Clustering of voltage-dependent sodium channels on axons depends on Schwann cell contact.

In myelinated nerves, segregation of voltage-dependent sodium channels to nodes of Ranvier is crucial for saltatory conduction along axons. As sodium channels associate and colocalize with ankyrin at nodes of Ranvier, one possibility is that sodium channels are recruited and immobilized at axonal sites which are specified by the subaxolemmal cytoskeleton, independent of glial cell contact. Alternatively, segregation of channels at distinct sites along the axon may depend on glial cell contact. To resolve this question, we have examined the distribution of sodium channels, ankyrin and spectrin in myelination-competent cocultures of sensory neurons and Schwann cells by immunofluorescence, using sodium channel-, ankyrin- and spectrin-specific antibodies. In the absence of Schwann cells, sodium channels, ankyrin and spectrin are homogeneously distributed on sensory axons. When Schwann cells are introduced into these cultures, the distribution of sodium channels dramatically changes so that channel clusters on axons are abundant, but ankyrin and spectrin remain homogeneously distributed. Addition of latex beads or Schwann cell membranes does not induce channel clustering. Our results suggest that segregation of sodium channels on axons is highly dependent on interactions with active Schwann cells and that continuing axon-glial interactions are necessary to organize and maintain channel distribution during differentiation of myelinated axons.     

The failing heart.

Cardiomyopathies are disorders affecting heart muscle that usually result in inadequate pumping of the heart. They are the most common cause of heart failure and each year kill more than 10,000 people in the United States. In recent years, there have been breakthroughs in understanding the molecular mechanisms involved in this group of conditions, with knowledge of the genetic basis for cardiomyopathies perhaps seeing the largest advance, enabling clinicians to devise improved diagnostic strategies and preparing the stage for new therapies.     

A calcium sensor in the sodium channel modulates cardiac excitability.

Sodium channels are principal molecular determinants responsible for myocardial conduction and maintenance of the cardiac rhythm. Calcium ions (Ca2+) have a fundamental role in the coupling of cardiac myocyte excitation and contraction, yet mechanisms whereby intracellular Ca2+ may directly modulate Na channel function have yet to be identified. Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. A naturally occurring mutation (A1924T) in the IQ domain altered hH1 function in a manner characteristic of the Brugada arrhythmia syndrome, but at the same time inhibited slow inactivation induced by Ca2+/CaM, yielding a clinically benign (arrhythmia free) phenotype.     

Effect of 15(R)-15-methyl-prostaglandin E2 on iron absorption in the rat

Summary The administration of 15(R)-15-methyl prostaglandin E₂ (15(R)-15-M-PGE₂) in vivo significantly diminished the uptake of⁵⁹Fe into blood, spleen, liver, femur and dried intestine of rats, whereas acetylsalicylic acid (ASA) increased the counts significantly. This effect of ASA was counteracted by 15(R)-15-M-PGE₂. It is suggested that prostaglandins (PGs) might play an important role in inhibiting iron absorption at the intestinal level.This work was supported by grant No.6638 from CONICET (Argentina). The technical assistance of Mrs María E. Castro and Norma Rizzo is gratefully acknowleged.     

Quantum Mechanics and Operational Probability Theory

We discuss a generalization of the standard notion of probability space and show that the emerging framework, to be called operational probability theory, can be considered as underlying quantal theories. The proposed framework makes special reference to the convex structure of states and to a family of observables which is wider than the familiar set of random variables: it appears as an alternative to the known algebraic approach to quantum probability.     

Comparative study of the karyotypes of two Egyptian species of bats,Taphozous perforatus andTaphozous nudiventris (Chiroptera: Mammalia)

A detailed karyotypic analysis of two Egyptian species of bats,Taphozous perforatus andTaphozous nudiventris, was made on the basis of conventional data and G-band patterns. No detectable karyotypic difference was found between the two species (2n=42, F.N. 64). By comparison of G-band patterns, some differences between the two species were seen in the corresponding autosomal pairs. These results are reported for the first time in Egypt.     

Pragmatism in Economic Methodology: The Duhem-Quine Thesis Revisited

Contemporary developments in economicmethodology have produced a vibrant agenda ofcompeting positions. These include, amongothers, constructivism, critical realism andrhetoric, with each contributing to the Realistvs. Pragmatism debate in the philosophies of thesocial sciences. A major development in theneo-pragmatist contribution to economicmethodology has been Quine's pragmatic assaulton the dogmas of empiricism, which are nowclearly acknowledged within contemporaryeconomic methodology. This assault isencapsulated in the celebrated Duhem-Quinethesis, which according to a number ofcontemporary leading philosophers of economics,poses a particularly serious methodologicalproblem for economics. This problem, asreflected in Hausman's analysis, consists ofthe inability of economics to learn fromexperience, thereby subverting the capacity totest economic theories. In this paper wedispute this position. Our argument is basedon a combination of Quine's holism with VanFraassen's constructive empiricism, especiallythe latter's analysis of empirical adequacy andhis pragmatic approach to explanation. Theresulting reorientation of economic methodologyrestores the capacity of economics to learnfrom experience and reinstates the imperativeof developing alternatives to orthodoxtheorizing in economics.     

Coalignment of vimentin intermediate filaments with microtubules depends on kinesin.

Intermediate filaments in most types of cultured cells coalign with microtubules. Depolymerization of microtubules results in collapse of vimentin and desmin intermediate filaments to the nucleus where they form a perinuclear cap. Collapse can also be induced by microinjection of antibodies against intermediate filament or microtubule proteins. Thus, two filament systems interact with each other. But the molecules mediating this interaction are unknown. One of the candidates for this role is a microtubule motor kinesin. Recent data showed that kinesin is involved in the plus end-directed movement of the membranous organelles along microtubules such as radial extension of lysosomes in macrophages and centrifugal movement of pigment in melanophores. Here we report that injection of the anti-kinesin antibody into human fibroblasts results in the redistribution of intermediate filaments to a tight perinuclear aggregate but had no effect on the distribution of microtubules. Thus, kinesin is involved not only in organelle movement but also in interaction of the two major cytoskeletal systems, intermediate filaments and microtubules.     

MeV Pb离子在非晶Si中的射程离散──离子束混合和增强扩散的影响

１．０ＭｅＶ２０８Ｐｂ离子在非晶Ｓｉ中的投影射程ＲＰ和射程偏差ΔＲＰ作为注量和温度二者的函数用背散射法进行测定．注量的变化范围为５×１０１３～７×１０１４ｃｍ－２．注入是在室温和ｔ＝－１２０℃下完成的．由由实验所确定的投影射程，射程偏差与注量或温度无关，并且分别等于２９５和７２．２ｎｍ．与ＴＲＩＭ８６的计算结果相比较，发现ＲＰ的偏离为１８％，而ΔＲＰ的偏离为３６％．ＲＰ和ΔＲＰ二者与注量及温度的无关性，排除了所观察到的与ＴＲＩＭ的矛盾是由于注入期间辐射增强扩散或离子束混合效应而引起的解释。