Unexpected roles for deacetylation in interferon- and cytokine-induced transcription.

Protein acetylation is a reversible modification that has been implicated in epigenetic regulation of gene expression. It is widely accepted that acetylation enzymes are present at transcriptionally active promoters and deacetylation enzymes associate with transcriptionally silent loci. These results notwithstanding, recent findings indicate that positive regulation of gene expression by interferons and other cytokines requires both acetylation and deacetylation.

Serum 25(OH)-vitamin D levels and bone metabolism in patients on maintenance hemodialysis.

Aims: An increasing amount of evidence suggests that 25-hydroxy vitamin D3 (25(OH)D3) may contribute to the bone health of patients with chronic kidney disease (CKD). The underlying vitamin D status of these patients, however, has often been neglected. In a cross-sectional study we assessed the association between vitamin D status and parathyroid function, bone turnover, bone mass and structure in patients on maintenance hemodialysis.

Design and synthesis of a solid-phase fluorescent mass tag.

In this study, we demonstrate the design of a new solid-phase fluorescent mass tag (FMT) that contains the following features: (1) the FMT is synthesized using Fmoc chemistry which is simple, rapid, and cost-effective; (2) lysine is used as a uniformly labeled amino acid (using stable isotopes) to allow 8 Da difference between "heavy" and "light" tags; (3) a fluorescent molecule is coupled to the isotope tag that allows a tagged peptide to be detected by online fluorescence; and (4) an iodoacetyl reactive group provides cysteine reactivity. Using MALDI-TOF MS and HPLC, we show that the FMT reagent can be used to label standard cysteine-containing peptides as well as cysteine-containing peptides from a BSA tryptic digest.

Indole-2-carboxamidines as novel NR2B selective NMDA receptor antagonists.

A novel series of indole-2-carboxamidine derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of the substituents on the indole skeleton as well as the substitution of the benzyl moiety on the biological activity of the compounds was studied. Compound 5a was po active in the formalin test in mouse.

[Effects of body mass index on bone mineral density in men].

Introduction: A strong positive association between body mass index and bone mineral density is well defined in postmenopausal osteoporosis, but not in men.

Aims: The primary goal of the current research was to investigate this association in case of men.

Methods: According to WHO criteria (T-score below -1.

Serum leptin, soluble leptin receptor, free leptin index and bone mineral density in patients with primary biliary cirrhosis.

Background/aim: The pathophysiology of osteoporosis in chronic liver diseases is unknown. Recent data suggest that serum leptin is associated with bone mineral density (BMD). In animal studies leptin was found to be a potent inhibitor of bone formation.

Histone deacetylases as transcriptional activators? Role reversal in inducible gene regulation.

Histone deacetylation enzymes have often been associated with the suppression of eukaryotic gene transcription. In contrast, recent studies of inducible gene regulation indicate that protein deacetylation can also be required as a transcriptional activation signal. The concept of protein deacetylation as a requirement for transcription activation seems to contradict earlier conclusions about the function of deacetylation in gene suppression.

Quantitative analysis of membrane proteins from breast cancer cell lines BT474 and MCF7 using multistep solid phase mass tagging and 2D LC/MS.

We introduce a new multistep mass tagging technique and show its utility for reducing sample complexity when coupled with two-dimensional liquid chromatography/nano-electrospray ionization ion trap mass spectrometry (2D LC/nano ESI-MS). Solid-phase mass tagging reagents were used to identify and obtain relative quantitation of membrane proteins from two established breast cancer cell lines, BT474 and MCF7. The results presented in this study show that sample complexity can be reduced with corresponding increases in protein identification and quantitation.

Composition and assembly of STAT-targeting ubiquitin ligase complexes: paramyxovirus V protein carboxyl terminus is an oligomerization domain.

Transcription regulators STAT1 and STAT2 are key components of the interferon signaling system leading to innate antiviral immunity. The related STAT3 protein is a regulator of interleukin-6-type cytokine signals and can contribute to both cell growth and death important for cancer gene regulation and tumor survival. These three STAT proteins are targeted for proteasome-mediated degradation by RNA viruses in the Rubulavirus genus of the Paramyxoviridae.

Is there any connection between the presence of kidney stones in primary hyperparathyroidism and the location of an underlying adenoma?

The majority of the patients with primary hyperparathyroidism (pHPT) recurrently produce kidney stones, while the rest have other clinical manifestations. The aim of this study was to examine the possibility of an association between the presence of kidney stones and the location of an underlying adenoma. This was a retrospective evaluation of the records of 91 patients (10 males, 81 females, mean age: 61.

Incorporation of single-wall carbon nanotubes into an organic polymer monolithic stationary phase for mu-HPLC and capillary electrochromatography.

Single-wall carbon nanotubes (SWNT) were incorporated into an organic polymer monolith containing vinylbenzyl chloride (VBC) and ethylene dimethacrylate (EDMA) to form a novel monolithic stationary phase for high-performance liquid chromatography (HPLC) and capillary electrochromatography (CEC). The retention behavior of neutral compounds on this poly(VBC-EDMA-SWNT) monolith was examined by separating a mixture of small organic molecules using micro-HPLC. The result indicated that incorporation of SWNT enhanced chromatographic retention of small neutral molecules in reversed-phase HPLC presumably because of their strongly hydrophobic characteristics.

Identification and quantification of eight flavones in root and shoot tissues of the medicinal plant huang-qin (Scutellaria baicalensis Georgi) using high-performance liquid chromatography with diode array and mass spectrometric detection.

A method of analysis of eight flavones using high-performance liquid chromatography (HPLC)-diode array detection (DAD)-mass spectrometry (MS) in root and aerial tissues of the medicinal plant Scutellaria baicalensis was developed. The identity of the analytes was confirmed using retention time, UV-vis and mass spectral comparisons to commercial standards. Both UV-vis and mass spectral patterns were characterized for glycosylated flavones.

The effect of intranasal salmon calcitonin therapy on bone mineral density in idiopathic male osteoporosis without vertebral fractures--an open label study.

The aim of this study was to examine the effect of intranasal salmon calcitonin therapy on bone mineral density (BMD) in idiopathic male osteoporosis without vertebral fractures. We conducted a randomized, open label, controlled trial in 71 male patients (mean age 59 +/- 6 years) suffering from idiopathic osteoporosis (femoral neck T-score < -2.5) without vertebral deformity.

Preparation and characterization of alkylated polymethacrylate monolithic columns for micro-HPLC of proteins.

Protein separations were carried out by micro-high performance liquid chromatography (micro-HPLC) with surface alkylated monolithic columns, which were prepared by in situ copolymerization of glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EGDMA) in the presence of dodecanol and toluene as porogens. First, glycidyl groups at the surface of the porous monolith were hydrolyzed with sulfuric acid. The hydroxyl groups thus formed were then reacted with n-alkyl chloride to form alkylated stationary phase.

Weapons of STAT destruction. Interferon evasion by paramyxovirus V protein.

The signal transducer and activator of transcription (STAT) family of proteins function to activate gene transcription downstream of myriad cytokine and growth factor signals. The prototype STAT proteins, STAT1 and STAT2, are required for innate and adaptive antimicrobial immune responses that result from interferon signal transduction. While many viruses have evolved the ability to avoid these antiviral cytokines, the Paramyxoviruses are distinct in their abilities to interfere directly with STAT proteins.

2D LC/MS analysis of membrane proteins from breast cancer cell lines MCF7 and BT474.

Membrane proteins play a central role in the interaction of the cell with its environment and in the function of subcellular organelles. The current study focused on developing a better understanding of the membrane proteome of two well-characterized breast cancer cell lines. Membranes from osmotically lysed BT474 and MCF7 cells were treated with cyanogen bromide followed by a combination of trypsin and Staphylococcus V8 protease to obtain hydrophilic peptides from membrane proteins.

The Jak-STAT pathway stimulated by interleukin 6.

Signal transducer and activator of transcription 3 (STAT3) is widely expressed and activated by a variety of growth-regulating signals as well as diverse cytokines that use gp130 signaling receptors. STAT3 is critical for embryonic development and stem cell biology, as well as inflammation, growth regulation, and multiple immune regulatory and homeostatic functions. The animation shows activation of STAT3 in response to interleukin 6 (IL6), a cytokine involved in triggering inflammation.

The Jak-STAT pathway stimulated by interferon gamma.

Different cytokines stimulate the Janus kinase (Jak) and signal transducer and activator of transcription (STAT) pathway. Interferon gamma (IFN-gamma) is a type II interferon that triggers antiviral and adaptive immune responses through a Jak-STAT signaling pathway. These pathways involve a similar paradigm whereby cytokine binding to the receptor activates the Jaks, which phosphorylate STATs leading to their dimerization, translocation to the nucleus, and activation of their transcription factor activity.

The Jak-STAT pathway stimulated by interferon alpha or interferon beta.

Type I interferons, such as interferon alpha and interferon beta (IFN-alpha and beta), signal through a Janus kinase (Jak) to signal transduction and activator of transcription (STAT) pathway to stimulate gene expression. In response to ligand binding, the receptors dimerize, Jaks phosphorylate STAT1 and STAT2, which then dimerize and interact with a third transcriptional regulator IFN regulatory factor 9 (IRF9) to stimulate gene expression. IFN-alpha is the main innate antiviral cytokine and is essential for effective immune response to viral infection.

The role of liquid chromatography in proteomics.

Proteomics represents a significant challenge to separation scientists because of the diversity and complexity of proteins and peptides present in biological systems. Mass spectrometry as the central enabling technology in proteomics allows detection and identification of thousands of proteins and peptides in a single experiment. Liquid chromatography is recognized as an indispensable tool in proteomics research since it provides high-speed, high-resolution and high-sensitivity separation of macromolecules.

NR2B receptors are involved in the mediation of spinal segmental reflex potentials but not in the cumulative motoneuronal depolarization in vitro.

Windup, the frequency dependent build-up of spinal neuronal responses is an electrophysiological model of the development of the central sensitization in the chronic pain states. NR2B subunit containing NMDA-type glutamate receptors are implicated in the windup of dorsal horn neurons, while their role at the motoneuronal level is controversial. The cumulative motoneuronal depolarization in hemisected rat spinal cord preparation is an in vitro model of windup.

Effect of a neuroprotective drug, eliprodil on cardiac repolarisation: importance of the decreased repolarisation reserve in the development of proarrhythmic risk.

1. The aim of this study was to analyse the effects of eliprodil, a noncardiac drug with neuroprotective properties, on the cardiac repolarisation under in vitro circumstances, under normal conditions and after the attenuation of the 'repolarisation reserve' by blocking the inward rectifier potassium current (I(K1)) current with BaCl(2). 2.

Host evasion by emerging paramyxoviruses: Hendra virus and Nipah virus v proteins inhibit interferon signaling.

Interferon (IFN) can activate Signal Transducer and Activator of Transcription (STAT) proteins to establish a cellular antiviral response and inhibit virus replication. Many viruses have evolved strategies to inhibit this antiviral mechanism, but paramyxoviruses are unique in their abilities to directly target the IFN-responsive STAT proteins. Hendra virus and Nipah virus (Henipaviruses) are recently emerged paramyxoviruses that are the causative agents of fatal disease outbreaks in Australia and peninsular Malaysia.

Capillary electrochromatography of peptides and proteins.

This paper reviews recent progress in bioanalysis using capillary electrochromatography (CEC), especially in the field of separation of proteins and peptides. Fundamentals of CEC are briefly discussed. Since most of the recent developments on CEC have focused on column technology, i.