The expression of brain-derived neurotrophic factor (BDNF) mRNA and the secretion of BDNF protein are tightly regulated by neuronal activity. Thus, BDNF has been proposed as a mediator of activity-dependent neural plasticity. Previous studies showed that dark rearing (DR) reduces BDNF mRNA levels in the primary visual cortex (V1), but the effects of visual experience on BDNF protein levels are unknown. We report that rearing in constant light or DR alters BDNF mRNA and protein levels in the retina, superior colliculus (SC), V1, hippocampus (HIPP), and cerebellum (CBL), although the changes in mRNA and protein are not always correlated. Most notably, DR increases BDNF protein levels in V1 although BDNF mRNA is decreased. BDNF protein levels also undergo diurnal changes. In the retina, V1, and SC, BDNF protein levels are higher during the light phase of the circadian cycle than during the dark phase. By contrast, in HIPP and CBL, the tissue concentration of BDNF protein is higher during the dark phase. The discrepancies between the experience-dependent changes in BDNF mRNA and protein suggest that via its effects on neuronal activity, early sensory experience alters the trafficking, as well as the synthesis, of BDNF protein. The circadian changes in BDNF protein suggest that BDNF could cause the diurnal modulation of synaptic efficacy in some neural circuits. The fluctuations in BDNF levels in nonvisual structures suggest a potential role of BDNF in mediating plasticity induced by hormones or motor activity.

A distinct class of aurora, called transpolar auroral arc (TPA) (in some cases called “theta” aurora), appears in the extremely high-latitude ionosphere of the Earth when interplanetary magnetic field (IMF) is northward. The formation and evolution of TPA offers clues about processes transferring energy and momentum from the solar wind to the magnetosphere and ionosphere during a northward IMF. However, their formation mechanisms remain poorly understood and controversial. We report a mechanism identified from multiple-instrument observations of unusually bright, multiple TPAs and simulations from a high-resolution three-dimensional (3D) global MagnetoHydroDynamics (MHD) model. The observations and simulations show an excellent agreement and reveal that these multiple TPAs are generated by precipitating energetic magnetospheric electrons within field-aligned current (FAC) sheets. These FAC sheets are generated by multiple-flow shear sheets in both the magnetospheric boundary produced by Kelvin–Helmholtz instability between supersonic solar wind flow and magnetosphere plasma, and the plasma sheet generated by the interactions between the enhanced earthward plasma flows from the distant tail (less than −100 RE) and the enhanced tailward flows from the near tail (about −20 RE). The study offers insight into the complex solar wind-magnetosphere-ionosphere coupling processes under a northward IMF condition, and it challenges existing paradigms of the dynamics of the Earth’s magnetosphere.

In Earth’s low atmosphere, hurricanes are destructive due to their great size, strong spiral winds with shears, and intense rain/precipitation. However, disturbances resembling hurricanes have not been detected in Earth’s upper atmosphere. Here, we report a long-lasting space hurricane in the polar ionosphere and magnetosphere during low solar and otherwise low geomagnetic activity. This hurricane shows strong circular horizontal plasma flow with shears, a nearly zero-flow center, and a coincident cyclone-shaped aurora caused by strong electron precipitation associated with intense upward magnetic field-aligned currents. Near the center, precipitating electrons were substantially accelerated to ~10 keV. The hurricane imparted large energy and momentum deposition into the ionosphere despite otherwise extremely quiet conditions. The observations and simulations reveal that the space hurricane is generated by steady high-latitude lobe magnetic reconnection and current continuity during a several hour period of northward interplanetary magnetic field and very low solar wind density and speed.

The term of “polar cap hot patch” is a newly identified high‐density plasma irregularity at high latitudes, which is associated with high electron temperature and particle precipitation, while a classical polar cap patch has lower electron temperature. To investigate characteristics of hot patches versus classical patches, five years of in situ database of plasma observations from the DMSP satellites was analyzed. For the first time, we show how the ion/electron temperature ratio (or temperature difference) can be used to distinguish between classical and hot patches. For classical patches (Ti/Te > 0.8 or Te < Ti + 600 K), the vertical ion flux is generally downward. For hot patches (Ti/Te < 0.8 or Te > Ti + 600 K), the vertical ion flux is generally upward. The highest upflow occurrence was found near the polar cap boundary, associated with hot patches, particle precipitation, strong convection speed, and localized field‐aligned currents. This result shows that the polar cap hot patches may play a very important role in solar wind‐magnetosphere‐ionosphere coupling processes.

Quantitative studies of ontogenetic changes in the levels of brain-derived neurotrophic factor (BDNF) mRNA and its effector, BDNF protein, are not available for the retinal projection system. We used an electrochemiluminescence immunoassay to measure developmental changes in the tissue concentration of BDNF within the hamster retina and superior colliculus (SC). In the SC, we first detected BDNF (about 9 pg/mg tissue) on embryonic day 14 (E14). BDNF protein concentration in the SC rises about fourfold between (E14) and postnatal day 4 (P4), remains at a plateau through P15, then declines by about one-third to attain its adult level by P18. By contrast, BDNF protein concentration in the retina remains low (about 1 pg/mg tissue) through P12, then increases 4.5-fold to attain its adult level on P18. The developmental changes in retinal and collicular BDNF protein concentrations are temporally correlated with multiple events in the structural and functional maturation of the hamster retinal projection system. Our data suggest roles for BDNF in the cellular mechanisms underlying some of these events and are crucial to the design of experiments to examine those roles.

A dual-purpose strategy aimed at enhancing the binding affinity for microtubules and improving the water solubility of docetaxel led to the design and synthesis of a series of C-2- and C-3'-modified analogues. Both aims were realized when the C-3' phenyl group present in docetaxel was replaced with a propargyl alcohol. The resulting compound, 3f, was able to overcome drug resistance in cultured P-gp-overexpressing tumor cells and showed greater activity than docetaxel against drug-resistant A2780/AD ovarian cancer xenografts in mice. In addition, the considerably lower hydrophobicity of 3f relative to both docetaxel and paclitaxel led to better aqueous solubility. A molecular model of tubulin-bound 3f revealed novel hydrogen-bonding interactions between the propargyl alcohol and the polar environment provided by the side chains of Ser236, Glu27, and Arg320.

Ten novel taxanes bearing modifications at the C2 and C13 positions of the baccatin core have been synthesized and their binding affinities for mammalian tubulin have been experimentally measured. The design strategy was guided by (i) calculation of interaction energy maps with carbon, nitrogen and oxygen probes within the taxane-binding site of β-tubulin, and (ii) the prospective use of a structure-based QSAR (COMBINE) model derived from an earlier series comprising 47 congeneric taxanes. The tubulin-binding affinity displayed by one of the new compounds (CTX63) proved to be higher than that of docetaxel, and an updated COMBINE model provided a good correlation between the experimental binding free energies and a set of weighted residue-based ligand-receptor interaction energies for 54 out of the 57 compounds studied. The remaining three outliers from the original training series have in common a large unfavourable entropic contribution to the binding free energy that we attribute to taxane preorganization in aqueous solution in a conformation different from that compatible with tubulin binding. Support for this proposal was obtained from solution NMR experiments and molecular dynamics simulations in explicit water. Our results shed additional light on the determinants of tubulin-binding affinity for this important class of antitumour agents and pave the way for further rational structural modifications.

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