Answer to the comments of K. Dobbin, J. Shih and R. Simon on the paper 'Evaluation of the gene-specific dye-bias in cDNA microarray experiments'.
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Algorithms↗
Biomedical subjects
J Aubert
Publications and source records attributed to J Aubert.
Determination of the differentially expressed genes in microarray experiments using local FDR.
BACKGROUND: Thousands of genes in a genomewide data set are tested against some null hypothesis, for detecting differentially expressed genes in microarray experiments. The expected proportion of false positive genes in a set of genes, called the False Discovery Rate (FDR), has been proposed to measure the statistical significance of this set. Various procedures exist for controlling the FDR. However the threshold (generally 5%) is arbitrary and a specific measure associated with each gene would be worthwhile. RESULTS: Using process intensity estimation methods, we define and give estimates of the local FDR, which may be considered as the probability for a gene to be a false positive. After a global assessment rule controlling the false positive error, the local FDR is a valuable guideline for deciding wether a gene is differentially expressed. The interest of the method is illustrated on three well known data sets. A R routine for computing local FDR estimates from p-values is available at http://www.inapg.fr/ens_rech/mathinfo/recherche/mathematique/outil.html. CONCLUSIONS: The local FDR associated with each gene measures the probability that it is a false positive. It gives the opportunity to compute the FDR of any given group of clones (of the same gene) or genes pertaining to the same regulation network or the same chromosomic region.
Acute Disease↗
Evaluation of inverse methods and head models for EEG source localization using a human skull phantom.
We used a real-skull phantom head to investigate the performances of representative methods for EEG source localization when considering various head models. We describe several experiments using a montage with current sources located at multiple positions and orientations inside a human skull filled with a conductive medium. The robustness of selected methods based on distributed source models is evaluated as various solutions to the forward problem (from the sphere to the finite element method) are considered. Experimental results indicate that inverse methods using appropriate cortex-based source models are almost always able to locate the active source with excellent precision, with little or no spurious activity in close or distant regions, even when two sources are simultaneously active. Superior regularization schemes for solving the inverse problem can dramatically help the estimation of sparse and focal active zones, despite significant approximation of the head geometry and the conductivity properties of the head tissues. Realistic head models are necessary, though, to fit the data with a reasonable level of residual variance.
Electroencephalography↗
Activation of extracellular signal-regulated kinases and CREB/ATF-1 mediate the expression of CCAAT/enhancer binding proteins beta and -delta in preadipocytes.
The essential role of CCAAT/enhancer binding proteins (C/EBPs) beta and delta for adipocyte differentiation has been clearly established. In preadipocytes, their expression is up-regulated by the activation of leukemia inhibitory factor receptor (LIF-R) and prostacyclin receptor (IP-R) via the extracellular signal-regulated kinase (ERK) pathway and cAMP production, respectively. However, the molecular mechanisms by which LIF and prostacyclin-induced signals are propagated to the nucleus and the transcription factors mediating ERK and cAMP-induced C/EBP gene expression were unknown. Here we report that both pathways share cAMP responsive element binding protein/activation transcription factor 1 (CREB/ATF-1) as common downstream effectors. LIF-R and IP-R activation induced binding of CREB and/or ATF-1 to C/EBP promoters and CREB-dependent transcription. Expression of dominant negative forms of CREB dramatically reduced the LIF- and prostacyclin-stimulated C/EBP beta and C/EBP delta expression. Upon stimulation of the IP-R, the ERK pathway was activated in a PKA-dependent manner. ERK activation by the PKA pathway was not required for CREB/ATF-1 phosphorylation but rather was necessary for CREB-dependent up-regulation of C/EBPs expression. Our findings suggest that ERK activation is required for CREB transcriptional activity, possibly by recruitment of a coactivator.
Activating Transcription Factor 1↗
Measurements of peptide and nonpeptide secretory products from adipocytes.
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6-Ketoprostaglandin F1 alpha↗
Prostacyclin IP receptor up-regulates the early expression of C/EBPbeta and C/EBPdelta in preadipose cells.
Prostacyclin (PGI(2)) and its stable analogue carbacyclin (cPGI(2)) are known to trigger the protein kinase A pathway after binding to the cell surface IP receptor and to promote or enhance terminal differentiation of adipose precursor cells to adipose cells. The early expression of C/EBPbeta and C/EBPdelta is known to be critical for adipocyte differentiation in vitro as well as in vivo. We report herein that in Ob1771 and 3T3-F442A preadipose cells, activation of the IP receptor by specific agonists (PGI(2), cPGI(2) and BMY 45778) is sufficient to up-regulate rapidly the expression of C/EBPbeta and C/EBPdelta. Cyclic AMP-elevating agents are able to substitute for IP receptor agonists, in agreement with the coupling of IP receptor to adenylate cyclase. Consistent with the fact that PGI(2) is released from preadipose cells and behaves as a paracrine/autocrine effector of adipose cell differentiation, the present results favor a key role of prostacyclin by means of the IP receptor and its intracellular signaling pathway in eliciting the critical early expression of both transcription factors.
3T3 Cells↗
[Hybridization and introgression between "full-fledged species". The case of Parnassius apollo and P. phoebus].
Two butterfly species living in the Alps, Parnassius apollo and P. phoebus, frequently hybridize in certain localities of this region. The features of this phenomenon have been previously studied by biometry and starch gel electrophoresis, but some points remained obscure. We present them in a study combining results from cellulose acetate electrophoresis and wing pattern biometry with a determination of the mitochondrial haplotype by a PCR-RFLP analysis in a sample of butterflies from the southern French Alps. It was already known that the male hybrids are fecund and thus that interspecific gene exchange could take place via backcrosses with the parent species. In the present case, combining the identification of mtDNA with the analysis of nuclear genotypes allows us to demonstrate that hybridization can involve both sexes of both species. Moreover, it suggests that at least some female hybrids are not sterile. The impact of Haldane's rule is therefore not very strong in the present case. However, although the prerequisites for introgression between the concerned species are fulfilled, at the level of both nuclear and mitochondrial genomes, no indication of such a phenomenon could be gathered in the studied sample.
Animals↗
Familial ureteral duplication and ureterocele: two sisters and their father.
We studied a family in which the father and his two daughters had ureteroceles involving the upper half of a duplex system. Our report gives additional evidence for the genetic background of ureteroceles.
Adult↗
[Schwannoma of the obturator nerve with urologic manifestations: report of a case].
Peripheral nerve tumors, which are called schwannomas because they arise from nerve sheath Schwann cells, are rare tumors than can develop at any site in the body but involve the limbs in over 50% of cases. Only 13% of schwannomas arise in the trunk; about 3% of schwannomas are retroperitoneal, and about 4% of retroperitoneal tumors are schwannomas. Pelvic schwannomas are equally uncommon and can develop in a broad range of structures. The most common presenting manifestation is a very large space-occupying lesion responsible for compression of neighboring organs. Excision of the tumor is often extremely difficult or impossible. Although obturator nerve schwannomas are exceedingly rare, their paravesical location is suggestive of he diagnosis. Computed tomography and magnetic resonance imaging are the most useful investigations, although they cannot determine the exact nature of the tumor. During surgery, every effort should be made to preserve the integrity of the nerve, although this is not always possible; obturator nerve injury does not seem associated with severe impairments.
Humans↗
[Impact of genital prolapse on the upper urinary tract].
UNLABELLED: The authors reviewed five cases of genital prolapse affecting the upper urinary tract and causing renal failure. CLINICAL CASES: Five patients aged 55 to 75 years presented with genital prolapse, which was known by the patient in 3 cases for a period of 2 to 30 year, but left untreated. All cases had induced bilateral dilatation of the uretero-pyelocaliceal cavities with severe obstructive renal failure in 3 cases, moderate renal failure in 2 cases and associated with hypertension in 2 cases. Repair of prolapse, preceded by upper urinary tract diversion by ureteric and bladder catheters in 3 cases or pessary + bladder catheter because of the patient's age in 2 cases, cured or improved renal failure in 4 patients; only one patient had to be treated by dialysis because of the severity of the residual renal failure severity. DISCUSSION: The frequency (4%) of aetiopathogenic mechanisms (ureteric compression, progressive stretching of the ureter and posterior tilting of the trigone) are analysed. The delayed onset of sudden deterioration and the varying degrees of severity of renal failure demand emergency treatment of stage III prolapse with primary diversion of the upper urinary tract, currently by double J stents, until correction or improvement of renal function, after which surgical repair of the prolapse can be performed according to the usual surgical rules. Intravenous urography is still indicated in this situation. Palliative treatment is only indicated in elderly patients or patients with a high operative risk. The best treatment remains prevention by detection and treatment of prolapse before the development of this fortunately rare complication. CONCLUSION: This short clinical series emphasizes that undiagnosed prolapse can still be complicated by repercussions on the upper urinary tract with a risk of renal failure.
Aged↗
Role of pathways for signal transducers and activators of transcription, and mitogen-activated protein kinase in adipocyte differentiation.
Members of the signal transducer and activator of transcription (STAT) family and the mitogen-activated protein kinase (MAPK) cascade play a major role in the regulation of cell growth and differentiation. This review concentrates on the role played by these pathways in the development of adipose cells. STATs are activated by both positive and negative modulators of adipocyte differentiation leading to the hypothesis that the STAT pathway may function in adipogenesis. The role of the p42/p44 MAPK pathway in adipocyte differentiation has recently been the subject of contradictory reports. Several molecular mechanisms are proposed to explain the opposing effects of MAPK activation in the programme of adipose cell differentiation.
Adipocytes↗
Leukemia inhibitory factor and its receptor promote adipocyte differentiation via the mitogen-activated protein kinase cascade.
Extracellular factors and intracellular signaling pathways involved in early events of adipocyte differentiation are poorly defined. It is shown herein that expression of leukemia inhibitory factor (LIF) and LIF receptor is developmentally regulated during adipocyte differentiation. Preadipocytes secrete bioactive LIF, and an antagonist of LIF receptor inhibits adipogenesis. Genetically modified embryonic stem (ES) cells combined with culture conditions to commit stem cells into the adipocyte lineage were used to examine the requirement of LIF receptor during in vitro development of adipose cells. The capacity of embryoid bodies derived from lifr(-/-) ES cells to undergo adipocyte differentiation is dramatically reduced. LIF addition stimulates adipocyte differentiation of Ob1771 and 3T3-F442A preadipocytes and that of peroxisome proliferator-activated receptor gamma2 ligand-treated mouse embryonic fibroblasts. Expression of the early adipogenic transcription factors C/EBPbeta and C/EBPdelta is rapidly stimulated following exposure of preadipose cells to LIF. The selective inhibitors of mitogen-activated protein kinase kinase, i.e. PD98059 and U0126, inhibit LIF-induced C/EBP gene expression and prevent adipocyte differentiation induced by LIF. These results are in favor of a model that implicates stimulation of LIF receptor in the commitment of preadipocytes to undergo terminal differentiation by controlling the early expression of C/EBPbeta and C/EBPdelta genes via the mitogen-activated protein kinase cascade.
Adipocytes↗
Molecular phylogeny of swallowtail butterflies of the tribe Papilionini (Papilionidae, Lepidoptera).
Swallowtail butterflies of the tribe Papilionini number about 225 species and are currently used as model organisms in several research areas, including genetics, chemical ecology and phylogenetics of host plant utilization and mimicry, mechanisms of speciation, and conservation. We have inferred phylogenetic relationships for a sample of 18 species of the genus Papilio (sensu lato) and five outgroup taxa by sequencing two stretches of mitochondrial DNA that correspond to segments 12886-13370 and 12083-12545 of Drosophila melanogaster mitochondrial DNA and consist of sections of the genes for the large ribosomal RNA and subunit 1 of NADH-dehydrogenase. Our data support the monophyly of Papilio and, within it, of several traditionally recognized subgroups. Species belonging to groups that utilize primarily Rutaceae as larval foodplants form two clusters, corresponding to Old World and American taxa, respectively, while two previously recognized clades-of American and South Asian-Austronesian origin-whose members were known to feed mostly on Lauraceae and Magnoliaceae, are observed to form a clade. The sister group of Papilio is found to be the South Asian genus Meandrusa, which also happens to feed on Lauraceae. The latter plant family is therefore the probable larval host of the ancestor Papilio and the shift to Rutaceae (which four-fifths of extant Papilio species use as foodplants) is more likely to have occurred only after the initial diversification of the genus.
Animals↗
Symptom characteristics and the development of tolerance with time in patients with indwelling double-pigtail ureteric stents.
OBJECTIVE: To determine the symptoms of and factors predicting the tolerance to double-pigtail ureteric stents, and the development of tolerance with time. PATIENTS AND METHODS: The study included 39 patients (median age 49.0 years, range 26-74; 24 men and 15 women) who were treated in our department for ureteric obstruction caused by benign conditions, excluding pregnancy and associated open surgery. All patients received a polyether-urethane double-pigtail ureteric stent (7 F, 28 cm long). Tolerance to the procedure was assessed using a questionnaire and a 10-cm linear visual analogue scale (VAS) at 24 h and again one week after placement, and on the day before stent removal. RESULTS: From the end of the first week to before removal of the stent, fewer patients reported dysuria, haematuria and having recourse to painkillers than during the first week. However, analysis of variance for repeated measures showed no significant difference between the VAS scores for first day, the first week and the day before removal, either overall or stratified by gender (P=0.15). A factorial analysis of variance analysing the VAS score for the first week as a function of gender, age and type of occupation (sedentary or mobile occupation) showed a significant effect only for gender (P=0.005) and gender-age interaction (P=0. 02): VAS scores were higher in men and particularly in younger men. CONCLUSION: Almost all patients with short-term placement of indwelling double-pigtail ureteric stents have untoward symptoms. Although some symptoms, e.g. dysuria and haematuria, significantly improve with time, the general tolerance remains unchanged. Tolerance in men, and particular in younger men, was significantly poorer.
Adaptation, Physiological↗
BTA stat and BTA TRAK: A comparative evaluation of urine testing for the diagnosis of transitional cell carcinoma of the bladder.
OBJECTIVE: We compared the BTA (bladder tumor antigen) stat test with the BTA TRAK assay in patients highly suspicious of bladder cancer. METHODS: The BTA stat and the BTA TRAK tests are two immunoassays that detect human complement factor H related protein in urine, employing the same antibody pair. The BTA stat is a qualitative test which can be performed in a consultation setting. The BTA TRAK is a quantitative test that is performed in the laboratory. Consecutive patients highly suspicious of bladder cancer were included in this prospective blinded trial to assess the clinical performances of the two methods. RESULTS: A total of 81 patients were tested using BTA stat and BTA TRAK before cystoscopy. A tumor was identified in 49 patients. BTA TRAK (38/49 true-positive cases) was more sensitive than BTA stat (32/49) in detecting bladder cancer (p < 0.05). When considering the subgroups of bladder cancer by stage and grade, the difference remained significant for low-grade and low-stage tumors. There was no significant difference between BTA TRAK and BTA stat as regards specificity (20/32 and 23/32 true-negative cases, respectively; p = 0.2). CONCLUSION: BTA TRAK with a cutoff of 14 U/ml had a significantly higher sensitivity than BTA stat in the detection of low-grade and low-stage bladder cancer.
Aged↗
Glucocorticoids and insulin promote plasminogen activator inhibitor 1 production by human adipose tissue.
Plasminogen activator inhibitor 1 (PAI-1) is likely to play a role in vascular disease, primarily in subjects with android obesity. It has been demonstrated that PAI-1 is overexpressed in adipose tissue from obese subjects and that visceral adipose tissue produced more PAI-1 than subcutaneous fat. In the present study, the effect of insulin and glucocorticoids, which are key mediators of adipose tissue metabolism, was examined in relation to PAI-1 synthesis by human adipose tissue explants (HAT), collagenase isolated human adipocytes (IHA), cultured human stromal cells (cSC), and differentiated adipocytes from the murine clonal cell line 3T3-F442A. A significant increase in PAI-1 antigen release (1.5-fold) from HAT was detectable after 16 h of treatment with insulin concentrations of at least 10(-8) mol/l. This was associated with a PAI-1 mRNA increase. Concomitant addition of insulin (10(-8) mol/l) to forskolin (5 x 10(-5) mol/l) reversed the decrease in PAI-1 antigen caused by forskolin alone. No effect on PAI-1 antigen was observed when insulin was incubated with IHA or cSC. 3T3 F442A cells were sensitive to insulin with a four- and twofold increase in PAI-1 antigen and mRNA levels, respectively, after 16 h of stimulation with 10(-8) mol/l. Dexamethasone (DXM) significantly enhanced PAI-1 antigen and mRNA expression by HAT (1.5- and 2.5-fold increase, respectively) at concentrations of at least 10(-8) mol/l. A higher stimulation was observed with IHA (sevenfold increase) and with the differentiated 3T3 F442 cell line. Cortisol was found to be less potent than DXM. No effect was observed when glucocorticoids were incubated with cSC. Coincubation of HAT with insulin (10(-7) mol/l) and DXM (10(-7) mol/l) led to an additive effect on PAI-1 synthesis. These results support the hypothesis that PAI-1 expression in human adipose tissue is controlled by insulin and glucocorticoids and may help to explain the increase in plasma PAI-1 levels observed in patients with android obesity.
3T3 Cells↗
[Hemorrhagic complications during percutaneous nephrolithotomy. Retrospective studies of 772 cases].
OBJECTIVES: To evaluate the haemorrhagic complications of PCNL, to analyse their management and to identify predisposing factors. MATERIAL AND METHODS: Out of a series of 772 cases of PCNL, 18 patients developed severe haemorrhage requiring a haemostatis procedure (2.3%): 13 males and 5 females with a mean age of 57 years (38-79), and one case on a solitary kidney. The mean time to onset of haemorrhage was 18 days (--48 days). RESULTS: Three nephrectomies for haemostatis were performed at the beginning of our experience. Renal arteriography was performed in 15 patients and was abnormal in 13 patients, showing 3 arteriovenous fistulas, 8 false aneurysms, 3 arteriolar injuries. All these vascular abnormalities were successfully treated by highly selective embolization. In 2 cases, arteriography was normal with a spontaneously favourable course. Comparison of the 2 groups of PCNL, with haemorrhage versus without haemorrhage, failed to demonstrate any risk factors. CONCLUSION: Severe haemorrhage following PCNL is a rare complication, but impossible to predict. Selective embolization allows control of bleeding and currently constitutes the treatment of choice.
Adult↗
[Schwannoma and the urinary tract. Concerning a tumor of the obdurator nerve].
Peripheral nerve tumours, called schwannomas, because they are derived from cells of the Schwann sheath, are rare tumours that can involve any part of the body, but are essentially located on the limbs, which represent more than 50% of cases. Schwannomas of the trunk and especially pelvic schwannomas are even rarer. A tumour arising from the obturator nerve is exceptional, but its paravesical location can facilitate the diagnosis, as in this case. The complementary investigations most frequently performed are CT and MRI, although they are unable to define the exact nature of the tumour. Surgery must try to preserve continuity of the nerve, but that is not always possible and does not appear to have any major consequences in this site.
Humans↗