Orthologous gene-expression profiling in multi-species models: search for candidate genes

Microarray-driven gene-expression profiles are generally produced and analyzed for a single specific experimental model. We have assessed an analytical approach that simultaneously evaluates multi-species experimental models within a particular biological condition using orthologous genes as linkers for the various Affymetrix microarray platforms on multi-species models of ventilator-associated lung injury. The results suggest that this approach may be a useful tool in the evaluation of biological processes of interest and selection of process-related candidate genes.     

Physiological Heterothallism and Sexuality in Euascomycetes: A Partial History

Copyright 1998 Academic Press.     

Differential Effector Engagement by Oncogenic KRAS

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Leaf malformation during early development in Sorghum. Evidence for an embryonic developmental window

Salt adaptation was induced in two successive generations of Sorghum bicolor , and the germination of their seeds was compared. When germinated in the absence of NaCl, the progeny of adapted plants displayed a specific malformation at the first two leaves, which was never observed in progeny of control plants. The frequency of leaf malformation was enhanced in progeny of the second generation of adapted plants, indicating a cumulative influence of salt adaptation. When germinated in the presence of 75 m M NaCl, seedlings from seeds of salt-adapted plants never displayed the leaf malformation, whereas it was observed on seedlings from seeds of control plants germinated in the presence of 75 m M NaCl. The occurrence of leaf malformation was analyzed for progeny of 20 salt-adapted plants germinated in the absence of NaCl. The link with the reproductive characters of the parents indicates a strong parental control on the expression of the leaf malformation. A comparison with previous data relative to the leaf malformation in Sorghum suggests the existence of a developmental window which 'opens'during embryo morphogenesis. This enables the imprinting of the embryo by the parent's physiological environment. This conclusion is related to other data describing a long-term maternal influence in plants.     

Probabilistic base calling of Solexa sequencing data

Background  

Solexa/Illumina short-read ultra-high throughput DNA sequencing technology produces millions of short tags (up to 36 bases) by parallel sequencing-by-synthesis of DNA colonies. The processing and statistical analysis of such high-throughput data poses new challenges; currently a fair proportion of the tags are routinely discarded due to an inability to match them to a reference sequence, thereby reducing the effective throughput of the technology.     

Effects of high-frequency jet ventilation on arterial baroreflex regulation of heart rate

Fifteen anesthetized mechanically ventilated patients recovering from multiple trauma were studied to compare the effects of high-frequency jet ventilation (HFJV) and continuous positive-pressure ventilation (CPPV) on arterial baroreflex regulation of heart rate. Systolic arterial pressure and right atrial pressure were measured using indwelling catheters. Electrocardiogram (ECG) and mean airway pressure were continuously monitored. Lung volumes were measured using two linear differential transformers mounted on thoracic and abdominal belts. Baroreflex testing was performed by sequential intravenous bolus injections of phenylephrine (200 micrograms) and nitroglycerin (200 micrograms) to raise or lower systolic arterial pressure by 20-30 Torr. Baroreflex regulation of heart rate was expressed as the slope of the regression line between R-R interval of the ECG and systolic arterial pressure. In each mode of ventilation the ventilatory settings were chosen to control mean airway pressure and arterial PCO2 (PaCO2). In HFJV a tidal volume of 159 +/- 61 ml was administered at a frequency of 320 +/- 104 breaths/min, whereas in CPPV a tidal volume of 702 +/- 201 ml was administered at a frequency of 13 +/- 2 breaths/min. Control values of systolic arterial pressure, R-R interval, mean pulmonary volume above apneic functional residual capacity, end-expiratory pulmonary volume, right atrial pressure, mean airway pressure, PaCO2, pH, PaO2, and temperature before injection of phenylephrine or nitroglycerin were comparable in HFJV and CPPV. Baroreflex regulation of heart rate after nitroglycerin injection was significantly higher in HFJV (4.1 +/- 2.8 ms/Torr) than in CPPV (1.96 +/- 1.23 ms/Torr).(ABSTRACT TRUNCATED AT 250 WORDS)     

Bending modes of DNA directly addressed by cryo-electron microscopy of DNA minicircles

We use cryo-electron microscopy (cryo-EM) to study the 3D shapes of 94-bp-long DNA minicircles and address the question of whether cyclization of such short DNA molecules necessitates the formation of sharp, localized kinks in DNA or whether the necessary bending can be redistributed and accomplished within the limits of the elastic, standard model of DNA flexibility. By comparing the shapes of covalently closed, nicked and gapped DNA minicircles, we conclude that 94-bp-long covalently closed and nicked DNA minicircles do not show sharp kinks while gapped DNA molecules, containing very flexible single-stranded regions, do show sharp kinks. We corroborate the results of cryo-EM studies by using Bal31 nuclease to probe for the existence of kinks in 94-bp-long minicircles.     

Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease

Background

Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD). Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogenesis.

Methods

The expression of TLR-2, TLR-4 and CD14 in monocytes was analyzed by flow cytometry. To study the functional responses of these receptors, monocytes were stimulated with peptidoglycan or lipopolysaccharide and the amounts of TNFα and IL-6 secreted were determined by ELISA.

Results

We found that the expression of TLR-2 was up-regulated in peripheral blood monocytes from COPD patients, either clinically stable or during AECOPD, as compared to never smokers or smokers with normal lung function. Upon stimulation with TLR-2 ligand monocytes from COPD patients secreted increased amounts of cytokines than similarly stimulated monocytes from never smokers and smokers. In contrast, the expressions of TLR-4 and CD14 were not significantly different between groups, and the response to lipopolysaccharide (a TLR-4 ligand) stimulation was not significantly different either. At discharge from hospital TLR-2 expression was down-regulated in peripheral blood monocytes from AECOPD patients. This could be due to the treatment with systemic steroids because, in vitro, steroids down-regulated TLR-2 expression in a dose-dependent manner. Finally, we demonstrated that IL-6, whose plasma levels are elevated in patients, up-regulated in vitro TLR-2 expression in monocytes from never smokers.

Conclusion

Our results reveal abnormalities in TLRs expression in COPD patients and highlight its potential relationship with systemic inflammation in these patients.

     

Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP

Negative regulation of mitogenic pathways is a fundamental process that remains poorly characterized. The angiotensin II AT2 receptor is a rare example of a 7-transmembrane domain receptor that negatively cross-talks with receptor tyrosine kinases to inhibit cell growth. In the present study, we report the molecular cloning of a novel protein, ATIP1 (AT2-interacting protein), which interacts with the C-terminal tail of the AT2 receptor, but not with those of other receptors such as angiotensin AT1, bradykinin BK2, and adrenergic beta(2) receptor. ATIP1 defines a family of at least four members that possess the same domain of interaction with the AT2 receptor, contain a large coiled-coil region, and are able to dimerize. Ectopic expression of ATIP1 in eukaryotic cells leads to inhibition of insulin, basic fibroblast growth factor, and epidermal growth factor-induced ERK2 activation and DNA synthesis, and attenuates insulin receptor autophosphorylation, in the same way as the AT2 receptor. The inhibitory effect of ATIP1 requires expression, but not ligand activation, of the AT2 receptor and is further increased in the presence of Ang II, indicating that ATIP1 cooperates with AT2 to transinactivate receptor tyrosine kinases. Our findings therefore identify ATIP1 as a novel early component of growth inhibitory signaling cascade.