четверг, 11 октября 2012 г.

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IJMS, Vol. 13, Pages 13030-13048: Binding of the Phage Display Derived Peptide CaIX-P1 on Human Colorectal Carcinoma Cells Correlates with the Expression of Carbonic Anhydrase IX

Posted: 11 Oct 2012 12:00 AM PDT

Phage display represents an attractive screening strategy for the identification of novel, specific binding ligands that could be used for tumor targeting. Recently, a new peptide (CaIX-P1) with affinity for human carbonic anhydrase IX (CAIX) was identified and evaluated. The aim of the present study is to characterize the properties of CaIX-P1 for targeting human colorectal carcinoma and investigate the correlation of peptide binding with the expression of carbonic anhydrase IX. Human colorectal carcinoma HCT116 and HT29 cells were investigated for CAIX expression using Western Blot analysis. Binding and competition studies of 125I-radiolabeled CaIX-P1 were performed on HCT116 cells in vitro. FACS analysis and fluorescence microscopy studies were carried out after cell incubation with fluorescein-labeled CaIX-P1 and rhodamine-labeled anti-human CAIX-mAb. Our studies revealed an enhanced in vitro expression of carbonic anhydrase IX in HCT116 and HT29 cells with increasing cell density. Binding of 125I-labeled-CaIX-P1 on HCT116 cells increased with increasing cell density and correlated to the CAIX expression. FACS analysis demonstrated a correlation of cell labeling between FITC-CaIX-P1 and rhodamine-labeled anti-CAIX-mAb in both HCT116 and HT29 cells. The results of our study indicate that the phage display identified peptide CaIX-P1 might be an attractive candidate for the development of a ligand targeting CAIX in colorectal cancer.

Polymers, Vol. 4, Pages 1627-1644: Novel Blend Membranes Based on Acid-Base Interactions for Fuel Cells

Posted: 11 Oct 2012 12:00 AM PDT

Fuel cells hold great promise for wide applications in portable, residential, and large-scale power supplies. For low temperature fuel cells, such as the proton exchange membrane fuel cells (PEMFCs) and direct methanol fuel cells (DMFCs), proton-exchange membranes (PEMs) are a key component determining the fuel cells performance. PEMs with high proton conductivity under anhydrous conditions can allow PEMFCs to be operated above 100 °C, enabling use of hydrogen fuels with high-CO contents and improving the electrocatalytic activity. PEMs with high proton conductivity and low methanol crossover are critical for lowering catalyst loadings at the cathode and improving the performance and long-term stability of DMFCs. This review provides a summary of a number of novel acid-base blend membranes consisting of an acidic polymer and a basic compound containing N-heterocycle groups, which are promising for PEMFCs and DMFCs.

Diagnostics, Vol. 2, Pages 52-56: Visual Suppression is Impaired in Spinocerebellar Ataxia Type 6 but Preserved in Benign Paroxysmal Positional Vertigo

Posted: 11 Oct 2012 12:00 AM PDT

Positional vertigo is a common neurologic emergency and mostly the etiology is peripheral. However, central diseases may mimic peripheral positional vertigo at their initial presentation. We here describe the results of a visual suppression test in six patients with spinocerebellar ataxia type 6 (SCA6), a central positional vertigo, and nine patients with benign paroxysmal positional vertigo (BPPV), the major peripheral positional vertigo. As a result, the visual suppression value of both diseases differed significantly; e.g., 22.5% in SCA6 and 64.3% in BPPV (p < 0.001). There was a positive correlation between the visual suppression value and disease duration, cerebellar atrophy, and CAG repeat length of SCA6 but they were not statistically significant. In conclusion, the present study showed for the first time that visual suppression is impaired in SCA6, a central positional vertigo, but preserved in BPPV, the major peripheral positional vertigo, by directly comparing both groups. The abnormality in the SCA6 group presumably reflects dysfunction in the central visual fixation pathway at the cerebellar flocculus and nodulus. This simple test might aid differential diagnosis of peripheral and central positional vertigo at the earlier stage of disease.disease.

IJMS, Vol. 13, Pages 13012-13029: Transcriptomic Analysis of Phenotypic Changes in Birch (Betula platyphylla) Autotetraploids

Posted: 11 Oct 2012 12:00 AM PDT

Plant breeders have focused much attention on polyploid trees because of their importance to forestry. To evaluate the impact of intraspecies genome duplication on the transcriptome, a series of Betula platyphylla autotetraploids and diploids were generated from four full-sib families. The phenotypes and transcriptomes of these autotetraploid individuals were compared with those of diploid trees. Autotetraploids were generally superior in breast-height diameter, volume, leaf, fruit and stoma and were generally inferior in height compared to diploids. Transcriptome data revealed numerous changes in gene expression attributable to autotetraploidization, which resulted in the upregulation of 7052 unigenes and the downregulation of 3658 unigenes. Pathway analysis revealed that the biosynthesis and signal transduction of indoleacetate (IAA) and ethylene were altered after genome duplication, which may have contributed to phenotypic changes. These results shed light on variations in birch autotetraploidization and help identify important genes for the genetic engineering of birch trees.

IJMS, Vol. 13, Pages 12994-13011: A Molecular Dynamics (MD) and Quantum Mechanics/Molecular Mechanics (QM/MM) Study on Ornithine Cyclodeaminase (OCD): A Tale of Two Iminiums

Posted: 11 Oct 2012 12:00 AM PDT

Ornithine cyclodeaminase (OCD) is an NAD+-dependent deaminase that is found in bacterial species such as Pseudomonas putida. Importantly, it catalyzes the direct conversion of the amino acid L-ornithine to L-proline. Using molecular dynamics (MD) and a hybrid quantum mechanics/molecular mechanics (QM/MM) method in the ONIOM formalism, the catalytic mechanism of OCD has been examined. The rate limiting step is calculated to be the initial step in the overall mechanism: hydride transfer from the L-ornithine's Cα–H group to the NAD+ cofactor with concomitant formation of a Cα=NH2+ Schiff base with a barrier of 90.6 kJ mol−1. Importantly, no water is observed within the active site during the MD simulations suitably positioned to hydrolyze the Cα=NH2+ intermediate to form the corresponding carbonyl. Instead, the reaction proceeds via a non-hydrolytic mechanism involving direct nucleophilic attack of the δ-amine at the Cα-position. This is then followed by cleavage and loss of the α-NH2 group to give the Δ1-pyrroline-2-carboxylate that is subsequently reduced to L-proline.

Molecules, Vol. 17, Pages 11978-11989: The Binding Affinity and Molecular Basis of the Structure-Binding Relationship between Urinary Tamm-Horsfall Glycoprotein and Tumor Necrosis Factor-α

Posted: 11 Oct 2012 12:00 AM PDT

In a previous study we noted significant THP binding to TNF-α, but did not explore the molecular basis of the structure-binding relationship. In this study, we used lectin-binding ELISA to assess the carbohydrate compositions of THP, BSA, IgG, TNF-α, and IFN-g. We identified β(1,4)-N-acetylglucosamine oligomers (GlcNAc) and GlcNAc/branched mannose in BSA, IgG, TNF-α, and THP, but not in IFN-g. These carbohydrate moieties mediated binding with THP. Small amounts of Siaα(2,3)Gal/ GalNAc, Sia(2,6)Gal/GalNAc, and mannose residues were also present in THP and TNF-α. Binding affinity (Kd) between THP and TNF-α by Scatchard plot analysis was 1.4–1.7 × 10−6 M, lower than antigen-antibody or ligand-receptor binding affinities. To elucidate the structure-binding relationship of THP-TNF-α, THP was digested with neuraminidase, β-galactosidase, O-sialoglycoprotein endopeptidase, carboxypeptidase Y, or proteinase K. β-galactosidase increased binding capacity of THP for TNF-α. Monosaccharide inhibition suggested that α-methyl-D-mannoside, GlcNAc, and GalNAc, but not sialic acid, suppress THP-TNF-α binding as detected by ELISA. We conclude that sugar-lectin and sugar-protein interactions between cognate sites in THP and TNF-α mediate their binding.

Golden Joystick Awards 2012: Best Handheld category – who are you voting for?

Posted: 11 Oct 2012 02:13 AM PDT

As voting for the Golden Joystick Awards 2012 enters its final weeks, we take a look at each of the individual categories. Today is the turn of Best

Storm Boat

Posted: 11 Oct 2012 01:42 AM PDT

Drive a speedy storm boat in deep sea and become the ultimate champion of year 2012.

Remote Sensing, Vol. 4, Pages 3022-3054: Simulations of Infrared Radiances over a Deep Convective Cloud System Observed during TC4: Potential for Enhancing Nocturnal Ice Cloud Retrievals

Posted: 11 Oct 2012 12:00 AM PDT

Retrievals of ice cloud properties using infrared measurements at 3.7, 6.7, 7.3, 8.5, 10.8, and 12.0 mm can provide consistent results regardless of solar illumination, but are limited to cloud optical thicknesses t < ~6. This paper investigates the variations in radiances at these wavelengths over a deep convective cloud system for their potential to extend retrievals of t and ice particle size De to optically thick clouds. Measurements from an imager, an interferometer, the Cloud Physics Lidar (CPL), and the Cloud Radar System (CRS) aboard the NASA ER-2 aircraft during the NASA TC4 (Tropical Composition, Cloud and Climate Coupling) experiment flight during 5 August 2007, are used to examine the retrieval potential of infrared radiances over optically thick ice clouds. Simulations based on coincident in situ measurements and combined cloud t from CRS and CPL measurements are comparable to the observations. They reveal that brightness temperatures at these bands and their differences (BTD) are sensitive to t up to ~20 and that for ice clouds having t > 20, the 3.7–10.8 µm and 3.7–6.7 µm BTDs are the most sensitive to De. Satellite imagery appears to be consistent with these results suggesting that t and De could be retrieved for greater optical thicknesses than previously assumed. But, because of sensitivity of the BTDs to uncertainties in the atmospheric profiles of temperature, humidity, and ice water content, and sensor noise, exploiting the small BTD signals in retrieval algorithms will be very challenging.

Molecules, Vol. 17, Pages 11965-11977: trans-Caryophyllene, a Natural Sesquiterpene, Causes Tracheal Smooth Muscle Relaxation through Blockade of Voltage-Dependent Ca2+ Channels

Posted: 11 Oct 2012 12:00 AM PDT

trans-Caryophyllene is a major component in the essential oils of various species of medicinal plants used in popular medicine in Brazil. It belongs to the chemical class of the sesquiterpenes and has been the subject of a number of studies. Here, we evaluated the effects of this compound in airway smooth muscle. The biological activities of trans-caryophyllene were examined in isolated bath organs to investigate the effect in basal tonus. Electromechanical and pharmacomechanical couplings were evaluated through the responses to K+ depolarization and exposure to acetylcholine (ACh), respectively. Isolated cells of rat tracheal smooth muscle were used to investigate trans-caryophyllene effects on voltage-dependent Ca2+ channels by using the whole-cell voltage-clamp configuration of the patch-clamp technique. trans-Caryophyllene showed more efficiency in the blockade of electromechanical excitation-contraction coupling while it has only minor inhibitory effect on pharmacomechanical coupling. Epithelium removal does not modify tracheal smooth muscle response elicited by trans-caryophyllene in the pharmacomechanical coupling. Under Ca2+-free conditions, pre-exposure to trans-caryophyllene did not reduce the contraction induced by ACh in isolated rat tracheal smooth muscle, regardless of the presence of intact epithelium. In the whole-cell configuration, trans-caryophyllene (3 mM), inhibited the inward Ba2+ current (IBa) to approximately 50% of control levels. Altogether, our results demonstrate that trans-caryophyllene has anti-spasmodic activity on rat tracheal smooth muscle which could be explained, at least in part, by the voltage-dependent Ca2+ channels blockade.

Powerball Winning Numbers for 10/10/2012

Posted: 10 Oct 2012 09:47 PM PDT

18 - 26 - 29 - 35 - 43 Powerball 28

Powerball Estimated Jackpot for 10/13/2012

Posted: 10 Oct 2012 09:47 PM PDT

Annuitized: $60 Million Cash Value: $38.7 Million

Mega Millions Winning Numbers for 10/09/2012

Posted: 10 Oct 2012 09:47 PM PDT

6 - 15 - 16 - 22 - 37 MegaBall 3 Megaplier 4

Mega Millions Estimated Jackpot for 10/12/2012

Posted: 10 Oct 2012 09:47 PM PDT

Annuitized: $53 Million Cash Value: $39.7 Million

Lotto Texas Winning Numbers for 10/10/2012

Posted: 10 Oct 2012 09:47 PM PDT

5 - 13 - 14 - 24 - 27 - 52

Lotto Texas Estimated Jackpot for 10/13/2012

Posted: 10 Oct 2012 09:47 PM PDT

Annuitized: $25 Million Cash Value: $19.0 Million

Texas Two Step Winning Numbers for 10/08/2012

Posted: 10 Oct 2012 09:47 PM PDT

1 - 4 - 16 - 33 Bonus Ball 3

Texas Two Step Advertised Jackpot for 10/11/2012

Posted: 10 Oct 2012 09:47 PM PDT

$200,000

Pick 3 Day Winning Numbers for 10/10/2012

Posted: 10 Oct 2012 09:47 PM PDT

8 - 5 - 4 Sum It Up = 17

Pick 3 Night Winning Numbers for 10/10/2012

Posted: 10 Oct 2012 09:47 PM PDT

5 - 5 - 8 Sum It Up = 18

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