Will operate for food.

After spending 15 years in university, Dr. Robert Patterson recently received the right to write FRCSC after his name, and then began to look for gainful employment as a general surgeon. It was a long and frustrating search. He recounts how he finally found work in northern Alberta, and wonders if next year''s residents will encounter the same shortage of opportunities that he discovered.     

Effect of cytochrome c on the linoleic acid-degrading activity of porcine leukocyte 12-lipoxygenase

Hemoproteins are known to have quasilipoxygenase activity that converts linoleic acid (LA) to its hydroperoxides. However, it is not still clear whether, like lipoxygenases, hemoproteins can produce LA hydroperoxides when the LA is part of a mixture containing many different saturated and unsaturated fatty acids. In this study, we found that such hemoprotein as cytochrome c (Cyt c) did not produce LA hydroperoxides from the phospholipase A(2) (PL-A(2)) hydrolysis products of egg yolk phosphatidylcholine (PC). We also found that traces of hydroperoxides and a high concentration of the target unsaturated fatty acid (LA) needs to be present in a fatty acid mixture before the quasi-lipoxygenase activity of Cyt c becomes apparent. We also attempted to elucidate how Cyt c interact with porcine leukocyte 12-lipoxygenase (12-LOX). Hemoproteins are known to possess pseudo-lipohydroperoxidase activity, and can remove the hydroperoxides of unsaturated fatty acids from a reaction mixture. However, we found that Cyt c catalyzed the reaction by which hydroperoxides degrade LA, and thus enhanced the LA-degrading activity of 12-LOX. This hemoprotein-induced promotion of the ability of 12-LOX to degrade LA was observed even when the reaction mixture contained many different saturated and unsaturated fatty acids.     

An Evolutionary Perspective on Linoleic Acid Synthesis in Animals

The diet of organisms generally provides a sufficient supply of energy and building materials for healthy growth and development, but should also contain essential nutrients. Species differ in their exogenous requirements, but it is not clear why some species are able to synthesize essential nutrients, while others are not. The unsaturated fatty acid, linoleic acid (LA; 18:2n-6) plays an important role in functions such as cell physiology, immunity, and reproduction, and is an essential nutrient in diverse organisms. LA is readily synthesized in bacteria, protozoa and plants, but it was long thought that all animals lacked the ability to synthesize LA de novo and thus required a dietary source of this fatty acid. Over the years, however, an increasing number of studies have shown active LA synthesis in animals, including insects, nematodes and pulmonates. Despite continued interest in LA metabolism, it has remained unclear why some organisms can synthesize LA while others cannot. Here, we review the mechanisms by which LA is synthesized and which biological functions LA supports in different organisms to answer the question why LA synthesis was lost and repeatedly gained during the evolution of distinct invertebrate groups. We propose several hypotheses and compile data from the available literature to identify which factors promote LA synthesis within a phylogenetic framework. We have not found a clear link between our proposed hypotheses and LA synthesis; therefore we suggest that LA synthesis may be facilitated through bifunctionality of desaturase enzymes or evolved through a combination of different selective pressures.     

Polyunsaturated fatty acids augment free radical generation in tumor cells in vitro

Polyunsaturated fatty acids (PUFAs) have been shown to inhibit both normal and tumor cell growth in vitro. As PUFAs are known to induce a respiratory burst and free radical generation in polymorphonuclear leukocytes and since free radicals are toxic to cells, we investigated the effect of PUFAs on a measure of free radical generation (nitroblue tetrazolium reduction) in normal human fibroblasts and breast cancer cells in vitro. Results suggested that linoleate (LA), gamma-linolenate (GLA), arachidonate (AA) and eicosapentaenoate (EPA) can enhance nitroblue tetrazolium reduction in tumor cells but not in normal cells. GLA, AA and EPA were 1 1/2 to 2 times more effective than LA in inducing free radical generation. This difference was not due to increased uptake of LA, AA and EPA by tumor cells. In fact, the uptake of LA was the same both in normal and tumor cells whereas that of AA and EPA occurred at approximately half the rate in the tumor cells compared to normal cells. This indicates that PUFA induced growth inhibition and cytotoxicity to tumor cells may, at least in part, be due to enhanced free radical generation.     

Endogenous production of lipoic acid is essential for mouse development

alpha-Lipoic acid (LA) is a cofactor for mitochondrial alpha-ketoacid dehydrogenase complexes and is one of the most potent, natural antioxidants. Reduction of oxidative stress by LA supplementation has been demonstrated in patients with diabetic neuropathy and in animal models. To determine how normal development or pathological conditions are affected by genetic alterations in the ability of mammalian cells to synthesize LA and whether dietary LA can circumvent its endogenous absence, we have generated mice deficient in lipoic acid synthase (Lias). Mice heterozygous for disruption of the Lias gene develop normally, and their plasma levels of thiobarbituric acid-reactive substances do not differ from those of wild-type mice. However, the heterozygotes have significantly reduced erythrocyte glutathione levels, indicating that their endogenous antioxidant capacity is lower than those of wild-type mice. Homozygous embryos lacking Lias appear healthy at the blastocyst stage, but their development is retarded globally by 7.5 days postcoitum (dpc), and all the null embryos die before 9.5 dpc. Supplementing the diet of heterozygous mothers with LA (1.65 g/kg of body weight) during pregnancy fails to prevent the prenatal deaths of homozygous embryos. Thus, endogenous LA synthesis is essential for developmental survival and cannot be replaced by LA in maternal tissues and blood.     

胸水中肺腺癌细胞与血清中PTN多效蛋白分子生物学的研究

通过检测PTN蛋白在肺腺癌患者术前血清标本及相对应的恶性胸水肺腺癌细胞2种不同标本中的表达及对比其表达的差异,探讨其诊断意义.利用Western-blot免疫印迹方法检测50例恶性胸水及相对应的术前血清,并对肺腺癌细胞进行石蜡包埋、免疫细胞化学检查.同时分别以10例正常献血者血清、20例胸水良性增生细胞作为对照.肺腺癌患者血清和恶性胸水细胞中PTN蛋白的表达分别高于对照组PTN蛋白的表达,恶性胸水中PTN蛋白的表达59.0％ (49/83)高于肺腺癌患者血清中PTN蛋白的表达32.5％ (27/83).差异均具有统计学意义(P＜0.05),恶性胸水肺腺癌细胞中的PTN蛋白表达和波形蛋白Vimentin呈正相关关系(P ＜0.01,r =0.728),而与钙粘连蛋白E-ca呈负相关.PTN蛋白在肺腺癌患者血清和恶性胸水细胞标本中高表达,恶性胸水肺腺癌细胞中PTN蛋白的表达高于血清中PTN蛋白的表达,肺腺癌细胞中PTN蛋白的表达与波形蛋白Vimentin表达相一致,肺腺癌细胞在转移过程中已发生了向间质细胞转化EMT的过程,同时增强了肺腺癌细胞的高侵袭性,而恶性胸水肺腺癌细胞PTN蛋白的高表达更促进了肺腺癌细胞的转移.提示对未发生胸水转移的肺腺癌患者进行血清中PTN蛋白的检测,对已发生胸水转移的肺腺癌患者同样要检测PTN蛋白,以期提高肺腺癌患者的诊断率.     

Anisotropic effects of the levator ani muscle during childbirth

Pelvic floor dysfunction and pelvic organ prolapse have been associated with damage to the levator ani (LA) muscle, but the exact mechanisms linking them remain unknown. It has been postulated that factors such as vaginal birth and ageing may contribute to long-term, irreversible LA muscle damage. To investigate the biomechanical significance of the LA muscle during childbirth, researchers and clinicians have used finite element models to simulate the second stage of labour. One of the challenges is to represent the anisotropic mechanical response of the LA muscle. In this study, we investigated the effects of anisotropy by varying the relative stiffness between the fibre and the matrix components, whilst maintaining the same overall stress–strain response in the fibre direction. A foetal skull was passed through two pelvic floor models, which incorporated the LA muscle with different anisotropy ratios. Results showed a substantial decrease in the magnitude of the force required for delivery as the fibre anisotropy was increased. The anisotropy ratio markedly affected the mechanical response of the LA muscle during a simulated vaginal delivery. It is apparent that we need to obtain experimental data on muscle mechanics in order to better approximate the LA muscle mechanical properties for quantitative analysis. These models may advance our understanding of the injury mechanisms of pelvic floor during childbirth.     

α-Lipoic acid modulates thiol antioxidant defences and attenuates exercise-induced oxidative stress in standardbred trotters

Several micronutrient supplementation strategies are used to cope with oxidative stress, although their benefits have recently been questioned. The aim of the present study was to examine the effects of DL-α-lipoic acid (LA) in response to acute exercise and during recovery in horses. Six standardbred trotters were tested on the treadmill before and after 5-week LA supplementation (25 mg/kg body weight/day). According to electron paramagnetic resonance measurements, strenuous aerobic exercise increased significantly free radical formation in the gluteus medius muscle, which was prevented by LA supplementation. The activities of thioredoxin reductase and glutathione reductase in muscle were significantly increased in LA-treated horses, but neither LA nor exercise affected muscle thioredoxin activity. LA increased the concentration of total glutathione in muscle at rest and during recovery. Treatment with LA blunted the exercise-induced increase in plasma oxygen radical absorbance capacity and decreased the post-exercise levels of lipid hydroperoxides in plasma and malondialdehyde in plasma and in muscle. These findings suggest that LA enhances thiol antioxidant defences and decreases exercise-induced oxidative stress in skeletal muscle.     

Ghrelin Modulates Lateral Amygdala Neuronal Firing and Blocks Acquisition for Conditioned Taste Aversion

Ghrelin is an orexigenic brain-gut hormone promoting feeding and regulating energy metabolism in human and rodents. An increasing number of studies have reported that ghrelin and its identified receptor, the growth hormone secretagogue receptor 1a (GHS-R1a), produces remarkably wide and complex functions and biological effects on specific populations of neurons in central nervous system. In this study, we sought to explore the in vivo effects of acute ghrelin exposure on lateral amygdala (LA) neurons at the physiological and behavioral levels. In vivo extracellular single-unit recordings showed that ghrelin with the concentration of several nanomolars (nM) stimulated spontaneous firing of the LA neurons, an effect that was dose-dependent and could be blocked by co-application of a GHS-R1a antagonist D-Lys3-GHRP-6. We also found that D-Lys3-GHRP-6 inhibited spontaneous firing of the LA neurons in a dose-dependent manner, revealing that tonic GHS-R1a activity contributes to orchestrate the basal activity of the LA neurons. Behaviorally, we found that microinfusion of ghrelin (12 ng) into LA before training interfered with the acquisition of conditioned taste aversion (CTA) as tested at 24 h after conditioning. Pre-treatment with either purified IgG against GHS-R1a or GHS-R1a antagonist blocked ghrelin’s effect on CTA memory acquisition. Ghrelin (12 ng) had no effect on CTA memory consolidation or the expression of acquired CTA memory; neither did it affect the total liquid consumption of tested rats. Altogether, our data indicated that ghrelin locally infused into LA blocks acquisition of CTA and its modulation effects on neuronal firing may be involved in this process.     

Incorporating local adaptation into forecasts of species’ distribution and abundance under climate change

Populations of many species are genetically adapted to local historical climate conditions. Yet most forecasts of species’ distributions under climate change have ignored local adaptation (LA), which may paint a false picture of how species will respond across their geographic ranges. We review recent studies that have incorporated intraspecific variation, a potential proxy for LA, into distribution forecasts, assess their strengths and weaknesses, and make recommendations for how to improve forecasts in the face of LA. The three methods used so far (species distribution models, response functions, and mechanistic models) reflect a trade‐off between data availability and the ability to rigorously demonstrate LA to climate. We identify key considerations for incorporating LA into distribution forecasts that are currently missing from many published studies, including testing the spatial scale and pattern of LA, the confounding effects of LA to nonclimatic or biotic drivers, and the need to incorporate empirically based dispersal or gene flow processes. We suggest approaches to better evaluate these aspects of LA and their effects on species‐level forecasts. In particular, we highlight demographic and dynamic evolutionary models as promising approaches to better integrate LA into forecasts, and emphasize the importance of independent model validation. Finally, we urge closer examination of how LA will alter the responses of central vs. marginal populations to allow stronger generalizations about changes in distribution and abundance in the face of LA.     

Direct electrochemistry of hemoglobin immobilized on gold electrode by Langmuir-Blodgett technique

In this research, we reported a novel method of forming hemoglobin (Hb)-linoleic acid (LA) Langmuir-Blodgett (LB) monolayer by spreading Hb solution directly onto the subphase covered with a layer of LA. This method is suitable for preparing electrochemical devices with protein-lipid LB film because almost no protein adsorbed on electrode surface before protein-lipid film transferred from air-water interface to electrode, which ensured better electrode activity. The compressibility of Hb-LA monolayer was used to character the phase transition during compression process. Optimal experimental conditions were obtained by analyzing pressure-time, pressure-area and pressure-compressibility curves. The direct electrochemistry of Hb, which was immobilized on Au electrode surface incorporated with LA layer by LB method, was investigated using cyclic voltammetry for the first time. The electrode modified with Hb-LA LB film holds high electrochemical activity and shows a fast direct electron transfer of Hb. Redox peak currents increased linearly with the increase of scan rate, indicating a surface-controlled electrode process. The electron transfer rate constant was 2.68+/-0.45 s-1. As a target of this research, this work provides a new way to prepare biomimetic film and biosensor.     

Sequence and structural diversity in endotoxin-binding dodecapeptides

For the study of sequence or structure requirement of short peptides for endotoxin binding, and to search for potential endotoxin antagonists, biopanning was carried out on a phage-displayed random dodecapeptide library against immobilized lipopolysaccharide (LPS) or lipid A (LA), the core toxic portion of LPS. Specific binding of selected phage-displayed peptides to LPS/LA was confirmed by surface plasmon resonance (SPR) analysis. These peptides are rich in basic and hydrophobic amino acids, especially histidine, proline and tryptophan, highlighting apparent amphiphilicity and bacterial membrane activity. These dodecapeptide sequences have no predictable secondary structure in solution, indicating the importance of a random structure before their interaction with LPS/LA. Sequence alignment reveals various potential secondary structures with these selected peptides, which contain specific signature motifs such as b(p)hb(p)hb(p), bbbb, hhhh (b-basic, p-polar, h-hydrophobic residue), capable of binding LPS/LA. However, none of these peptides exhibit a significant calculated structural amphiphilicity while assuming a secondary structure. This study suggests that for these short dodecapeptides to bind LPS/LA, the potential for their structural adaptation is more important than an amphipathic structure.     

Codonopsis draco Ramp. (桔梗科) 的身份鉴定，特别提及它的濒危状态

Pampanini于1910年发表了桔梗科采自湖北西部的一个新种Codonopsis draco。此后100年无人提起它。最近作者在进行党参属及其近缘类群的专著研究中发现它就是1984年发表的刺萼参Echinocodon lobophyllus DY. Hong, 也采自湖北西部。本文作了新组合。刺萼参在湖北郧西的分布点已经消失,至今仅知道陕西东南部两个地点有少量植株,可见刺萼参已处于濒危状态。因为它是单种属,对其保护应予特别关注。     

Codonopsis draco Ramp．（桔梗科）的身份鉴定，特别提及它的濒危状态

Pampanini于1910年发表了桔梗科采自湖北西部的一个新种Codonopsis draco。此后100年无人提起它。最近作者在进行党参属及其近缘类群的专著研究中发现它就是1984年发表的刺萼参Echinocodon lobophyllus D．Y．Hong,也采自湖北西部。本文作了新组合。刺萼参在湖北郧西的分布点已经消失,至今仅知道陕西东南部两个地点有少量植株,可见刺萼参已处于濒危状态。因为它是单种属,对其保护应予特别关注。     

Role of eNOS-derived NO in the postischemic anti-inflammatory effects of antecedent ethanol ingestion in murine small intestine

Ingestion of low levels of ethanol 24 h before [ethanol preconditioning (EPC)] ischemia and reperfusion (I/R) prevents postischemic leukocyte rolling (LR) and adhesion (LA), effects that were abolished by adenosine A(2) receptor (ADO-A(2)R) antagonists or nitric oxide (NO) synthase (NOS) inhibitors. The aims of this study were to determine whether NO derived from endothelial NOS (eNOS) during the period of ethanol exposure triggered entrance into this preconditioned state and whether these events were initiated by an ADO-A(2)R-dependent mechanism. Ethanol or distilled water vehicle was administered to C57BL/6J [wild type (WT)] or eNOS-deficient (eNOS-/-) mice by gavage. Twenty-four hours later, the superior mesenteric artery was occluded for 45 min. LR and LA were quantified by intravital microscopy after 30 and 60 min of reperfusion. I/R increased LR and LA in WT mice, effects that were abolished by EPC or NO donor preconditioning (NO-PC). NO-PC was not attenuated by coincident administration of an ADO-A(2)R antagonist. I/R increased LR and LA in eNOS-/- mice to levels comparable with those noted in WT animals. However, EPC only slightly attenuated postischemic LR and LA, whereas NO-PC remained effective as a preconditioning stimulus in eNOS-/- mice. Preconditioning with an ADO-A(2)R agonist (which we previously demonstrated prevents I/R-induced LR and LA in WT animals) failed to attenuate these postischemic adhesive responses in eNOS-/- mice. Our results indicate that EPC is triggered by NO formed secondary to ADO-A(2)R-dependent eNOS activation during the period of ethanol exposure 24 h before I/R.     

The composition of pericarp,cell aging,and changes in water absorption in two tomato genotypes: mechanism,factors, and potential role in fruit cracking

Cracking, a serious problem in many fruits, may cause significant economic losses. It may occur when internal pressure cannot sustain by the epidermis any longer. Water absorption and epidermis are among the most important factors that associated with cracking. To determine whether pericarp composition and its mechanical performance, endogenous cell wall disassembly, and water-absorbing capacity influences tomato fruit cracking, we grew a cracking-resistant genotype ‘LA1698’ and susceptible genotype ‘LA2683’. The results illustrated that the cuticle and subcutaneous layer were thicker in ‘LA1698’ than in ‘LA2683’. Compared with ‘LA2683’, the fruit firmness, consistency, and bursting strength of ‘LA1698’ were all higher. Fruits of ‘LA1698’ had decreased activities of polygalacturonase, β-galactosidase, and cellulose, which can disassemble the polysaccharide network. As a result, it had reduced water-soluble pectin and more covalently and ionically bound pectin that can crosslink with Ca²⁺ and B. These fruits also have a greater abundance of hemicelluloses. In addition, ‘LA1698’ had higher SOD activities and lower relative conductivity, meaning its cells might have a better biological activity to resist changes of the external environment (such as water variation) and to prevent fruit cracking. However, POD in ‘LA2683’ was more abundant than in ‘LA1698’. ‘LA1698’ produced juice with lower total soluble solids, which led to a lower initial water-absorbing ability and difference between the exocarp and mesocarp. In conclusion, a stronger pericarp and cells with a better biological activity in addition to the lower water-absorbing difference between the exocarp and mesocarp made ‘LA1698’ more resistant to cracking.     

Expression of cFABP and PPAR in trophoblast cells: effect of PPAR ligands on linoleic acid uptake and differentiation

Throughout gestation, fetal growth depends, in part, on placental transfer of maternal essential fatty acid (EFA) and long-chain polyunsaturated fatty acid. All fatty acid (FA) can cross lipid bilayer by simple diffusion, such as those in the syncytiotrophoblasts, the multinucleated, terminally differentiated trophoblast cells. The trophoblasts differentiation process is accompanied by an increase of human chorionic gonadotropin (hCG) secretion and an inhibition of Human Achaete-Scute Homologue-2 expression (Hash-2). Furthermore, a number of FA-binding proteins (FABPs) have been identified in membrane and cytoplasm of mammalian cells, which are thought to facilitate the transfer of FA across membranes and their intracellular channeling. Thus, the aim of this study was to investigate the implication of cFABPs in linoleic acid (LA) uptake by human trophoblast cells according to differentiation. Moreover, since peroxisome proliferator-activated receptor (PPARs) regulate the expression of cFABP and play an important role in trophoblast cells differentiation, the effects of PPARs ligands are verified on cFABP expression and differentiation. Herein, we reported the increase of the expression of liver and heart FABP (L- and H-FABP) upon differentiation of trophoblast cells, an inhibition of PPAR alpha and beta, while PPAR gamma levels remains unchanged. The nonselective peroxisome-proliferating agents, bezafibrate and LA, impaired trophoblast differentiation, and reduced L- and H-FABP expression. Furthermore, cobalt, a chemical agent known to mimic hypoxia, inhibits trophoblast cells differentiation and diminishes H-, L-FABP and PPARs expression. Finally, both treatments show no influence on LA uptake by trophoblast cells. In conclusion, this study showed that there is no correlation between the expression of H- and L-FABP and LA uptake by trophoblast cells and that bezafibrate and LA greatly impaired trophoblast cells differentiation.     

玉米叶夹角形成的遗传基础与分子机制解析*

玉米产量取决于植株捕获光能和固定CO₂合成有机化合物的效率。叶夹角是株型重要性状之一,较小叶夹角有利于提高玉米植株光合作用效率和种植密度,因而有利于提高玉米产量。研究表明玉米叶夹角为多基因控制的复杂数量性状,其遗传力较高,主要受基因的加性效应调控。目前,利用数量性状位点(quantitative trait loci, QTL)定位和全基因组关联分析(genome-wide association study, GWAS)等方法已鉴定数百个玉米叶夹角相关QTL;结合突变体分析等方法,已克隆数十个调控叶夹角关键基因,这为了解玉米叶夹角遗传机制提供了重要参考。由于前人研究所采用群体、分析方法及参考基因组版本不同,各研究之间所鉴定QTL差异较大,因此无法客观揭示叶夹角性状的遗传规律。为此,通过总结前人所定位叶夹角相关QTL和单核苷酸多态性(single nucleotide polymorphism,SNP)位点并构建一致性图谱,鉴定出叶夹角性状定位热点区间,并对调控叶夹角的已知基因进行功能分类。这不仅为了解玉米叶夹角的遗传结构、推动叶夹角相关重要基因克隆提供数据支撑,也对进一步开发叶夹角相关分子标记,指导玉米分子育种和提高玉米产量提供有益指导。     

Low Left Atrial Compliance Contributes to the Clinical Recurrence of Atrial Fibrillation after Catheter Ablation in Patients with Structurally and Functionally Normal Heart

Stiff left atrial (LA) syndrome was initially reported in post-cardiac surgery patients and known to be associated with low LA compliance. We investigated the physiological and clinical implications of LA compliance by estimating LA pulse pressure (LApp) among patients with atrial fibrillation (AF) and structurally and functionally normal heart. Among 1038 consecutive patients with LA pressure measurements before AF ablation, we included 334 patients with structurally and functionally normal heart (81.7% male, 54.1±10.6 years, 77.0% paroxysmal AF) after excluding those with hypertension, diabetes, and previous ablation or cardiac surgery. We measured LApp (peak-nadir LA pressure) at the beginning of the ablation procedure and compared the values with clinical parameters and the AF recurrence rate.AF patients with normal heart were younger and more frequently male and had paroxysmal AF, a lower body mass index, and a lower LApp compared to others (all p<0.05).Based on the median value, the low LA compliance group (LApp≥13mmHg) had a smaller LA volume index and lower LA voltage (all p<0.05) compared to the high LA compliance group. During a mean follow-up of 16.7±11.8 months, low LA compliance was independently associated with two fold-higher risk of clinical AF recurrence (HR:2.202; 95%CI:1.077–4.503; p = 0.031).Low LA compliance, as determined by an elevated LApp, was associated with a smaller LA volume index and lower LA voltage and independently associated with higher clinical recurrence after catheter ablation in AF patients with structurally and functionally normal heart.