Toward a mechanism for GroEL.GroES chaperone activity: an ATPase-gated and -pulsed folding and annealing cage.

Free GroEL binds denatured proteins very tightly: it retards the folding of barnase 400-fold and catalyzes unfolding fluctuations in native barnase and its folding intermediate. GroEL undergoes an allosteric transition from its tight-binding T-state to a weaker binding R-state on the cooperative binding of nucleotides (ATP/ADP) and GroES. The preformed GroEL.GroES.nucleotide complex retards the folding of barnase by only a factor of 4, and the folding rate is much higher than the ATPase activity that releases GroES from the complex. Binding of GroES and nucleotides to a preformed GroEL.denatured-barnase complex forms an intermediately fast-folding complex. We propose the following mechanism for the molecular chaperone. Denatured proteins bind to the resting GroEL.GroES.nucleotide complex. Fast-folding proteins are ejected as native structures before ATP hydrolysis. Slow-folding proteins enter chaperoning cycles of annealing and folding after the initial ATP hydrolysis. This step causes transient release of GroES and formation of the GroEL.denatured-protein complexes with higher annealing potential. The intermediately fast-folding complex is formed on subsequent rebinding of GroES. The ATPase activity of GroEL.GroES is thus the gatekeeper that selects for initial entry of slow-folding proteins to the chaperone action and then pumps successive transitions from the faster-folding R-states to the tighter-binding/stronger annealing T-states. The molecular chaperone acts as a combination of folding cage and an annealing machine.

Effect of Cage-Induced Stereotypies on Measures of Affective State and Recurrent Perseveration in CD-1 and C57BL/6 Mice.

Stereotypies are abnormal repetitive behaviour patterns that are highly prevalent in laboratory mice and are thought to reflect impaired welfare. Thus, they are associated with impaired behavioural inhibition and may also reflect negative affective states. However, in mice the relationship between stereotypies and behavioural inhibition is inconclusive, and reliable measures of affective valence are lacking. Here we used an exploration based task to assess cognitive bias as a measure of affective valence and a two-choice guessing task to assess recurrent perseveration as a measure of impaired behavioural inhibition to test mice with different forms and expression levels of stereotypic behaviour. We trained 44 CD- 1 and 40 C57BL/6 female mice to discriminate between positively and negatively cued arms in a radial maze and tested their responses to previously inaccessible ambiguous arms. In CD-1 mice (i) mice with higher stereotypy levels displayed a negative cognitive bias and this was influenced by the form of stereotypy performed, (ii) negative cognitive bias was evident in back-flipping mice, and (iii) no such effect was found in mice displaying bar-mouthing or cage-top twirling. In C57BL/6 mice neither route-tracing nor bar-mouthing was associated with cognitive bias, indicating that in this strain these stereotypies may not reflect negative affective states. Conversely, while we found no relation of stereotypy to recurrent perseveration in CD-1 mice, C57BL/6 mice with higher levels of route-tracing, but not bar-mouthing made more repetitive responses in the guessing task. Our findings confirm previous research indicating that the implications of stereotypies for animal welfare may strongly depend on the species and strain of animal as well as on the form and expression level of the stereotypy. Furthermore, they indicate that variation in stereotypic behaviour may represent an important source of variation in many animal experiments.

Proceedings of the Faraday Society.

Mode of access: Internet.

Ueber Faraday's Kraftlinien /

"Transact. of t. Cambr. Phil. Soc. vol. 10, p. 27, gelesen am 10. Dec. 1855 und 11. Febr. 1856, Maxw. Scient. pap. vol. 1, p. 155."

An expendable cage to separate the urine and feces of rats in tracer experiments /

"Contract No. At-40-1-Gen-33."

Cage birds.

Mode of access: Internet.

On the Theraphosidae of the lower Amazons: being an account of the new genera and species of this group of spiders discovered during the expedition of the steamship 'Faraday' up the river Amazons.

Reprinted from the Proceedings of the Zoological Society of London, June 16, 1896.

La volaille saine. Comment la choisir et l'elever ou le vade-mecum de l'eleveur de volaille (ainsi que quelques notes sur les oiseaux de cage.

Mode of access: Internet.

Canaries and cage birds; history, care and treatment,

Mode of access: Internet.

North Palace, Room C, panel 16, Lion Hunt: A lion released from a cage

Nineveh (deserted settlement), Iraq; 5 ft. 5 in.x 4 ft.; gypsum

Cage-bird hybrids,

Printed in Great Britain.

What Maisie knew : In the cage ; The pupil /

Mode of access: Internet.

Molecular spectra and molecular structure; a general discussion held by the Faraday society, September, 1929.

cover-title

The book of cage birds.

Advertisements: p. [279]-282.