Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain

Background  

Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA)-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation.     

Repellency and toxicity of mint oil granules to red imported fire ants (Hymenoptera: Formicidae)

Repellency and toxicity of 2% mint oil granules were evaluated against worker red imported fire ants. Solenopsis invicta Buren, in a series of laboratory and field experiments. In continuous exposure experiments, LT50 values ranged from 1.2 h with 164.8 mg/cm2 of 2% mint oil granules to 15.3 h with 1.65 mg/cm2 of granules. LT50 values declined exponentially with increasing rate of mint oil granules. Limited exposure to 164.8 mg/cm2 mint oil granules resulted in > 50% knock down (KD) after 30 min; however, there was no KD at 15 min. Twenty-four hour mortality increased linearly with increasing exposure time. Mean repellency of worker red imported fire ants ranged from 49.2 +/- 5.4% for 0 mg/cm2 (untreated control) of mint oil granules at 30 min to 100% for 147.8 mg/cm2 of mint oil granules at 3 h. Repellency increased with increasing milligrams per square centimeter of mint oil granules and exposure time. In field tests, 100% of mounds opened and treated with mint oil granules were abandoned 5 d after treatment and ants had relocated or formed satellite mounds by 2 d after treatment. Unopened mounds treated topically with mint oil granules were not abandoned, but ants formed satellite mounds 2 d after treatment. Mint oil granules could provide another tool for red imported fire ant integrated pest management, particularly in situations in which conventional insecticides would be inappropriate.     

Protein structure similarity from principle component correlation analysis

Background  

Owing to rapid expansion of protein structure databases in recent years, methods of structure comparison are becoming increasingly effective and important in revealing novel information on functional properties of proteins and their roles in the grand scheme of evolutionary biology. Currently, the structural similarity between two proteins is measured by the root-mean-square-deviation (RMSD) in their best-superimposed atomic coordinates. RMSD is the golden rule of measuring structural similarity when the structures are nearly identical; it, however, fails to detect the higher order topological similarities in proteins evolved into different shapes. We propose new algorithms for extracting geometrical invariants of proteins that can be effectively used to identify homologous protein structures or topologies in order to quantify both close and remote structural similarities.     

Role of extracellular charged amino acids in the yeast alpha-factor receptor

The yeast pheromone receptor, Ste2p, is a G protein coupled receptor that initiates cellular responses to alpha-mating pheromone, a 13 residue peptide that carries a net positive charge at physiological pH. We have examined the role of extracellular charged groups on the receptor in response to the pheromone. Substitutions of Asn or Ala for one extracellular residue, Asp275, affected both pheromone binding and signaling, suggesting that this position interacts directly with ligand. The other seven extracellular acidic residues could be individually replaced by polar residues with no detectable effects on receptor function. However, substitution of Ala for each of these seven residues resulted in impairment of signaling without affecting pheromone binding, implying that the polar nature of these residues promotes receptor activation. In contrast, substitution of Ala for each of the six positively charged residues at the extracellular surface of Ste2p did not affect signaling.     

Conditional random pattern model for copy number aberration detection

Background  

DNA copy number aberration (CNA) is very important in the pathogenesis of tumors and other diseases. For example, CNAs may result in suppression of anti-oncogenes and activation of oncogenes, which would cause certain types of cancers. High density single nucleotide polymorphism (SNP) array data is widely used for the CNA detection. However, it is nontrivial to detect the CNA automatically because the signals obtained from high density SNP arrays often have low signal-to-noise ratio (SNR), which might be caused by whole genome amplification, mixtures of normal and tumor cells, experimental noise or other technical limitations. With the reduction in SNR, many false CNA regions are often detected and the true CNA regions are missed. Thus, more sophisticated statistical models are needed to make the CNAs detection, using the low SNR signals, more robust and reliable.     

Structure and activity of DmmA, a marine haloalkane dehalogenase

DmmA is a haloalkane dehalogenase (HLD) identified and characterized from the metagenomic DNA of a marine microbial consortium. Dehalogenase activity was detected with 1,3-dibromopropane as substrate, with steady-state kinetic parameters typical of HLDs (K_m = 0.24 ± 0.05 mM, k_cat = 2.4 ± 0.1 s⁻¹). The 2.2-Å crystal structure of DmmA revealed a fold and active site similar to other HLDs, but with a substantially larger active site binding pocket, suggestive of an ability to act on bulky substrates. This enhanced cavity was shown to accept a range of linear and cyclic substrates, suggesting that DmmA will contribute to the expanding industrial applications of HLDs.     

Semi-supervised drug-protein interaction prediction from heterogeneous biological spaces

Background

Predicting drug-protein interactions from heterogeneous biological data sources is a key step for in silico drug discovery. The difficulty of this prediction task lies in the rarity of known drug-protein interactions and myriad unknown interactions to be predicted. To meet this challenge, a manifold regularization semi-supervised learning method is presented to tackle this issue by using labeled and unlabeled information which often generates better results than using the labeled data alone. Furthermore, our semi-supervised learning method integrates known drug-protein interaction network information as well as chemical structure and genomic sequence data.

Results

Using the proposed method, we predicted certain drug-protein interactions on the enzyme, ion channel, GPCRs, and nuclear receptor data sets. Some of them are confirmed by the latest publicly available drug targets databases such as KEGG.

Conclusions

We report encouraging results of using our method for drug-protein interaction network reconstruction which may shed light on the molecular interaction inference and new uses of marketed drugs.

     

Effects of moisture on the toxicity of inorganic and organic insecticidal dust formulations to German cockroaches (Blattodea: Blattellidae)

Toxicity of boric acid (40-99% [AI]), silica gel, eugenol, and deltamethrin dust formulations to adult male German cockroaches, Blattella germanica (L.), was evaluated at five different relative humidities ranging from 0 to 100% and in the presence of 0 to 1 ml of water. Victor boric acid dust was generally the most toxic boric acid formulation at all relative humidities, despite having the lowest percentage (40%) of boric acid; however, this was the only formulation to have sucrose and other edible ingredients. There was no consistent effect of relative humidity on dust toxicity; LT50 values of Roach Prufe (98% boric acid), Victor, and Drione (silica gel and synergized pyrethrins) increased significantly linearly with relative humidity, whereas other formulations were unaffected. The LT50 values of all boric acid-based dust formulations declined exponentially when wetted with increasing volumes of water. Water did not affect the toxicity of deltamethrin and eugenol dusts, but it caused a linear decline in toxicity of silica gel (Dri-Die). The toxicity of a formulation containing silica gel and synergized pyrethrins (Drione) increased exponentially with increasing amounts of water. Moisture in the form of relative humidity does not strongly affect the toxicity of most insecticidal dust formulations. Presence of water, however, increases the toxicity of boric acid dusts and Drione. Toxicity of the hydrophobic deltamethrin (DeltaDust) and eugenol (EcoPCO D) dusts were unaffected by water.