Untersuchungen über das Verhalten von Tumorgewebe in Diffusionskammern gegenüber eindringenden Wirtszellen bei tumorresistenten Ratten

Summary Tumour cells in diffusion chambers, which were implanted in tumour-resistant rats, were only destroyed by penetrating immunized host cells when membrane filters of large pore size were used, whereas with filters of small pore size the tumour cells survived and remained virulent.     

Architecture and functional properties of the CFTR channel pore

The main function of the cystic fibrosis transmembrane conductance regulator (CFTR) is as an ion channel for the movement of small anions across epithelial cell membranes. As an ion channel, CFTR must form a continuous pathway across the cell membrane—referred to as the channel pore—for the rapid electrodiffusional movement of ions. This review summarizes our current understanding of the architecture of the channel pore, as defined by electrophysiological analysis and molecular modeling studies. This includes consideration of the characteristic functional properties of the pore, definition of the overall shape of the entire extent of the pore, and discussion of how the molecular structure of distinct regions of the pore might control different facets of pore function. Comparisons are drawn with closely related proteins that are not ion channels, and also with structurally unrelated proteins with anion channel function. A simple model of pore function is also described.     

Permeability coefficients of the egg-case membrane of Scyliorhinus canicula L

The cleidoic egg-case of the dogfish appears to have a highly porous and permeable outer membrane, the pore radius being computed to be 13.6 A. It does not present any physiological barrier to small molecules and therefore constitutes an open ionic and osmotic system for the embryo. Being a porous protein membrane it may be of value as a model for molecular transport mechanisms.     

Timing is everything: the regulation of type III secretion

Type Three Secretion Systems (T3SSs) are essential virulence determinants of many Gram-negative bacteria. The T3SS is an injection device that can transfer bacterial virulence proteins directly into host cells. The apparatus is made up of a basal body that spans both bacterial membranes and an extracellular needle that possesses a channel that is thought to act as a conduit for protein secretion. Contact with a host-cell membrane triggers the insertion of a pore into the target membrane, and effectors are translocated through this pore into the host cell. To assemble a functional T3SS, specific substrates must be targeted to the apparatus in the correct order. Recently, there have been many developments in our structural and functional understanding of the proteins involved in the regulation of secretion. Here we review the current understanding of protein components of the system thought to be involved in switching between different stages of secretion.     

Permeability coefficients of the egg-case membrane ofScyliorhinus canicula L.

Summary The cleidoic egg-case of the dogfish appears to have a highly porous and permeable outer membrane, the pore radius being computed to be 13.6 Å. It does not present any physiological barrier to small molecules and therefore constitutes an open ionic and osmotic system for the embryo. Being a porous protein membrane it may be of value as a model for molecular transport mechanisms.     

Complementary replica of freeze-fractured human lymphocyte nuclei

Complementary replicas of freeze-fractured human lymphocyte nuclei were obtained, and were studied with the electron microscope. Complementarity was evident in cross-fractured nuclear pore complexes and in particle-free membrane areas. Explanations for the observed structural peculiarities are considered.     

The preprotein translocase of the outer mitochondrial membrane: receptors and a general import pore

Cytosol-synthesized preproteins destined for the mitochondria are transported across the outer membrane by the translocase of the mitochondrial outer membrane (TOM complex). This dynamic transport machinery can be divided into receptors that recognize preprotein targeting signals and components of the general import pore complex that mediate preprotein transport across the outer membrane. This review focuses on recent studies dealing with the central questions regarding the pore-forming subunits, and architecture and gating of the translocation channel of the outer membrane.     

Pharyngeal cavity and the gills are the target organ for the repellent action of pardaxin in shark

Pardaxin, an active principle of the repellent secretion of the Red Sea flatfish, Pardachirus marmoratus, elicited severe struggling, mouth paralysis, and transient increase in urea leakage from the gills only when administered to the medium bathing the shark's pharyngeal cavity and gills. An apparatus was constructed which prevents a mixing of the outflow from shark's gills with water bathing its surface skin. It is concluded that in sharks the gills and/or the pharyngeal cavity are the target organ for the repellent action of pardaxin.     

Fluorescence spectroscopy and molecular dynamics simulations in studies on the mechanism of membrane destabilization by antimicrobial peptides

Since their initial discovery, 30 years ago, antimicrobial peptides (AMPs) have been intensely investigated as a possible solution to the increasing problem of drug-resistant bacteria. The interaction of antimicrobial peptides with the cellular membrane of bacteria is the key step of their mechanism of action. Fluorescence spectroscopy can provide several structural details on peptide–membrane systems, such as partition free energy, aggregation state, peptide position and orientation in the bilayer, and the effects of the peptides on the membrane order. However, these “low-resolution” structural data are hardly sufficient to define the structural requirements for the pore formation process. Molecular dynamics simulations, on the other hand, provide atomic-level information on the structure and dynamics of the peptide–membrane system, but they need to be validated experimentally. In this review we summarize the information that can be obtained by both approaches, highlighting their versatility and complementarity, suggesting that their synergistic application could lead to a new level of insight into the mechanism of membrane destabilization by AMPs.     

Host defense peptides as new weapons in cancer treatment

In the last decade intensive research has been conducted to determine the role of innate immunity host defense peptides (also termed antimicrobial peptides) in the killing of prokaryotic and eukaryotic cells. Many antimicrobial peptides damage the cellular membrane as part of their killing mechanism. However, it is not clear what makes cancer cells more susceptible to some of these peptides, and what the molecular mechanisms underlying these activities are. Two general mechanisms were suggested: (i) plasma membrane disruption via micellization or pore formation, and (ii) induction of apoptosis via mitochondrial membrane disruption. To be clinically used, these peptides need to combine high and specific anticancer activity with stability in serum. Although so far very limited, new studies have paved the way for promising anticancer host defense peptides with a new mode of action and with a broad spectrum of anticancer activity.     

Pharyngeal cavity and the gills are the target organ for the repellent action of pardaxin in shark

Summary Pardaxin, an active principle of the repellent secretion of the Red Sea flatfish,Pardachirus marmoratus, elicited severe struggling, mouth paralysis, and transient increase in urea leakage from the gills only when administered to the medium bathing the shark's pharyngeal cavity and gills. An apparatus was constructed which prevents a mixing of the outflow from shark's gills with water bathing its surface skin. It is concluded that in sharks the gills and/or the pharyngeal cavity are the target organ for the repellent action of pardaxin.     

Many mechanisms, one entrance: membrane protein translocation into the nucleus

The inner nuclear membrane harbors a unique set of membrane proteins, many of which interact with nuclear intermediate filaments and chromatin components and thus play an important role in nuclear organization and gene expression regulation. These membrane proteins have to be constantly transported into the nucleus from their sites of synthesis in the ER to match the growth of the nuclear membrane during interphase. Many mechanisms have evolved to enable translocation of these proteins to the nucleus. The full range of mechanisms goes from rare autophagy events to regulated translocation using the nuclear pore complexes. Though mechanisms involving nuclear pores are predominant, within this group an enormous mechanistic range is observed from free diffusion through the peripheral channels to many distinct mechanisms involving different nucleoporins and other components of the soluble protein transport machinery in the central channels. This review aims to provide a comprehensive insight into this mechanistic diversity.     

塑料排水板堆载预压软基处理变形观察分析

采用塑料排水板堆载预压法对某软土路基工程进行处理,对路基变形及孔隙水压力等进行了严密观测;同时采取浅层沉降监测、深层沉降监测、孔隙水压力监测、地下水位观测等手段,以及地表沉降、孔隙水压力等变化规律,推算出预压荷载下的最终沉降量和固结度,深入分析塑料排水板堆载预压软土地基处理方法的加固效果。分析结果表明,该方法能有效地加快软基的固结沉降,提高地基土的稳定性和承载力,可供软土地基处理设计与施工参考。     

Membrane fusion: the process and its energy suppliers

Membrane fusion constitutes a pivotal process in eukaryotic cell physiology. Both specialized proteins and membrane lipids play key roles in fusion. Here, our current understanding of the mechanism of membrane fusion is reviewed. The focus is on the relatively simple and well-understood proteinaceous fusion machinery of enveloped viruses and the physical properties of lipids that appear to be of great relevance for fusion progression. Recent observations suggest that viral fusion proteins use packed conformational energy and bilayer-destabilizing domains to (i) bring participating membranes into intimate contact, (ii) merge proximal lipid monolayers through highly curved stalk/hemifusion intermediates, and (iii) generate a lipid-containing fusion pore, thereby terminating the fusion process. Received 4 January 2002; received after revision 3 April 2002; accepted 5 April 2002     

淹没状态下河道植物偏斜高度与糙率的关系

利用室内变坡水槽,模拟了复式河道滩地3种植物对漫滩水流的干扰作用,并借助声学多普勒测速仪（ADV）施测了不同垂线、不同测点的瞬时流速,计算了不同条件下的河道糙率。基于水动力及植物柔性变形分析,建立了淹没状态下的植物河道糙率计算的基本关系,反映出糙率值不仅与水流动力条件有关,还与植物类型、淹没高度、布置及其自身力学性能有关,同时,利用试验资料及理论分析成果,进一步获取了植物河道的附加糙率值,借此分析与评价河道植物对水流阻力的影响程度。     

The gating of the CFTR channel

Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel expressed in the apical membrane of epithelia. Mutations in the CFTR gene are the cause of cystsic fibrosis. CFTR is the only ABC-protein that constitutes an ion channel pore forming subunit. CFTR gating is regulated in complex manner as phosphorylation is mandatory for channel activity and gating is directly regulated by binding of ATP to specific intracellular sites on the CFTR protein. This review covers our current understanding on the gating mechanism in CFTR and illustrates the relevance of alteration of these mechanisms in the onset of cystic fibrosis.     

The biogenesis and function of eukaryotic porins.

Like most other mitochondrial proteins porin is synthesized in the cytosol and imported posttranslationally into the outer mitochondrial membrane. This transport follows the general rules for mitochondrial protein import with a few aberrations: a) porin contains an uncleaved NH2-terminal signal sequence, b) also its carboxyterminus might be involved in the import process, and c) this transport does not seem to require a membrane potential delta psi, although it is ATP-dependent. Most likely the actual import step occurs at contact sites between the outer and the inner mitochondrial membrane and involves at least one receptor protein. Although porin is known to be the major gate through the outer mitochondrial membrane, its absence only causes transient respiratory problems in yeast cells. This could mean a) that there is a bypass for some mitochondrial functions in the cytosol and/or b) that there are alternative channel proteins in the outer membrane. The first idea is supported by the overexpression of cytosolic virus-like particles in yeast cells lacking porin and the second by the occurrence of residual pore activity in mitochondrial outer membrane purified from porinless mutant cells.     

Pathophysiology of mitochondrial cell death control

Mitochondria have been recently recognized to play a major role in the control of apoptosis or programmed cell death. Permeabilization of mitochondrial membranes, a decisive feature of early cell death, is regulated by members of the Bcl-2 family which interact with the permeability transition pore complex (PTPC). Thus, the cytoprotective oncoprotein Bcl-2 stabilizes the mitochondrial membrane barrier function, whereas the tumor suppressor protein Bax permeabilizes mitochondrial membranes. The regulation of membrane permeabilization is intertwined with that of the bioenergetic and redox functions of mitochondria. The implications of alterations in the composition of the PTPC and in mitochondrial function for the pathophysiology of cancer (reduced apoptosis) and neurodegeneration (enhanced apoptosis) are discussed.     

Inhibition of diuresis in the tsetse fly (Glossina morsitans) by ouabain and acetazolamide.

Acetazolamide and ouabain, metabolic inhibitors which interfere with certain membrane transport systems, reduce the rate of water elimination by male Glossina morsitans morsitans. The results suggest that water is transported across membranes during diuresis and that a ouabain sensitive Na+K+ATPase and an acetazolamide-sensitive carbonic anhydrase are involved in diuresis.