Mutations in the PTEN induced putative kinase 1 (PINK1) gene cause an autosomal recessive form of Parkinson disease (PD). So far, no substrates of PINK1 have been reported, and the mechanism by which PINK1 mutations lead to neurodegeneration is unknown. Here we report the identification of TNF receptor-associated protein 1 (TRAP1), a mitochondrial molecular chaperone also known as heat shock protein 75 (Hsp75), as a cellular substrate for PINK1 kinase. PINK1 binds and colocalizes with TRAP1 in the mitochondria and phosphorylates TRAP1 both in vitro and in vivo. We show that PINK1 protects against oxidative-stress-induced cell death by suppressing cytochrome c release from mitochondria, and this protective action of PINK1 depends on its kinase activity to phosphorylate TRAP1. Moreover, we find that the ability of PINK1 to promote TRAP1 phosphorylation and cell survival is impaired by PD-linked PINK1 G309D, L347P, and W437X mutations. Our findings suggest a novel pathway by which PINK1 phosphorylates downstream effector TRAP1 to prevent oxidative-stress-induced apoptosis and implicate the dysregulation of this mitochondrial pathway in PD pathogenesis.

Aquaculture is emerging as the fastest growing food-producing industry in the world because of the increasing demand for food fish consumption. However, the intensive culture of food fish has led to outbreaks of various bacterial diseases, resulting in annual economic losses to the aquaculture industry estimated at billions of dollars worldwide. Feeding infected fish with antibiotic-medicated food is a general practice but has led to antibiotic resistance development in bacterial pathogen, resulting in a higher dose requirement for effective control, a matter of increasing public concern. Therefore, alternatives to antibiotics that give similar or enhanced protection to aquatic animals are urgently needed. Various vaccines have been developed recently to combat bacterial diseases in aquaculture. The purpose of this review is to summarize the major bacterial pathogens in aquaculture and the development of vaccines as alternatives to antibiotics to protect aquatic animals from these bacterial diseases.

Three isolates (AL09-71, AL09-72, and AL09-73) of Aeromonas hydrophila were cultured from infected channel catfish Ictalurus punctatus during a disease outbreak in west Alabama, USA, in August 2009. Sequence analysis of the 16S-23S rDNA intergenic spacer region (ISR), cpn60, gyrB, and rpoD genes of the 3 strains revealed that the 3 strains were closely related to each other, sharing 97 to 99% nucleotide sequence similarities. However, ISR sequences of the 3 isolates from 2009 shared only 64% nucleotide sequences with AL98-C1B, a 1998 isolate of A. hydrophila cultured from diseased fish in Alabama. Sequences of cpn60, gyrB, and rpoD from the 3 isolates from 2009 shared 91 to 95% homologies with AL98-C1B. Based on both LD50 and LD95 values of intraperitoneal injection assays, the virulences of the 3 isolates from 2009 were not significantly different from each other, but were at least 200-fold more virulent than AL98-C1B, indicating that the 3 west Alabama isolates of A. hydrophila from 2009 were highly virulent to channel catfish.

To access the relative potency of pesticides to control adult mosquitoes, 19 pesticides with various modes of action were evaluated against Aedes aegypti, Culex quinquefasciatus Say, and Anopheles quadrimaculatus Say. On the basis of 24-h LD 50 values after topical application, the only pesticide that had higher activity than permethrin was Þpronil, with LD 50 values lower than per-methrin for 107-, 4,849-, and 2-fold against Ae. aegypti, Cx. quinquefasciatus Say, and An. quadrimacu-latus Say, respectively. Abamectin, imidacloprid, spinosad, diazinon, and carbaryl showed slightly lower activity than permethrin (20-fold). However, bifenazate showed very low activity against the three mosquito species tested, with LD 50 values higher than permthrin for 1000-fold. On the basis of 24-h LD 50 values, Cx. quinquefasciatus was the least susceptible species to nine pesticides tested (DNOC, azocyclotin, chlorfenapyr, carbaryl, spinosad, imidaclorid, diazinon, abamectin, and per-methrin), whereas Ae. aegypti was the least susceptible species to six pesticides tested (dicofol, amitraz, propargite, hydramethylnon, cyhexatin, and diafenthiuron), and An. quadrimaculatus was the least susceptible species to four pesticides tested (bifenazate, pyridaben, indoxacarb, and Þpronil). Our results revealed that different species of mosquitoes had different susceptibility to pesticides, showing the need to select the most efÞcacious compounds for the least susceptible mosquito species to achieve successful mosquito control.

Mosquitoes that transmit human diseases are of major importance to the international public health community. Pesticides remain a major component of integrated programs to control these medically important species. However, very few types of pesticides are currently registered for mosquito control. A high-throughput screening method using first-instar larvae of Aedes aegypti was created and evaluated in our laboratory to quickly screen large numbers of chemicals for activity against mosquitoes. LC50 values of a representative group of compounds were determined using this high-throughput screening method and compared with LD50 values determined by topical application against female adults of Ae. aegypti. Our results show that this high-throughput screening method is suitable for screening large numbers of candidate chemicals quickly to identify effective compounds.