4:2:1 conduction of an AF initiating trigger

A 44 year old male with idiopathic dilated cardiomyopathy was undergoing persistent atrial fibrillation (AF) ablation. Following antral ablation, AF terminated into a regular narrow complex rhythm. Earliest activation was mapped to a focus in the superior vena cava (SVC) which was conducted in a 2:1 ratio to the atria which in turn was conducted with 2:1 ratio to the ventricles, resulting in an unusual 4:2:1 conduction of the SVC tachycardia. 1:1 conduction of the SVC tachycardia to the atrium preceded initiation of AF. During AF, SVC tachycardia continued unperturbed. Sinus rhythm was restored following catheter ablation of the focus.     

Estimating the potential refolding yield of recombinant proteins expressed as inclusion bodies

Recombinant protein production in bacteria is efficient except that insoluble inclusion bodies form when some gene sequences are expressed. Such proteins must undergo renaturation, which is an inefficient process due to protein aggregation on dilution from concentrated denaturant. In this study, the protein-protein interactions of eight distinct inclusion-body proteins are quantified, in different solution conditions, by measurement of protein second virial coefficients (SVCs). Protein solubility is shown to decrease as the SVC is reduced (i.e., as protein interactions become more attractive). Plots of SVC versus denaturant concentration demonstrate two clear groupings of proteins: a more aggregative group and a group having higher SVC and better solubility. A correlation of the measured SVC with protein molecular weight and hydropathicity, that is able to predict which group each of the eight proteins falls into, is presented. The inclusion of additives known to inhibit aggregation during renaturation improves solubility and increases the SVC of both protein groups. Furthermore, an estimate of maximum refolding yield (or solubility) using high-performance liquid chromatography was obtained for each protein tested, under different environmental conditions, enabling a relationship between "yield" and SVC to be demonstrated. Combined, the results enable an approximate estimation of the maximum refolding yield that is attainable for each of the eight proteins examined, under a selected chemical environment. Although the correlations must be tested with a far larger set of protein sequences, this work represents a significant move beyond empirical approaches for optimizing renaturation conditions. The approach moves toward the ideal of predicting maximum refolding yield using simple bioinformatic metrics that can be estimated from the gene sequence. Such a capability could potentially "screen," in silico, those sequences suitable for expression in bacteria from those that must be expressed in more complex hosts.     

The characteristics of action potential and nonselec-tive cation current of cardiomyocytes in rabbit superior vena cava

As a special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cava (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may in-crease or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can in-crease or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyo-cytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.     

Profiles of digestive enzymes of two competing planktivores,silver carp and gizzard shad,differ

Typically, studies in digestive physiology in fish focus on a few enzymes and provide insight into the specific processes of the enzyme in a targeted species. Comparative studies assessing a wide number of digestive enzymes on fishes that compete for food resources are lacking, especially in the context of an introduced species. It is generally thought that the invasive silver carp (SVC; Hypophthalmichthys molitrix) directly compete for food resources with the native gizzard shad (GZS; Dorosoma cepedianum) in waters where they coexist. We compared 19 digestive enzymes between SVC and GZS throughout a year and in two rivers in the Midwestern United States: Illinois River and Wabash River. All digestive enzymes analyzed were detected in both SVC and GZS in both rivers. However, the profiles of the digestive enzymes varied by species. Alkaline phosphatase, valine arylamidase, acid phosphatase, naphthol-AS-BI-phosphohydrolase and N-acetyl-β-glucosaminidase were all much higher in SVC than in GZS. Differences between digestive enzyme profiles were also observed between rivers and months. This study demonstrates the utility of using an ecological approach to compare physiological features in fishes.     

Successful Implantation of Transvenous Pacing System via Persistent Left Superior Vena Cava and Coronary Sinus in Small Children

Transvenous pacemaker implantation tends to be difficult in the setting of a persistent left superior vena cava (SVC) and an absent or inaccessible right SVC. We report two small children in whom transvenous pacing leads were successfully inserted via a persistent left SVC. This technique was safe in our cases; however, favorable long-term result has yet to be demonstrated.     

Successful Implantation of Transvenous Pacing System via Persistent Left Superior Vena Cava and Coronary Sinus in Small Children

Transvenous pacemaker implantation tends to be difficult in the setting of a persistent left superior vena cava (SVC) and an absent or inaccessible right SVC. We report two small children in whom transvenous pacing leads were successfully inserted via a persistent left SVC. This technique was safe in our cases; however, favorable long-term result has yet to be demonstrated.     

A linear ablating system in the left and right atrium: feasibility, catheter performance and clinical results

IntroductionWe describe the use of a ablating system to compartmentalise and regionally isolate the atria in paroxysmal and persistent atrial fibrillation (AF).Methods40 patients were studied, 25 paroxysmal AF and 14 persistent AF. One patient enrolled was later found to be in left atrial flutter and was excluded. The Cardima Revelation® TX catheter system with Intellitemp® Radiofrequency (RF) energy control device and a Medtronic Atakar® RF generator were used to place wide area circumferential ablations to achieve conduction block into the left and right sided pulmonary veins. Roof lines and mitral isthmus lines were also performed. In patients with persistent AF and in repeat procedures, right atrial compartmentalisation was performed with an anterior superior vena cava (SVC) to inferior vena cava (IVC) line and a septal SVC to IVC line.ResultsAt 6 months, 18 of the 39 patients were asymptomatic, 10 had improved symptoms and 22 were in sinus rhythm. In the paroxysmal group, 11 were asymptomatic, 7 had improved symptoms and 16 (64%) were in sinus rhythm. In the persistent group, 7 were asymptomatic, 3 had improved symptoms and 6 (43%) were in sinus rhythm. The total group AF burden was 37.8 ± 5.4 hrs pre-procedure and 23.1 ± 5.1 hrs at 6 months post procedure. Mean temperature, impedance and power recorded at each pole demonstrated effective power delivery at all poles. No catheter charring was observed, complication rates were comparable to standard AF ablation technique.ConclusionLinear ablation in the left and right atria to mimic Cox’s Maze is feasible and safe using this ablating system.     

Left superior vena cava, a remnant of embryological development

A 46-year-old Brugada syndrome patient underwent insertion of a dual-chamber implantable cardioverter- defibrillator (ICD), revealing a left-sided superior vena cava (SVC), (figure 1), running, characteristically, left from the sternum and flowing into the great cardiac vein. Following this course, the atrial lead was placed in the right atrium (RA) (figure 2, arrow, note dorsal position). The ventricular lead was inserted through the connecting anonymous vein between left and right SVC (figure 1, double arrow), into the right SVC and right ventricle (RV). The presence of a left superior vena cava results from the persistence of the embryonic left anterior cardinal vein. This anomaly is present in approximately 0.5% of the general population and in 3 to 5% of persons with other congenital heart defects, as established by autopsy.     

The characteristics of action potential and nonselective cation current of cardiomyocytes in rabbit superior vena cava

As a special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cava (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD₉₀ at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (I _Ns) in both SVC and RA cardiomyocytes. The peak density of I _Ns in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase I _Ns in SVC cardiomyocytes. The agonist or the antagonist of I _Ns may increase or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of I _Ns between them; the agonist or the antagonist of I _Ns can increase or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyocytes. I _Ns in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.     

β-Adrenergic stimulation induces pro-arrhythmic activity in the caval vein myocardial tissue

Electrical activity of the right superior vena cava (SVC) is considered as a source of the atrial fibrillation. We have shown that bioelectrical properties of the SVC myocardium differ from those of the working atrial myocardium. Electrically evoked action potential duration in SVC is significantly shorter, the resting membrane potential in both stimulated and quiescent SVC preparations is significantly more positive than in atria. Activation of β-adrenoreceptors in SVC myocardium leads to a series of action potentials, and this process depends on protein kinase A. Probably, β-adrenergic stimulation enhances SVC arrhythmogenesis in vivo.     

An optimized live bacterial delivery vehicle safely and efficaciously delivers bacterially transcribed therapeutic nucleic acids

There is an unmet need for delivery platforms that realize the full potential of next-generation nucleic acid therapeutics. The in vivo usefulness of current delivery systems is limited by numerous weaknesses, including poor targeting specificity, inefficient access to target cell cytoplasm, immune activation, off-target effects, small therapeutic windows, limited genetic encoding and cargo capacity, and manufacturing challenges. Here we characterize the safety and efficacy of a delivery platform comprising engineered live, tissue-targeting, non-pathogenic bacteria (Escherichia coli SVC1) for intracellular cargo delivery. SVC1 bacteria are engineered to specifically bind to epithelial cells via a surface-expressed targeting ligand, to allow escape of their cargo from the phagosome, and to have minimal immunogenicity. We describe SVC1's ability to deliver short hairpin RNA (shRNA), localized SVC1 administration to various tissues, and its minimal immunogenicity. To validate the therapeutic potential of SVC1, we used it to deliver influenza-targeting antiviral shRNAs to respiratory tissues in vivo. These data are the first to establish the safety and efficacy of this bacteria-based delivery platform for use in multiple tissue types and as an antiviral in the mammalian respiratory tract. We expect that this optimized delivery platform will enable a variety of advanced therapeutic approaches.     

Combining One‐sided and Two‐sided Confidence Interval Procedures for Successive Comparisons of Ordered Treatment Effects

Lee and Spurrier (1995) present one‐sided and two‐sided confidence interval procedures for making successive comparisons between ordered treatments. Their procedures have important applications for problems where the treatments can be assumed to satisfy a simple ordering, such as for a sequence of increasing dose‐levels of a drug. The two‐sided procedure provides both upper and lower bounds on the differences between successive treatments, whereas the one‐sided procedure only provides lower bounds on these differences. However, the one‐sided procedure allows sharper inferences regarding which treatments can be declared to be better than their previous ones. In this paper we apply the results obtained in Hayter , Miwa , and Liu (2000) to develop a new procedure which combines the good aspects of both the one‐sided and the two‐sided procedures. This new procedure maintains the inferential sensitivity of the one‐sided procedure while also providing both upper and lower bounds on the differences between successive treatments. Some new critical points are needed which are tabulated for the balanced case where the sample sizes are all equal. The application of the new procedure is illustrated with an example.     

Non-right sidedness: an association with lower IL-2 production.

Using a laterality questionnaire, 138 normal healthy individuals were classified as right-sided and 25 as non-right sided. Interleukin-2 (IL-2) was generated from whole blood obtained from these subjects using mitogen (PHA) stimulation. IL-2 was quantitated in picograms/ml using an enzyme immunoassay (ELISA). Additionally, sera from these subjects were tested for 7 autoantibodies by standard serological methods. As compared to right sided subjects, non-right sided individuals had significantly lower IL-2 production. Non-right sided individuals with autoantibodies had significantly lower IL-2 production than right sided subjects with or without autoantibodies, but did not differ significantly from their non-right sided counterparts without autoantibodies. These data support the increasing evidence for the differential and lateralized regulation of immune functions by the right and left cerebral regions.     

The likelihood of aggregation during protein renaturation can be assessed using the second virial coefficient

Protein aggregation is commonly observed during protein refolding. To better understand this phenomenon, the intermolecular interactions experienced by a protein during unfolding and refolding are inferred from second virial coefficient (SVC) measurements. It is accepted that a negative SVC is indicative of protein-protein interactions that are attractive, whereas a positive SVC indicates net repulsive interactions. Lysozyme denatured and reduced in guanidinium hydrochloride exhibited a decreasing SVC as the denaturant was diluted, and the SVC approached zero at approximately 3 M GdnHCl. Further dilution of denaturant to renaturation conditions (1.25 M GdnHCl) led to a negative SVC, and significant protein aggregation was observed. The inclusion of 500 mM L-arginine in the renaturation buffer shifted the SVC to positive and suppressed aggregation, thereby increasing refolding yield. The formation of mixed disulfides in the denatured state prior to refolding also increased protein solubility and suppressed aggregation, even without the use of L-arginine. Again, the suppression of aggregation was shown to be caused by a shift from attractive to repulsive intermolecular interactions as reflected in a shift from a negative to a positive SVC value. To the best of our knowledge, this is the first time that SVC data have been reported for renaturation studies. We believe this technique will aid in our understanding of how certain conditions promote renaturation and increase protein solubility, thereby suppressing aggregation. SVC measurements provide a useful link, for protein folding and aggregation, between empirical observation and thermodynamics.     

Molecular Analysis of Spring Viraemia of Carp Virus in China: A Fatal Aquatic Viral Disease that Might Spread in East Asian

Spring viraemia of carp (SVC) is a fatal viral disease for cyprinid fish, which is caused by spring viraemia of carp virus (SVCV). To date, no SVC outbreak has been reported in China. Between 1998 and 2002, outbreaks of SVC were reported in ornamental and wild fish in Europe and America, imported from multiple sources including China. Based on phylogenetic analysis, the viral strain isolated from America was shown to be originated from Asia. These outbreaks not only resulted in huge economic losses, but also raise an interesting question as to whether SVCV really exists in China and if so, is it responsible for SVC outbreaks? From 2002 to 2006, we screened 6700 samples from ornamental fish farms using the cell culture method of the Office International des Epizooties (OIE), and further verified the presence of SVCV by ELISA and real-time quantitative RT-PCR. Two infected samples were found and the complete genome of SVCV was sequenced from one of the isolates, termed SVCV-C1. Several unique hallmarks of SVCV-C1 were identified, including six amino acid (KSLANA) insertion in the viral RNA-dependent RNA polymerase (L) protein and ten nucleotide insertion in the region between glycoprotein (G) and L genes in European SVCV strains. Phylogenetic tree analysis of the full-length G protein of selected SVCV isolates from the United Kingdom and United States revealed that G proteins could be classified into Ia and Id sub genogroups. The Ia sub genogroup can be further divided into newly defined sub genogroups Ia-A and Ia-B. The isolates derived from the United States and China including the SVCV-C1 belongs to in the Ia-A sub genogroup. The SVCV-C1 G protein shares more than 99% homology with the G proteins of the SVCV strains from England and the United States, making it difficult to compare their pathogenicity. Comparison of the predicted three-dimensional structure based on the published G protein sequences from five SVCV strains revealed that the main differences were in the loops of the pleckstrin homology domains. Since SVCV is highly pathogenic, we speculate that SVC may therefore pose a serious threat to farmed cyprinid fish in China.     

Two-Sided Edge Effect Studies and the Restoration of Endangered Ecosystems

Edge effect is the modification of ecological patterns and processes that occur around the edge of two adjacent ecosystems. Depending on their aim, edge effect studies have adopted one of the following methodological approaches: (1) the one‐sided approach—which studies ecological patterns and processes from an edge to the interior of just one of the habitats and (2) the two‐sided approach—which studies ecological patterns and processes across the whole gradient from the interior of one habitat to the interior of the other habitat, passing through the edge zone. A database containing information on 317 published papers revealed that both methodological approaches were equally used until the end of the 1980s. During the 1990s, the question of how organisms respond to habitat destruction and fragmentation led to an abrupt increase in the number of one‐sided studies. Recently, however, two‐sided studies have become more frequent. In this review, we put forth theoretical arguments of why the two‐sided edge effect approach can produce a broader understanding of the ecological processes associated with edges. We highlight that two‐sided edge effect studies must become more experimental and predictive, focusing on the factors controlling edge dynamics. Finally, we point out that two‐sided edge effect studies have the potential to create a positive research agenda for the restoration and expansion of endangered ecosystems.     

PDIA1和EF1D在左侧和右侧结肠癌差异表达的实验研究

目的：初步确定蛋白质二硫化异构酶A1和延伸因子1-delta为左侧和右侧结肠癌中差异表达蛋白,为左侧和右侧结肠癌在肿瘤生物学方面的差异提供分子遗传学依据。方法：收集人左侧结肠癌（LSCC）和右侧结肠癌（RSCC）组织标本,进行二维凝胶电泳、质谱分析和生物信息学分离和鉴定左右侧结肠癌中差异表达蛋白质,进一步应用RT—PCR、WesternBlot和免疫组织化学技术检测蛋白质二硫化畀构酶A1和延伸因子1-delta在左侧和右侧结肠癌中的表达状态。结果：筛选并成功鉴定出左侧和右侧结肠癌中16种差异表达蛋白质,与右侧结肠癌比较,lO种蛋白在左侧结肠癌表达上调,6种蛋白在左侧结肠癌表达下调,其中蛋白质二硫化异构酶A1在左侧结肠癌中表达上调,延伸因子1-delta在左侧结肠癌中表达下调,并通过RT-PCR、Western Blot和免疫组化方法证实了在左侧和右侧结肠癌中该两种蛋白表达的差异,与蛋白质组学结果一致。结论：左侧结肠癌和右侧结肠癌的蛋白质组存在差异,其中蛋白质二硫化异构酶A1和延伸因子1—delta在mRNA和蛋白水平均存在差异,这些可能是左侧和右侧结肠癌生物学行为差异的原因。     

Effect of heat stress on cardiac output and systemic vascular conductance during simulated hemorrhage to presyncope in young men

During moderate actual or simulated hemorrhage, as cardiac output decreases, reductions in systemic vascular conductance (SVC) maintain mean arterial pressure (MAP). Heat stress, however, compromises the control of MAP during simulated hemorrhage, and it remains unknown whether this response is due to a persistently high SVC and/or a low cardiac output. This study tested the hypothesis that an inadequate decrease in SVC is the primary contributing mechanism by which heat stress compromises blood pressure control during simulated hemorrhage. Simulated hemorrhage was imposed via lower body negative pressure (LBNP) to presyncope in 11 passively heat-stressed subjects (increase core temperature: 1.2 ± 0.2°C; means ± SD). Cardiac output was measured via thermodilution, and SVC was calculated while subjects were normothermic, heat stressed, and throughout subsequent LBNP. MAP was not changed by heat stress but was reduced to 45 ± 12 mmHg at the termination of LBNP. Heat stress increased cardiac output from 7.1 ± 1.1 to 11.7 ± 2.2 l/min (P < 0.001) and increased SVC from 0.094 ± 0.018 to 0.163 ± 0.032 l·min(-1)·mmHg(-1) (P < 0.001). Although cardiac output at the onset of syncopal symptoms was 37 ± 16% lower relative to pre-LBNP, presyncope cardiac output (7.3 ± 2.0 l/min) was not different than normothermic values (P = 0.46). SVC did not change throughout LBNP (P > 0.05) and at presyncope was 0.168 ± 0.044 l·min(-1)·mmHg(-1). These data indicate that in humans a cardiac output adequate to maintain MAP while normothermic is no longer adequate during a heat-stressed-simulated hemorrhage. The absence of a decrease in SVC at a time of profound reductions in MAP suggests that inadequate control of vascular conductance is a primary mechanism compromising blood pressure control during these conditions.     

改进支持向量分类用于蝶类自动鉴别

昆虫自动识别是重要的新兴研究领域, 其中特征筛选与恰当地将多分类转化为二分类是两个关键步骤。本文基于支持向量分类, 提出了一种新的多类昆虫自动鉴别方法: 先以初始样本互作转换将多分类转化为二分类, 再以可交换核函数消除互作样本中初始样本排列顺序不同的影响, 继以非线性筛选去除无关特征与冗余特征并给出各保留特征相对重要性排序, 最后以简单投票决策校正独立预测结果。新方法应用于2科7种蝶类自动鉴别, 以前翅9个翅脉交叉点距离为初始特征, 种、科阶元26、24个随机初始测试样本均获得了100%的准确鉴别。新方法在昆虫自动识别等多分类领域有广泛应用前景。     

PDIA1 和EF1D 在左侧和右侧结肠癌差异表达的实验研究

目的:初步确定蛋白质二硫化异构酶A1和延伸因子1-delta为左侧和右侧结肠癌中差异表达蛋白,为左侧和右侧结肠癌在肿瘤生物学方面的差异提供分子遗传学依据。方法:收集人左侧结肠癌(LSCC)和右侧结肠癌(RSCC)组织标本,进行二维凝胶电泳、质谱分析和生物信息学分离和鉴定左右侧结肠癌中差异表达蛋白质,进一步应用RT-PCR、Western Blot和免疫组织化学技术检测蛋白质二硫化异构酶A1和延伸因子1-delta在左侧和右侧结肠癌中的表达状态。结果:筛选并成功鉴定出左侧和右侧结肠癌中16种差异表达蛋白质,与右侧结肠癌比较,10种蛋白在左侧结肠癌表达上调,6种蛋白在左侧结肠癌表达下调,其中蛋白质二硫化异构酶A1在左侧结肠癌中表达上调,延伸因子1-delta在左侧结肠癌中表达下调,并通过RT-PCR、Western Blot和免疫组化方法证实了在左侧和右侧结肠癌中该两种蛋白表达的差异,与蛋白质组学结果一致。结论:左侧结肠癌和右侧结肠癌的蛋白质组存在差异,其中蛋白质二硫化异构酶A1和延伸因子1-delta在mRNA和蛋白水平均存在差异,这些可能是左侧和右侧结肠癌生物学行为差异的原因。