activities.     

Plasma aminotransferase measurements in the marmoset (Callithrix jacchus)

Plasma aminotransferase values were measured in a large number of samples from male and female marmosets. There were no differences due to age or sex for either AST or ALT. Haemolysis affected values for both enzymes, though the effect on ALT was greater.