Efficient and isoform-selective inhibition of cellular gene expression by peptide nucleic acids.

Peptide nucleic acids (PNAs) are a potentially powerful approach for the recognition of cellular mRNA and the inhibition of gene expression. Despite their promise, the rules for using antisense PNAs have remained obscure, and antisense PNAs have been used sparingly in research. Here we investigate the ability of PNAs to be effective antisense agents inside mammalian cells, to inhibit expression of human caveolin-1 (hCav-1), and to discriminate between its alpha and beta isoforms.

[A new membrane-permeable peptide from human].

Objective: To study the translocation ability of a new protein domain (Circadian locomotor output cycles kaput protein's DNA-binding peptide, hCLOCK's DNA_BIND) from human through the membrane.

Method: hCLOCK's DNA_BIND, which was chemically synthesized and labeled with FITC at N-terminal, was incubated with the vascular endothelial cell (ECV-304) and primary culture neuroglial cells in the culture medium, the distribution of it was observed on a fluorescence microscope.

Result: hCLOCK's DNA_BIND has the ability to translocate through the cell membrane and accumulate in the nucleus.

RNA interference in mammalian cells by chemically-modified RNA.

RNA interference (RNAi) is proving to be a robust and versatile technique for controlling gene expression in mammalian cells. To fully realize its potential in vivo, however, it may be necessary to introduce chemical modifications to optimize potency, stability, and pharmacokinetic properties. Here, we test the effects of chemical modifications on RNA stability and inhibition of gene expression.

Explanation of vegetation succession in subtropical southern China based on ecophysiological characteristics of plant species.

A stomatal conductance model and a photosynthesis model were applied to field measurements of transpiration and photosynthesis of seven tree species growing in subtropical southern China. Parameter values of drought resistance and tolerance and biochemical assimilation capacity were obtained by means of nonlinear statistical regression, and were used to quantify species succession. The analysis indicated that the models adequately described the ecophysiological behavior of the trees under various environmental conditions.

New aspects of formation of 1,2-cyclic phosphates by phospholipase C-delta1.

Phosphoinositide-specific phospholipase C-delta1 (PI-PLC-delta1) cleaves phosphatidylinositol 4,5-bisphosphate (PI-4,5-P(2), 1), 5-phosphate (PI-5-P, 2) and 4-phosphate (PI-4-P, 3) to form the mixture of the corresponding 4,5-, 5- and 4-phosphorylated inositol 1,2-cyclic phosphate (IcP) and 1-phosphate (IP) (4-6 and 7-9, respectively). In this work, we have studied the rates of the cleavage and the ratios of the cyclic-to-acyclic phosphate products under various pH and Ca(2+) concentration conditions using 31P NMR to monitor the reactions. In agreement with the previous report (Kim et al.

Adaptation and temporal decorrelation by single neurons in the primary visual cortex.

Limiting redundancy in the real-world sensory inputs is of obvious benefit for efficient neural coding, but little is known about how this may be accomplished by biophysical neural mechanisms. One possible cellular mechanism is through adaptation to relatively constant inputs. Recent investigations in primary visual (V1) cortical neurons have demonstrated that adaptation to prolonged changes in stimulus contrast is mediated in part through intrinsic ionic currents, a Ca2+-activated K+ current (IKCa) and especially a Na+-activated K+ current (IKNa).

A novel calcium-dependent bacterial phosphatidylinositol-specific phospholipase C displaying unprecedented magnitudes of thio effect, inverse thio effect, and stereoselectivity.

Understanding the potential range of enzymatic thio effects (kO/kS) is of great value when using sulfur-substituted phosphate analogues to study phosphoryl transfer reactions in enzymes and ribozymes. Herein we report that a newly discovered Ca2+-dependent Streptomyces antibioticus phosphatidylinositol-specific phospholipase C and its mutants display unprecedented magnitudes of thio effect, inverse thio effect, and RP/SP stereoselectivity. We demonstrate that for a single enzyme the bridging thio effect can vary from 0.

Antisense inhibition of gene expression in cells by oligonucleotides incorporating locked nucleic acids: effect of mRNA target sequence and chimera design.

Use of antisense oligonucleotides is a versatile strategy for achieving control of gene expression. Unfortunately, the interpretation of antisense-induced phenotypes is sometimes difficult, and chemical modifications that improve the potency and specificity of antisense action would be useful. The introduction of locked nucleic acid (LNA) bases into oligonucleotides confers exceptional improvement in binding affinity, up to 10 degrees C per substitution, making LNAs an exciting option for the optimization of antisense efficacy.

Complications and conversions in myeloproliferative disorders: an analysis of 356 cases.

Objective: To investigate the complications and conversions in myeloproliferative disorders (MPD).

Methods: Three hundred and fifty six patients with MPD were reviewed, including 78 with etiologic thrombocythemia (ET), 93 with primary myelofibrosis (MF), 185 with polythythemia vera (PV). The clinical observation, follow-up, analysis with SPSS statistic software were performed.

Adrenalectomy abrogates reduction of 12-O-tetradecanoylphorbol-13-acetate-induced extracellular signal-regulated protein kinase activity in the epidermis of dietary energy-restricted SENCAR mice: implications of glucocorticoid hormone.

Previous studies in this laboratory demonstrated that dietary energy restriction (DER), a potent inhibitor of skin carcinogenesis, markedly suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced extracellular signal-regulated protein kinase (ERK) activity in mouse epidermis. Intact adrenal glands have been reported to be important in the inhibition of skin tumor promotion by food restriction. We investigated the role of adrenal glands and corticosterone in the DER effect on ERK activity.