Delineation of the HLA-DR region and the residues involved in the association with the cytoskeleton

Whereas the association of major histocompatibility complex (MHC) class II molecules with the cytoskeleton and their recruitment into lipid rafts play a critical role during cognate T/antigen-presenting cell interactions, MHC class II-induced signals, regions, and residues involved in their association and recruitment have not yet been fully deciphered. In this study, we show that oligomerization of HLA-DR molecules induces their association with the cytoskeleton and their recruitment into lipid rafts. The association of oligomerized HLA-DR molecules with the cytoskeleton and their recruitment into lipid rafts occur independently. Furthermore, the association with the cytoskeleton is HLA-DR-specific, since oligomerization of HLA-DP triggers its recruitment only into lipid rafts. HLA-DR molecules devoid of both alpha and beta cytoplasmic tails did not associate with the cytoskeleton, but their recruitment into lipid rafts was unimpeded. Deletion of either the alpha or beta cytoplasmic tail did not affect the association of HLA-DR with the cytoskeleton and/or recruitment into lipid rafts. HLA-DR molecules that were devoid of the alpha cytoplasmic chain and that had their beta cytoplasmic chain replaced with the HLA-DP beta chain or with a beta chain in which the residues at positions Gly(226)-His(227)-Ser(228) were substituted by alanine no longer associated with the cytoskeleton. They were, however, still recruited into lipid rafts. Together, these results support the involvement of different regions of the cytoplasmic tails in the association and the recruitment of HLA-DR into different compartments. The differential behavior of HLA-DP and -DR with respect to their association with the cytoskeleton may explain the previously described difference in their transduced signals.     

Target RNA-directed tailing and trimming purifies the sorting of endo-siRNAs between the two Drosophila Argonaute proteins

In flies, 22-23-nucleotide (nt) microRNA duplexes typically contain mismatches and begin with uridine, so they bind Argonaute1 (Ago1), whereas 21-nt siRNA duplexes are perfectly paired and begin with cytidine, promoting their loading into Ago2. A subset of Drosophila endogenous siRNAs-the hairpin-derived hp-esiRNAs-are born as mismatched duplexes that often begin with uridine. These would be predicted to load into Ago1, yet accumulate at steady-state bound to Ago2. In vitro, such hp-esiRNA duplexes assemble into Ago1. In vivo, they encounter complementary target mRNAs that trigger their tailing and trimming, causing Ago1-loaded hp-esiRNAs to be degraded. In contrast, Ago2-associated hp-esiRNAs are 2'-O-methyl modified at their 3' ends, protecting them from tailing and trimming. Consequently, the steady-state distribution of esiRNAs reflects not only their initial sorting between Ago1 and Ago2 according to their duplex structure, length, and first nucleotide, but also the targeted destruction of the single-stranded small RNAs after their loading into an Argonaute protein.     

Viral transport and the cytoskeleton

In the past decade, studies into the way in which intracellular bacterial pathogens hijack and subvert their hosts have provided many important insights into regulation of the actin cytoskeleton and cell motility, in addition to increasing our understanding of the infection process. Viral pathogens, however, may ultimately unlock more cellular secrets as they are even more dependent on their hosts during their life cycle.     

Fluctuations in amino acid-H3 incorporation into the proteins of the isolated retina]

The rate of amino acid incorporation into the mouse retina proteins was measured in dynamics of dark adaptation and at different terms of their stimulation by light. It was found that variations in dry weight of the ganglion retinal cells and in the incorporation of amino acids into their proteins occurred rhythmically, with the period of about one hour.     

Getting to know the Amakwerre-kwerre: the socio-economic circumstances of Zimbabwean day labourers in South Africa

Over the past decade, in the face of volatile economic conditions at home, there has been an influx of Zimbabweans into South Africa looking for work and a better life. Many of these jobseekers have moved into the day labourer market, offering their services on street corners and other pickup points in the main metropolitan areas. While their working and living conditions leave much to be desired and their pay is very uncertain, Zimbabwean day labourers – with better education – often are the preferred candidates for the limited jobs on offer and earn more than their counterparts in South Africa. Not surprisingly, South African day labourers often resent Zimbabwean workers in the country. This study is the first of its kind in that it delves into the hopes, fears and daily routines of Zimbabwean day labourers, and offers new perspectives on this important economic segment.     

Naive-like Conversion Overcomes the Limited Differentiation Capacity of Induced Pluripotent Stem Cells

Although induced pluripotent stem (iPS) cells are indistinguishable from ES cells in their expression of pluripotent markers, their differentiation into targeted cells is often limited. Here, we examined whether the limited capacity of iPS cells to differentiate into neural lineage cells could be mitigated by improving their base-line level of pluripotency, i.e. by converting them into the so-called “naive” state. In this study, we used rabbit iPS and ES cells because of the easy availability of both cell types and their typical primed state characters. Repeated passages of the iPS cells permitted their differentiation into early neural cell types (neural stem cells, neurons, and glial astrocytes) with efficiencies similar to ES cells. However, unlike ES cells, their ability to differentiate later into neural cells (oligodendrocytes) was severely compromised. In contrast, after these iPS cells had been converted to a naive-like state, they readily differentiated into mature oligodendrocytes developing characteristic ramified branches, which could not be attained even with ES cells. These results suggest that the naive-like conversion of iPS cells might endow them with a higher differentiation capacity.     

降解芳烃微生物的多样性

芳烃是一类生物异源物质,自然微生物群落利用其对环境的适应性,对这类物质由陌生到适应,微生物群落的遗传背景发生了变化,降解芳烃的微生物呈现出多样性,本文系统介绍了降解芳烃微生物的特性,物种资源,环境适应,遗传背景及演变;介绍了各遗传型物种的功能基因数量,表达及调控方式,指明芳烃环境污染的生物修复主要取决于高效工程构造及代谢过程的控制。     

A composite model for establishing the microtubule arrays of the neuron

Neurons generate two distinct types of processes, termed axons and dendrites, both of which rely on a highly organized array of microtubules for their growth and maintenance. Axonal microtubules are uniformly oriented with their plus ends distal to the cell body, whereas dendritic microtubules are nonuniformly oriented. In neither case are the microtubules attached to the centrosome or any detectable structure that could establish their distinct patterns of polarity orientation. Studies from our laboratory over the past few years have led us to propose the following model for the establishment of the axonal and dendritic microtubule arrays. Microtubules destined for these processes are nucleated at the centrosome within the cell body of the neuron and rapidly released. The released microtubules are then transported into developing axons and dendrites to support their growth. Early in neuronal development, the microtubules are transported with their plus ends leading into immature processes that are the common progenitors of both axons and dendrites. This sets up a uniformly plus-end-distal pattern of polarity orientation, which is preserved in the developing axon. In the case of the dendrite, the plus-end-distal microtubules are joined by another population of microtubules that are transported into these processes with their minus-ends leading. Implicit in this model is that neurons have specialized machinery for regulating the release of microtubules from the centrosome and for transporting them with great specificity.     

Causes of the failure of antibiotic prophylaxis of inhalation anthrax and clearance of the spores from the lungs

The number ofBacillus anthracis spores in the lung of guinea-pigs infected by inhalation shows a rapid exponential drop during the first days after inhalation, while the number of those which infiltrate into the tracheobronchial nodes diminishes gradually. Combined prophylaxis with penicillin and serum does not influence the rate of clearance of the spores from the lung or their infilatration into the trachebronchial nodes, but inhibits their proliferation there. The delay in the death of infected guinea-pigs after this treatment is related to the relatively large number of spores surviving in the tracheobronchial nodes rather than to their actual number in the lungs.     

Molecular organization of the intestinal brush border

The brush border of enterocytes represents one of the more specialized apical poles of epithelial cells. It is formed by particularly well-developed apical plasma membrane microvilli, whose shape is ensured by a highly organized cytoskeleton. The molecular organization of the cytoskeleton is described. Whereas several cytoskeleton proteins are ubiquitous, villin is highly specific for intestinal cells and can be used as a differentiation marker of these cells. The major glycoproteins, in particular hydrolases, of the brush border membrane have been characterized. They have many common structural features, in particular their mode of integration into the membrane by their N-terminal hydrophobic sequences that also plays the role of the 'signal peptide' responsible for their co-translational insertions into the endoplasmic reticulum. Studies on the biosynthesis and intracellular pathway of aminopeptidase N strongly suggest that sorting of apical and basolateral glycoproteins could occur after their integration into the basolateral domain.     

Geometric control of the cell cycle

How do cells sense their own size and shape? And how does this information regulate progression of the cell cycle? Our group, in parallel to that of Paul Nurse, have recently demonstrated that fission yeast cells use a novel geometry-sensing mechanism to couple cell length perception with entry into mitosis. These rod-shaped cells measure their own length by using a medially-placed sensor, Cdr2, that reads a protein gradient emanating from cell tips, Pom1, to control entry into mitosis. Budding yeast cells use a similar molecular sensor to delay entry into mitosis in response to defects in bud morphogenesis. Metazoan cells also modulate cell proliferation in response to their own shape by sensing tension. Here I discuss the recent results obtained for the fission yeast system and compare them to the strategies used by these other organisms to perceive their own morphology.     

Drosophila germline invasion by the endogenous retrovirus gypsy: involvement of the viral env gene

The endogenous retrovirus gypsy is expressed at high levels in mutant flamenco female flies. Gypsy viral particles extracted from such flies can infect naive flamenco individuals raised in the presence of these extracts mixed into their food. This results in the integration of new proviruses into the germline genome. These proviruses can then increase their copy number by (1) expression in the flamenco female somatic cells, (2) transfer into the oocyte and (3) integration into the genome of the progeny. Surprisingly, unlike the infection observed in the feeding experiments, this strategy of endogenous proviral multiplication does not seem to involve the expression of the viral env gene.     

The role of the ileum in the control of food intake and intestinal adaptation

Studies on animals that drastically reduce their food intake after having a jejunoileal bypass or an ileal transposition surgery suggest that the lower ileum may play a major role in the control of daily food intake. In this study, eight rats were given slow continuous infusions of either 18, 28, or 38 mL of their normal liquid diet directly into their upper ileum. They reduced their daily intake in a compensatory way for the two smaller infusions and in a more than compensatory way for the large infusion. The later results suggests that the large infusion may have caused the rats some discomfort, which led to a lower food intake. This was tested in a conditioned aversion paradigm with an ileal infusion of 26 mL of the diet into eight naive rats. These rats showed a strong aversion to the ileal infusion. Infusion of the same amount of diet into the stomach of eight other rats failed to demonstrate an aversion and showed that the procedures of the experiment did not produce the aversion. The infusion of relatively small amounts of liquid diet into the ileum produces an internal signal that reduces intake and is regulatory. A second process in which ileal infusion causes discomfort leads eventually to a more than regulatory decrease in daily intake.     

Theoretical approaches for understanding the self-organized formation of the Golgi apparatus

Eukaryotic cells fold their membranes into highly organized structures called membrane-bound organelles. Organelles display characteristic structures and perform specialized functions related to their structures. Focusing on the Golgi apparatus, we provide an overview of recent theoretical studies to explain the mechanism of the architecture of the Golgi apparatus. These studies are classified into two categories: those that use equilibrium models to describe the robust Golgi morphology and those that use non-equilibrium models to explain the stationarity of the Golgi structures and the constant streaming of membrane traffic. A combinational model of both categories was used for computational reconstruction of the de novo Golgi formation process, which might provide an insight into the integrated understanding of the Golgi structure.     

Iron-containing granules in the syncytiotrophoblast of the human chorionic villi

The syncytiotrophoblast of the human chorionic villi during earlier stages of gestation contains abundant granules derived from Golgi complexes. The granules often include very electron-dense lamellae in their interior, and X-ray microanalysis revealed the presence of iron in these lamellae. It is, therefore, supposed that iron particles absorbed into the syncytiotrophoblast are transported to Golgi complexes and integrated into these lamellae. No evidences that the granules are released from the cells by exocytosis have been proved. Thus, one possibility to their nature might be considered, that is they play a role in lysosomal storage of iron during earlier stages when the capillaries in the chorionic stroma are undeveloped and so have little ability to transport iron into the fetal circulation.     

Blood supply of the bed nucleus of the stria terminalis in rat

Summary The topographical distribution of the blood vessels in the bed nucleus of the stria terminalis (NIST) has been mapped in rats. Arteries and veins were visualized in red and blue by using a double-ink perfusion technique. Arteries supplying the NIST arise from the anterior cerebral artery directly or through the anterior communicating and interhemispheric arteries. Only a few, dorsal branches derive from the medial cerebral artery through thalamostriatal arteries. According to their terminal branches, NIST arteries can be divided into five groups: medial, ventral, lateral, septal and dorsal, which have only a relatively small overlap in their territories. About 90% of veins from the NIST drain into the major basal veins. Medial branches run into the perioptic and interhemispheric veins, while the ventral branches and the large lateral vein drain directly into the anterior cerebral vein. A small proportion of NIST veins run dorsalward into the vena cerebri magna via thalamostriatal veins.     

Habits of the Home: Spatial Hegemony and the Structuration of House and Society in Brazil

This article examines the relation between spatial structure and social practice in a Brazilian fishing town. The sociospatial division of the Brazilian house into rooms with distinct social functions and role relationships helps to define the domestic practices of the family members and socializes them into a conception of social interaction that influences their economic and public practices outside the home. However, the hegemony of this domestic sociospatial structure is not autonomous, but rather stands in dynamic interaction with the public and economic dimensions of the household's reproduction in society. A comparison between canoe fishermen and boat fishermen demonstrates that their different involvement in the economic and public domains of the town affects their interpretation of the architectural structure of the house and differentiates their domestic practices.     

Protein structure and import into the peroxisomal matrix

Proteins destined for the peroxisomal matrix are synthesized in the cytosol, and imported post-translationally. It has been previously demonstrated that stably folded proteins are substrates for peroxisomal import. Mammalian peroxisomes do not contain endogenous chaperone molecules. Therefore, it is possible that proteins are required to fold into their stable, tertiary conformation in order to be imported into the peroxisome. These investigations were undertaken to determine whether proteins rendered incapable of folding were also substrates for import into peroxisomes. Reduction of albumin resulted in a less compact tertiary structure as measured by analytical centrifugation. Microinjection of unfolded albumin molecules bearing the PTS1 targeting signal resulted in their import into peroxisomes. Kinetic analysis indicated that native and unfolded molecules were imported into peroxisomes at comparable rates. While import was unaffected by treatment with cycloheximide, hsc70 molecules were observed to be imported along with the unfolded albumin molecules. These results indicate that proteins, which are incapable of assuming their native conformation, are substrates for peroxisomal import. When combined with previous observations demonstrating the import of stably folded proteins, these results support the model that tertiary structure has no effect on protein import into the peroxisomal matrix .