On the structure of the iron-sulfur complex in the two-iron ferredoxins

Recent spectroscopic and magnetic susceptibility studies of the iron center in the two-iron ferredoxins provide criteria which any model for the iron-sulfur complex in these proteins must satisfy. These criteria are most stringent for parsley and spinach ferredoxin: the reduced proteins contain a high-spin ferric atom antiferromagnetically exchange-coupled (presumably via sulfide bridging ligands) to a high-spin ferrous atom. In the oxidized proteins the iron atoms are antiferromagnetically spin-coupled, high-spin ferric atoms. Arguments are given to substantiate the claim that the ferrous atom in the reduced protein is ligated by four sulfur atoms in a distorted tetrahedral configuration: two are the bridging sulfides, two are cysteinyl sulfurs. A treatment of proton contact shifts based upon the above model is pertinent to proton magnetic resonance data already available and provides a means to identify directly the ligands at both iron atoms via further PMR experiments.     

Global revascularization: the role of the cardiologist

There are compelling reasons for cardiologists to undertake a more global approach to patients with peripheral vascular diseases: atherosclerosis is a 'systemic' disease frequently causing both coronary and peripheral vascular problems in the same patient; coronary artery disease is the most common cause of morbidity and mortality in patients with peripheral vascular disease; and peripheral vascular disease negatively impacts the management of angina pectoris and congestive heart failure. There are four major areas of special interest to the cardiologist: (1) iliac arteries (vascular access), (2) renal arteries (hypertension and volume overload), (3) subclavian arteries (coronary steal with a left internal mammary artery [LIMA] graft), and (4) carotid arteries (stroke). Technical skills necessary to perform coronary angioplasty are transferable to the peripheral vasculature. However, an understanding of the natural history of peripheral disease, patient and lesion selection criteria, and knowledge of other treatment alternatives are essential to performing these procedures safely and effectively. Appropriate preparation and training, and a team approach, including an experienced vascular surgeon, are both desirable and necessary before interventional cardiologists who are inexperienced in the treatment of peripheral vascular disease attempt percutaneous peripheral angioplasty. There are inherent advantages for patients when the cardiologist performing the procedure is also a clinician. Judgments regarding the indications, timing, and risk/benefit ratio of procedures are enhanced by a long-term relationship between physician and patient. Finally, in view of the increased incidence of coronary artery disease in patients with atherosclerotic peripheral vascular disease, the participation of a cardiologist in their care seems appropriate.     

Structure of the cross-striated adductor muscle of the scallop

The structure of the cross-striated adductor muscle of the scallop has been studied by electron microscopy and X-ray diffraction using living relaxed, glycerol-extracted (rigor), fixed and dried muscles. The thick filaments are arranged in a hexagonal lattice whose size varies with sarcomere length so as to maintain a constant lattice volume. In the overlap region there are approximately 12 thin filaments about each thick filament and these are arranged in a partially disordered lattice similar to that found in other invertebrate muscles, giving a thin-to-thick filament ratio in this region of 6:1.The thin filaments, which contain actin and tropomyosin, are about 1 μm long and the actin subunits are arranged on a helix of pitch 2 × 38.5 nm. The thick filaments, which contain myosin and paramyosin, are about 1.76 μm long and have a backbone diameter of about 21 nm. We propose that these filaments have a core of paramyosin about 6 nm in diameter, around which the myosin molecules pack. In living relaxed muscle, the projecting myosin heads are symmetrically arranged. The data are consistent with a six-stranded helix, each strand having a pitch of 290 nm. The projections along the strands each correspond to the heads of one or two myosin molecules and occur at alternating intervals of 13 and 16 nm. In rigor muscle these projections move away from the backbone and attach to the thin filaments.In both living and dried muscle, alternate planes of thick filaments are staggered longitudinally relative to each other by about 7.2 nm. This gives rise to a body-centred orthorhombic lattice with a unit cell twice the volume of the basic filament lattice.     

北京地区蕨类植物区系分析

对北京地区蕨类植物区系进行了初步分析,研究表明,北京共有蕨类植物77种,隶属于19科34属,以蹄盖蕨科、岩蕨科、鳞毛蕨科、卷柏科等为优势科,以岩蕨属、卷柏属、铁角蕨属等为优势属,科内及属内分化程度较低,种类组成贫乏;地理成分以温带成分占优势,有11属为温带分布属,占非世界分布属总数的61．11％,除世界种和中国特有种外,全为温带性质的种;生境特点以石生为主,大多数种类分布在北京西部和北部的山区;与河北的关系最为密切,其次为山西、内蒙、辽宁、山东,与秦岭也有一定的联系,与西藏的关系疏远。     

Vortical flow in the utricle and the ampulla: a computational study on the fluid dynamics of the vestibular system

We present a computational study of the fluid dynamics in healthy semicircular canals (SCCs) and the utricle. The SCCs are the primary sensors for angular velocity and are located in the vestibular part of the inner ear. The SCCs are connected to the utricle that hosts the utricular macula, a sensor for linear acceleration. The transduction of angular motion is triggered by the motion of a fluid called endolymph and by the interaction of this fluid with the sensory structures of the SCC. In our computations, we observe a vortical flow in the utricle and in the ampulla (the enlarged terminal part of the SCCs) which can lead to flow velocities in the utricle that are even higher than those in the SCCs. This is a fundamentally new result which is in contrast to the common belief that the fluid velocities in the utricle are negligible from a physiological point of view. Moreover, we show that the wall shear stresses in the utricle and the ampulla are maximized at the positions of the sensory epithelia. Possible physiological and clinical implications are discussed.     

Analysing the yeast complexome—the Complex Portal rising to the challenge

The EMBL-EBI Complex Portal is a knowledgebase of macromolecular complexes providing persistent stable identifiers. Entries are linked to literature evidence and provide details of complex membership, function, structure and complex-specific Gene Ontology annotations. Data are freely available and downloadable in HUPO-PSI community standards and missing entries can be requested for curation. In collaboration with Saccharomyces Genome Database and UniProt, the yeast complexome, a compendium of all known heteromeric assemblies from the model organism Saccharomyces cerevisiae, was curated. This expansion of knowledge and scope has led to a 50% increase in curated complexes compared to the previously published dataset, CYC2008. The yeast complexome is used as a reference resource for the analysis of complexes from large-scale experiments. Our analysis showed that genes coding for proteins in complexes tend to have more genetic interactions, are co-expressed with more genes, are more multifunctional, localize more often in the nucleus, and are more often involved in nucleic acid-related metabolic processes and processes where large machineries are the predominant functional drivers. A comparison to genetic interactions showed that about 40% of expanded co-complex pairs also have genetic interactions, suggesting strong functional links between complex members.     

Fine structural studies of the nervous system and the apical organ in the planula larva of the sea anemone Anthopleura elegantissima

The nervous system of the planula larva of Anthopleura elegantissima consists of an apical organ, one type of endodermal receptor cell, two types of ectodermal receptor cells, central neurons and nerve plexus. Both interneural and neuromuscular synapses are found in the nerve plexus. The apical organ is a collection of about 100 long, columnar cells each bearing a long cilium and a collar of about 10 microvilli. The cilia of the apical organ are twisted together to form an apical tuft. The ciliary rootlets of the apical organ cells are extremely long, reaching to the basal processes of the cells adjacent to the mesoglea. All three types of sensory cells are tall and slender in profile and are identified by the presence of one or more of the following features: microtubules, small vesicles, membrane-bound granules and synapses. The interneurons are bipolar cells with somas restricted to the aboral end, adjacent to the apical organ. All synapses observed are polarized or asymmetrical. A diagram including all the elements of the nervous system is presented and the possible functions of the nervous system are discussed in relation to larval behavior.     

Requirements for the insertion of the Sindbis envelope glycoproteins into the endoplasmic reticulum membrane

Previous work has shown that the Sindbis structural proteins, core, the internal protein, and PE2 and E1, the integral membrane glycoproteins are synthesized as a polyprotein from a 26S mRNA; core PE2 and E1 are derived by proteolytic cleavage of a nascent chain. Newly synthesized core protein remains on the cytoplasmic side of the endoplasmic reticulum while newly synthesized PE2 and E1 are inserted into the lipid bilayer, presumably via their amino-termini. PE2 and E1 are glycosylated as nascent chains. Here, we examine a temperature-sensitive mutant of Sindbis virus which fails to cleave the structural proteins, resulting in the production of a polyprotein of 130,000 mol wt in which the amino-termini of PE2 and E1 are internal to the protein. Although the envelope sequences are present in this protein, it is not inserted into the endoplasmic reticulum bilayer, but remains on the cytoplasmic side as does the core protein in cells infected with wild-type Sindbis virus. We have also examined the fate of PE2 and E1 in cells treated with tunicamycin, an inhibitor of glycosylation. Unglycosylated PE2 and E1 are inserted normally into the lipid bilayer as are the glycosylated proteins. These results are consistent with the notion that a specific amino-terminal sequence is required for the proper insertion of membrane proteins into the endoplasmic reticulum bilayer, but that glycosylation is not required for this insertion.     

Ultrastructure of the synapses of the initial axonal segment of the pyramidal neuron

Ultrastructure of the proximal part of the axon in the neurons, identified according to a number of morphological signs as pyramidal, has been studied in the layer III of the cat cerebral hemisphere sensomotor cortex. In sections, tangential to the cortical surface, in the initial axonal segment, a submembranous osmophilic layer and fasciculi of microtubules are revealed. On the initial segment spines are found, they contain cysterns resembling by their structure the spine system of the dendritic spines. Axonal terminals revealed along the axonal distribution are in contact both with the axonal trunk and with the spines. Regarding the initial segment, they are presynaptic, contain oval synaptic vesicles and form symmetric axo-axonal synapses only. In transversal sections axonal terminals are detected, arranging on the surface of the initial segment mostly as single ones, in longitudinal sections they are seen as clusters. Analysing the author's data and those from the literature, a conclusion is made that in intact animals the synaptic contacts at the initial segment of the axon are the only form of axo-axonal synapses in the neocortex.     

Expanding the cellular molecular chaperone network through the ubiquitous cochaperones

Cellular environments are highly complex and contain a copious variety of proteins that must operate in unison to achieve homeostasis. To guide and preserve order, multifaceted molecular chaperone networks are present within each cell type. To handle the vast client diversity and regulatory demands, a wide assortment of chaperones are needed. In addition to the classic heat shock proteins, cochaperones with inherent chaperoning abilities (e.g., p23, Hsp40, Cdc37, etc.) are likely used to complete a system. In this review, we focus on the HSP90-associated cochaperones and provide evidence supporting a model in which select cochaperones are used to differentially modulate target proteins, contribute to combinatorial client regulation, and increase the overall reach of a cellular molecular chaperone network. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).     

Electron Microscopic Observations of the Carotid Body of the Cat

Carotid bodies were removed from cats, fixed in buffered 1 per cent osmic acid, embedded in deaerated, nitrogenated methacrylate, and cut into thin sections for electron microscopic study. The carotid body is seen to be composed of islands of chemoreceptor and sustentacular cells surrounded by wide irregular sinusoids. These cells are separated from the sinusoids by relatively broad interstitial spaces which are filled with collagen, fibroblasts, and many unmyelinated nerve fibers with their Schwann cell sheaths. The chemoreceptor cells are surrounded by the flattened, multiprocessed sustentacular cells which serve to convey the axons from an interstitial to a pericellular location. These sustentacular cells are assumed to be lemmoblastic in origin. Relatively few axons are seen to abut on the chemoreceptor cells. The cytoplasm of the chemoreceptor cell is characterized by numerous small mitochondria, units of granular endoplasmic reticulum, a small Golgi complex, and a variety of vesicles. There are many small vesicles diffusely scattered throughout the cytoplasm. In addition, there is a small number of dark-cored vesicles of the type which has been previously described in the adrenal medulla. These are usually associated with the Golgi complex. These findings are discussed in relation to the concepts of the origin of the chemoreceptor cell and the nature of the synapse.     

On the ontogeny of the haptor and the evolution of the Monogenea

Data on the ontogeny of the posterior haptor of monogeneans were obtained from more than 150 publications and summarised. These data were plotted into diagrams showing evolutionary capacity levels based on the theory of a progressive evolution of marginal hooks, anchors and other attachment components of the posterior haptor in the Monogenea (Malmberg, 1986). 5 + 5 unhinged marginal hooks are assumed to be the most primitive monogenean haptoral condition. Thus the diagrams were founded on a 5 + 5 unhinged marginal hook evolutionary capacity level, and the evolutionary capacity levels of anchors and other haptoral attachement components were arranged according to haptoral ontogenetical sequences. In the final plotting diagram data on hosts, type of spermatozoa, oncomiracidial ciliation, sensilla pattern and protonephridial systems were also included. In this way a number of correlations were revealed. Thus, for example, the number of 5 + 5 marginal hooks correlates with the most primitive monogenean type of spermatozoon and with few sensillae, many ciliated cells and a simple protonephridial system in the oncomiracidium. On the basis of the reviewed data it is concluded that the ancient monogeneans with 5 + 5 unhinged marginal hooks were divided into two main lines, one retaining unhinged marginal hooks and the other evolving hinged marginal hooks. Both main lines have recent representatives at different marginal hook evolutionary capacity levels, i.e. monogeneans retaining a haptor with only marginal hooks. For the main line with hinged marginal hooks the name Articulon-choinea n. subclass is proposed. Members with 8 + 8 hinged marginal hooks only are here called Proanchorea n. superord. Monogeneans with unhinged marginal hooks only are here called Ananchorea n. superord. and three new families are erected for its recent members: Anonchohapteridae n. fam., Acolpentronidae n. fam. and Anacanthoridae n. fam. (with 7 + 7, 8 + 8 and 9 + 9 unhinged marginal hooks, respectively). Except for the families of Articulonchoinea (e.g. Acanthocotylidae, Gyrodactylidae, Tetraonchoididae) Bychowsky's (1957) division of the Monogenea into the Oligonchoinea and Polyonchoinea fits the proposed scheme, i.e. monogeneans with unhinged marginal hooks form one old group, the Oligonchoinea, which have 5 + 5 unhinged marginal hooks, and the other group form the Polyonchoinea, which (with the exception of the Hexabothriidae) has a greater number (7 + 7, 8 + 8 or 9 + 9) of unhinged marginal hooks. It is proposed that both these names, Oligonchoinea (sensu mihi) and Polyonchoinea (sensu mihi), will be retained on one side and Articulonchoinea placed on the other side, which reflects the early monogenean evolution. Except for the members of Ananchorea [Polyonchoinea], all members of the Oligonchoinea and Polyonchoinea have anchors, which imply that they are further evolved, i.e. have passed the 5 + 5 marginal hook evolutionary capacity level (Malmberg, 1986). There are two main types of anchors in the Monogenea: haptoral anchors, with anlages appearing in the haptor, and peduncular anchors, with anlages in the peduncle. There are two types of haptoral anchors: peripheral haptoral anchors, ontogenetically the oldest, and central haptoral anchors. Peduncular anchors, in turn, are ontogenetically younger than peripheral haptoral anchors. There may be two pairs of peduncular anchors: medial peduncular anchors, ontogentically the oldest, and lateral peduncular anchors. Only peduncular (not haptoral) anchors have anchor bars. Monogeneans with haptoral anchors are here called Mediohaptanchorea n. superord. and Laterohaptanchorea n. superord. or haptanchoreans. All oligonchoineans and the oldest polyonchoineans are haptanchoreans. Certain members of Calceostomatidae [Polyonchoinea] are the only monogeneans with both (peripheral) haptoral and peduncular anchors (one pair). These monogeneans are here called Mixanchorea n. superord. Polyonchoineans with peduncular anchors and unhinged marginal hooks are here called the Pedunculanchorea n. superord. The most primitive pedunculanchoreans have only one pair of peduncular anchors with an anchor bar, while the most advanced have both medial and lateral peduncular anchors; each pair having an anchor bar. Certain families of the Articulonchoinea, the Anchorea n. superord., also have peduncular anchors (parallel evolution): only one family, the Sundanonchidae n. fam., has both medial and lateral peduncular anchors, each anchor pair with an anchor bar. Evolutionary lines from different monogenean evolutionary capacity levels are discussed and a new system of classification for the Monogenea is proposed.In agreeing to publish this article, I recognise that its contents are controversial and contrary to generally accepted views on monogenean systematics and evolution. I have anticipated a reaction to the article by inviting senior workers in the field to comment upon it: their views will be reported in a future issue of this journal. EditorIn agreeing to publish this article, I recognise that its contents are controversial and contrary to generally accepted views on monogenean systematics and evolution. I have anticipated a reaction to the article by inviting senior workers in the field to comment upon it: their views will be reported in a future issue of this journal. Editor     

The position of the Haplotaxidae in the evolution of oligochaete annelids

The Haplotaxidae have all the characteristics to support the hypothesis that they are the living descendents of the stem forms from which all of the Oligochaeta Clitellata (Orders Lumbriculida, Haplotaxida, Lumbricida, Tubificida) can be derived. The Aphanoneura are distinct from the Clitellata and are raised to a separate Class. There is no evidence to support the view that the elaborate setae of many Tubificida are derived from a polychaete ancestry; both are held to be independent modifications to aquatic life derived from a simple burrowing protoannelid with lumbricine setae.     

生物医药关键技术发展趋势

近年来,生物医药研究人员正在药物的设计、发现、试验、制备,以及检测技术、其他诸如纳米、信息、光学等高技术的融合应用方面致力于更新观念的研究开发,并已取得众多突破,在相关领域形成新的技术趋势。在药物设计方面,随着遗传信息方面的研究进展越来越快,核酸为靶的药物设计已成为新的热点;在疫苗方面,基因疫苗的研制已成为新方向,其技术应用趋向可调控、更安全、更高效生产等,科研人员同时还致力于解决基因疫苗的安全性;在治疗方面,抗体工程和组织工程分别成为药物治疗和组织器官再造的热点;新型药物输送技术正成为业界追逐的目标,药物传输公司正在开发多技术平台,提高药物的效能,减少不良反应和降低成本;药物安全问题已在全球范围内达成共识,美、英、日、欧盟等国均在积极开展药物安全性方面的研究,开发药物安全监测系统;疾病诊断与检测的新技术表现为更高效、准确、快速、早期的趋势,科研人员同时还致力于降低诊断检测产品的价格,以使更多人受益;IT技术、光电技术、纳米技术等新技术正被积极应用于生物医药领域,为大型制药公司和生物技术公司提供药物发现、设计、毒性研究等更新途径的新技术系统。     

An anatomy-based coordinate system for the description of the kinematic displacements in the human knee

The effects and interaction of the anatomical displacements in the human knee are a prerequisite to an accurate assessment and communication of the kinematic data. For the kinematic information to be used to improve diagnosis and treatment, and for better prosthetic design and installation, there must be clear, concise, and universal definitions of the displacements. In general, the displacements are defined as three translations and three rotations. In this paper, anatomic landmarks on the femur and on the tibia are used to define the locations and orientations of the six displacement axes; i.e. three translational and three rotational displacement axes. The most commonly accepted kinematic representation of the knee joint, in the literature, is a special geometry three-cylindric open chain in which the axes of the cylindric joints are defined according to the rotational displacement axes. The sequentially adjacent joint axes are assumed to not only intersect but to intersect at right-angles. The open chain permits a total of six degrees of freedom between a Cartesian reference frame attached to the femur and a Cartesian reference frame attached to the tibia. In this paper, the three rotational axes are shown to be skewed and off-set from each other, therefore, a three-cylindric open chain with skewed joint axes is proposed to measure the six displacements between the two reference frames. The authors believe that the proposed open chain is the most general to date and provides a more realistic representation of the displacements in the knee. To illustrate the significance of the reference frames on the interpretation of measured data, the anterior/posterior drawer is plotted against per cent gait cycle for three existing open chains and the proposed open chain.     

The role of the lymphoid system in the regulation of the blood glucose level.

Recent findings have led to a new hypothesis in which it is proposed that the immune system plays a role in regulating the increase in blood glucose levels after a meal. The relevant findings are: (1) the primary lymphoid tissue, the lymph nodes are mostly present within adipose tissue depots throughout the body (there are at least 12 such depots and about 10 (12) lymphocytes, 99% of which are present in lymph nodes); (2) lymphocytes and other immune cells utilize glucose at a high rate but almost all of it is converted to lactate which accumulates in the cells prior to release; (3) glutamine, some of which is synthesized in muscle from glucose, is utilized at a high rate by immune cells, the end-product of which is mainly aspartate, which also accumulates in the cells prior to release; and (4) finally, there is a common blood supply to the lymph node and the adipose tissue depot and the blood flow through the depot and hence the node is increased after a meal. It is proposed that, after a meal, some of the absorbed glucose is taken up from the blood by the lymphocytes and converted to lactate and glutamine is converted to aspartate. These are released slowly into the blood from where they are removed and converted to glycogen by the liver. Hence the immune cells provide a temporary buffer for glucose in the form of lactate and aspartate and, in this way, restrict the rise in blood glucose during and after a meal.     

Stochasticity in the adaptive dynamics of evolution: the bare bones

First a population model with one single type of individuals is considered. Individuals reproduce asexually by splitting into two, with a population-size-dependent probability. Population extinction, growth and persistence are studied. Subsequently the results are extended to such a population with two competing morphs and are applied to a simple model, where morphs arise through mutation. The movement in the trait space of a monomorphic population and its possible branching into polymorphism are discussed. This is a first report. It purports to display the basic conceptual structure of a simple exact probabilistic formulation of adaptive dynamics.     

The effects of changes of the tonicity of the bathing fluid upon the tension generated by atrial trabeculae isolated from the heart of the frog, Rana pipiens.

Raising the tonicity of the fluid bathing frog atrial trabeculae has three effects: an initial sustained relaxation, which depends on muscle length and probably originates from structures other than the contractile apparatus; an increase in contractility, which takes the form of a transient contracture if the muscle has previously undergone a high-potassium or a low-sodium contracture, and a further rise in contractility on return to isotonic fluid (off response). The hypertonic contractures, in high-potassium or sodium-free fluids, are antagonized by local anaesthetics and in Na-free media they are unaffected by removal of extracellular coat, whereas the 'off responses' are insensitive to both experimental manoeuvres. Hypotonic fluids applied in Na-free solutions evoke a phasic and a tonic contracture, neither of which are sensitive to local anaesthetics. The tonic response is reduced by lowering the [Ca]o, and occurs at tonicities where the permeability of the cell membrane is likely to have increased. The phasic part of the hypotonic contracture resembles the 'off response' which follows exposure to hypertonic solution. The effects of hypertonic fluids and of caffeine on frog heart are alike, and are also similar to the responses induced by the same experimental manoeuvres in skeletal muscle. The results can be interpreted by assuming that the intracellular relaxing system in frog heart is sensitive to changes in tonicity, and could be functionally divided.     

Dressing the mind properly for the game

Game theory as a theoretical and empirical approach to interaction has spread from economics to psychology, political science, sociology and biology. Numerous social interactions-foraging, talking, trusting, coordinating, competing-can be formally represented in a game with specific rules and strategies. These same interactions seem to rely on an interweaving of mental selves, but an effective strategy need not depend on explicit strategizing and higher mental capabilities, as less sentient creatures or even lines of software can play similar games. Human players are distinct because we are less consistent and our choices respond to elements of the setting that appear to be strategically insignificant. Recent analyses of this variable response have yielded a number of insights into the mental approach of human players: we often mentalize, but not always; we are endowed with social preferences; we distinguish among various types of opponents; we manifest different personalities; we are often guided by security concerns; and our strategic sophistication is usually modest.