Ena/VASP proteins regulate cortical neuronal positioning

Development of the multilayered cerebral cortex involves extensive regulated migration of neurons arising from the deeper germinative layers of the mammalian brain. The anatomy and formation of the cortical layers has been well characterized; however, the underlying molecular mechanisms that control the migration and the final positioning of neurons within the cortex remain poorly understood. Here, we report evidence for a key role of Ena/VASP proteins, a protein family implicated in the spatial control of actin assembly and previously shown to negatively regulate fibroblast cell speeds, in cortical development. Ena/VASP proteins are highly expressed in the developing cortical plate in cells bordering Reelin-expressing Cajal-Retzius cells and in the intermediate zone through which newly born cells migrate. Inhibition of Ena/VASP function through retroviral injections in utero led to aberrant placement of early-born pyramidal neurons in the superficial layers of both the embryonic and the postnatal cortex in a cell-autonomous fashion. The abnormally placed pyramidal neurons exhibited grossly normal morphology and polarity. Our results are consistent with a model in which Ena/VASP proteins function in vivo to control the position of neurons in the mouse neocortex.     

Enhanced learning and memory in GAT1 heterozygous mice

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The termination of GABA transmission is through the action of a family of membrane proteins, called GABA transporters (GAT1-4). It is well established that GABA system is involved in the modulation of memory. Our previous study showed that homozygous GAT1(-/-) mice exhibited impaired hippocampus-dependent learning and memory. To evaluate the impact of endogenous reduced GABA reuptake on mice cognitive behaviors, the ability of learning and memory of heterozygous GAT1(+/-) mice was detected by the passive avoidance paradigm and Morris water maze. The hole board paradigm was also used to measure changes in anxiety-related behavior or exploratory behavior in such mice. As one form of synaptic plasticity, long-term potentiation was recorded in the mouse hippocampal CA1 area. We found that GAT1(+/-) mice displayed increased learning and memory, decreased anxiety-like behaviors, and highest synaptic plasticity compared with wild-type and homozygous GAT1(-/-) mice. Our results suggest that a moderate reduction in GAT1 activity causes the enhancement of learning and memory in mice.     

Structure insights into mechanisms of ATP hydrolysis and the activation of human heat-shock protein 90

The activation of molecular chaperone heat-shock protein 90 (Hsp90) is dependent on ATP binding and hydrolysis, which occurs in the N-terminal domains of protein. Here, we have determined three crystal structures of the N-terminal domain of human Hsp90 in native and in complex with ATP and ATP analog, providing a clear view of the catalytic mechanism of ATP hydrolysis by Hsp90. Additionally, the binding of ATP leads the N-terminal domains to be an intermediate state that could be used to partially explain why the isolated N-terminal domain of Hsp90 has very weak ATP hydrolytic activity.     

Abundance and age of viable resting eggs of the calanoid copepod Boeckella poppei Mrázek in sediments: evidence of egg banks in two Antarctic maritime lakes

The existence of egg banks not only ensures the survival of zooplankton through harsh periods, but could also affect microevolutionary dynamics. Whether zooplankton at high latitudes can build up an egg bank in sediments, as occurs at lower latitudes, is still unknown. The distribution and age of viable resting eggs of the calanoid copepod Boeckella poppei Mrázek in sediments of two small freshwater lakes on King George Island were determined by slicing sediment cores at 1-cm intervals. Most viable resting eggs were found near the sediment surface, with abundance sharply declining to very low values at the depth of 5?cm, although eggs were present as deep as 9?cm in the sediments of Yanouhu Lake. The egg abundances in Xihu Lake and Yanouhu Lake were estimated to be 9.2?×?10⁴ and 7.2?×?10⁴?eggs?m^?2, respectively. ²¹⁰Pb dating indicated a relatively constant sedimentation rate (0.023?cm?year^?1) in Xihu Lake, which was used to estimate the mean age (46.8?year), the maximum age (195.7?year), and the mortality rate (1.64?% year^?1) of resting eggs of B. poppei in Xihu Lake. The accumulation of resting eggs with long-term viability in sediments provided the first evidence for the existence of egg banks in two Antarctic maritime lakes. An egg bank may serve as an overwintering strategy for B. poppei in Antarctica, enhance their ability to cope with random extreme changes, and contribute to their broad distribution.     

Mangiferin aglycone attenuates radiation-induced damage on human intestinal epithelial cells

Recent studies suggest that mangiferin aglycone (norathyriol) has great potential as a novel radioprotector without any known toxic side effects. In this study, we assessed the protective effects of mangiferin aglycone against radiation-induced injuries on normal human intestinal epithelial cells (HIECs), while using mangiferin as a reference compound. The in vitro experiments showed that pretreatment of either mangiferin aglycone or mangiferin could inhibit cytotoxic effects of ionizing irradiation (IR) on HIECs. Cellular changes were estimated by measuring cell viability, clonogenic surviving rate, and apoptotic rate. Compared to mangiferin, we found mangiferin aglycone had greater radioprotective effects of mangiferin aglycone on HIECs. It has been demonstrated that the cytotoxicity of ionizing radiation relates to its capacity to induce DNA damage. In view of this, we monitored DNA double-strand breaks (DSBs) using γH2AX foci formation to test whether mangiferin aglycone and mangiferin could modulate genotoxic effects of radiation. It shows that mangiferin aglycone could eliminate 46.8% of the total DSBs of the cells exposed to 2 Gy IR, which is significantly better than mangiferin. Complementing earlier results from our group, it appears possible to conclude that mangiferin aglycone presents potential useful effects on IR-induced damage and may be a better radioprotective agent than mangiferin therapeutically.     

Predicting protein oxidation sites with feature selection and analysis approach

Protein oxidation is a ubiquitous post-translational modification that plays important roles in various physiological and pathological processes. Owing to the fact that protein oxidation can also take place as an experimental artifact or caused by oxygen in the air during the process of sample collection and analysis, and that it is both time-consuming and expensive to determine the protein oxidation sites purely by biochemical experiments, it would be of great benefit to develop in silico methods for rapidly and effectively identifying protein oxidation sites. In this study, we developed a computational method to address this problem. Our method was based on the nearest neighbor algorithm in which, however, the maximum relevance minimum redundancy and incremental feature selection approaches were incorporated. From the initial 735 features, 16 features were selected as the optimal feature set. Of such 16 optimized features, 10 features were associated with the position-specific scoring matrix conservation scores, three with the amino acid factors, one with the propensity of conservation of residues on protein surface, one with the side chain count of carbon atom deviation from mean, and one with the solvent accessibility. It was observed that our prediction model achieved an overall success rate of 75.82%, indicating that it is quite encouraging and promising for practical applications. Also, the 16 optimal features obtained through this study may provide useful clues and insights for in-depth understanding the action mechanism of protein oxidation.     

Larval settlement and metamorphosis of the mussel Mytilus coruscus in response to natural biofilms

Settlement and metamorphosis of pediveliger larvae of Mytilus coruscus in response to natural biofilms was investigated in the laboratory. Pediveliger larvae settled and metamorphosed in response to biofilms and post-larval settlement and metamorphosis increased with biofilm age. The activity of the biofilm was positively correlated with biofilm age, dry weight, bacterial density and diatom density, but had no apparent relationship with chlorophyll a concentration. The change in bacterial community composition corresponding to biofilm age may explain differences in the age-dependent inducing activities of biofilms, which in turn may play an important role in larval settlement in this species.     

Interactions between different generation HIV-1 fusion inhibitors and the putative mechanism underlying the synergistic anti-HIV-1 effect resulting from their combination

We previously reported that the combinatorial use of T20 and T1144, the first and next generations of HIV fusion inhibitors, containing different functional domains resulted in synergistic anti-HIV-1 effect, but this effect diminished when T20 and T1144 were covalently linked together. To elucidate the mechanism underlying this synergistic anti-HIV-1 effect, we studied the interactions between T20 and T1144 either in a mixture state or in a covalently linked state. T20 alone in solution was largely featureless, while T1144 alone was in α-helical trimeric conformation. When mixed in solution, T20 and T1144 showed a loose and transient interaction, with a moderate 10% α-helical content increase, but this interaction was greatly enhanced in the linked state, and T20 and T1144 showed ～100% α-helical content. These results suggested that the loose and transient interaction between T20 and T1144 may destabilize the T1144 trimer, which makes its otherwise shielded binding sites more accessible to N-terminal heptad repeat (NHR) and increases its associating rate, thus increasing its anti-HIV-1 potency against the temporarily exposed target in NHR and causing the synergistic anti-HIV-1 effect. However, the strong interaction between T20 and T1144 in the covalently linked state may shield their NHR-binding sites, resulting in reduction of the synergistic effect.