The Architect of Neurotransmission in C. elegans : How FLP-3 Neuropeptides' Structures Direct their Function.

Neuropeptides direct functions in the nervous, endocrine, and immune systems of all animals by altering the activity at neural synapses. A single neuropeptide gene can be post-translationally modified to create multiple active peptides. These individual active peptides can have unique functions and drive discrete binding partners. We have previously shown that specific peptides encoded by the C. elegans neuropeptide gene, flp- 3, have sex-specific roles in response to a pheromone released by hermaphrodite C. elegans, ascaroside #8 (ascr#8). Using structural predictions of select FLP-3 neuropeptides, we identify individual amino acids within specific neuropeptides that regulate specific behaviors suggesting structure-function relationships of neuropeptides in regulate sex-specific behaviors.

Molecular characterization of Cryptosporidium spp. from migratory ducks around Tokachi subprefecture, Hokkaido, Japan.

Cryptosporidium, a waterborne protozoan parasite, has a substantial veterinary and medical impact worldwide. This parasite is more often recognized during waterborne outbreaks because of its resistance to chlorine disinfection, small size making it difficult to inactivate/eliminate through filtration, and presence in many animal species including humans. Migratory waterfowl, in addition to acting as mechanical carriers of Cryptosporidium oocysts, can also serve as natural reservoirs of infection by host-specific Cryptosporidium species. For better understanding of the extent of genetic diversity and inter-relationships among avian isolates of Cryptosporidium, 200 fecal samples of migratory ducks from the Tokachi subprefecture, Hokkaido, Japan were collected and analyzed by nested PCR (N-PCR) at the 18S rRNA gene. N-PCR revealed that 11.5% (23/200) were positive for Cryptosporidium spp. Among all samples, sequence analysis identified that 10% (20/200) were 98-100% identical to Cryptosporidium avian genotype III. On the other hand, 1.5% (3/200) were 99-100% identical to C. baileyi. This is the first molecular study reporting the prevalence of Cryptosporidium in migratory ducks in Japan. Genetic diversity among Cryptosporidium isolates from humans and birds has been reported worldwide. Nevertheless, further studies are important to assess genetic variety and to elucidate the transmission dynamics of Cryptosporidium parasites.

Factors Influencing the Potency of Alzheimer Inhibitors: Computational and Docking Studies.

Density functional theory (B3LYP/6-31G [d]) is performed to study the effect of molecular and electronic structures of the investigated ß-secretase 1 (BACE1) Alzheimer's inhibitors on their biological activities and discuss the correlation between their inhibition efficiencies and quantum chemical descriptors. IC50 values of the investigated compounds are mostly affected by the substituted R2 phenyl moiety. The calculations show that the presence of electron withdrawing group increases the half maximal inhibitory concentration (IC50). Structure-activity relationship studies show that the electronic descriptors, energy of high occupied molecular orbital, ΔE, lipophilicity, hardness, and ionization potential index, are the most significant descriptors for the correlation with IC50. Molecular docking simulation is performed to explain the mode of interaction between the most potent drug and the binding sites of the BACE1 target. A good correlation between the experimental and the theoretical data confirms that the quantum chemical methods are successful tools for the discovery of novel BACE1 drugs.