Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target

The 2.7 A crystal structure of the 55-kDa N-terminal breakage-reunion domain of topoisomerase (topo) IV subunit A (ParC) from Streptococcus pneumoniae, the first for the quinolone targets from a gram-positive bacterium, has been solved and reveals a 'closed' dimer similar in fold to Escherichia coli DNA gyrase subunit A (GyrA), but distinct from the 'open' gate structure of Escherichia coli ParC. Unlike GyrA whose DNA binding groove is largely positively charged, the DNA binding site of ParC exhibits a distinct pattern of alternating positively and negatively charged regions coincident with the predicted positions of the grooves and phosphate backbone of DNA. Based on the ParC structure, a new induced-fit model for sequence-specific recognition of the gate (G) segment by ParC has been proposed. These features may account for the unique DNA recognition and quinolone targeting properties of pneumococcal type II topoisomerases compared to their gram-negative counterparts.     

Phase-resetting curve determines how BK currents affect neuronal firing

BK channels are large conductance potassium channels gated by calcium and voltage. Paradoxically, blocking these channels has been shown experimentally to increase or decrease the firing rate of neurons, depending on the neural subtype and brain region. The mechanism for how this current can alter the firing rates of different neurons remains poorly understood. Using phase-resetting curve (PRC) theory, we determine when BK channels increase or decrease the firing rates in neural models. The addition of BK currents always decreases the firing rate when the PRC has only a positive region. When the PRC has a negative region (type II), BK currents can increase the firing rate. The influence of BK channels on firing rate in the presence of other conductances, such as I _m and I _h , as well as with different amplitudes of depolarizing input, were also investigated. These results provide a formal explanation for the apparently contradictory effects of BK channel antagonists on firing rates.     

中国新归化种广布苋的分布及其与腋花苋的关系

本文报道了中国苋科苋属的一新记录归化植物——广布苋(Amaranthus graecizans L．)。该种植株常匍匐,叶片狭长椭圆形至线状披针形,有时线形或菱形卵形,长至少为宽的2.5倍,花被片3枚,近等长,与中国有分布的本属其他物种有所区别。该种原产于欧洲地中海地区、非洲北部至亚洲西部,归化于欧洲其他地区、东亚、澳大利亚、北美洲以及我国的河南、河北和山东等地区。该种易与苋属其他种类相混淆,因此其在我国的分布区可能被低估。此外,本文还对该种的种下等级以及该种的相似种进行了区分,并对该种下亚种Amaranthus graecizans subsp. thellungianus (Nevski) Gusev与国内文献记载的腋花苋(Amaranthus roxburghianus Kung)之间的关系作了说明与澄清。     

Research progress on the immune mechanism of the silkworm Bombyx mori

The silkworm Bombyx mori L., representing an important economic insect and one of the best models for studying insect immunity, possesses an efficient and sophisticated innate immune system against invasive microorganisms. The innate immune system basically includes humoural immunity and cellular immunity. The humoural immunity, which functions via molecules including humoural factors, lysozymes, phenoloxidase, hemolin, lectins and, in particular, antimicrobial peptides, plays a central role in eliminating the invading pathogens. The cellular immunity is primarily carried out and mediated by plasmatocytes and granular cells of haemocytes in the haemolymph, usually followed by melanization. Additionally, apoptosis, a primary viral defence for insects lacking adaptive immunity, comprises an important part of the silkworm immune system. Currently, there is still the lack of a comprehensive and systematic understanding of the molecular mechanisms of silkworm immunity. We review the latest research progress on silkworm immune mechanisms, including phenoloxidase‐dependent melanization and apoptosis, which is conducive to improving our understanding of the silkworm immune mechanism, clarifying the relationship of various immune mechanisms, and also providing a theoretical basis and reference for the future research of insect immunity.     

Acid Ceramidase Promotes Nuclear Export of PTEN through Sphingosine 1-Phosphate Mediated Akt Signaling

The tumor suppressor PTEN is now understood to regulate cellular processes at the cytoplasmic membrane, where it classically regulates PI3K signaling, as well as in the nucleus where multiple roles in controlling cell cycle and genome stability have been elucidated. Mechanisms that dictate nuclear import and, less extensively, nuclear export of PTEN have been described, however the relevance of these processes in disease states, particularly cancer, remain largely unknown. We investigated the impact of acid ceramidase on the nuclear-cytoplasmic trafficking of PTEN. Immunohistochemical analysis of a human prostate tissue microarray revealed that nuclear PTEN was lost in patients whose tumors had elevated acid ceramidase. We found that acid ceramidase promotes a reduction in nuclear PTEN that is dependent upon sphingosine 1-phosphate-mediated activation of Akt. We were further able to show that sphingosine 1-phosphate promotes formation of a complex between Crm1 and PTEN, and that leptomycin B prevents acid ceramidase and sphingosine 1-phosphate mediated loss of nuclear PTEN, suggesting an active exportin-mediated event. To investigate whether the tumor promoting aspects of acid ceramidase in prostate cancer depend upon its ability to export PTEN from the nucleus, we used enforced nuclear expression of PTEN to study docetaxel-induced apoptosis and cell killing, proliferation, and xenoengraftment. Interestingly, while acid ceramidase was able to protect cells expressing wild type PTEN from docetaxel, promote proliferation and xenoengraftment, acid ceramidase had no impact in cells expressing PTEN-NLS. These findings suggest that acid ceramidase, through sphingosine 1-phosphate, promotes nuclear export of PTEN as a means of promoting tumor formation, cell proliferation, and resistance to therapy.