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Dominique Joly

Publications and source records attributed to Dominique Joly.

At least 19 recordsLinked to original sources
PubMed2006

Male and female effects on sperm precedence in the giant sperm species Drosophila bifurca.

Sperm competition is expected to be a driving force in sexual selection. In internally fertilized organisms, it occurs when ejaculates from more than one male are present simultaneously within the female's reproductive tract. It has been suggested that greater sperm size may improve the competitive ability of sperm, but studies provide contradictory results depending on the species. More recently, the role of females in the evolution of sperm morphology has been pointed out. We investigate here the male and female effects that influence sperm precedence in the giant sperm species, Drosophila bifurca Patterson & Wheeler. Females were mated with two successive males, and the paternity outcomes for both males were analyzed after determining sperm transfer and storage. We found very high values of last male sperm precedence, suggesting a strong interaction between rival sperm. However, the data also indicate high frequencies of removal of the sperm of the first male from the female reproductive tract prior to any interaction with the second male. This implies that successful paternity depends mainly on successful sperm storage. Knowing what happens to the sperm within females appears to be a prerequisite for disentangling post-copulatory sexual interactions between males and females.

Animals↗
PubMed2006

Laminin 5 regulates polycystic kidney cell proliferation and cyst formation.

Renal cyst formation is the hallmark of autosomal dominant polycystic kidney disease (ADPKD). ADPKD cyst-lining cells have an increased proliferation rate and are surrounded by an abnormal extracellular matrix (ECM). We have previously shown that Laminin 5 (Ln-5, a alpha(3)beta(3)gamma(2) trimer) is aberrantly expressed in the pericystic ECM of ADPKD kidneys. We report that ADPKD cells in primary cultures produce and secrete Ln-5 that is incorporated to the pericystic ECM in an in vitro model of cystogenesis. In monolayers, purified Ln-5 induces ERK activation and proliferation of ADPKD cells, whereas upon epidermal growth factor stimulation blocking endogenously produced Ln-5 with anti-gamma(2) chain antibody reduces the sustained ERK activation and inhibits proliferation. In three-dimensional gel culture, addition of purified Ln-5 stimulates cell proliferation and cyst formation, whereas blocking endogenous Ln-5 strongly inhibits cyst formation. Ligation of alpha(6)beta(4) integrin, a major Ln-5 receptor aberrantly expressed by ADPKD cells, induces beta(4) integrin phosphorylation, ERK activation, cell proliferation, and cyst formation. These findings indicate that Ln-5 is an important regulator of ADPKD cell proliferation and cystogenesis and suggest that Ln-5 gamma(2) chain and Ln-5-alpha(6)beta(4) integrin interaction both contribute to these phenotypic changes.

Cell Line↗
PubMed2006

The polycystin 1-C-terminal fragment stimulates ERK-dependent spreading of renal epithelial cells.

Polycystin 1, the product of the PKD1 gene, is mutated in autosomal dominant polycystic kidney disease, a disease characterized by renal cyst formation and progressive renal failure. We show that expression of the C-terminal domain of human polycystin-1 (PKD1-CT) triggers spreading of isolated inner medullary collecting duct cells, a process mediated by Erk. As inner medullary collecting duct cells spread, PKD1-CT localizes to cell-extracellular matrix contacts, interacts with focal adhesion proteins Fak and paxillin, and stimulates Fak phosphorylation, paxillin phosphorylation, Fak-paxillin association, and formation of small focal complexes. PKD1-CT-mediated spreading requires membrane localization and the integrity of the C-terminal protein binding sites. We additionally show that Pkd1 null proximal tubule cells generated from Pkd1(flox/-):TSLargeT mice by in vitro Cre recombinase transfection demonstrate diminished spreading when compared with Pkd(flox/-) heterozygous parental cells. These findings suggest that membrane-bound PC1 has a central role in regulating morphogenic protein signaling at cell-matrix interfaces in non-confluent cells.

Animals↗
PubMed2006

[Continued late referral of patients with chronic kidney disease. Causes, consequences, and approaches to improvement].

OBJECTIVES: Efforts in recent years have aimed at increasing physicians' awareness of the frequent and harmful consequences of late referral to nephrologists of patients with chronic kidney disease (CKD), shown in repeated concordant studies. We sought to determine whether these efforts have led to improved predialysis care of these patients. METHODS: This study included all 1391 consecutive patients who began maintenance dialysis at Necker Hospital between January 1989 and December 2000. We examined baseline data and outcomes and determined for four three-year periods the percentage of patients who received early specialized care (at least 6 months before onset of dialysis). RESULTS: Late referral (<6 months before dialysis) did not change significantly over the four periods, remaining around 30%, even during the most recent period (1998-2000). Clinical condition and laboratory indicators of patients referred early but not those referred late improved in the latest period, compared with the initial period (1989-1991). Overall, prevalence of major cardiovascular events (myocardial or cerebral infarction, peripheral arteriopathy, or heart failure) was more than twice as high in patients who received nephrologic care for less than 6 months and nearly twice as high even in those followed 6-35 months than in patients followed for at least 36 months before beginning dialysis. Subsequent mortality after maintenance dialysis was also significantly higher in patients with late referral than in those followed at least 3 years before dialysis. Multivariate Cox proportional model analysis identified graded duration of predialysis nephrologic care as a significant independent factor predictive of risk of mortality while on dialysis. CONCLUSION: Late referral of CKD patients for specialist care remains frequent, around 30%, although it is most often unjustified. Late referral deprives the patient of early implementation of a reno- and cardioprotective therapeutic strategy that reduces cardiovascular comorbidity and mortality. Better coordinated cooperation between family doctors and nephrologists, through the implementation of regional healthcare networks, now appears as the most effective way to improve the care of CKD patients.

Acute Kidney Injury↗
PubMed2005

[Dialysis therapy for end stage renal disease in octogenarians].

End stage renal disease (ESRD) patients aged 80+ years raise the most difficult problems with respect to indication and dialysis therapy management because of the burden of heavy comorbidity, frequent cognitive disorders/and presumed short life expectancy. Some patients are withheld dialysis and follow a "conservative" treatment. However, most elderly patients are started on a chronic dialysis program and experience a substantial prolongation of life, with a satisfactory mental perception of the quality of life. Still, much remains to be done in this field: early nephrologic referral and psychosocial support should improve both the process of decision-making and the overall results of renal replacement therapy in this age group.

Aged, 80 and over↗
PubMed2005

[Nephrolithiasis-induced ESRD: frequency, causes and prevention].

Nephrolithiasis still remains a too frequent - and under-appreciated - cause of end-stage renal disease (ESRD), and this is all the most unfortunate since such an untoward course is now preventable in most cases. Among 1391 patients who started maintenance dialysis at Necker hospital between 1989 and 2000, nephrolithiasis was identified as the cause of ESRD in 45 of them, an overall prevalence of 3.2%. Infection stones accounted for 42.2% of cases, calcium stones for 26.7%, uric acid stones for 17.8% and hereditary diseases for 13.3%. The proportion of nephrolithiasis-associated ESRD declined from 4.7% to 2.2% from the 1989-1991 to the 1998-2000 period, as a result of the decreased incidence of ESRD in patients with infection and calcium nephrolithiasis. Based on our observations and on published reports, it emerges that most cases of nephrolithiasis-associated ESRD were due to sub-optimal management (especially in the case of infection or cystine stones) or to late (or erroneous) etiologic diagnosis, precluding early institution of appropriate therapeutic measures. In particular, several patients with primary hyperoxaluria or 2,8-dihydroxyadeninuria were diagnosed while already on dialysis or after unsuccessful kidney transplantation, due to wrong initial diagnosis. In conclusion, thanks to recent advances in diagnosis and management of stone formers, ESRD should now be prevented in the great majority of patients, at the condition of early etiologic diagnosis based on accurate morphoconstitutional analysis of calculi and metabolic evaluation, and early implementation of appropriate preventive medical treatment.

Diagnostic Errors↗
PubMed2005

Impaired formation of desmosomal junctions in ADPKD epithelia.

Mutations in polycystin-1 (PC-1) are responsible for autosomal dominant polycystic kidney disease (ADPKD), characterized by formation of fluid-filled tubular cysts. The PC-1 is a multifunctional protein essential for tubular differentiation and maturation found in desmosomal junctions of epithelial cells where its primary function is to mediate cell-cell adhesion. To address the impact of mutated PC-1 on intercellular adhesion, we have analyzed the structure/function of desmosomal junctions in primary cells derived from ADPKD cysts. Primary epithelial cells from normal kidney showed co-localization of PC-1 and desmosomal proteins at cell-cell contacts. A striking difference was seen in ADPKD cells, where PC-1 and desmosomal proteins were lost from the intercellular junction membrane, despite unchanged protein expression levels. Instead, punctate intracellular expression for PC-1 and desmosomal proteins was detected. The N-cadherin, but not E-cadherin was expressed in adherens junctions of ADPKD cells. These data together with co-sedimentation analysis demonstrate that, in the absence of functional PC-1, desmosomal junctions cannot be properly assembled and remain sequestered in cytoplasmic compartments. Taken together, our results demonstrate that PC-1 is crucial for formation of intercellular contacts. We propose that abnormal expression of PC-1 causes disregulation of cellular adhesion complexes leading to increased proliferation, loss of polarity and, ultimately, cystogenesis.

Cadherins↗
PubMed2005

Sexual selection and mating advantages in the giant sperm species, Drosophila bifurca.

Mate choice may be exercised by either sex; however, females are generally choosier than males because they invest more in their gametes. Female choice is often based on direct benefits, such as better reproductive output, whereas male choice appears to be based on differences in female fecundity. However, when gamete production is limited, sexual selection theories predict that mate choice will be decisive for reproductive success in both sexes. Here, we investigate how mating advantage is achieved in Drosophila bifurca, a giant sperm species in which both sexes produce only a few gametes. Our initial expectations were as follows: (1) females would discriminate against sperm-depleted males to avoid fertility cost; and (2) males would discriminate against inseminated females to reduce sperm competition and increase the assurance of paternity of individual gametes. Differences in courtship behaviors were analyzed with regard to the sexual maturity, which is reached after 22 days in males at 21 degrees C, and the reproductive history of both sexes (inseminated versus virgin for females, and sperm-depleted versus sperm-loaded for males). Our results show that: (1) sexual immaturity precludes mating in both sexes; (2) virgin females do not discriminate between sperm-loaded and sperm-depleted males, and (3) males mate preferentially with virgin females, because inseminated females fend off the male, which tended to bring male courtship to an end. Female remating was limited, but increased significantly when the first male was sperm-depleted. Contrary to our initial expectations, these findings suggest that male sperm depletion does not affect female mating preference, whereas the success of male courtship is driven by female behavior. The possibility that female remating was only promoted in response to low sperm transfer is discussed in relation to the gametic system of this species.

Animals↗
PubMed2004

Paxillin serves as an ERK-regulated scaffold for coordinating FAK and Rac activation in epithelial morphogenesis.

Activation of the hepatocyte growth factor (HGF) receptor in epithelial cells results in lamellipodia protrusion, spreading, migration, and tubule formation. We have previously reported that these morphogenic effects are dependent on MAPK activation at focal adhesions. In the present study we demonstrate that activated ERK phosphorylates paxillin on serine 83 and that mutation of this site eliminates HGF-stimulated increased association of paxillin and FAK in subconfluent cells. Failure to activate FAK at focal adhesions results in a loss of FAK-PI 3-kinase association and the marked reduction of Rac activation after HGF stimulation. Expression of paxillin mutants that disrupt ERK association or phosphorylation inhibits HGF-induced cell spreading, migration, and tubulogenesis. These data demonstrate that the paxillin-MAPK complex serves as a central regulator of HGF-stimulated FAK and Rac activation in the vicinity of focal adhesions, thus promoting the rapid focal adhesion turnover and lamellipodia extension that are required for migratory and tubulogenic responses.

Animals↗
PubMed2004

Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions.

von Hippel-Lindau (VHL) disease arises from mutations in the VHL gene and predisposes patients to develop a variety of tumors in different organs. In the kidney, single or multiple cysts and renal cell carcinomas (RCC) may occur. Both inter- and intrafamilial heterogeneity in clinical expression are well recognized. To identify VHL-dependent genetic factors, we investigated the renal phenotype in 274 individuals from 126 unrelated VHL families in whom 92 different VHL mutations were characterized. The incidence of renal involvement was increased in families with mutations leading to truncated protein (MLTP) or large rearrangement, as compared to families with missense changes (81 vs. 63%, respectively; P=0.03). In the latter group, we identified two mutation cluster regions (MCRs) associated with a high risk of harboring renal lesions: MCR-1 (codons 74-90) and MCR-2 (codons 130-136). In addition, the incidence of RCC was higher in families with MLTP than in families with missense changes (75 vs. 57%; P=0.04). Furthermore, mutations within MCR-1 but not MCR-2 conferred genetic susceptibility to develop RCC. Overall, our data argued for a substantial contribution of the genetic change in the VHL gene to susceptibility to renal phenotype in VHL patients.

Adult↗
PubMed2004

Sperm size evolution in Drosophila: inter- and intraspecific analysis.

Numerous reports were devoted to the variation of sperm length in relation to sperm competition amongst species. However, studies on intraspecific variations of sperm size are very scarce and the number of sperm measured, very limited. This paper investigates within-individual, between-individual and between-population variation of sperm length in the two cosmopolitan species, D. simulans and D. melanogaster. Sperm length distributions are completely discriminated against with these two species, with the mean values equal to 1.121 +/- 0.002 and 1.989 +/- 0.008 mm, respectively. Results of intraspecific variation show a contrasting pattern between the two species. The mode of sperm length distributions is much less variable in D. simulans than in D. melanogaster. The sperm size divergence is unaffected whenever the two species are in sympatry (tested at 'Evolution Canyon', Mount Carmel, Israel) or in allopatry, but the two species react differentially to abiotic local factors. D. melanogaster, in contrast to D. simulans, shows a clinal pattern in sperm size associated with drought. We discussed this pattern in relation to the potential role of sperm length in the ongoing process of non-random mating and incipient sympatric speciation observed in this locality in D. melanogaster.

Analysis of Variance↗
PubMed2004

Heat induced male sterility in Drosophila melanogaster: adaptive genetic variations among geographic populations and role of the Y chromosome.

We analyzed genetic variation among geographically diverse populations of Drosophila and showed that tropical flies are more tolerant than temperate ones to heat-induced male sterility, as assessed by the presence of both motile sperm and progeny production. In tropical populations, the temperature inducing 50% sterility (median threshold) is 1 degrees C above the value for temperate populations (30.4 vs. 29.4 degrees C). When transferred to a mild permissive temperature (21 degrees C), males recover fertility. Recovery time is proportional to pre-adult culture temperature. At these temperatures, recovery time is greater for temperate than for tropical populations. Crosses between a temperate and a tropical strain (F1, F2 and successive backcrosses) revealed that the Y chromosome was responsible for much of the geographic variation. Sterile males exhibited diverse abnormalities in the shape and position of sperm nuclei. However, impairment of the spermatid elongation seems to be the major factor responsible for sperm inviability. Heat-induced male sterility seems to be quite a general phenomenon in Drosophilid species and variation of threshold temperatures may be important for explaining their geographic distributions.

Adaptation, Physiological↗
PubMed2004

ESRD caused by nephrolithiasis: prevalence, mechanisms, and prevention.

BACKGROUND: The contribution of nephrolithiasis-related end-stage renal disease (ESRD) to patients requiring renal replacement therapy has never been specifically evaluated. METHODS: Of the entire cohort of 1,391 consecutive patients who started maintenance dialysis therapy at our nephrology department between January 1989 and December 2000, a total of 45 patients (21 men) had renal stone disease as the cause of ESRD and constitute the study material. Type and cause of renal stone disease was determined in the 45 patients, as well as the change in prevalence of nephrolithiasis-related ESRD with time during this 12-year period. RESULTS: The overall proportion of nephrolithiasis-related ESRD was 3.2%. Infection (struvite) stones accounted for 42.2%; calcium stones, 26.7%; uric acid nephrolithiasis, 17.8%; and hereditary diseases (including primary hyperoxaluria type 1 and cystinuria), 13.3% of cases. Women were predominant among patients with infection and calcium stones, whereas men were predominant among patients with uric acid or hereditary stone disease. The proportion of patients with nephrolithiasis-related ESRD decreased from 4.7% in the triennial period 1989 to 1991 to 2.2% in the most recent period, 1998 to 2000 ( P = 0.07). This tendency to a decreasing prevalence mainly was caused by a rarefaction of infection and calcium stones with time, whereas frequencies of uric acid and hereditary stone disease remained essentially unchanged. CONCLUSION: Severe forms of nephrolithiasis remain an underestimated cause of potentially avoidable ESRD and need for renal replacement therapy. These findings highlight the crucial importance of accurate stone analysis and metabolic evaluation to provide early diagnosis and proper therapy for conditions that may lead to ESRD through recurrent stone formation and/or parenchymal crystal infiltration.

Adult↗
PubMed2003

[Frequency of anaemia and indications for treatment with epoetin in chronic renal failure at the pre-dialysis stage].

OBJECTIVES: To determine the degree of anaemia corresponding to the decreasing levels of renal function in patients with chronic renal failure (CRF) and not yet on dialysis, and to assess the indications for treatment with recombinant erythropoeitin (epoetin). METHODS: We studied the relationship between haemoglobin (Hb) concentration and creatinine clearance (Ccr) in 403 consecutive patients with CRF regularly monitored in nephrology consultations between January 1 and June 30, 1999, and who received appropriate iron and vitamin supplementation. These patients were then followed-up until June 30, 2000 or until maintenance dialysis was initiated. RESULTS: There was a significant and close correlation between the degree of anaemia and renal dysfunction. An Hb value<11 g/dl (corresponding to the present threshold for the indication of epoetin) was observed in 62% of patients with creatinine levels>400 micromol/l and in 58% when Ccr was<20 ml/mn/1.73 m2. Whatever the level of CRF, the degree of anaemia was higher in the women than in the men. Among the 123 patients who had to start maintenance dialysis during the observation period, 85 (69%) were treated with epoetin before dialysis was started. CONCLUSION: In patients with CRF, clinically symptomatic anaemia is more frequent than imagined, and early treatment is required. Regular monitoring of Hb and iron levels is mandatory in order to allow patients to benefit from timely initiation of epoetin and thus prevent the development of disabling asthenia and other deleterious consequences of anaemia.

Adult↗
PubMed2003

Beta4 integrin and laminin 5 are aberrantly expressed in polycystic kidney disease: role in increased cell adhesion and migration.

Extracellular matrix alterations have been suggested to be part of the early events occurring in Autosomal Dominant Polycystic Kidney Disease (ADPKD), a disease characterized by formation of renal cysts and progressive renal failure. Here we report that cDNA array analysis identified beta(4) integrin aberrant expression in ADPKD cells. Furthermore, laminin 5 (Ln-5), the main alpha(6)beta(4) integrin ligand, was also found to be abnormally expressed in ADPKD. Studies performed with ADPKD cyst-lining epithelial cells (CC) by comparison with normal tubular cells indicate that integrin alpha(6)beta(4)-Ln-5 interactions are involved in cellular events of potential importance for cystogenesis: 1) laminin 5 is a preferential adhesion substrate for CC, mainly through alpha(6)beta(4) interaction, 2) CC increased haptotactic and chemotactic motility depends on the presence of Ln-5 and requires integrin alpha(3)beta(1) cooperation, and 3) CC haptotactic or chemotactic migration is specifically increased by mAb-mediated beta(4) integrin ligation, through an alpha(3)beta(1) integrin-dependent and independent pathway, respectively. These results highlight the role of Ln-5 and alpha(6)beta(4) integrin in adhesive and motility properties of cyst-lining epithelial cells, and further suggest that integrins and extracellular matrix modifications may be of general relevance to kidney epithelial cell cyst formation.

Adult↗
PubMed2003

The sperm roller: a modified testicular duct linked to giant sperm transport within the male reproductive tract.

The male reproductive tracts of Drosophila display considerable variation in the relative size of their components, notably of the testes, but there are few structural differences between species. Here we report a remarkable coiled structure separating the testes from the seminal vesicles in the giant sperm species Drosophila bifurca. This evolutionary novelty, known as the 'sperm roller', seems to be an exaggeration in the size of the testicular duct as revealed by light and electron microscopic observations. It consists of a tubular monocellular epithelium lying on the basal laminae and muscle and conjunctive cells. The lumen of the roller contains crypts. The apical membrane of the epithelial cells presents numerous long microvilli protruding into the lumen. The sperm roller structure is probably involved in managing sperm during their transit through the male genital tract, because sperm are seen in bundles at the base of the testis, whereas they are singly rolled up by the time they enter the seminal vesicles. The hypercoiling of the individual spermatozoon within the roller probably occurs as the result of an osmotic process produced by features of the epithelial wall and the dramatically increased exchange surface. This is the first report of a specialized device of this type in Drosophila or, more generally, in insects.

Animals↗
PubMed2003

Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis.

Activation of the hepatocyte growth factor (HGF) receptor c-met results in the regulation of cell-matrix interactions, including the MAPK-dependent stimulation of epithelial cell morphogenesis. In the present study we demonstrate that HGF stimulates the localization of ERK to sites of cell-matrix interactions and that this is mediated by the tyrosine phosphorylation-dependent association of inactive ERK and the focal adhesion complex protein paxillin. In addition, paxillin was found to associate with the upstream MAP kinases Raf and MEK, resulting in a complex that can mediate localized ERK activation. Mutation of the ERK binding site in paxillin prevented HGF-stimulated ERK-paxillin association and eliminated HGF-induced cell spreading and branching process formation. These experiments reveal that paxillin-dependent ERK activation at sites of cell-matrix interaction is critical for HGF-stimulated epithelial morphogenesis.

Animals↗