Demonstration of spontaneous chiral symmetry breaking in asymmetric Mannich and Aldol reactions

Spontaneous symmetry breaking in reactive systems, known as a rare physical phenomenon and for the Soai autocatalytic irreversible reaction, might in principle also occur in other, more common asymmetric reactions when the chiral product is capable to promote its formation and an element of "nonlinearity" is involved in the reaction scheme. Such phenomena are long sought after in chemistry as a possible explanation for the biological homochirality of biomolecules. We have investigated homogeneous organic stereoselective Mannich and Aldol reactions, in which the product is capable to form H-bridged complexes with the prochiral educt, and found by applying NMR spectroscopy, HPLC analysis, and optical rotation measurements 0.3-50.8% of random product enantiomeric excess under essentially achiral reaction conditions. These findings imply a hitherto overlooked mechanism for spontaneous symmetry breaking and, hence, a novel approach to the problem of absolute asymmetric synthesis and could have also potential significance for the conundrum of homochirality.     

Movements of foraging king penguins through marine mesoscale eddies

Despite increasing evidence that marine predators associate with mesoscale eddies, how these marine features influence foraging movements is still unclear. This study investigates the relationship of at-sea movements of king penguins to mesoscale eddies using oceanographic remote sensing and movement data from 43 individual trips over 4 years. Simultaneous satellite measurements provided information on gradients of sea surface temperature and currents associated with eddies determined from altimetry. Penguins tended to swim rapidly with currents as they travelled towards foraging zones. Swimming speed indicative of foraging occurred within mesoscale fronts and strong currents associated with eddies at the Polar Front. These results demonstrate the importance of mesoscale eddies in directing foraging efforts to allow predators to rapidly get to rich areas where high concentrations of prey are likely to be encountered. When returning to the colony to relieve the incubating partner or to feed the chick, the birds followed a direct and rapid path, seemingly ignoring currents.     

Role of calcium mobilization in the regulation of spontaneous transient outward currents in porcine coronary artery myocytes

The purpose of the present study was to further study the characteristics and regulation of spontaneous transient outward currents (STOCs) in freshly isolated porcine coronary artery smooth muscle cells (ASMCs). STOCs were recorded using the perforated whole-cell patch-clamp configuration. STOCs were voltage-dependent and superimposed stochastically onto whole-cell Ca2 -activated-K (BKCa) currents. Charybdotoxin (ChTX, 200 nmol/L), a selective blocker of BKCa channels, completely inhibited STOCs within 10 min. STOCs activity was greatly suppressed when extracellular Ca2 concentration decreased from 1.8 mmol/L to 200 nmol/L, further removal of Ca2 abolished STOCs activity. Ca2 ionophore A23187 (10 μmol/L) increased STOCs activity significantly. Verapamil (20 μmol/L) and CdCl2 (200 μmol/L), two kinds of organic L-type voltage-dependent Ca2 channels (L-VDCCs) antagonists, had little effect on STOCs. In addition, the ryanodine receptors (RyRs) agonist caffeine (5 mmol/L) significantly activated STOCs. Application of ryanodine (50 μmol/L) to block RyRs abolished STOCs, subsequent washout of ryanodine or application of caffeine failed to reproduce STOCs activity. Inhibition of inositol 1,4,5-trisphosphate receptors (IP3Rs) by 2APB (40 μmol/L) greatly suppressed the activity of STOCs, application of caffeine (5 mmol/L) in the presence of 2APB caused a burst of outward currents followed by inhibition of STOCs. These results suggest that STOCs in porcine coronary ASMCs are mediated by BKCa channels. Extracellular Ca2 is essential for STOCs activity, while Ca2 entry through L-VDCCs has little effect on STOCs. Intracellular Ca2 release induced by RyRs is responsible for the regulation of STOCs, whereas IP3Rs might also be involved.     

Roles of glutamate and GABA receptors in setting the developmental timing of spontaneous synchronized activity in the developing mouse cortex

Spontaneous, synchronized electrical activity (SSA) plays important roles in nervous system development, but it is not clear what causes it to start and stop at the appropriate times. In previous work, we showed that when SSA in neonatal mouse cortex is blocked by TTX in cultured slices during its normal time of occurrence (E17-P3), it fails to stop at P3 as it does in control cultured slices, but instead persists through at least P10. This indicates that SSA is self-extinguishing. Here we use whole-cell recordings and [Ca2+]i imaging to compare control and TTX-treated slices to isolate the factors that normally extinguish SSA on schedule. In TTX-treated slices, SSA bursts average 4 s in duration, and have two components. The first, lasting about 1 s, is mediated by AMPA receptors; the second, which extends the burst to 4 s and is responsible for most of the action potential generation during the burst, is mediated by NMDA receptors. In later stage (P5-P9) control slices, after SSA has declined to about 4% of its peak frequency, bursts lack this long NMDA component. Blocking this NMDA component in P5-P9 TTX-treated slices reduces SSA frequency, but not to the low values found in control slices, implying that additional factors help extinguish SSA. GABA(A) inhibitors restore SSA in control slices, indicating that the emergence of GABA(A)-mediated inhibition is another major factor that helps terminate SSA.     

Coemergence of regularity and complexity during neural network development

With the growing recognition that rhythmic and oscillatory patterns are widespread in the brain and play important roles in all aspects of the function of our nervous system, there has been a resurgence of interest in neuronal synchronized bursting activity. Here, we were interested in understanding the development of synchronized bursts as information-bearing neuronal activity patterns. For that, we have monitored the morphological organization and spontaneous activity of neuronal networks cultured on multielectrode-arrays during their self-executed evolvement from a mixture of dissociated cells into an active network. Complex collective network electrical activity evolved from sporadic firing patterns of the single neurons. On the system (network) level, the activity was marked by bursting events with interneuronal synchronization and nonarbitrary temporal ordering. We quantified these individual-to-collective activity transitions using newly-developed system level quantitative measures of time series regularity and complexity. We found that individual neuronal activity before synchronization was characterized by high regularity and low complexity. During neuronal wiring, there was a transient period of reorganization marked by low regularity, which then leads to coemergence of elevated regularity and functional (nonstochastic) complexity. We further investigated the morphology-activity interplay by modeling artificial neuronal networks with different topological organizations and connectivity schemes. The simulations support our experimental results by showing increased levels of complexity of neuronal activity patterns when neurons are wired up and organized in clusters (similar to mature real networks), as well as network-level activity regulation once collective activity forms.     

丙种球蛋白联合地屈孕酮治疗复发性流产的效果及对患者免疫功能和血清炎症因子水平的影响

目的:探讨丙种球蛋白联合地屈孕酮治疗复发性流产的效果及对患者免疫功能和血清炎症因子水平的影响。方法:选择2016年1月-2017年12月我院收治的82例复发性流产患者为研究对象,将其随机分为两组。对照组采用单纯口服地屈孕酮,每次10 mg,每天2次;观察组在对照组基础上联合静脉滴注丙种球蛋白500 mg/(kg·d)。比较两组治疗前后的血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)以及白介素-10(IL-10)水平,CD4~+/CD8~+、CD8~+以及CD4~+及保胎成功率。结果:治疗后,观察组治愈14例,有效18例,无效9例,治疗有效率为78.05%(32/41),明显高于对照组[60.98%(25/41)](P0.05);两组治疗后的血清TNF-α、CD8~+水平较治疗前明显降低(P0.05),血清IL-6、IL-10、CD4~+/CD8~+以及CD4~+水平较治疗前明显升高(P0.05),且观察组血清TNF-α、CD8~+水平明显低于对照组(P0.05),血清IL-6、IL-10、CD4~+/CD8~+以及CD4~+水平明显高于对照组(P0.05)。观察组的保胎成功率为82.93%(34/41),明显高于对照组[31.71%(13/41)](P0.05)。结论:丙种球蛋白联合地屈孕酮可以有效增强复发性流产患者体内的免疫功能,减少调节炎症因子的表达,提高保胎成功率.     

Synchronous Bursting Can Arise from Mutual Excitation, Even When Individual Cells are not Endogenous Bursters

Mutual excitation between two neurons is generally thought to raise the excitation level of each neuron or, if they are both bursty, to act to synchronize their bursts. If only one is bursty, it can induce synchronized bursts in the other cell. Here we show that two nonbursty cells can be induced to burst in synchrony by mutual excitatory synaptic connections, provided the presynaptic threshold for graded synaptic transmission ateach synapse is at a different level. This mechanism may operate in a recently discovered network in the lobster Homarus gammarus.By a duality between presynaptic threshold and injected current, we also show that two identical, nonbursty, mutual excitatory cells could be induced to burst in synchrony by injecting differing amounts of current inthe two cells. Finally we show that differential oscillations betweentwo mutual excitatory cells could be stopped by a slow-tailedhyperpolarizing current pulse into one cell or a slow-taileddepolarizing pulse into the other.