Probing binding specificity of the sucrose transporter AtSUC2 with fluorescent coumarin glucosides.

The phloem sucrose transporter, AtSUC2, is promiscuous with respect to substrate recognition, transporting a range of glucosides in addition to sucrose, including naturally occurring coumarin glucosides. We used the inherent fluorescence of coumarin glucosides to probe the specificity of AtSUC2 for its substrates, and determined the structure-activity relationships that confer phloem transport in vivo using Arabidopsis seedlings. In addition to natural coumarin glucosides, we synthesized new compounds to identify key structural features that specify recognition by AtSUC2.

The RNA-editing enzyme ADAR1 controls innate immune responses to RNA.

The ADAR RNA-editing enzymes deaminate adenosine bases to inosines in cellular RNAs. Aberrant interferon expression occurs in patients in whom ADAR1 mutations cause Aicardi-Goutières syndrome (AGS) or dystonia arising from striatal neurodegeneration. Adar1 mutant mouse embryos show aberrant interferon induction and die by embryonic day E12.

Conflict RNA modification, host-parasite co-evolution, and the origins of DNA and DNA-binding proteins1.

Nearly 150 different enzymatically modified forms of the four canonical residues in RNA have been identified. For instance, enzymes of the ADAR (adenosine deaminase acting on RNA) family convert adenosine residues into inosine in cellular dsRNAs. Recent findings show that DNA endonuclease V enzymes have undergone an evolutionary transition from cleaving 3' to deoxyinosine in DNA and ssDNA to cleaving 3' to inosine in dsRNA and ssRNA in humans.

Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature.

Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) and thereby potentially alter the information content and structure of cellular RNAs. Notably, although the overwhelming majority of such editing events occur in transcripts derived from Alu repeat elements, the biological function of non-coding RNA editing remains uncertain. Here, we show that mutations in ADAR1 (also known as ADAR) cause the autoimmune disorder Aicardi-Goutières syndrome (AGS).

A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast centromeres.

A defining feature of centromeres is the presence of the histone H3 variant CENP-A(Cnp1). It is not known how CENP-A(Cnp1) is specifically delivered to, and assembled into, centromeric chromatin. Through a screen for factors involved in kinetochore integrity in fission yeast, we identified Sim3.

Effect of selenium supplementation on biochemical markers and outcome in critically ill patients.

Background & Aims: This study aimed to assess the effect of high dose selenium (Se) supplementation on Se status in blood, oxidative stress, thyroid function and possible effects on requirement for renal replacement therapy (RRT) in severely septic patients admitted to the intensive care unit (ICU).

Methods: This prospective single-centre study was carried out in 40 septic ICU patients who were randomized to high dose Se (Se+ group, N=18 (474, 316, 158 microg/day), each for 3 consecutive days followed by a standard dose of 31.6 microg/day of Se given as sodium selenite whereas the control group (Se-, N=22) received only the standard dose of Se.

HLA-DR regulation and the influence of GM-CSF on transcription, surface expression and shedding.

Low surface HLA-DR expression is a feature in sepsis. However, the mechanisms that regulate HLA-DR expression have not been elucidated. The current study investigates regulation of HLA-DR gene transcription, post transcriptional events and shedding of surface HLA-DR, as well as the regulation of HLA-DR by GM-CSF and an immunomodulatory cytokine.

Methylation: lost in hydroxylation?

Methylation of histone tails is a key determinant in forming active and silent states of chromatin. Histone methylation was regarded as irreversible until the recent identification of a lysine-specific histone demethylase (LSD1), which acts specifically on mono- and dimethylated histone H3 lysine 4. Here, we propose that the fission yeast protein Epe1 is a putative histone demethylase that could act by oxidative demethylation.

Is low monocyte HLA-DR expression helpful to predict outcome in severe sepsis?

Objective: Low monocyte human leukocyte antigen-DR (HLA-DR) expression has been reported to be an indicator of poor survival in critically ill septic patients. We assessed its usefulness as a prognostic indicator in order to identify possible interventions to normalise HLA-DR expression in those patients with lowered monocyte HLA-DR.

Design: HLA-DR expression was measured on separated monocytes of septic patients, using flow cytometry, and HLA-DR upregulation was measured by the same techniques after ex vivo stimulation with granulocyte macrophage colony stimulating factor (GM-CSF).

Gelsolin domains 4-6 in active, actin-free conformation identifies sites of regulatory calcium ions.

Structural analysis of gelsolin domains 4-6 demonstrates that the two highest-affinity calcium ions that activate the molecule are in domains 5 and 6, one in each. An additional calcium site in domain 4 depends on subsequent actin binding and is seen only in the complex. The uncomplexed structure is primed to bind actin.

Low plasma granulocyte-macrophage colony stimulating factor is an indicator of poor prognosis in sepsis.

Objective: Monocyte dysfunction has been shown to be associated with adverse consequences in septic patients. The cytokine growth factor granulocyte-macrophage colony stimulating factor (GM-CSF) may be required for optimal monocyte function in these patients. The current study investigates whether plasma GM-CSF levels were significantly different in septic patients and whether there was an association with prognosis.

Characterisation of heterogeneous solid surfaces by multiple probe, temperature-programmed inverse gas chromatography (IGC). A feasibility study.

A method is described for the characterisation of the surfaces of powdered solids by temperature programmed, multiple-probe, inverse gas chromatography. This modification of "traditional" inverse gas chromatography (IGC) allows rapid screening of solid surfaces to compare the adsorptive behaviour of pairs or sets of surfaces. This feasibility study examined the criteria for selection of a suitable probe set and approaches to the analysis and interpretation of the data generated.