摘要:

AbstractTo date, the effective management of HIV‐1 infection by anti‐retroviral drugs has proved remarkably difficult to achieve. This is primarily due to the ease with which HIV‐1 becomes resistant to drugs which initially may be very effective at blocking viral replication. In a recent issue ofScience, two promising new AIDS treatments were reported. The first described the use of retroviral‐type zinc finger structures found in the HIV‐1 nucleocapsid protein as targets for anti‐retroviral drugs(1). The second demonstrated the feasibility of the reverse transcriptase inhibitor (R)‐9‐(2‐phosphonylmethoxypropyl) adenine as a postexposure prophylaxis in blocking H

ISSN:0265-9247    

DOI:10.1002/bies.950180502

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractDevelopmental coordination is vital in the temporally coordinated appearance of cell types within the precise spatial architecture of the vertebrate brain and this, combined with the rich interplay between the developing brain and its target organs, is a biological problem of monumental complexity. An example is the genesis and subsequent integration of the neuroendocrine hypothalamus and the pituitary. Two recent papers(1,2)use the developing hypothalamo‐pituitary axis in order to gather a deeper understanding of these integrative mechanisms. In addition, they show that a sub‐family of homeodomain factors, the POU‐domain proteins, play a critical role in coordinating the respective ontogenies of the hypothalamus and the pitu

ISSN:0265-9247    

DOI:10.1002/bies.950180503

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractA gene is described as imprinted if its pattern of expression depends on whether it passed the previous generation in a male or female germ line. A recent paper(1)reports that imprinted genes have fewer and smaller introns than a control set of genes. The differences are striking but their interpretation is unclear. The loss of introns after a gene becomes imprinted is not sufficient to explain why imprinted genes have fewer introns than average, because related unimprinted genes also have few introns. Similarly, small introns appear to be a property of chromosomal region rather than of imprinting status itself, because neighboring unimprinted genes also have small introns.

ISSN:0265-9247    

DOI:10.1002/bies.950180504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractDuring embryogenesis, the basic axon scaffold of the nervous system is formed by special axons that pioneer pathways between groups of cells. To find their way, the pioneer growth cones detect specific cues in their extracellular environment. One of these guidance cues is netrin. Observations and experimental manipulations in vertebrates and nematodes have shown that netrin is a bifunctional guidance cue that can simultaneously attract and repel axons. During the formation of this basic axon scaffold inCaenorhabditis elegans, the netrin UNC‐6 is expressed by neuroglia and pioneer neurons, providing hierarchical guidance cues throughout the animal. Each cue has a characteristic role depending on the cell type, its position and the developmental stage. These roles include activities as global, decussation and labeled‐pathway cues. This hierarchical model of UNC‐6 netrin‐mediated guidance suggests a method by which guidance cues can direct formation of basic axon scaffolds in developing nervous

ISSN:0265-9247    

DOI:10.1002/bies.950180505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractMaize develops separate male and female flowers in different locations on a single plant. Male flowers develop at the tip of the shoot in the tassel, and female flowers develop on the ears, which terminate short branches. The development of male flowers in tassels and female flowers in ears is the result of selective abortion of pistils or stamens, respectively, in developing florets. Genetic analysis has shown that stamen abortion and pistil abortion are under the control of two different genetic pathways. Local levels of the plant hormone gibberellic acid determine whether or not stamens are suppressed. Pistil abortion is under the regulation of thetassel seedgenes, one of which has been shown to encode a short‐chain alcohol dehydrogenase. Thetassel seedgenes play a role in regulating the fate of inflorescence meristems as well as pistil primordium fat

ISSN:0265-9247    

DOI:10.1002/bies.950180506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractGlucocorticoid hormones are effective in controlling inflammation, but the mechanisms that confer this action are largely unknown. Recent advances in this field have shown that both positive and negative regulation of gene expression are necessary for this process. The genes whose activity are modulated in the anti‐inflammatory process code for several cytokines, adhesion molecules and enzymes. Most of them do not carry a classical binding site for regulation by a glucocorticoid receptor, but have instead regulatory sequences for transcription factors such as AP‐1 or NF‐κ. This makes them unusual targets for glucocorticoid action and emphasizes the need for novel regulatory mechanisms. Recent studies describe an important contribution by protein‐protein interactions, in which several domains of the receptor participate; these studies provide a better understanding of the action of the receptor and offer opportunities for the design of steroidal compounds that could function more effectively as anti‐inflamma

ISSN:0265-9247    

DOI:10.1002/bies.950180507

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractLysosomes are the site of degradation of obsolete intracellular material during autophagy and of extracellular macromolecules following endocytosis and phagocytosis. The membrane of lysosomes and late endosomes is enriched in highly glycosylated transmembrane proteins of largely unknown function. Significant progress has been made in recent years towards elucidating the pathways by which these lysosomal membrane proteins are delivered to late endosomes and lysosomes. While some lysosomal membrane proteins follow the constitutive secretory pathway and reach lysosomes indirectlyviathe cell surface and endocytosis, others exit thetrans‐Golgi network in clathrin‐coated vesicles for direct delivery to endosomes and lysosomes. Sorting from the Golgi or the plasma membrane into the endosomal system is mediated by signals encoded by the short cytosolic domain of these proteins. This review will discuss the role of lysosomal membrane proteins in the biogenesis of the late endosomal and lysosomal membranes, with particular emphasis on the structural features and molecular mechanisms underlying the intracellular trafficking of these prote

ISSN:0265-9247    

DOI:10.1002/bies.950180508

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractAmphibian metamorphosis is a post‐embryonic process that systematically transforms different tissues in a tadpole. Thyroid hormone plays a causative role in this complex process by inducing a cascade of gene regulation. While natural metamorphosis does not occur until endogenous thyroid hormone has been synthesized, tadpoles are competent to respond to exogenous thyroid hormone shortly after hatching. In addition, even though the metamorphic transitions of individual organs are all controlled by thyroid hormone, each occurs at distinct developmental stages. Recent molecular studies suggest that this competence of premetamorphic tadpoles to respond to the hormone and the developmental stage‐dependent regulation of tissue‐specific transformations are determined in part by the levels of thyroid hormone receptors and the concentrations of cellular free thyroid hormone. In addition, at least two genes, encoding a cytosolic thyroid hormone binding protein and a 5‐deiodinase, respectively, are likely to be critical players in regulating cellular free thyroid hormone concentrations. This review discusses how all of these molecuar components coordinate to induce amphibian metamorphosis in a correct spatial and temporal manner. These studies provde us with general clues as to how and why tissues become competent to respond to hormonal

ISSN:0265-9247    

DOI:10.1002/bies.950180509

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractMany loci inDrosophilaexhibit dosage effects on single phenotypes. In the case of modifiers of position‐effect variegation, increases and decreases in dosage can have opposite effects on variegating phenotypes. This is seemingly paradoxical: if each locus encodes a limiting gene product sensitive to dosage decreases, then increasing the dosage of any one should have no effect, because the others should remain limiting. An earlier model put forward to resolve this paradox suggested that dosage‐dependent modifiers encode protein subunits of a macromolecular complex that is sensitive to mass action equilibrium conditions. Because chemical equilibria are dynamic, however, such hypothetical complexes will be unstable to an extent that is inconsistent with the known properties of molecules that make up chromatin. An alternative model accounts for the dosage effects in terms of interactions between structural proteins that bind at multiple linked sites. These might include indirect interactions occurring between regulatory proteins and genes for structural proteins or their protein products. The large number of direct and inverse regulatory genes which are known to exist inDrosophilacould account for the apparent genetic complexity that is seen for modifiers of position‐effect variegation and for other systems of phenotypic modific

ISSN:0265-9247    

DOI:10.1002/bies.950180510

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractThe function of meiotic recombination has remained controversial, despite recent inroads into mechanisms. Ideas concerning a possible role of recombination in the elimination or efficient incorporation of mutations have been backed by theoretical studies but have lacked empirical support. Recent investigations into the basis for local variations in recombination frequency in yeast have uncovered a strong association between recombination initiation sites and transcriptional regulatory sequences. Other recent studies indicate a strong correlation between transcription and mutation rates in yeast genes. Taken together, these data imply that distributions of recombination and mutation frequencies may be strongly correlated. This suggests that recombination may be targeted to genomic sites of high mutation frequency; such a ‘mutation‐tracking’ function would clearly aid in the shuffling of mutations to break up unfavorable and create favorable allelic combinations. Moreover, recent insights into the mechanism of gene conversion in yeast reveal a very strong inherent bias in favor of alleles on the non‐initiating homolog. Combined with mutation tracking, these findings suggest a novel and general mechanism by which allelic gene conversion may act to eliminate mu

ISSN:0265-9247    

DOI:10.1002/bies.950180511

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY