The control of CD4<Superscript>+</Superscript>CD25<Superscript>+</Superscript>Foxp3<Superscript>+</Superscript>regulatory T cell survival

   

CD4⁺CD25⁺Foxp3⁺ regulatory T (T_reg) cells are believed to play an important role in suppressing autoimmunity and maintaining peripheral tolerance. How their survival is regulated in the periphery is less clear. Here we show that T_reg cells express receptors for gamma chain cytokines and are dependent on an exogenous supply of these cytokines to overcome cytokine withdrawal apoptosis in vitro. This result was validated in vivo by the accumulation of T_reg cells in Bim^-/- and Bcl-2 tg mice which have arrested cytokine deprivation apoptosis. We also found that CD25 and Foxp3 expression were down-regulated in the absence of these cytokines. CD25⁺ cells from Scurfy mice do not depend on cytokines for survival demonstrating that Foxp3 increases their dependence on cytokines by suppressing cytokine production in T_reg cells. Our study reveals that the survival of T_reg cells is strictly dependent on cytokines and cytokine producing cells because they do not produce cytokines. Our study thus, demonstrates that different gamma chain cytokines regulate T_reg homeostasis in the periphery by differentially regulating survival and proliferation. These findings may shed light on ways to manipulate T_reg cells that could be utilized for their therapeutic applications.     

Functional comparison of plasma-membrane Na<Superscript>+</Superscript>/H<Superscript>+</Superscript> antiporters from two pathogenic <Emphasis Type="Italic">Candida</Emphasis> species

Background  

The virulence of Candida species depends on many environmental conditions. Extracellular pH and concentration of alkali metal cations belong among important factors. Nevertheless, the contribution of transporters mediating the exchange of alkali metal cations for protons across the plasma membrane to the cell salt tolerance and other physiological properties of various Candida species has not been studied so far.     

Crystal structures of <Emphasis Type="Italic">Leptospira interrogans</Emphasis> FAD-containing ferredoxin-NADP<Superscript>+</Superscript> reductase and its complex with NADP<Superscript>+</Superscript>

Background  

Ferredoxin-NADP(H) reductases (FNRs) are flavoenzymes that catalyze the electron transfer between NADP(H) and the proteins ferredoxin or flavodoxin. A number of structural features distinguish plant and bacterial FNRs, one of which is the mode of the cofactor FAD binding. Leptospira interrogans is a spirochaete parasitic bacterium capable of infecting humans and mammals in general. Leptospira interrogans FNR (LepFNR) displays low sequence identity with plant (34% with Zea mays) and bacterial (31% with Escherichia coli) FNRs. However, LepFNR contains all consensus sequences that define the plastidic class FNRs.     

A link of Ca<Superscript>2+</Superscript> to cAMP oscillations in <Emphasis Type="Italic">Dictyostelium</Emphasis>: the calmodulin antagonist W-7 potentiates cAMP relay and transiently inhibits the acidic Ca<Superscript>2+</Superscript>-store

Background  

During early differentiation of Dictyostelium the attractant cAMP is released periodically to induce aggregation of the cells. Here we pursue the question whether pulsatile cAMP signaling is coupled to a basic Ca²⁺-oscillation.     

Analysis of a <Emphasis Type="Italic">c</Emphasis><Subscript>0</Subscript><Emphasis Type="Italic">t-1</Emphasis> library enables the targeted identification of minisatellite and satellite families in <Emphasis Type="Italic">Beta vulgaris</Emphasis>

Background  

Repetitive DNA is a major fraction of eukaryotic genomes and occurs particularly often in plants. Currently, the sequencing of the sugar beet (Beta vulgaris) genome is under way and knowledge of repetitive DNA sequences is critical for the genome annotation. We generated a c ₀ t-1 library, representing highly to moderately repetitive sequences, for the characterization of the major B. vulgaris repeat families. While highly abundant satellites are well-described, minisatellites are only poorly investigated in plants. Therefore, we focused on the identification and characterization of these tandemly repeated sequences.     

Disruption of actin filaments induces mitochondrial Ca<Superscript>2+</Superscript> release to the cytoplasm and [Ca<Superscript>2+</Superscript>]<Subscript>c</Subscript> changes in <Emphasis Type="Italic">Arabidopsis</Emphasis>root hairs

Background  

Mitochondria are dynamic organelles that move along actin filaments, and serve as calcium stores in plant cells. The positioning and dynamics of mitochondria depend on membrane-cytoskeleton interactions, but it is not clear whether microfilament cytoskeleton has a direct effect on mitochondrial function and Ca²⁺ storage. Therefore, we designed a series of experiments to clarify the effects of actin filaments on mitochondrial Ca²⁺ storage, cytoplasmic Ca²⁺ concentration ([Ca²⁺]_c), and the interaction between mitochondrial Ca²⁺ and cytoplasmic Ca²⁺ in Arabidopsis root hairs.     

Characterization of the metabolic shift between oxidative and fermentative growth in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> by comparative <Superscript>13</Superscript>C flux analysis

Background  

One of the most fascinating properties of the biotechnologically important organism Saccharomyces cerevisiae is its ability to perform simultaneous respiration and fermentation at high growth rate even under fully aerobic conditions. In the present work, this Crabtree effect called phenomenon was investigated in detail by comparative ¹³C metabolic flux analysis of S. cerevisiae growing under purely oxidative, respiro-fermentative and predominantly fermentative conditions.     

Regulatory role of E-NTPase/E-NTPDase in Ca<Superscript>2+</Superscript>/Mg<Superscript>2+</Superscript> transport via gated channel

Background  

E-NTPase/E-NTPDase is activated by millimolar concentrations of Ca²⁺ or Mg²⁺ with a pH optimum of 7.5 for the hydrolysis of extracellular NTP and NDP. It has been generally accepted that E-NTPase/E-NTPDase plays regulatory role in purinergic signalling, but other functions may yet be discovered.     

<Emphasis Type="Italic">In vivo</Emphasis> molecular imaging of experimental joint inflammation by combined <Superscript>18</Superscript>F-FDG positron emission tomography and computed tomography

Introduction  

The purpose of this work was to establish and validate combined small animal positron emission tomography - computed tomography (PET/CT) as a new in vivo imaging method for visualisation and quantification of joint inflammation.     

Proteomic screen in the simple metazoan <Emphasis Type="Italic">Hydra</Emphasis> identifies 14-3-3 binding proteins implicated in cellular metabolism,cytoskeletal organisation and Ca<Superscript>2+</Superscript> signalling

Background  

14-3-3 proteins have been implicated in many signalling mechanisms due to their interaction with Ser/Thr phosphorylated target proteins. They are evolutionarily well conserved in eukaryotic organisms from single celled protozoans and unicellular algae to plants and humans. A diverse array of target proteins has been found in higher plants and in human cell lines including proteins involved in cellular metabolism, apoptosis, cytoskeletal organisation, secretion and Ca²⁺ signalling.     

cAMP controls cytosolic Ca<Superscript>2+</Superscript> levels in <Emphasis Type="Italic">Dictyostelium discoideum</Emphasis>

Background  

Differentiating Dictyostelium discoideum amoebae respond upon cAMP-stimulation with an increase in the cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) that is composed of liberation of stored Ca²⁺ and extracellular Ca²⁺-influx. In this study we investigated whether intracellular cAMP is involved in the control of [Ca²⁺]_i.     

An ancient spliceosomal intron in the ribosomal protein L7a gene (<Emphasis Type="Italic">Rpl7a</Emphasis>) of <Emphasis Type="Italic">Giardia lamblia</Emphasis>

Background  

Only one spliceosomal-type intron has previously been identified in the unicellular eukaryotic parasite, Giardia lamblia (a diplomonad). This intron is only 35 nucleotides in length and is unusual in possessing a non-canonical 5' intron boundary sequence, CT, instead of GT.     

Identification and characterization of bovine regulator of telomere length elongation helicase gene (<Emphasis Type="Italic">RTEL</Emphasis>): molecular cloning,expression distribution,splice variants and DNA methylation profile

Background  

The genetic basis of telomere length heterogeneity among mammalian species is still not well understood. Recently, a gene named regulator of telomere length elongation helicase (RTEL) was identified and predicted to be an essential participant in species-specific telomere length regulation in two murine species. To obtain broader insights into its structure and biological functions and to ascertain whether RTEL is also a candidate gene in the regulation of telomere length diversity in other mammalian species, data from other mammals may be helpful.     

Crystal structure of nitrogen regulatory protein IIA<Superscript>Ntr</Superscript> from <Emphasis Type="Italic">Neisseria meningitidis</Emphasis>

Background  

The NMB0736 gene of Neisseria meningitidis serogroup B strain MC58 encodes the putative nitrogen regulatory protein, IIA^Ntr (abbreviated to NM-IIA^Ntr). The homologous protein present in Escherichia coli is implicated in the control of nitrogen assimilation. As part of a structural proteomics approach to the study of pathogenic Neisseria spp., we have selected this protein for structure determination by X-ray crystallography.     

Eukaryotic signaling pathways targeted by <Emphasis Type="Italic">Salmonella</Emphasis> effector protein AvrA in intestinal infection <Emphasis Type="Italic">in vivo</Emphasis>

Background  

The Salmonella AvrA gene is present in 80% of Salmonella enterica serovar strains. AvrA protein mimics the activities of some eukaryotic proteins and uses these activities to the pathogen's advantage by debilitating the target cells, such as intestinal epithelial cells. Therefore, it is important to understand how AvrA works in targeting eukaryotic signaling pathways in intestinal infection in vivo. In this study, we hypothesized that AvrA interacts with multiple stress pathways in eukaryotic cells to manipulate the host defense system. A whole genome approach combined with bioinformatics assays was used to investigate the in vivo genetic responses of the mouse colon to Salmonella with or without AvrA protein expression in the early stage (8 hours) and late stage (4 days). Specifically, we examined the gene expression profiles in mouse colon as it responded to pathogenic Salmonella stain SL1344 (with AvrA expression) or SB1117 (without AvrA expression).     

Identification of <Emphasis Type="Italic">Burkholderia mallei</Emphasis> and <Emphasis Type="Italic">Burkholderia pseudomallei</Emphasis> adhesins for human respiratory epithelial cells

Background  

Burkholderia pseudomallei and Burkholderia mallei cause the diseases melioidosis and glanders, respectively. A well-studied aspect of pathogenesis by these closely-related bacteria is their ability to invade and multiply within eukaryotic cells. In contrast, the means by which B. pseudomallei and B. mallei adhere to cells are poorly defined. The purpose of this study was to identify adherence factors expressed by these organisms.