Tobacco smoke: unraveling a controversial subject.

Cigarettes are a modern and industrial form of tobacco use and obviously involve more than just tobacco. A multitude of physical processes and chemical reactions occur inside the burning zone of a cigarette. Cigarette smoke is an aerosol of liquid droplets (the particulate phase) suspended within a mixture of gases and semi-volatile compounds. Two kinds of smoke with different composition and properties are produced during smoking: mainstream smoke inhaled by the smoker and sidestream smoke, which is released into the environment between puffs from the lit end of the cigarette. Several techniques and modifications have altered the design of the cigarette during the last 50 years and changed smoke composition, with the effect of lower tar and nicotine smoke yields. An enormous amount of research has been done since the 1950s on smoke composition. With regard to the numerous toxic or carcinogenic constituents identified in tobacco smoke, there is a strong focus in the industry and with the authorities on the over 40 compounds, called "Hoffmann analytes". The yields of tar and nicotine in mainstream smoke of a cigarette brand as printed on the pack are measured with smoking machines under highly standardized conditions. Yields must comply with regulatory limits set in a number of countries. Smoking by machine is different from the smoking behavior of humans. There is a growing movement to develop more "realistic" methods to estimate smoke yields. But it is unclear whether alternative smoking regimens are more representative of human smoking behavior and provide better predictions of human exposure. Tobacco smoke has strong biological and toxicological effects in vitro and in vivo. There is an obvious need for developing a unified and validated testing approach particularly for the assessment of additives and the evaluation of new potentially reduced exposure products (PREPs). This paper gives a comprehensive overview of cigarette design, the composition and toxicity testing of smoke, and the way machines and people smoke - with links to the more detailed literature.

The hydrophobic amino acid residues in the membrane-proximal C tail of the G protein-coupled vasopressin V2 receptor are necessary for transport-competent receptor folding.

It is believed that the membrane-proximal C tail of the G protein-coupled receptors forms an additional alpha helix with amphipathic properties (helix 8). It was previously shown for the vasopressin V2 receptor (V2R) that a conserved dileucine motif (L(339), L(340)) in this putative helix 8 is necessary for endoplasmic reticulum (ER) to Golgi transfer of the receptor. Here, we demonstrate that the other hydrophobic residues forming the non-polar side of this helix (F(328), V(332) and L(336)) are also transport-relevant. In contrast, the multiple serine residues contributing to the more hydrophilic side (S(330), S(331), S(333), S(334), S(338)) do not influence receptor trafficking. In addition, we show unambiguously by the use of pharmacological chaperones that the hydrophobic residues of the putative helix 8 do not form a transport signal necessary for receptor sorting into ER to Golgi vesicles. Instead, they are necessary to establish a transport-competent folding state in the early secretory pathway.