Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands

Potassium channels are essential for maintaining a normal ionic balance across cell membranes. Central to this function is the ability of such channels to support transmembrane ion conduction at nearly diffusion-limited rates while discriminating for K+ over Na+ by more than a thousand-fold. This selectivity arises because the transfer of the K+ ion into the channel pore is energetically favoured, a feature commonly attributed to a structurally precise fit between the K+ ion and carbonyl groups lining the rigid and narrow pore. But proteins are relatively flexible structures that undergo rapid thermal atomic fluctuations larger than the small difference in ionic radius between K+ and Na+. Here we present molecular dynamics simulations for the potassium channel KcsA, which show that the carbonyl groups coordinating the ion in the narrow pore are indeed very dynamic ('liquid-like') and that their intrinsic electrostatic properties control ion selectivity. This finding highlights the importance of the classical concept of field strength. Selectivity for K+ is seen to emerge as a robust feature of a flexible fluctuating pore lined by carbonyl groups.     

Base stacking controls excited-state dynamics in A.T DNA

Solar ultraviolet light creates excited electronic states in DNA that can decay to mutagenic photoproducts. This vulnerability is compensated for in all organisms by enzymatic repair of photodamaged DNA. As repair is energetically costly, DNA is intrinsically photostable. Single bases eliminate electronic energy non-radiatively on a subpicosecond timescale, but base stacking and base pairing mediate the decay of excess electronic energy in the double helix in poorly understood ways. In the past, considerable attention has been paid to excited base pairs. Recent reports have suggested that light-triggered motion of a proton in one of the hydrogen bonds of an isolated base pair initiates non-radiative decay to the electronic ground state. Here we show that vertical base stacking, and not base pairing, determines the fate of excited singlet electronic states in single- and double-stranded oligonucleotides composed of adenine (A) and thymine (T) bases. Intrastrand excimer states with lifetimes of 50-150 ps are formed in high yields whenever A is stacked with itself or with T. Excimers limit excitation energy to one strand at a time in the B-form double helix, enabling repair using the undamaged strand as a template.     

Use of centrifugal-gravity concentration for rejection of talc and recovery improvement in base-metal flotation

The possibility of using a centrifugal-gravity concentrator to reject Mg-bearing minerals and minimize metal losses in the flotation of base metals was evaluated. Sample characterization, batch scoping tests, pilot-scale tests, and regrind-flotation tests were conducted on a Ni flotation tailings stream. Batch tests revealed that the Mg grade decreased dramatically in the concentrate products. Pilot-scale testing of a continuous centrifugal concentrator (Knelson CVD6) on the flotation tailings revealed that a concentrate with a low mass yield, low Mg content, and high Ni upgrade ratio could be achieved. Under optimum conditions, a concentrate at 6.7% mass yield was obtained with 0.85% Ni grade at 12.9% Ni recovery and with a low Mg distribution (1.7%). Size partition curves demonstrated that the CVD also operated as a size classifier, enhancing the rejection of talc fines. Overall, the CVD was capable of rejecting Mg-bearing minerals. Moreover, an opportunity exists for the novel use of centrifugal-gravity concentration for scavenging flotation tailings and/or after comminution to minimize amount of Mg-bearing minerals reporting to flotation.     

开放式喷射汽车风洞的尺寸和效率

近年来,世界各地汽车企业已建成许多汽车风洞,并在不久的将来会有更多汽车风洞的规划与建设。在风洞规划设计阶段确定的许多功能与参数决定了其整个运行生命周期,并影响建设和运行成本。本文研究通过适当选择3/4开口风洞的试验段几何尺寸,可以使早期的传统风洞中因有限截面发生的流动干扰在很大程度上得到补偿或减少到可忽略不计的程度。研究表明：对于具有不同堵塞度的各种车辆,流动干扰误差出乎意料地可以忽略,因此不需要对试验数据进行修正,这使得汽车风洞试验形成“自由”气流条件;试验阶段的初步尺寸可以比如今常见的情况小很多,也不影响测量结果的准确度,这带来了更低的建设成本,也降低了风洞系统运行的能源需求;自由射流的不稳定性必须被考虑,且射流长度不应该超过某个上限。     

Energetics of ion conduction through the K+ channel.

K+ channels are transmembrane proteins that are essential for the transmission of nerve impulses. The ability of these proteins to conduct K+ ions at levels near the limit of diffusion is traditionally described in terms of concerted mechanisms in which ion-channel attraction and ion-ion repulsion have compensating effects, as several ions are moving simultaneously in single file through the narrow pore. The efficiency of such a mechanism, however, relies on a delicate energy balance-the strong ion-channel attraction must be perfectly counterbalanced by the electrostatic ion-ion repulsion. To elucidate the mechanism of ion conduction at the atomic level, we performed molecular dynamics free energy simulations on the basis of the X-ray structure of the KcsA K+ channel. Here we find that ion conduction involves transitions between two main states, with two and three K+ ions occupying the selectivity filter, respectively; this process is reminiscent of the 'knock-on' mechanism proposed by Hodgkin and Keynes in 1955. The largest free energy barrier is on the order of 2-3 kcal mol-1, implying that the process of ion conduction is limited by diffusion. Ion-ion repulsion, although essential for rapid conduction, is shown to act only at very short distances. The calculations show also that the rapidly conducting pore is selective.     

Induction of lactation in precancerous hyperplastic alveolar nodules in the mammary gland of C3H/He Crgl mice

Résumé La sécrétion lactée se produit dans les nodules alvéolaires hyperplastiques de la glande mammaire des souris femelles intactes de la souche C3H/He Crgi, à la suite de l'administration du cortisol et de l'stradiol, mais non pas après l'emploi de l'strogène avec le progestérone. Lorsque l'hypophyse, l'ovaire et la glande surrénale ont été enlevés, les nodules montrent une sécrétion lactée sous l'effet du cortisol et de la mammotropine ou de la somatotropine et indiquent une sensibilité différentielle aux combinaisons hormonales lactogènes.