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In the mammalian lung, an apparently homogenous mesh of capillary vessels surrounds each alveolus, forming the vast respiratory surface across which oxygen transfers to the blood.sup.1. Here we use single-cell analysis to elucidate the cell types, development, renewal and evolution of the alveolar capillary endothelium. We show that alveolar capillaries are mosaics; similar to the epithelium that lines the alveolus, the alveolar endothelium is made up of two intermingled cell types, with complex 'Swiss-cheese'-like morphologies and distinct functions. The first cell type, which we term the 'aerocyte', is specialized for gas exchange and the trafficking of leukocytes, and is unique to the lung. The other cell type, termed gCap ('general' capillary), is specialized to regulate vasomotor tone, and functions as a stem/progenitor cell in capillary homeostasis and repair. The two cell types develop from bipotent progenitors, mature gradually and are affected differently in disease and during ageing. This cell-type specialization is conserved between mouse and human lungs but is not found in alligator or turtle lungs, suggesting it arose during the evolution of the mammalian lung. The discovery of cell type specialization in alveolar capillaries transforms our understanding of the structure, function, regulation and maintenance of the air-blood barrier and gas exchange in health, disease and evolution. Single-cell analysis of blood vessels in the alveolus, the site of chronic disease and virus-induced lung injury, reveals two intermingled endothelial cell types with specialized gas exchange and stem cell functions., Author(s): Astrid Gillich [sup.1] [sup.2] [sup.3] , Fan Zhang [sup.3] , Colleen G. Farmer [sup.4] , Kyle J. Travaglini [sup.1] [sup.2] [sup.3] , Serena Y. Tan [sup.5] , Mingxia Gu [...]

The cell microenvironment, which is critical for stem cell maintenance, contains both cellular and non-cellular components, including secreted growth factors and the extracellular matrix.sup.1-3. Although Notch and other signalling pathways have previously been reported to regulate quiescence of stem cells.sup.4-9, the composition and source of molecules that maintain the stem cell niche remain largely unknown. Here we show that adult muscle satellite (stem) cells in mice produce extracellular matrix collagens to maintain quiescence in a cell-autonomous manner. Using chromatin immunoprecipitation followed by sequencing, we identified NOTCH1/RBPJ-bound regulatory elements adjacent to specific collagen genes, the expression of which is deregulated in Notch-mutant mice. Moreover, we show that Collagen V (COLV) produced by satellite cells is a critical component of the quiescent niche, as depletion of COLV by conditional deletion of the Col5a1 gene leads to anomalous cell cycle entry and gradual diminution of the stem cell pool. Notably, the interaction of COLV with satellite cells is mediated by the Calcitonin receptor, for which COLV acts as a surrogate local ligand. Systemic administration of a calcitonin derivative is sufficient to rescue the quiescence and self-renewal defects found in COLV-null satellite cells. This study reveals a Notch-COLV-Calcitonin receptor signalling cascade that maintains satellite cells in a quiescent state in a cell-autonomous fashion, and raises the possibility that similar reciprocal mechanisms act in diverse stem cell populations.Muscle stem cell quiescence in mice is maintained by a Notch-Collagen V-CALCR signalling pathway that is activated and sustained in a cell-autonomous fashion., Author(s): Meryem B. Baghdadi [sup.1] [sup.2] [sup.3] , David Castel [sup.4] [sup.5] , Léo Machado [sup.6] , So-ichiro Fukada [sup.7] , David E. Birk [sup.8] , Frederic Relaix [sup.6] , [...]

The p38 subgroup of the mitogen-activated protein kinase superfamily has four isoforms: p38[alpha], p38[beta], p38[delta] and p38[gamma]. Whereas p38[alpha] is involved in inflammation, proliferation, differentiation and apoptosis, the biological functions of p38[beta], p38[delta] and p38[gamma] are not understood completely. Many p38[alpha] inhibitors with diverse chemical structures and modes of protein interaction have been designed on the basis of their ability to compete with ATP for binding to p38[alpha]. Although some of these inhibitors show anti-inflammatory effects in animal models, they have repeatedly failed in clinical trials, highlighting the need for better approaches to inhibitor design. Here, we discuss alternative strategies that might lead to better p38 inhibitors, including non-ATP-competitive inhibitors and inhibitors that are targeted to other components of the signaling pathway.

The endothelial glycocalyx mediates interactions between the blood flow and the endothelium. This study aims to evaluate, quantitatively, effects of structural change of the glycocalyx on stress distribution and shear rate on endothelial cells. In the study, the endothelial glycocalyx is modeled as a surface layer of fiber matrix and when exposed to laminar shear flow, the matrix deforms. Fluid velocity and stress distribution inside the matrix and on cell membranes are studied based on a binary mixture theory. Parameters, such as the height and porosity of the matrix and the drag coefficient between fluid and matrix fibrils, are based on available data and estimation from experiments. Simple theoretical solutions are achieved for fluid velocity and stress distribution in the surface matrix. Degradation of the matrix, e.g., by enzyme digestion, is represented by reductions in the volume fraction of fibrils, height, and drag coefficient. From a force balance, total stress on endothelial surface remains constant regardless of structural alteration of the glycocalyx. However, the stress that is transmitted to endothelial cells by direct 'pulling' of fiber branches of the glycocalyx is reduced significantly. Fluid shear rate at the cell membrane, on the other hand, increases. The study gives quantitative insight into the effect of the structural change of the glycocalyx on the shear rate and pulling stress on the endothelium. Results can be used to interpret experiments on effects of the glycocalyx in shear induced endothelial responses. [DOI: 10.1115/1.2720909]

In recent years, the quartz crystal microbalance (QCM) has been established as a sensitive analytical tool to monitor the attachment and spreading of mammalian cells to in vitro surfaces. Due to its superior time resolution, the device is capable of reading even subtle differences in cell adhesion kinetics. However, thickness shear mode piezoresonators, which are the core component of the QCM approach, can be used not only as a sensor but also as an actuator when the oscillation amplitude of the crystal is increased so that molecular recognition at the solid-liquid interface is disturbed. In this study, we have addressed the impact of elevated lateral oscillation amplitudes on the adhesion kinetics of three mammalian cell lines. We used AT-cut piezoresonators with a fundamental resonance frequency of 5 MHz, and the analytical readout was performed by impedance analysis. Formation of stable cell-substrate contacts is retarded or entirely blocked when the lateral oscillation amplitude (in the center of the resonator) exceeds values higher than 20 nm. Shear oscillations of similar amplitude were, however, not sufficient to displace attached cells from the surface. Moreover, the experimental data prove that the normal QCM readout with oscillation amplitudes smaller than 1 nm is, indeed, non-invasive with respect to mammalian cells.

Erythropoetin (EPO), a stimulator of erythropoiesis, was previously shown to stimulate angiogenesis and proliferation of endothelial cells. Here, we investigated and compared the influence of EPO on cell number, proliferation, apoptosis, migration, and differentiation of endothelial cells in intact mouse embryoid bodies (EB), isolated endothelial cells from EB (EBEC), and adult human endothelial progenitor cells (hEPC). EB were treated with EPO (0.5 U/ml) immediately after plating was completed (day 5+0) or 3 days later. EPO treatment was continued until days 5+3 or 5+6. Cultured EBEC were treated 3 days after being plated, and primary hEPC from young healthy adults were treated 5 days after being plated with EPO for 48 h. Immunohistochemistry was performed with anti-PECAM (CD31), anti-Ki67, antiCD34, anti-CD133, anti-EphB4, and anti-ephrinB2 antibodies. In all, mouse EB and EBEC and hEPC, EPO-treatment resulted in increased number of endothelial cells, increased proliferation, decreased apoptosis, and enhanced migration. In EB, this EPO effect was most pronounced when treatment was begun early (day 5+0) and was accompanied by an enhanced endothelial tube formation. In EBEC and hEPC, EPO shifted the phenotypic differentiation toward an increased ratio of EphB4-positive cells, i.e., toward a venous phenotype. These results are consistent with an important role of EPO for the number, proliferation, apoptosis, function, and phenotypical development of immature endothelial cells, which persists from early development through adulthood. They provide additional and further evidence for a strong interrelation between hematopoiesis and vasculogenesis/angiogenesis (sharing the same pathways), which may be important in many physiological and pathophysiological conditions. embryoid body; endothelial cells; endothelial progenitor cells; mononuclear cells

A major open question of systems biology is how genetic and molecular components interact to create phenotypes at the cellular level. Although much recent effort has been dedicated to inferring effective regulatory influences within small networks of genes, the power of microarray bioinformatics has yet to be used to determine functional influences at the cellular level. In all cases of data-driven parameter estimation, the number of model parameters estimable from a set of data is strictly limited by the size of that set. Rather than infer parameters describing the detailed interactions of just a few genes, we chose a larger-scale investigation so that the cumulative effects of all gene interactions could be analyzed to identify the dynamics of cellular-level function. By aggregating genes into large groups with related behaviors (megamodules), we were able to determine the effective aggregate regulatory influences among 12 major gene groups in murine B lymphocytes over a variety of time steps. Intriguing observations about the behavior of cells at this high level of abstraction include: (i) a medium-term critical global transcriptional dependence on ATP-generating genes in the mitochondria, (ii) a longer-term dependence on glycolytic genes, (iii) the dual role of chromatin-reorganizing genes in transcriptional activation and repression, (iv) homeostasis-favoring influences, (v) the indication that, as a group, G protein-mediated signals are not concentration-dependent in their influence on target gene expression, and (vi) short-term-activating/long-term-repressing behavior of the cell-cycle system that reflects its oscillatory behavior. module | network

The interaction of cells with the extracellular matrix (ECM) form of fibronectin (FN) triggers changes in growth, migration, and cytoskeletal organization that differ from those generated by soluble FN. As cells deposit and remodel their FN matrix, the exposure of new epitopes may serve to initiate responses unique to matrix FN. To determine whether a matricryptic site within the III1 module of FN modulates cell growth or cytoskeletal organization, a recombinant FN with properties of matrix FN was constructed by directly linking the cryptic, heparin-binding COOH-terminal fragment of III1 (III1H) to the integrin-binding III8-10 modules (glutathione-S-transferase [GST]-III1 H,8-10). GST-III1 H,8-10 specifically stimulated increases in cell growth and contractility; integrin ligation alone was ineffective. A construct lacking the integrin-binding domain (GST-III1H,2-4) retained the ability to stimulate cell contraction, but was unable to stimulate cell growth. Both GST-III1H,2-4 and matrix FN colocalized with caveolin and fractionated with low-density membrane complexes by a mechanism that required heparan sulfate proteoglycans. Disruption of caveolae inhibited the FN- and III1H-mediated increases in cell contraction and growth. These data suggest that a portion of ECM FN partitions into lipid rafts and differentially regulates cytoskeletal organization and growth, in part, through the exposure of a neoepitope within the conformationally labile III1 module.

The development of an optical channel, a new analytical technique for evaluating the elasticity of biological cells, is described in this study. Two types of erythrocyte cells, i.e., young and old cells, were examined via their introduction into a flowing medium, to which a laser beam was focused in the opposite direction. An erythrocyte cell is trapped in a laser beam by a gradient force, moves in the downstream direction, and is then elongated at the beam waist. The change in shape was measured directly using a microscope equipped with a charge-coupled-device camera. It is probable the main driving force for the cell deformation is a shear stress generated by a medium flow, since an estimate of the gradient force suggests that it is too small to change the shape of an erythrocyte. The average values of the elongation of young and old cells were 2.4 [+ or -] 0.6 and 2.1 [+ or -] 0.5, respectively. These values are in reasonably good agreement with values obtained using a rheoscope method. The deformation was measured without any physical contact to the solid surface, and therefore, damage to cells such as these are minimal.

Research has been conducted on PDC-109, the main component of bovine seminal plasma. The examination of the binding effect of PDC-109 to membranes on the lipid phase structure and physical properties has been conducted.

Results indicate that application of high pressure on the beer spoiling bacteria Lactobacillus plantarum TMW1.460, causes sublethal injury to 99.99% of cells at exponential inactivation phase. Data show that injured cells are metabolically active and partially viable with damaged membranes.

The DNA ligase requirement during nucleotide excision repair (NER) and base excision repair (BER) of the yeast S. cerevisiae was determined via a cell-free system. Cells response to DNA damage induced by radiation and many chemicals through excision repair of DNA. NER and BER are the two major excision repair pathways in eukaryote. These repair pathways are completed by a DNA ligation step. The results revealed that the Cdc9 protein catalyzes the ligation step of excision repair in yeast cell-free extracts.

A study was conducted to examine the functions of interferon (INF)-alpha and INF-beta in cell pathology. Double-antibody radioimmunoassay was carried out to obtain insulin concentrations in cell-conditioned channels and acid-ethanol cell extracts while beta-TC6-F7 cultures were treated with cytokines for insulin production studies. Results suggested that the local expression of INF-alpha in islet may influence insulitis.

When demand for cholesterol rises in mammalian cells, the sterol regulatory element (SRE) binding proteins (SREBPs) are released from their membrane anchor through proteolysis. Then, the N-terminal region enters the nucleus and activates genes of cholesterol uptake and biosynthesis. Basic helix-loop-helix (bHLH) proteins such as SREBPs bind to a palindromic DNA sequence called the E-box (5[prime]-CANNTG-3[prime]). However, SREBPs are special because they also bind direct repeat elements called SREs. Importantly, sterol regulation of all promoters studied thus far is mediated by SREBP binding only to SREs. To study the reason for this we converted the direct repeat SRE from the sterol-regulated low-density lipoprotein receptor promoter into an E-box. In this report we show that SREBPs are still able to bind and activate this promoter however, sterol regulation is lost. The results are consistent with the mutant promoter being a target for promiscuous activation by constitutively expressed E-box binding bHLH proteins that are not regulated by cholesterol. Kim and coworkers [Kim, J. B., Spotts, G. D., Halvorsen, Y.-D., Shih, H.-M., Ellenberger, T., Towle, H. C. & Spiegelman, B. M. (1995) Mol. Cell. Biol. 15, 2582-2588] demonstrated that the dual DNA binding specificity of SREBPs is caused by a specific tyrosine in the conserved basic region of the DNA binding domain that corresponds to an arginine in all other bHLH proteins that recognize only E-boxes. Taken together the data suggest an evolutionary mechanism where a DNA binding protein along with its recognition site have coevolved to ensure maximal specificity and sensitivity in a crucial nutritional regulatory response.

Apurinic/apyrimidinic (AP) endonuclease (APE; EC 4.2.99.18) plays a central role in repair of DNA damage due to reactive oxygen species (ROS) because its DNA 3[prime]-phosphoesterase activity removes 3[prime] blocking groups in DNA that are generated by DNA glycosylase/AP-lyases during removal of oxidized bases and by direct ROS reaction with DNA. The major human APE (APE-1) gene is activated selectively by sublethal levels of a variety of ROS and ROS generators, including ionizing radiation, but not by other genotoxicants - e.g., UV light and alkylating agents. Increased expression of APE mRNA and protein was observed both in the HeLa S3 tumor line and in WI 38 primary fibroblasts, and it was accompanied by translocation of the endonuclease to the nucleus. ROS-treated cells showed a significant increase in resistance to the cytotoxicity of such ROS generators as [H.sub.2][O.sub.2] and bleomycin, but not to UV light. This 'adaptive response' appears to result from enhanced repair of cytotoxic DNA lesions due to an increased activity of APE-1, which may be limiting in the base excision repair process for ROS-induced toxic lesions.

Cell directional orientation or shape polarization is the first cellular step in neutrophil locomotion. To better understand how chemoattractants interact with cells, we studied neutrophil polarization (or shape changes) during exposure to a temporally decreasing chemoattractant signal of N-formyl-methionyl-leucyl-phenylalanine (FMLP) in the absence of a spatial concentration gradient. To accomplish this objective, we used a manifold of differing FMLP concentrations attached to a stopped-flow microscope chamber. Spatial gradients of a fluorescent chemotactic peptide could not be detected in the chamber by using microfluorometry. When FMLP was injected at continually increasing concentrations at 10-s intervals, the shape and relative direction of the neutrophil persisted. However, when temporally decreasing FMLP concentrations were injected, [approximately equal to]80% of the cells changed their direction with 44% of the total cells swinging about to 180 [degrees] [+ or -] 15 [degrees]. Most of these directional changes involved dissolution of both the lamellipodium and uropod and reformation of these structures 180 [degrees] from their original positions. This research suggests that neutrophils reverse their morphological polarity when exposed to temporally decreasing ligand concentrations by 'remembering' their ligand exposure history and relative direction.

Cell surface receptors that mediate endocytosis cluster into clathrin-coated pits, which pinch off to form vesicles that transport the receptors and their ligands. This multi-step process requires the coordinated action of many factors, including GTP-hydrolyzing proteins such as dynamin and regulators of actin cytoskeleton assembly. We note herein that sequestration of heterotrimeric G protein [Beta][Gamma], subunits in intact cells strongly inhibits clathrin-coated pit-mediated endocytosis and causes rearrangement of the actin cytoskeleton. Our results suggest that cells contain a pool of free [Beta][Gamma] and that it functions constitutively to permit endocytosis.

The AGLCL Epstein-Barr virus (EBV) growth-transformed cell line is incapable of inducing tumors in nude mice. When the cells were transfected with a 1.3-kb CATR1 antisense cDNA construct, progressively growing lymphomas could be induced in nude mice. Chromosome analysis of the parental, transfected, and tumor cells revealed that a chromosomal translocation t(8; 14)(q24.1; q32) had occurred in the transfected cells and was retained in cells derived from tumors. Moreover, enhanced c-myc expression, usually associated with this translocation, was either unchanged or under-expressed. These data suggest that the malignant transformation of the EBV growth-transformed cells was independent of c-myc expression and suggest that the CATR1 gene may act synergistically with the chromosomal translocation facilitating the conversion of AGLCL cells from a growth-transformed state to a malignant phenotype.

A study was conducted to examine the penetration and intracellular migration of a loligomer into eukaryotic cell lines to characterize the broadness and extent of their localization features. The loligomer was characterized by a five-amino acid, C-terminal region and eight identical N-terminal arms connected through a branched lysine polymer. Results indicated that the study construct can transfer large molecular entities, including plasmids.

Research was conducted to test whether the tumor suppressor gene product , p19(super Arf) hinders oncogenic transformation in primary cells and whether its role is abrogated when p53 is neutralized by viral oncoproteins and dominant-negative mutants. Cell cultures were monitored and maintained by calcium phosphate using the same amounts of DNA as in p53 degradation. Results showed high levels of genetic instability in p53 and that potent tumor suppressor activity resulted from the encoding of unrelated antioncogenic proteins with cooperating modes of action.

Research was conducted to test whether syntaxin 5 act as a common component of the fusion pathways that rebuild Golgi cisternae from mitotic Golgi fragments. Proteins were fractionated by SDS-PAGe and then transferred to nitrocellulose while several forms of recombinant syntaxin 5 were determined by compromising the cytoplasmic domain. Results indicated a role for the p47 cofactor on the p97 pathway and showed that p97/947 exists as a stable cytosolic complex.

A network of proposed linkages characterizes the relationship between chromatin structure and the regulation of transcription factors by RNA polymerase. The protein subunit complex is an integral and equimolar component of the mediator and holoenzyme of the RNA polymerase II complex and chromatin remodeling machines. A part of the RNA polymerase II functions as a large complex called RNA polymerase II holoenzyme while the core chromatin assembly reaction is mediated by a core histone chaperone and an ATP-utilizing chromatin assembly and remodeling factor.

The Hsp70 and Hsp60 chaperones recognize hydrophobic surface in the context of extended and collapsed conformations bounded by local enclosure of the chain or by global enclosure of the polypeptide in a central cavity. These chaperones are characterized by a set of abundant cellular machines that aid in protein folding processes and binding to nonnative proteins associated with the bacterial cytoplasmic homolog. Substrates undergo several cycles of binding and release at a stoichiometry of a single Hsp70 monomer per substrate molecule.

A quantitative device was developed to analyz the cellular and molecular mechanisms of mechanotransduction in relation to homogeneous equibiaxial strain in cultured cells. The practical experimental device that can produce equibiaxial strains of 0-10% is composed of a plating area and a multiwell device with seven 10-mm. diameter wells. The biocompatible device can be utilized in experiments that are characterized by multiple treatments, small sample sizes and conservation of reagents.

Two dimensional gel electrophoresis reveals that bacteria respond to a decrease in temperature with the introduction of a class of proteins called cold-induced proteins (CIPs). Three small acidic proteins show highest relative induction after a cold shock and belong to a class of proteins having CspB as one of its members. CspB affects the induction level of many CIPs. The CIPs present in B. subtilis have a broad spectrum of functional applications in cellular physiology.

Muller cells are the principal glial cells of the retina, assuming many of the functions carried out by astrocytes, oligodendrocytes and ependymal cells in other CNS regions. Muller cells express numerous voltage-gated channels and neurotransmitter receptors, which recognize a variety of neuronal signals and trigger cell depolarization and intracellular [Ca.sup.2+] waves. In turn, Muller cells modulate neuronal activity by regulating the extracellular concentration of neuroactive substances, including: (I) [K.sup.+], which is transported via Muller-cell spatial-buffering currents; (2) glutamate and GABA, which are taken up by Muller-cell high-affinity carriers; and (3) [H.sup.+], which is controlled by the action of Muller-cell [Na.sup.+]-HC[O.sub.[3.sup.-]] co-transport and carbonic anhydrase. The two-way communication between Muller cells and retinal neurons indicates that Muller cells play an active role in retinal function. Trends Neurosci. (1996) 19, 307-312

Adherens junctions assembly during Drosophila embryogenesis fails to take place when armadillo is absent. Drosophila armadillo is a homologue of vertebrate beta-catenin and is major part of the adherens junction protein complex. Lack of armadillo produces defects in cell-cell adhesion, as epithelial cells of the embryo lose adhesion, round up, and become mesenchymal. Mutation in cells causes loss of normal cell polarity. These alterations in the integrity of epithelia inhibit the morphogenetic movements of gastrulation.

Centrosome functioning and duplication in Drosophila embryos require normal cortical nuclei. The cortical cytoskeleton determines the orientation of centrosome separation, which takes place on a plane parallel to the plasma membrane. Free centrosomes do not form spindles. Their duplication, separation, and modulation of astral microtubules synchronizes with adjacent related centrosomes. Many abnormal nuclei withdraw into the interior after aphidicolin-treatment, while their centrosomes stay on the cortex. These centrosomes fail to show normal separation, duplication, and modulation.

The spatial and temporal dynamics of two intracellular second messengers, cAMP and [Ca.sup.2+], were simultaneously monitored in living cells by digital fluorescence ratio imaging using FICRhR, a single-excitation dual-emission cAMP indicator, and fura-2, a dual-excitation single-emission [Ca.sup.2+] probe. In single C6-2B glioma cells, isoproterenol- or forskolin-evoked cAMP accumulation (measured in vivo as an increased FICRhR emission ratio) was reduced when cytosolic free [Ca.sup.2+] concentration was elevated before, simultaneously with, or after cAMP activation. However, in REF-52 fibroblasts, [Ca.sup.2+] neither prevented nor reduced forskolin-stimulated cAMP production. These results provide novel in vivo evidence for the [Ca.sup.2+] modulation of the cAMP transduction pathway in C6-2B cells. The simultaneous microscopic measurement of cAMP and [Ca.sup.2+] kinetics in single cells makes it now possible to study the regulatory interactions between these second messengers at the cellular and even the subcellular level.

The signalling activity of cytokine receptors requires the association of the receptors with one or more members of a once obscure family termed the Janus kinases (JAKs). The JAK molecules link the binding of ligands to tyrosine phosphorylation of signalling proteins. The cytokine receptors stimulate signalling pathways using phosphotyrosine. The membrane-distal and the membrane-proximal regions of the receptors are necessary for signalling. The haematopoietic cell phosphatase inhibits the activity of these receptors while phosphatase Syp increases the activity.

Analysis of the ATP levels, fatty acid compositions and protein profiles during the transition from the spiral to the coccoid form of the Campylobacter jejuni, indicate that the cocci formation is not an effective process. The cocci formed at 4 degree centigrade and the spiral form participate in the contamination cycle of C. jejuni. At low temperatures the fatty acid composition of cocci and spiral forms are same, the levels of intracellular ATP are highest and there is no change in the protein profiles.

Single-channel measurements and noise analysis show that in volume-sensitive organic osmolyte/anion channel (VSOAC) current activation occurs by abrupt switching of single channels from an OFF state to an ON state. Increase in whole-cell anion current is due to an increase in the number of active channels in the cell membrane. Stationary noise analysis estimates of the unitary conductance of VSOAC can vary by nearly 15-fold.

A study in J-774 macrophages and fibroblasts of the effect of apoprotein E (apo E) on the cell intake of VLDL-size and IDL-size triacylglycerol-phospholipid emulsion particles reveals that cell intake of both size emulsion particles are enhanced by apo E. Cell intake of larger particles is greater than the intake of IDL-size particles. Particle intake in macrophages is greater than in fibroblasts. A non-receptor-mediated cell intake of VLDL-size and IDL-size particles is observed at physiological concentrations of triglyceride-rich particles.

The organic nitrates are interesting examples of drugs that undergo biotransformation at their site of action to generate the active form of the drug. Furthermore, tolerance to the vasodilator effects of organic nitrates is associated with impairment of this metabolic activation process. Despite considerable research effort, the intracellular processes and the chemical reaction pathways by which organic nitrates are converted to their active form are still unresolved. This review by Brian Bennett and colleagues summarizes the characteristics of organic-nitrate biotransformation in vascular smooth muscle, the difficulties encountered when assessing this biotransformation, and the evidence for the role of two identified vascular biotransformation systems (glutathione-S-transferases and the cytochrome P450 system) in the metabolic activation of organic nitrates.

The monoclonal antibody (mAB) GL3 specific for gamma/delta T cells is used to treat mice to explore the biological function of these cells. These cells are modulated in vivo by the anti-gamma/delta T-cell receptor monoclonal antibody GL3. alpha/beta T-cell reactivity is significantly affected by this modulation. Control of alpha/beta T-cell activation in vivo is influenced by gamma/delta T cells.

The ultrastructure of Candida albicans cells which can be stimulated to excrete extracellular proteinase (EPR) was examined. Electron microscopy using alkaline bismuth staining showed golgi-like bodies and secretory vesicles in the cells of the C. albicans. The number of these structures did not increase after EPR induction. The periphery of the induced cells were seen to sport several flocculent granules. Although, the location of the EPR is undefined, the EPR may probably be excreted through the constitutive secretory pathway.

Fab fragments of amyotrophic lateral sclerosis (ALS) immunoglobin G (IgG) influences the calcium channels of mammalian skeletal muscle that are sensitive to dihydropyridine (DHP). IgG fab fragments are synthesized from the sera or plasma of ALS patients and introduced into isolated rat skeletal muscle fibers in vitro. Peak voltage gated, calcium currents are decreased, but there is inconsiderable change in the peak calcium current kinetics. There is a change in the cell function due to direct interaction between antibodies from sera of ALS patients and voltage gated calcium channels.

Fluorescent tag can be affixed to proteins or genetic structures of interest. Fluorescent tag can be affixed to proteins or genetic structures of interest., Author Affiliations: DNA tags could help scientists to study ion channels (yellow), which allow specific ions to pass through the membrane of nerve cells (green). [see PDF for image] Credit: [...]

Byline: Gaurang. Gupta, Sharatchandra. Athanikar, Varadraj. Pai, Kikkeri. Naveen Introduction Giant cells are formed by fusion of various cells such as macrophage, epithelioid cells, monocytes, etc., These are multi-nucleated, [sup][1] [...]