Invertebrate immune systems specific, quasi-specific, or nonspecific?

Until recently, it was widely accepted that invertebrates fail to show a high degree of specificity and memory in their immune strategies. Recent reports have challenged this view such that our understanding of the capabilities of the invertebrate immune systems needs to be reassessed. This account critically reviews the available evidence that suggests the existence of a high degree of memory and specificity in some invertebrates and seeks mechanistic explanations of such observations. It is postulated that elevated levels of phagocytosis may be a partial explanation for this phenomenon.     

Is agonist self-inhibition at the nicotinic acetylcholine receptor a nonspecific action?

Agonist concentration-response relationships at nicotinic postsynaptic receptors were established by measuring 86Rb+ efflux from acetylcholine receptor rich native Torpedo membrane vesicles under three different conditions: integrated net ion efflux (in 10 s) from untreated vesicles, integrated net efflux from vesicles in which most acetylcholine sites were irreversibly blocked with alpha-bungarotoxin, and initial rates of efflux (5-100 ms) from vesicles that were partially blocked with alpha-bungarotoxin. Exposure to acetylcholine, carbamylcholine, suberyldicholine, phenyltrimethylammonium, or (-)-nicotine over 10(8)-fold concentration ranges results in bell-shaped ion flux response curves due to stimulation of acetylcholine receptor channel opening at low concentrations and inhibition of channel function at 60-2000 times higher concentrations. Concentrations of agonists that inhibit their own maximum 86Rb+ efflux by 50% (KB values) are 110, 211, 3.0, 39, and 8.9 mM, respectively, for the agonists listed above. For acetylcholine and carbamylcholine, KB values determined from both 10-s and 15-ms efflux measurements are the same, indicating that the rate of agonist-induced desensitization increases to maximum at concentrations lower than those causing self-inhibition. For all partial and full agonists studied, Hill coefficients for self-inhibition are close to 1.0. Concentrations of agonists up to 8 times KB did not change the order parameter reported by a spin-labeled fatty acid incorporated in Torpedo membranes. We conclude that agonist self-inhibition cannot be attributed to a general nonspecific membrane perturbation. Instead, these results are consistent with a saturable site of action either at the lipid-protein interface or on the acetylcholine receptor protein itself.     

Biochemical properties,homology, and genetic variation of Drosophila “nonspecific” esterases

The biochemical properties and tissue distribution of two major, soluble "nonspecific" esterases have been studied in Drosophila melanogaster, D. pseudoobscura, and related species. The "alpha-like" activity is due to a monomer enzyme (MW congruent to 60 kd) having a nonspecific tissue distribution, which was inhibited by p-hydroxymercuribenzoate (5 X 10(-4)M) plus eserine (1 X 10(-5)M) and was relatively unstable during polyacrylamide gel electrophoresis. Electrophoretograms of this enzyme could be enhanced by treating gels with beta-mercaptoethanol before staining. This procedure allowed the identification of a new alpha-esterase (Est-4) in D. pseudoobscura. The "beta-like" esterase activity (EC 3.1.1.1) is due to a dimer (MW congruent to 120 kd) in most Drosophila species. D. melanogaster and its siblings (D. simulans and D. mauritiana) were exceptions in which this enzyme had an unusual tissue distribution (increased activity in the male reproductive system) and was a monomer (MW congruent to 60 kd). Differences in the genetic variability of these esterases are discussed and interpreted by a population expansion model rather than by differences in biochemical properties of enzyme forms.     

Hydrophobicity and conformational change as mechanistic determinants for nonspecific modulators of amyloid β self-assembly

The link between many neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, and the aberrant folding and aggregation of proteins has prompted a comprehensive search for small organic molecules that have the potential to inhibit such processes. Although many compounds have been reported to affect the formation of amyloid fibrils and/or other types of protein aggregates, the mechanisms by which they act are not well understood. A large number of compounds appear to act in a nonspecific way affecting several different amyloidogenic proteins. We describe here a detailed study of the mechanism of action of one representative compound, lacmoid, in the context of the inhibition of the aggregation of the amyloid β-peptide (Aβ) associated with Alzheimer's disease. We show that lacmoid binds Aβ(1-40) in a surfactant-like manner and counteracts the formation of all types of Aβ(1-40) and Aβ(1-42) aggregates. On the basis of these and previous findings, we are able to rationalize the molecular mechanisms of action of nonspecific modulators of protein self-assembly in terms of hydrophobic attraction and the conformational preferences of the polypeptide.     

The role of nonspecific serum factors in the antibody response to the ΦX 174 bacteriophage

The role of the “antibody cofactor” and of other heat-labile serum components (complement) in the neutralization of the ?X 174 bacteriophage by means of specific antibodies was studied. Sera of white mice, guinea-pigs and rabbits obtained mainly early after phage administration were investigated. The character of antibodies was estimated from their sensitivity to 2-mercaptoethanol or else by chromatography on Sephadex G-200. Sera from the first days after the administration of the phage containing mostly type 19S antibodies, and sera from later periods after the administration containing mostly type 7S antibodies, were tested. (Some evidence was also obtained about the formation of slowly sedimenting antibodies sensitive to 2-mercaptoethanol in the rabbit.) With a single exception the tested sera showed no significant decrease of the neutralization activity after 30-mins. heating at 56°C or at 60°C and no increase of the neutralization power could be observed after the application of homologous or normal mouse serum. It is concluded that the heat-labile components of normal sera including the complement and the “antibody cofactor” play no role in specific phage neutralization.     

Allozyme variation of nonspecific esterases in Russian sturgeon (Acipenser güldenstädti Brandt

Electrophoresis in 7% polyacrylamide gel was used to analyze nonspecific esterases from different organs and tissues of Russian sturgeon. The basic enzymatic activity was observed the four zymogram zones. In sixteen cases the patterns of isozyme distribution in these zones allowed to consider them as allele systems (14 polymorphic and 2 monomorphic) corresponding to the four structural genes. The observed genotype frequencies of the nine of these systems (EST-1* of brain and intestine; EST-2* of serum and intestine; EST-3* of spleen and kidney; and EST-4* of spleen, brain, and heart) were largely concordant with Hardy-Weinberg proportions for codominant disomic inheritance. Genetic control of other polymorphic systems is unknown, but, high enzymatic activity of these esterases, sufficient for qualitative electrophretic detection, permits utilization of these polymorphisms for phenotypic monitoring of Russian sturgeon populations.     

The α-helical membrane spanning domain of cytochrome b5 interacts with cytochrome P450 via nonspecific interactions

Cytochrome b₅ (cyt b₅) is an amphipathic membrane-bound heme protein found in the endoplasmic reticulum of eukaryotes. It consists of three domains, an N-terminal cytosolic, hydrophilic domain containing the heme, a short flexible linker and an α-helical membrane-spanning domain. This study investigated whether there are specific side chain helix–helix packing interactions between the COOH-terminal membrane anchor of cyt b₅ and cytochrome P450 (cyt P450) 2B4 in a purified reconstituted system. Alanine was inserted at six positions in the membrane anchor of cyt b₅. Insertion of alanine into an α-helix causes all amino acids at its carboxyl terminus to be rotated by 100°. The ability of the alanine insertion mutants of cyt b₅ to bind to cyt P450 2B4 was similar to that of the wild-type protein as was the ability of the mutant cyts b₅ to stimulate the metabolism of the anesthetic, methoxyflurane. These results demonstrate that the C-terminal hydrophobic α-helix of cyt b₅ does not interact with cyt P450 2B4 through a specific stereochemical fit of amino acid side chains, but rather through nonspecific interactions.     

Physiological modulators of cyclosporin A-insensitive nonspecific permeability of the inner membrane of liver mitochondria induced by calcium ions and α,ω-hexadecanedioic acid

Long-chain saturated α,ω-dioic acids can induce nonspecific permeability of the inner membrane (pore opening) of liver mitochondria loaded with Ca²⁺ or Sr²⁺ by the mechanism insensitive to cyclosporin A (CsA). In this work we found that 200 μM Ca²⁺ and 20 μM α,ω-hexadecanedioic acid (HDA) in the presence of 1 μM CsA induced high-amplitude swelling of liver mitochondria (pore opening) only in the presence of succinate as oxidation substrate. Under these conditions protonophore uncoupler of oxidative phosphorylation 2,4-dinitrophenol at the concentration of 75 μM, which is optimal for its uncoupling activity, inhibited mitochondrial swelling induced by Ca²⁺ and HDA, despite the presence of succinate in the incubation medium. Natural uncouplers of oxidative phosphorylation, oleic and linoleic acids, produced a similar effect. These data suggest that energization of organelles, which promotes Ca²⁺ transport into the matrix, is one of the basic requirements of pore opening in liver mitochondria induced by Ca²⁺ and HDA. It is shown that ATP at the physiological concentration of 2 mM inhibits HDA-induced high-amplitude swelling of mitochondria by reducing free Ca²⁺ concentration in the medium. ADP at the same concentration had a similar effect. This modulating effect of nucleotides apparently is attributable to their ability to chelate calcium ions. Polycation spermine, which is known as an inhibitor of the classical CsA-sensitive pore, at the physiological concentration of 1 mM inhibited CsA-insensitive swelling of liver mitochondria induced by sequential addition of Ca²⁺ and HDA. It is assumed that such action of spermine is due to its ability to shield the negative surface charges on the inner membrane of mitochondria. Bovine serum albumin (BSA), which is able to bind free fatty acids and thus prevent the induction of Ca²⁺-dependent pore, inhibited HDA-induced swelling of mitochondria. However, at the same BSA/fatty acid molar ratio inhibitory effect of BSA was much less pronounced if HDA was used as the pore inducer instead of palmitic acid. Apparently, this can be accounted by the fact that BSA binds α,ω-dioic acids weaker than their monocarboxylic analogues.     

"蛛丝马迹"之"马"

“蛛丝马迹”是人人皆知的成语 ,一般辞典的解释 ,“马迹”就是马经过后留下的痕迹或马脚印。蛛丝马迹比喻事情留下来的隐约可寻的痕迹和线索。可是 ,仔细推敲后发现 ,这样的解释是很难成立的。从事理来说 ,蛛丝是很不明显的 ,那么与之并列的马迹也应该是很不明显的 ,可是 ,作为家畜的马是个庞然大物 ,除了在水泥 ,柏油路上 ,它留下的脚印与痕迹应该是很明显的。蜘蛛的丝与高头大马的迹 ,可以说是风马牛不相及的 ,是很难放在一起相提并论的。从结构来说 ,很明显 ,这一成语中 ,“蛛丝”与“马迹”是并列的结构 ,“蛛丝”就是蛛的丝 ,是偏正关…     

"蚍蜉"非"匹夫"

你们好,我是《化石》这本书的小读,叫张野青,家住牛庄高中家属楼,在牛庄镇南关小学六年级一班读书,我觉得这本书很好。但我在2004年第一期上发现了错误,在《曾霸世界的巨鬣狗》这篇章中有一句话：‘与大象相争如匹夫撼树’中的‘匹夫’两字写错了,应该是‘蚍蜉’两字,这两字是当大蚂蚁讲的,意思是比喻力量很小而想动摇强大的事物,自不量力。这些也是我从字典中得到的,我想是原错了,应该改正。     

A historical perspective of the biophysics of the thrombin–heparin system: an example of nonspecific binding and the consequent parking problem in action

Difficulties are encountered in the thermodynamic characterization of interactions between a protein ligand and a linear acceptor, such as a polynucleotide or a polysaccharide, because of the involvement of more than one unit of the polymer chain in each attachment of a protein molecule. Complications arise from the fact that random attachment of ligand to the polymer chain, each unit of which is a potential binding site, initially leads to suboptimal location of protein molecules along the polymer chain—a situation that has to be rectified before the attainment of thermodynamic equilibrium can be realized. Kinetic as well as thermodynamic consequences of such nonspecific binding, termed the parking problem, therefore need to be considered in any quantitative characterization of the interaction between a large ligand and a linear polymer acceptor chain. Results for the thrombin–heparin interaction have been used to illustrate a thermodynamic characterization of nonspecific binding that takes into account these consequences of the parking problem.     

浅析"综合征"与"症"

生物学试验教材,常提到几种遗传病,如指甲髌骨综合征、苯丙酮尿症、21-三体综合征、特纳氏综合征(即性腺发育不良)等。对于“综合征”与“症”．许多学生很难弄懂,为帮助学生理解,现解析如下：     

"脚气"是"脚气病"吗?

问 :“脚气”是“脚气病”吗 ?答 :足癣俗称“脚气”。“脚气”是因霉菌感染足部而引起的一种传染性皮肤病 ,多见于成年人 ,病程缓慢 ,有不同程度的搔痒。“脚气”的发生部位多在足趾缝或足底 ,这是由于趾间缝隙小 ,汗液蒸发较差 ,适于霉菌的繁殖。主要有水疱型、鳞屑型、趾间糜烂型和增厚型 4种类型。“脚气病”是人体缺乏维生素 B1而起的一种疾病。主要症状是四肢无力 ,肌肉疼痛萎缩 ,皮肤逐渐失去感觉 ,麻痹和麻木 ,从脚部开始向心脏发展 ,心脏扩大 ,呼吸困难严重者甚至死亡。所以 ,“脚气”与“脚气病”是两种不同的疾病。“脚气”是“…     

试论"描述"与"概述"的区别

在本市举办的一次初中生物学教师新教材培训会上,一位教师提出了这样一个问题：“《全日制义务教育生物课程标准(实验稿)》(以下简称《课程标准》)中的两个知识性目标动词——‘描述’与‘概述’的区别是什么?”《课程标准》中的知识性目标动词共计37个,“描述”与“概述”只是其中的两个。但在《课程标     

"差异显著"还是"有统计学意义"

统计分析中常用P>0．05(或0．01,下同),P<0．05作为统计结论的依据。过去我们认为如果P<0．05,则表示两组“差异显著”,“差异具有显著性”,或“差别有显著意义”。如果P>0．05,则认为“差异不显著”,“差异无显著性”．或“差别无显著意义”。但是,现在关于统计结论的表述国内外都有所变化:1)在P<0．05时,统计结论应是“有统计学意义”,或“拒绝无效假设H0(μ1=μ2),接受备选假设H1(μ1≠μ2)”;2)在P>0．05时,则应是“无统计学意义”,或“不拒绝无效假设H0”,注意此时不提及备选假设H1(因为不拒绝H0不等于接受H0,对H0可以说:拒绝或不拒绝;而对H1只能说:接受H1),除此之外的其他说法均不妥当。这就是说,P>0．05难以给出确切的统计结论。     

对"扩散"和"渗透"的讨论

自由扩散和协助扩散都是可自由运动的微粒通过热运动而发生的2种过膜扩散．生物体内的渗透是自由水通过生物膜的协助扩散。     

"概率"与"比例"问题的辨析

首先看下面2个问题： [问题1]基因型为AaBbCc的雄性个体（Aa、Bb和Cc3对等位基因均独立遗传）所产生的精子中，基因型为ABC的精子所占的比例为____。