Coherent Neutron Scattering and Collective Dynamics in the Protein,GFP

Collective dynamics are considered to be one of the major properties of soft materials, including biological macromolecules. We present coherent neutron scattering studies of the low-frequency vibrations, the so-called boson peak, in fully deuterated green fluorescent protein (GFP). Our analysis revealed unexpectedly low coherence of the atomic motions in GFP. This result implies a low amount of in-phase collective motion of the secondary structural units contributing to the boson peak vibrations and fast conformational fluctuations on the picosecond timescale. These observations are in contrast to earlier studies of polymers and glass-forming systems, and suggest that random or out-of-phase motions of the β-strands contribute greater than two-thirds of the intensity to the low-frequency vibrational spectra of GFP.     

Synthesis and profiling of benzylmorpholine 1,2,4,5-tetraoxane analogue N205: Towards tetraoxane scaffolds with potential for single dose cure of malaria

A series of aryl carboxamide and benzylamino dispiro 1,2,4,5-tetraoxane analogues have been designed and synthesized in a short synthetic sequence from readily available starting materials. From this series of endoperoxides, molecules with in vitro IC50s versus Plasmodium falciparum (3D7) as low as 0.84?nM were identified. Based on an assessment of blood stability and in vitro microsomal stability, N205 (10a) was selected for rodent pharmacokinetic and in vivo antimalarial efficacy studies in the mouse Plasmodium berghei and Plasmodium falciparum Pf3D70087/N9 severe combined immunodeficiency (SCID) mouse models. The results indicate that the 4-benzylamino derivatives have excellent profiles with a representative of this series, N205, an excellent starting point for further lead optimization studies.     

Water temperature fluctuations and territoriality in the intertidal zone: two possible explanations for the elevational distribution of body size in Graus nigra

On the central coast of Chile, distribution of body size in Graus nigra varied with tidal pool height. With the objective of determining whether environmental temperature is one of the possible causes which explains the observed distribution pattern, two behavioural responses were analysed during an experimental period of increasing water temperature: number of opercular movements (an indirect measure of energy expenditure) and activity levels. The interactions of temperature × time and body size × time had a significant effect on the number of opercular movements. At low temperatures (13–15° C), large fish reached a maximum number of opercular movements, while small fish reached a maximum only at high temperatures (23–25° C). The interaction temperature × time had a significant effect on activity levels of different body sizes. In general, large fish appeared to be less active than small fish, however, at very high temperatures (24–26° C) all individuals increased their activity levels. These data indicate that small fish are acclimatized to live in a wider range of temperatures (13–23° C), and, for fish of all body sizes, the highest temperatures (23–26° C) probably constitute a suboptimal microhabitat. Strong territoriality was observed, with large individuals displacing smaller individuals. These data suggest that temperature is an important factor in explaining why large individuals are not present in high tidal pools (high temperatures), whereas territoriality explains why small individuals are not in low tidal pools (habitat of large individuals).     

Isosojagol,a coumestan from Phaseolus coccineus

A novel coumestan isolated from Phaseolus coccineus has been characterized as 3,9-dihydroxy-10-(γ,γ-dimethylallyl)-coumestan and named isosojagol.