Cannabidiol interactions with voltage-gated sodium channels

Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels

Isolation and characterization of Neisseria musculi sp. nov., from the wild house mouse

Neisseria have been isolated from or detected in a wide range of animals, from nonhuman primates and felids to a rodent, the guinea pig (Liu et al., 2015). By means of selective culture, biochemical testing, Gram staining and PCR screening for the Neisseria-specific Internal Transcribed Spacer region of the rRNA operon, we isolated four strains of Neisseria from the oral cavity of the wild house mouse, Mus musculus subspecies domesticus. The isolates are highly related and form a separate clade in the genus, as judged by rMLST and core gene tree analyses. One isolate, provisionally named Neisseria musculi sp. nov. (type strain AP2031T = DSM 101846T = CCUG 68283T = LMG 29261T), was studied further. AP2031/N. musculi grows well in vitro. It is naturally competent, taking up DNA in a DUS and pilT-dependent manner, and is amenable to genetic manipulation. These and other genomic attributes of N. musculi make it an ideal candidate for use in developing a mouse model for studying Neisseria-host interactions

Isolation and characterization of Neisseria musculi sp. nov., from the wild house mouse

Neisseria have been isolated from or detected in a wide range of animals, from nonhuman primates and felids to a rodent, the guinea pig (Liu et al., 2015). By means of selective culture, biochemical testing, Gram staining and PCR screening for the Neisseria-specific Internal Transcribed Spacer region of the rRNA operon, we isolated four strains of Neisseria from the oral cavity of the wild house mouse, Mus musculus subspecies domesticus. The isolates are highly related and form a separate clade in the genus, as judged by rMLST and core gene tree analyses. One isolate, provisionally named Neisseria musculi sp. nov. (type strain AP2031T = DSM 101846T = CCUG 68283T = LMG 29261T), was studied further. AP2031/N. musculi grows well in vitro. It is naturally competent, taking up DNA in a DUS and pilT-dependent manner, and is amenable to genetic manipulation. These and other genomic attributes of N. musculi make it an ideal candidate for use in developing a mouse model for studying Neisseria-host interactions

Isolation and characterization of a new species of Neisseria, Neisseria musculi, from the wild house mouse

Neisseria have been isolated from or detected in a wide range of animals, from nonhuman primates and felids to a rodent, the guinea pig (Liu et al., 2015). By means of selective culture, biochemical testing, Gram staining and PCR screening for the Neisseria-specific Internal Transcribed Spacer region of the rRNA operon, we isolated four strains of Neisseria from the oral cavity of the wild house mouse, Mus musculus subspecies domesticus. The isolates are highly related and form a separate clade in the genus, as judged by rMLST and core gene tree analyses. One isolate, provisionally named Neisseria musculi sp. nov. (type strain AP2031T = DSM 101846T = CCUG 68283T = LMG 29261T), was studied further. AP2031/N. musculi grows well in vitro. It is naturally competent, taking up DNA in a DUS and pilT-dependent manner, and is amenable to genetic manipulation. These and other genomic attributes of N. musculi make it an ideal candidate for use in developing a mouse model for studying Neisseria-host interactions

Polybrominated diphenyl ethers (PBDEs) in background air around the Aegean: implications for phase partitioning and size distribution

The occurrence and atmospheric behavior of tri- to deca-polybrominated diphenyl ethers (PBDEs) were investigated during a 2-week campaign concurrently conducted in July 2012 at four background sites around the Aegean Sea. The study focused on the gas/particle (G/P) partitioning at three sites (Ag. Paraskevi/central Greece/suburban, Finokalia/southern Greece/remote coastal, and Urla/Turkey/rural coastal) and on the size distribution at two sites (Neochorouda/northern Greece/rural inland and Finokalia/southern Greece/remote coastal). The lowest mean total (G + P) concentrations of ∑7PBDE (BDE-28, BDE-47, BDE-66, BDE-99, BDE-100, BDE-153, BDE-154) and BDE-209 (0.81 and 0.95 pg m−3, respectively) were found at the remote site Finokalia. Partitioning coefficients, KP, were calculated, and their linear relationships with ambient temperature and the physicochemical properties of the analyzed PBDE congeners, i.e., the subcooled liquid pressure (PL°) and the octanol-air partition coefficient (KOA), were investigated. The equilibrium adsorption (PL°-based) and absorption (KOA-based) models, as well as a steady-state absorption model including an equilibrium and a non-equilibrium term, both being functions of log KOA, were used to predict the fraction Φ of PBDEs associated with the particle phase. The steady-state model proved to be superior to predict G/P partitioning of BDE-209. The distribution of particle-bound PBDEs across size fractions < 0.95, 0.95–1.5, 1.5–3.0, 3.0–7.2, and > 7.2 μm indicated a positive correlation between the mass median aerodynamic diameter and log PL° for the less brominated congeners, whereas a negative correlation was observed for the high brominated congeners. The potential source regions of PBDEs were acknowledged as a combination of long-range transport with short-distance sources