Venom-Derived Peptide Modulators of Cation-Selective Channels: Friend, Foe or Frenemy.

Ion channels play a key role in our body to regulate homeostasis and conduct electrical signals. With the help of advances in structural biology, as well as the discovery of numerous channel modulators derived from animal toxins, we are moving toward a better understanding of the function and mode of action of ion channels. Their ubiquitous tissue distribution and the physiological relevancies of their opening and closing suggest that cation channels are particularly attractive drug targets, and years of research has revealed a variety of natural toxins that bind to these channels and alter their function. In this review, we provide an introductory overview of the major cation ion channels: potassium channels, sodium channels and calcium channels, describe their venom-derived peptide modulators, and how these peptides provide great research and therapeutic value to both basic and translational medical research.

CSP and takeout genes modulate the switch between attraction and repulsion during behavioral phase change in the migratory locust.

Behavioral plasticity is the most striking trait in locust phase transition. However, the genetic basis for behavioral plasticity in locusts is largely unknown. To unravel the molecular mechanisms underlying the behavioral phase change in the migratory locust Locusta migratoria, the gene expression patterns over the time courses of solitarization and gregarization were compared by oligonucleotide microarray analysis. Data analysis revealed that several gene categories relevant to peripheral olfactory perception are strongly regulated in a total of 1,444 differentially expressed genes during both time courses. Among these candidate genes, several CSP (chemosensory protein) genes and one takeout gene, LmigTO1, showed higher expression in gregarious and solitarious locusts, respectively, and displayed opposite expression trends during solitarization and gregarization. qRT-PCR experiments revealed that most CSP members and LmigTO1 exhibited antenna-rich expressions. RNA interference combined with olfactory behavioral experiments confirmed that the CSP gene family and one takeout gene, LmigTO1, are involved in the shift from repulsion to attraction between individuals during gregarization and in the reverse transition during solitarization. These findings suggest that the response to locust-emitted olfactory cues regulated by CSP and takeout genes is involved in the behavioral phase change in the migratory locust and provide a previously undescribed molecular mechanism linked to the formation of locust aggregations.

Simvastatin combined with nifedipine enhances endothelial cell protection by inhibiting ROS generation and activating Akt phosphorylation.

AIM: To investigate the protective effects of simvastatin (Sim) combined with nifedipine (Nif) on endothelial cells and elucidate the action mechanism. METHODS: Human umbilical vein endothelial cells (HUVEC) were used. mRNA and protein levels were measured by using reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting, respectively. Intracellular calcium and reactive oxygen species (ROS) were detected using confocal microscopy. The Griess assay was used to evaluate nitric oxide (NO) release. RESULTS: Treatment of HUVEC with H(2)O(2) 100 micromol/L for 30 min inhibited the mRNA and protein expression of endothelial nitric oxide synthase (eNOS). With increased concentrations of Nif, eNOS mRNA and protein levels increased (P<0.05). Combined treatment with Sim 1.0 micromol/L and Nif 1.0 micromol/L significantly increased the mRNA and protein expression of eNOS and NO release compared with Sim or Nif alone (P<0.05). The combination significantly lowered the intracellular ROS level (P<0.05), which was correlated with the increase in eNOS and NO, but there was no visible change in intracellular calcium (P>0.05). Compared with individual drug treatment, Akt phosphorylation and the ratio of p-eNOS/eNOS were up-regulated in the combination group, and this effect was inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002. CONCLUSION: The Sim-Nif combination effectively protects HUVEC against H(2)O(2) injury by inhibiting intracellular ROS generation, increasing the ratio of p-eNOS/eNOS and up-regulating Akt phosphorylation.

Biodrying of municipal solid waste with high water content by combined hydrolytic-aerobic technology.

The high water content of municipal solid waste (MSW) will reduce the efficiency of mechanical sorting, consequently unfavorable for beneficial utilization. In this study, a combined hydrolytic-aerobic biodrying technology was introduced to remove water from MSW. The total water removals were proved to depend on the ventilation frequency and the temporal span in the hydrolytic stage. The ventilation frequency of 6 times/d was preferable in the hydrolytic stage. The hydrolytic span should not be prolonged more than 4 d. At this optimal scenario, the final water content was 50.5% reduced from the initial water content of 72.0%, presenting a high water removal efficiency up to 78.5%. A positive correlation was observed between the organics losses and the water losses in both hydrolytic and aerobic stages (R = 0.944, p < 0.01). The evolutions of extracellular enzyme activities were shown to be consistent with the organics losses.