Analysis of differently expressed proteins and transcripts in gills of Penaeus vannamei after yellow head virus infection

In this proteomic analysis of gills from yellow head virus (YHV)-infected Penaeus vannamei, we identified 13 spots with up-regulated protein expression levels and five spots with down-regulated levels. LC-nanoESI-MS/MS indicated that the up-regulated proteins included enzymes in the glycolytic pathway, the tricarboxylic acid cycle and amino acid metabolism. The other up-regulated proteins were arginine kinase, imaginal disk growth factor (IDGF) and a Ras-like GTP binding protein. By contrast, expression levels were reduced for an SCP-calcium binding protein (SCP), actin-1, a valosin-containing protein, and Rab11. Time-course assays by real time RT-PCR revealed no significant increase in mRNA level of glycolytic enzymes and arginine kinase. However, a significant decrease in SCP mRNA was observed. The present results are consistent with previously published work and suggest that a decrease in SCP expression may play an important role in the shrimp response to viral infections in general.     

NaCI胁迫对UV-B辐射诱导的绿豆环丁烷嘧啶二聚体和紫外吸收物质含量变化的影响

将2个对UV-B敏感性不同的绿豆品种‘秦豆-20’和‘中绿-1’幼苗放在培养室内,进行0.4W/m~2 UV-B辐射和0.4%NaCl胁迫的单独或复合处理,研究了NaCl胁迫对UV-B辐射诱导的DNA伤害和修复的影响。结果显示:在NaCl胁迫下,(1)在光下抗UV-B的品种‘中绿-1’的环丁烷嘧啶二聚体(CPD)累积量降低,而敏感品种‘秦豆-20’的CPD累积量未发生变化;(2)两品种CPD形成量均比无NaCl胁迫时低;(3)抗UV-B品种DNA的光、暗修复能力均比无NaCl胁迫时高:(4)而敏感品种DNA的光修复能力比无NaCl胁迫时低、暗修复能力未发生变化。另外,CPD形成量与紫外吸收物含量间具有明显的负相关性。说明NaCl胁迫不仅影响2个绿豆品种幼苗的CPD形成量,而且影响DNA的光、暗修复能力,进而导致了CPD累积量发生变化,由此影响了幼苗的UV-B敏感性。结果也暗示CPD形成量的变化是由于紫外吸收物质含量的不同所导致的。     

Syntheses, crystal structures, and magnetic properties of two cyclic dimer M2L2 complexes constructed from a new nitronyl nitroxide ligand and M(hfac)2 (M = Cu, Mn)

Two new binuclear radical complexes derived from a new long nitronyl nitroxide ligand, 2-[4-(5-pyrimidyl)phenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (4-NITPhPyrim), and M(hfac)₂ (M²⁺ = Cu²⁺, Mn²⁺; hfac⁻ = hexafluoroacetylacetonato), [Cu(hfac)₂(4-NITPhPyrim)]₂ · 4H₂O (1) and [Mn(hfac)₂(4-NITPhPyrim)]₂ · 4H₂O (2), were synthesized as well as characterized structurally and magnetically. X-ray analysis indicates that 1 and 2 are rectangle-like centrosymmetric dimer M₂L₂ complexes. Magnetic measurements indicate that there are two types of magnetic exchanges in 1: the ferromagnetic (FM) exchange between the Cu(II) ion and the directly bonded nitroxide unit (J₁ = 24.20 cm⁻¹) and the weak FM exchange of Cu-NIT through the pyrimidine and phenyl rings (J₂ = 0.62 cm⁻¹). Besides the strong antiferromagnetic (AFM) coupling between the Mn(II) ion and the directly bonded nitroxide unit (J = −87.61 cm⁻¹), there is a weak FM interaction between the two Mn-NIT pairs (θ = 0.39 K) in 2.     

DNA光修复酶修复紫外损伤的DNA

DNA光修复酶在蓝光驱动下,利用黄素腺嘌呤二核苷酸（FAD）分子的黄素酶作为催化辅助因子,来修复紫外线诱导的环丁烷嘧啶二聚体（CPD）和嘧啶（6-4）嘧啶酮的DNA损伤产物。通过无根发育树,综述了DNA光修复酶/隐花色素家族的分类;详细地阐述两种DNA光修复酶的结构、光损伤后产生的嘧啶二聚体的结构及光修复过程;最后回顾了DNA光修复酶的研究现状并展望该领域的发展前景。     

Anti‐angiogenic effect of quercetin and its 8‐methyl pentamethyl ether derivative in human microvascular endothelial cells

Angiogenesis is involved in many pathological states such as progression of tumours, retinopathy of prematurity and diabetic retinopathy. The latter is a more complex diabetic complication in which neurodegeneration plays a significant role and a leading cause of blindness. The vascular endothelial growth factor (VEGF) is a powerful pro‐angiogenic factor that acts through three tyrosine kinase receptors (VEGFR‐1, VEGFR‐2 and VEGFR‐3). In this work we studied the anti‐angiogenic effect of quercetin (Q) and some of its derivates in human microvascular endothelial cells, as a blood retinal barrier model, after stimulation with VEGF‐A. We found that a permethylated form of Q, namely 8MQPM, more than the simple Q, is a potent inhibitor of angiogenesis both in vitro and ex vivo. Our results showed that these compounds inhibited cell viability and migration and disrupted the formation of microvessels in rabbit aortic ring. The addition of Q and more significantly 8MQPM caused recoveries or completely re‐establish the transendothelial electrical resistance (TEER) to the control values and suppressed the activation of VEGFR2 downstream signalling molecules such as AKT, extracellular signal‐regulated kinase, and c‐Jun N‐terminal kinase. Taken together, these data suggest that 8MQPM might have an important role in the contrast of angiogenesis‐related diseases.     

Patient non-attendance at urgent referral appointments for suspected cancer and its links to cancer diagnosis and one year mortality: A cohort study of patients referred on the Two Week Wait pathway

BackgroundThe ‘Two Week Wait’ policy aims to ensure patients with suspected cancer are seen within two weeks of referral. However, patient non-attendance can result in this target being missed. This study aimed to identify predictors of non-attendance; and analyse the relationship between attendance and outcomes including cancer diagnosis and early mortality.MethodsA cohort study of 109,433 adults registered at 105 general practices, referred to a cancer centre within a large NHS hospital trust (April 2009 to December 2016) on the ‘Two Week Wait’ pathway.Results5673 (5.2%) patients did not attend. Non-attendance was largely predicted by patient factors (younger and older age, male gender, greater deprivation, suspected cancer site, earlier year of referral, greater distance to the hospital) over practice factors (greater deprivation, lower Quality and Outcomes Framework score, lower cancer conversion rate, lower cancer detection rate). 10,360 (9.6%) patients were diagnosed with cancer within six months of referral (9.8% attending patients, 5.6% non-attending patients). Among these patients, 2029 (19.6%) died within 12 months of diagnosis: early mortality risk was 31.3% in non-attenders and 19.2% in attending patients.ConclusionsNon-attendance at urgent referral appointments for suspected cancer involves a minority of patients but happens in predictable groups. Cancer diagnosis was less likely in non-attending patients but these patients had worse early mortality outcomes than attending patients. The study findings have implications for cancer services and policy.     

Blockade ofNMDA receptors differentially affectsD-1 andD-2 mediated turning behavior in the 6-hydroxydopamine model of Parkinson

Summary In rats with unilateral lesion of the nigrostriatal dopaminergic pathway, L-DOPA induces contralateral turning through activation of denervated D-1 and D-2 receptors. Blockade of N-methyl-D-aspartate (NMDA) receptors by the non-competitive antagonist (+)MK-801, potentiated the contralateral turning induced by L-DOPA as well as that induced by the D-1 agonist SKF 38393, while D-2 mediated turning was almost completely inhibited. Administration of the D-1 antagonist SCH 23390 blocked (+)MK-801-induced potentiation of L-DOPA contralateral turning, confirming the D-1 nature of the effects observed. Immunohistochemical studies on the early gene c-fos, which is known to be activated by stimulation of supersensitive D-1 receptors, revealed sparse c-fos positive nuclei in the lesioned CPu after SKF 38393, while after combined administration of (+)MK-801 and SKF 38393 dense labelling was obtained. Blockade of NMDA receptors, differentially affects D-1 and D-2 mediated turning behavior, suggesting that different neuronal pathways are involved in the mediation of D-1 and D-2 responses.     

Voltage clamp fluorometry: Combining fluorescence and electrophysiological methods to examine the structure-function of the Na/K-ATPase

This paper summarizes our recent work investigating the conformational dynamics and structural arrangement of the Na⁺/K⁺-ATPase using voltage clamp fluorometry as well as the latest biochemical, biophysical and structural results from other laboratories. Our research has been focused on combining site-specific fluorophore labeling on the alpha, beta and/or gamma subunit with electrophysiological studies to investigate partial reactions of the ion pump by monitoring changes in fluorescence intensity following voltage pulses and/or solution exchange. As a consequence of these studies, we have been able to identify a residue on the beta subunit, which following labeling with tetramethylrhodamine-6-maleimide can be used as a reporter group to monitor the conformational state of the holoenzyme. Furthermore, we have been able to delineate distance constraints between the alpha, beta and gamma subunits and to examine the relative movements of these proteins during ion transport. Concurrent to this research, significant advancements have been made in understanding the molecular mechanism of the Na⁺/K⁺-ATPase. Thus, our research will be compared with the results from other groups and future experimental directions will be proposed.