Does lethal control of top‐predators release mesopredators? A re‐evaluation of three Australian case studies

Top‐predators can sometimes be important for structuring fauna assemblages in terrestrial ecosystems. Through a complex trophic cascade, the lethal control of top‐predators has been predicted to elicit positive population responses from mesopredators that may in turn increase predation pressure on prey species of concern. In support of this hypothesis, many relevant research papers, opinion pieces and literature reviews identify three particular case studies as supporting evidence for top‐predator control‐induced release of mesopredators in Australia. However, many fundamental details essential for supporting this hypothesis are missing from these case studies, which were each designed to investigate alternative aims. Here, we re‐evaluate the strength of evidence for top‐predator control‐induced mesopredator release from these three studies after comprehensive analyses of associated unpublished correlative and experimental data. Circumstantial evidence alluded to mesopredator releases of either the European Red Fox (Vulpes vulpes) or feral Cat (Felis catus) coinciding with Dingo (Canis lupus dingo) control in each case. Importantly, however, substantial limitations in predator population sampling techniques and/or experimental designs preclude strong assertions about the effect of lethal control on mesopredator populations from these studies. In all cases, multiple confounding factors and plausible alternative explanations for observed changes in predator populations exist. In accord with several critical reviews and a growing body of demonstrated experimental evidence on the subject, we conclude that there is an absence of reliable evidence for top‐predator control‐induced mesopredator release from these three case studies. Well‐designed and executed studies are critical for investigating potential top‐predator control‐induced mesopredator release.     

Dill (Anethum graveolens L.) seed essential oil induces Candida albicans apoptosis in a metacaspase-dependent manner

Dill (Anethum graveolens L.) has been used in traditional Uighur medicine for its various pharmacological activities. Previous studies have suggested that dill seed essential oil (DSEO) has anti-Candida potential and the mechanism of its action also has been studied. Our study examined whether DSEO induces apoptosis in the human pathogen Candida albicans ATCC 64550. Our results indicate that C. albicans ATCC 64550 cells treated with DSEO show some typical apoptosis characters, such as decrease in adenosine triphosphatase (ATPase) activity, chromatin condensation, nuclear fragmentation, and phosphatidylserine (PS) exposure. The DSEO promoted cytochrome c (cyt c) release and metacaspase activation, which resulted in C. albicans ATCC 64550 apoptosis. l-cysteine prevented the DSEO-induced nuclear fragmentation, PS externalization, and metacaspase activation, thus indicating that the reactive oxygen species (ROS) is an important mediator of DSEO-induced apoptosis. To our knowledge, this study is the first to report the induction of apoptosis of this pathogen with concomitant metacaspase activation by DSEO.     

双歧三联活菌胶囊对结肠癌术后化疗相关性腹泻患者 肠黏膜通透性的影响及疗效观察

目的探讨双歧三联活菌胶囊对结肠癌术后化疗相关性腹泻患者肠黏膜通透性的影响及疗效观察。方法选取70例结肠癌术后行辅助化疗发生化疗相关性腹泻患者,随机分为观察组和对照组,每组35例。两组患者均予以口服蒙脱石散、静脉补液或口服补液和纠正水电解质酸碱平衡紊乱等常规治疗。观察组患者加用双歧三联活菌胶囊420 mg/次,3次/d,温开水溶解后口服。观察两组患者治疗前和治疗72 h后血清二胺氧化酶（DAO）和肿瘤坏死因子-α（TNF-α）水平的变化,并比较临床疗效及药物不良反应。结果治疗72 h后,两组患者DAO和TNF-α水平均有不同程度下降（P〈0.05或P〈0.01）,且观察组下降程度较对照组更明显（P〈0.05）;同时观察组患者临床总有效率（94.29%）明显高于对照组（74.29%）（χ2=5.29,P〈0.05）,两组患者治疗期间无明显的药物不良反应。结论双歧三联活菌胶囊用于治疗结肠癌术后化疗相关性腹泻具有较好的疗效及安全性,能降低血清DAO和TNF-α水平,具有降低肠黏膜的通透性功能。     

慢性下肢静脉曲张性溃疡的病原菌分布及耐药性分析

目的观察绍兴市人民医院血管外科慢性下肢静脉曲张性溃疡（CLU）患者的病原菌分布以及耐药特点,为临床合理用药提供依据。方法对该院血管外科2012年1月至2013年12月的CLU患者,其溃疡面渗出物培养出的病原菌及耐药性进行回顾性分析。结果病原菌分布较广泛,以铜绿假单胞菌和金黄色葡萄球菌为主。金黄色葡萄球菌对青霉素G的耐药率最高,达到97.37%,对红霉素和克林霉素的耐药率分别为60.53%和55.26%,对利奈唑烷和万古霉素全部敏感。铜绿假单胞菌对抗生素的敏感性较好。结论 CLU患者感染的病原菌分布广泛,且易多重感染,临床在采用外科治疗的同时,宜合理使用抗生素,针对不同患者采取个体化、系统化治疗方案,以提高治愈率,降低复发率。     

Intrinsic Disorder Mediates Cooperative Signal Transduction in STIM1

Intrinsically disordered domains have been reported to play important roles in signal transduction networks by introducing cooperativity into protein–protein interactions. Unlike intrinsically disordered domains that become ordered upon binding, the EF-SAM domain in the stromal interaction molecule (STIM) 1 is distinct in that it is ordered in the monomeric state and partially unfolded in its oligomeric state, with the population of the two states depending on the local Ca^2 + concentration. The oligomerization of STIM1, which triggers extracellular Ca^2 + influx, exhibits cooperativity with respect to the local endoplasmic reticulum Ca^2 + concentration. Although the physiological importance of the oligomerization reaction is well established, the mechanism of the observed cooperativity is not known. Here, we examine the response of the STIM1 EF-SAM domain to changes in Ca^2 + concentration using mathematical modeling based on in vitro experiments. We find that the EF-SAM domain partially unfolds and dimerizes cooperatively with respect to Ca^2 + concentration, with Hill coefficients and half-maximal activation concentrations very close to the values observed in vivo for STIM1 redistribution and extracellular Ca^2 + influx. Our mathematical model of the dimerization reaction agrees quantitatively with our analytical ultracentrifugation-based measurements and previously published free energies of unfolding. A simple interpretation of these results is that Ca^2 + loss effectively acts as a denaturant, enabling cooperative dimerization and robust signal transduction. We present a structural model of the Ca^2 +-unbound EF-SAM domain that is consistent with a wide range of evidence, including resistance to proteolytic cleavage of the putative dimerization portion.     

Evaluation of a Novel Laser-assisted Coronary Anastomotic Connector - the Trinity Clip - in a Porcine Off-pump Bypass Model

To simplify and facilitate beating heart (i.e., off-pump), minimally invasive coronary artery bypass surgery, a new coronary anastomotic connector, the Trinity Clip, is developed based on the excimer laser-assisted nonocclusive anastomosis technique. The Trinity Clip connector enables simplified, sutureless, and nonocclusive connection of the graft to the coronary artery, and an excimer laser catheter laser-punches the opening of the anastomosis. Consequently, owing to the complete nonocclusive anastomosis construction, coronary conditioning (i.e., occluding or shunting) is not necessary, in contrast to the conventional anastomotic technique, hence simplifying the off-pump bypass procedure. Prior to clinical application in coronary artery bypass grafting, the safety and quality of this novel connector will be evaluated in a long-term experimental porcine off-pump coronary artery bypass (OPCAB) study. In this paper, we describe how to evaluate the coronary anastomosis in the porcine OPCAB model using various techniques to assess its quality. Representative results are summarized and visually demonstrated.     

Monitoring of Systemic and Hepatic Hemodynamic Parameters in Mice

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. However, due to the small size of the mouse, technical details of the intraoperative monitoring procedure suitable for the mouse were rarely described. Previously we have reported a monitoring procedure to obtain hemodynamic parameters for rats. Now, we adapted the procedure to acquire systemic and hepatic hemodynamic parameters in mice, a species ten-fold smaller than rats. This film demonstrates the instrumentation of the animals as well as the data acquisition process needed to assess systemic and hepatic hemodynamics in mice. Vital parameters, including body temperature, respiratory rate and heart rate were recorded throughout the whole procedure. Systemic hemodynamic parameters consist of carotid artery pressure (CAP) and central venous pressure (CVP). Hepatic perfusion parameters include portal vein pressure (PVP), portal flow rate as well as the flow rate of the common hepatic artery (table 1). Instrumentation and data acquisition to record the normal values was completed within 1.5 h. Systemic and hepatic hemodynamic parameters remained within normal ranges during this procedure.This procedure is challenging but feasible. We have already applied this procedure to assess hepatic hemodynamics in normal mice as well as during 70% partial hepatectomy and in liver lobe clamping experiments. Mean PVP after resection (n= 20), was 11.41±2.94 cmH₂O which was significantly higher (P<0.05) than before resection (6.87±2.39 cmH₂O). The results of liver lobe clamping experiment indicated that this monitoring procedure is sensitive and suitable for detecting small changes in portal pressure and portal flow rate. In conclusion, this procedure is reliable in the hands of an experienced micro-surgeon but should be limited to experiments where mice are absolutely needed.     

A new tool for monoclonal antibody analysis: Application of IdeS proteolysis in IgG domain-specific characterization

Monoclonal antibody (mAb) products are extraordinarily heterogeneous due to the presence of a variety of enzymatic and chemical modifications, such as deamidation, isomerization, oxidation, glycosylation, glycation, and terminal cyclization. The modifications in different domains of the antibody molecule can result in different biological consequences. Therefore, characterization and routine monitoring of domain-specific modifications are essential to ensure the quality of the therapeutic antibody products. For this purpose, a rapid and informative methodology was developed to examine the heterogeneity of individual domains in mAb products. A recently discovered endopeptidase, IdeS, cleaves heavy chains below the hinge region, producing F(ab')₂ and Fc fragments. Following reduction of disulfide bonds, three antibody domains (LC, Fd, and Fc/2) can be released for further characterization. Subsequent analyses by liquid chromatography/mass spectrometry, capillary isoelectric focusing, and glycan mapping enable domain-specific profiling of oxidation, charge heterogeneity, and glycoform distribution. When coupled with reversed phase chromatography, the unique chromatographic profile of each molecule offers a simple strategy for an identity test, which is an important formal test for biopharmaceutical quality control purposes. This methodology is demonstrated for a number of IgGs of different subclasses (IgG1, IgG2, IgG4), as well as an Fc fusion protein. The presented technique provides a convenient platform approach for scientific and formal therapeutic mAb product characterization. It can also be applied in regulated drug substance batch release and stability testing of antibody and Fc fusion protein products, in particular for identity and routine monitoring of domain-specific modifications.