Direct and correlated responses to selection in two lines of rabbits selected for feed efficiency under ad libitum and restricted feeding: III. Digestion and excretion of nitrogen and minerals.

Two rabbit lines have been created to result in better feed efficiency: the ConsoResidual line was selected for a lower residual feed intake under ad libitum feeding, and the ADGrestrict line was selected for higher ADG under restricted feeding (-20% of ad libitum). The present study aimed to analyze the digestion and excretion of N and minerals from 29 to 63 d of age of these 2 lines compared with an unselected control line (G0) under 2 feeding levels (ad libitum or restricted). The ADGrestrict line had greater digestibility compared with G0 (+1.3% for OM and N; < 0.05), and the ConsoResidual line had intermediate values. There was no genetic line effect on the digestibility of N and P and on minerals concentrations (P, Zn, and Cu) in the feces and in the urine. The N balance was improved for the 2 selected lines (+5%; < 0.05), leading to a reduced N output through the feces (0.06 g/d compared with G0; < 0.001) and the urine (-0.07 g/d; < 0.05) and to an improved N retention ratio (+3% compared with G0). Over the whole fattening period (d 29-63), significant differences were observed among lines only when fed ad libitum, with 13% greater DM fecal output and 5% greater N fecal output for G0. The N excretion in urine was 2 g less in the 2 selected lines, leading to a reduction of total N release of 4.4 g (compared with G0). The P excretion in feces (12 g) or urine (0.1 g) did not differ among the 3 lines. Over the whole fattening period and for ad libitum-fed rabbits, the 5% improvement in feed efficiency ( < 0.01) for the 2 selected lines corresponded to 400 g less feed intake (-8%) and to 20 g less N intake. The fecal excretion of the ADGrestrict and ConsoResidual lines were reduced by 200 g DM ( < 0.01), corresponding to 417 g fresh matter and 5 g of N. The excretion in minerals (P, Zn, and Cu) was not affected by the line. The feeding level strongly reduced the fecal and urine outputs (-50 and -60%, respectively; < 0.001). Higher digestibility coefficients ( < 0.001) were found in restricted-fed rabbits for OM (+6%), N (+8%), and P (+11%). The N balance was substantially improved by the restriction, with 40% less total (feces + urine) N excretion ( < 0.001). The P balance was improved by the restriction (0.469 vs. 0.360). Over the fattening period, the P fecal output was 37% less (-6 g) with 24% less feed intake and the Zn and Cu outputs were reduced by 27 (-130 mg) and 29% (-30 mg), respectively.

Direct and correlated responses to selection in two lines of rabbits selected for feed efficiency under ad libitum and restricted feeding: I. Production traits and gut microbiota characteristics.

To get insights into selection criteria for feed efficiency, 2 rabbit lines have been created: the ConsoResidual line was selected for residual feed intake (RFI) with ad libitum feeding and the ADGrestrict line was selected for ADG under restricted feeding (-20% of voluntary intake). The first objective of this study was to evaluate, after 9 generations of selection, the direct and correlated responses to selection on production traits in the 2 lines for traits recorded during growth. Second, applying the 2 feeding conditions used for selection to both selected lines plus the control unselected line (generation 0, G0) in a 2 × 3 factorial trial, the line performances were compared and the gut microbiota of the lines was characterized. The correlated responses in feed conversion ratio (FCR) were remarkably equivalent in both selected lines (-2.74 genetic σ) but correlated responses in other traits were notably different. In the ConsoResidual line, selection for decreased RFI resulted in a small negative correlated response in BW at 63 d old (BW63) and in a null response in ADG. In the ADGrestrict line, on the contrary, the correlated response in BW63 was substantial (+1.59 σ). The 2 selected lines had a FCR reduced by 0.2 point compared with the G0 line, and the same difference was found in both feeding regimens ( < 0.001). Indeed, selection on ADG would lead to heavier animals with no significant reduction of feed costs, whereas selection on RFI leads to lower feed costs and no increase of animal BW under ad libitum feeding. Altogether, our results do not suggest any genotype × environment interaction in the response to feeding regimens. The intestinal microbial communities from efficient rabbits differed from their unselected counterparts in terms of fermentation end products and microbial phylotypes, suggesting a central role of these microbes in the better feed efficiency of the rabbits.

Direct and correlated responses to selection in two lines of rabbits selected for feed efficiency under ad libitum and restricted feeding: II. Carcass and meat quality.

To get insights into selection criteria for feed efficiency, 2 rabbit lines have been created: the ConsoResidual line was selected for residual feed intake (RFI) with ad libitum feeding and the ADGrestrict line was selected for ADG under restricted feeding. The aim of the present study was to evaluate the impact on carcass and meat quality of the genetic selections. This comparison was performed using 2 different feeding strategies corresponding to the selection design. Carcass and meat quality traits were recorded for the 3 lines (ConsoResidual, ADGrestrict, and an unselected control [generation 0 {G0}]) in the 2 feeding systems (ad libitum and restricted) for 163 animals. Concerning the line effect, the BW at 63 d old was higher for the ADGrestrict line compared with the G0 and ConsoResidual lines ( < 0.0001). There was no line effect on the gastrointestinal tract. The rabbits did not exhibit a different carcass yield but showed different carcass traits. Indeed, the ConsoResidual rabbits had a higher hind leg yield ( < 0.0001) but no difference in the meat-to-bone ratio of the hind leg. On the contrary, the ADGrestrict line had a higher proportion of forelegs plus thoracic cage ( = 0.03). We also found lower perirenal ( < 0.0001) and scapular fat yields ( < 0.0001) in ConsoResidual rabbits. The ADGrestrict line had an intermediate perirenal fat yield compared with the other 2 lines. The G0 line always exhibited higher fat yields. Concerning meat quality, the ConsoResidual rabbits showed a lower ultimate pH ( < 0.0001) and higher water loss (drip and cooking loss; < 0.002) compared with the G0 and ADGrestrict rabbits. The feeding level had a strong effect on the gastrointestinal tract ( = 0.0004) and the carcass yield ( = 0.001). The latter was decreased in restricted rabbits. The effects of feeding strategy on meat quality were detrimental in the case of restricted feeding. Even if the ultimate pH was slightly higher in restricted rabbits ( = 0.0002), the carcass chilling loss ( = 0.0005) and the drip loss during 6 d ( < 0.0001) were higher. The selection on ADG with restricted access to feed seems to be less adversely correlated with carcass traits and meat quality traits but it leads to an increase in the live weight of the rabbits. Adversely, the selection on RFI, without affecting growth rate, would not modify age at slaughter because growth rate is not affected, but it might induce detrimental effects on meat quality.

Resistance to infectious diseases is a heritable trait in rabbits.

Selection for disease resistance is a powerful way to improve the health status of herds and to reduce the use of antibiotics. The objectives of this study were to estimate 1) the genetic parameters for simple visually assessed disease syndromes and for a composite trait of resistance to infectious disease including all syndromes and 2) their genetic correlations with production traits in a rabbit population. Disease symptoms were recorded in the selection herds of 2 commercial paternal rabbit lines during weighing at the end of the test (63 and 70 d of age, respectively). Causes of mortality occurring before these dates were also recorded. Seven disease traits were analyzed: 3 elementary traits visually assessed by technicians on farm (diarrhea, various digestive syndromes, and respiratory syndromes), 2 composite traits (all digestive syndromes and all infectious syndromes), and 2 mortality traits (digestive mortality and infectious mortality). Each animal was assigned only 1 disease trait, corresponding to the main syndrome ( = 153,400). Four production traits were also recorded: live weight the day before the end of test on most animals ( = 137,860) and cold carcass weight, carcass yield, and perirenal fat percentage of the carcass on a subset of slaughtered animals ( = 13,765). Records on both lines were analyzed simultaneously using bivariate linear animal models after validation of consistency with threshold models applied to logit-transformed traits. The heritabilities were low for disease traits, from 0.01 ± 0.002 for various digestive syndromes to 0.04 ± 0.004 for infectious mortality, and moderate to high for production traits. The genetic correlations between digestive syndromes were high and positive, whereas digestive and respiratory syndromes were slightly negatively correlated. The genetic correlations between the composite infectious disease trait and digestive or respiratory syndromes were moderate. Genetic correlations between disease and production traits were favorable. Our results indicate that it is possible to select rabbits using visually assessed disease syndromes without the need for a trade-off between health and production traits. Using a composite criterion that includes all infectious syndromes is easy to implement and heritable and is, therefore, a promising way to improve the general disease resistance in livestock species.

The direct-maternal genetic correlation has little impact on genetic evaluations.

Obtaining unbiased estimates of the direct-maternal genetic correlation proves far from straightforward for several reasons. Consequently, the use of such over- or underestimated correlations may introduce errors in genetic evaluation models. The objective of our study was to evaluate how the value of the direct-maternal genetic correlation affects EBV. Direct, maternal, and total breeding values were predicted for the ADG or weight at weaning for 3 different species (sheep, rabbits, and pigs) using models that differ depending on the fixed value of the direct-maternal genetic correlation (ranging from -0.9 to 0.9) as well as a model in which the correlation was estimated. The results were consistent between species. The direct-maternal genetic correlation had a greater impact on the estimated maternal genetic effects than on direct effects. The lowest correlations between maternal breeding values obtained with different models were -0.20, -0.01, and -0.72 in pigs, sheep, and rabbits, respectively, whereas for the direct breeding value, the lowest correlations were 0.45, 0.90, and 0.95 in pigs, sheep, and rabbits, respectively. The total EBV, calculated as the unweighted sum of direct and maternal genetic effects, did not differ greatly between the models, the lowest correlations between total breeding values being 0.93, 0.98, and 0.97 for pigs, sheep, and rabbits, respectively. Given the uncertainty associated with estimating the direct-maternal genetic correlation, setting its value to 0 in genetic evaluation models appears to be a good compromise.

Genetic modeling of feed intake.

With the development of automatic self-feeders and electronic identification, automated, repeated measurements of individual feed intake (FI) and BW are becoming available in more species. Consequently, genetic models for longitudinal data need to be applied to study FI or related traits. To handle this type of data, several flexible mixed-model approaches exist such as character process (CPr), structured antedependence (SAD), or random regression (RR) models. The objective of this study was to compare how these different approaches estimate both the covariance structure between successive measurements of FI and genetic parameters and their ability to predict future performances in 3 species (rabbits, ducks, and pigs). Results were consistent between species. It was found that the SAD and CPr models fit the data better than the RR models. Estimations of genetic and phenotypic correlation matrices were quite consistent between SAD and CPr models, whereas correlations estimated with the RR model were not. Structured antedependence and CPr models provided, as expected and in accordance with previous studies, a decrease of the correlations with the time interval between measurements. The changes in heritability with time showed the same trend for the SAD and RR models but not for the CPr model. Our results show that, in comparison with the CPr model, the SAD and RR models have the advantage of providing stable predictions of future phenotypes 1 wk forward whatever the number of observations used to estimate the parameters. Therefore, to study repeated measurements of FI, the SAD approach seems to be very appropriate in terms of genetic selection and real-time managements of animals.

The length of productive life can be modified through selection: an experimental demonstration in the rabbit.

The objective of this study was to assess the feasibility of selecting for functional longevity in rabbits, defined as an ability to delay involuntary culling. Functional longevity was measured as the total number of AI performed after the first kindling. Breeding values were estimated using a discrete survival model. Male parents were selected on the basis of their progeny test results, and the efficiency of selection was estimated in the second generation, as was the correlated response on reproduction traits. A total of 48 males were progeny tested, based on the longevity of 10 daughters bred in 2 different farms. Based on their estimated genetic merit, 5 "high longevity" (HL) and 5 "low longevity" (LL) males were selected divergently and produced a new generation (5 bucks/sires and 10 daughters/bucks). A difference in longevity (+0.75 AI, i.e., 32 d) was observed between the 2 lines. In farm 1, the differences were mainly due to culling (26% in the LL line vs. 14% in the HL line) whereas mortality was similar in the 2 lines. In farm 2, mortality and culling were both higher in the LL line than in the HL line (33 vs. 15% and 19 vs. 7%, respectively). There was no difference between the 2 lines in terms of the reproduction traits recorded for each kindling. Nevertheless, because of the difference in the litter number between the 2 lines, the sum of young rabbits born alive per doe over her lifetime and the sum of young rabbits weaned per doe were higher in the HL line (+5 kits; P < 0.01). Selection for functional longevity using survival analysis is feasible for modifying lifetime reproduction traits.

Genetic parameters for two selection criteria for feed efficiency in rabbits.

Improvement of feed efficiency can be achieved by genetic selection directly on feed to BW gain ratio or for alternative traits. In the present study, 2 different traits were explored in the growing rabbit and their heritability and genetic correlations with traits recorded between weaning (30 d) and 63 d of age: i) residual feed intake (RFI), to select animals having low ad libitum feed intake independently from their production level, and ii) ADG under restricted feeding (ADGR; with a restriction level of 80% compared with ad libitum feeding of a control group), to select animals having high growth rate despite limited feed intake. To study these traits, 2 rabbit lines were established named i) ConsoResidual line and ii) ADGrestrict line. Under ad libitum or restricted feeding, it comes to select animals that waste less energy for maintenance, metabolism, or activity and retain more for tissue deposition. The selection process was similar in both lines. Data comprised records from generations 0 to 6 for about 1,800 rabbits per line measured for their BW at weaning and 63 d of age (BW63) and their individual feed consumption. Under ad libitum feeding, the heritability estimates were moderate for RFI (0.16 ± 0.05), ADG (0.19 ± 0.05), and feed conversion ratio (FCR; 0.22 ± 0.05). The high genetic correlation estimated between RFI and FCR (0.96 ± 0.03) was in accordance with the literature. The genetic correlation between RFI and ADG traits was not significant. Thus, selection for low RFI with ad libitum feeding was confirmed as a potential trait to improve FCR and reduce feed intake, with little effect on ADG. To our knowledge, there is no previous selection experiment on growing rabbits with restricted feeding. Our heritability estimates for ADGR and feed conversion ratio under restricted feeding (FCRR) were moderate (0.22 ± 0.06 and 0.23 ± 0.07, respectively) and had very high negative genetic correlation. Both selection criteria were found with high and favorable genetic correlations with feed efficiency recorded under each feeding regimen. However, their different genetic correlations with BW at weaning and at 63 d of age (BW63R; respectively, 0.85 and 0.17 for RFI and -0.25 and 0.81 for ADGR) suggested different impacts on major production traits that need further analyses to decipher the relative advantages of the 2 selection criteria, together with interactions between genotypes and feeding regimen.

Tissue healing during degradation of a long-lasting bioresorbable gamma-ray-sterilised poly(lactic acid) mesh in the rat: a 12-month study.

AIM: The purpose was to evaluate soft-tissue healing after poly(lactic acid) (PLA(94)) mesh implantation in a rat model. METHODS: Full-thickness abdominal wall defects were created in 108 Wistar rats, and reconstructed with 83 PLA(94) and 25 lightweight polypropylene (PPL) meshes. The meshes were previously gamma-ray sterilised with 25, 75 or 125 kGy to accelerate PLA(94) degradation. RESULTS: The inflammatory response in PLA(94) was significantly less pronounced and collagen organisation significantly better than in PPL. The higher the level of gamma-radiation, the higher the incidence of abdominal wall herniation (22.2, 31.3 and 52.6% with 25, 75 and 125 kGy, respectively). No herniation occurred in the PPL group. Tensile strength was dramatically reduced after gamma-ray-sterilised PLA(94) mesh implantation. CONCLUSION: The gamma-ray-sterilised PLA(94) mesh was poor in preventing abdominal wall hernia recurrences in a rat model.

Survival analysis in two lines of rabbits selected for reproductive traits.

The objective of the study was to analyze the reproductive longevity of 2 selected lines of rabbits. The first one was the Prat line, a line selected in Spain on litter size at weaning, and raised in overlapping generations. The second one was a French line, the A1077 line, selected on litter size at birth and individual weight at 63 d of age, managed in batches, and artificially inseminated with discrete generations. Reproductive longevity was measured beginning at the first successful mating, assessed by a pregnancy diagnosis in the Prat line, and at the first kindling in the A1077 line. In the A1077 line, culling for infertility occurred after 3 unsuccessful artificial inseminations. The trait analyzed, defined as the doe length of productive life (LPL), was the time in days between date of the first positive pregnancy diagnosis and date of culling or death in the Prat line. In the A1077 line, the trait was the number of AI after the first kindling. Effects included in the model were year-season, litter size at birth, reproductive cycle or physiological status x cycle interaction, age at first mating, batch (only for the A1077 line), and additive genetic value of the animal as a random effect. Survival analyses were carried out with a Cox model for the Prat line and a discrete model for the A1077 line. The estimated heritability values for LPL were around 0.16 in the Prat and A1077 lines with a model including physiological status x cycle interaction effect. Removing this effect from the model led to an increase in estimated genetic variance with h2 = 0.24 and 0.19 in the Prat and A1077 lines, respectively. Including the traits LPL and number of AI from first fertile mating or AI in selection programs could increase reproductive longevity and decrease the replacement rate.

Heat shock-induced degradation of Msn2p, a Saccharomyces cerevisiae transcription factor, occurs in the nucleus.

In the yeast Saccharomyces cerevisiae, the zinc finger transcription factor Msn2p is a central component of the general stress response. It is activated in response to a wide variety of environmental changes, including physicochemical stresses as well as nutritional starvation, and induces the expression of a large set of genes required for cellular adaptation. The transcriptional activity of Msn2p in response to stresses is transient, and must therefore be strictly controlled. It is mainly regulated by reversible translocation from the cytoplasm to the nucleus upon the onset of stress, under the control of the cAMP-APK and the TOR pathways. In this report, we describe a new level of control: heat shock-induced degradation of Msn2p by the 26S proteasome. This degradation occurs in the nucleus and is further enhanced when Msn2p is fully active. Moreover, we show that the cyclin-dependent protein kinase Srb10p, a component of the transcription machinery, plays a role in the enhanced degradation of Msn2p upon heat shock. These findings provide new insights into the mechanisms by which Msn2p is transiently activated in response to stress.

Selective enzymatic degradations of poly(L-lactide) and poly(epsilon-caprolactone) blend films.

Solution cast films were prepared from poly(L-lactide) (PLLA) and poly(epsilon-caprolactone) (PCL) as well as from three blends, namely B75, B50, and B25 with PLLA/PCL proportions of 75/25, 50/50, and 25/75, respectively. The enzymatic degradation of square samples (10 x 10 x 0.2 mm) cut from the films was investigated at 37 degrees C in a pH = 8.6 Tris buffer containing proteinase K or in a pH = 7.0 phosphate buffer containing Pseudomonas lipase. It was confirmed that proteinase K can degrade amorphous domains of PLLA, but cannot degrade crystalline PLLA or PCL. In contrast, Pseudomonas lipase can degrade both amorphous and crystalline PCL but cannot degrade PLLA. The two faces of solution cast films showed different morphologies due to the solvent evaporation process. The lower face appeared more crystalline than the upper face because of the plasticizing effect of solvent entrapped inside which allowed crystallization to proceed. Therefore, the lower face was more resistant to enzymatic attack by proteinase K in the cases of PLLA and the blends. The two polymers in the blends exhibited well separated crystalline domains. PCL seemed to constitute the continuous phase of the blends with formation of large size spherulites when the PCL content was over 50%. The selective degradation of PCL or PLLA components revealed the inner morphology of the blends where microspherelike or islandlike patterns were observed.

Ssa1p chaperone interacts with the guanine nucleotide exchange factor of ras Cdc25p and controls the cAMP pathway in Saccharomyces cerevisiae.

We have found that the guanine nucleotide exchange factor for ras, Cdc25p, interacts with Ssa1p in Saccharomyces cerevisiae. This interaction was observed with GST-fused Cdc25p polypeptides and confirmed by coimmunoprecipitation with the endogenous Cdc25p. Hsp82 appeared also to be co-immunoprecipitated with Cdc25p, albeit to a lower level than Hsp70. In a strain deleted for SSA1 and SSA2, we observed a reduced cellular content of Cdc25p. Consistent with a reduced activity of the cAMP-dependent PKA pathway, the rate of accumulation of both trehalose and glycogen was stimulated in the ssa-deleted strain. Expression of SSA1 reversed these effects, whereas co-expression of SSA1 and PDE2 restored high accumulation. The expression of genes repressed by cAMP, GAC1 and TPS1, fused to beta-galactosidase, was also stimulated by deletion of SSA genes. The effect of ssa deletion on glycogen accumulation was lost in a strain deleted for CDC25 rescued by the RAS2ile152 allele. Altogether, these results lead to the conclusion that Ssa1p positively controls the cAMP pathway through Cdc25p. We propose that this connection plays a critical role in the adaptation of cells to stress conditions.

Dimerization of Cdc25p, the guanine-nucleotide exchange factor for Ras from Saccharomyces cerevisiae, and its interaction with Sdc25p.

The oligomerization state of Cdc25p, the guanine nucleotide exchange factor for ras from yeast, was analyzed using different complementary approaches. The two-hybrid system showed that the C-terminal part of Cdc25p (Cdc25-Ct) can interact with itself but also with Sdc25p-Ct, the corresponding part of Sdc25p, the other guanine exchange factor from yeast. The homotropic interaction of Cdc25p-Ct has been confirmed in yeast using immunoprecipitation experiments with epitope-tagged and beta-galactosidase-fused polypeptides. No other component was required for this interaction, since dimerization was shown to occur with material synthesized in vitro. The size of Cdc25-Ct produced in Escherichia coli has been directly measured on gel filtration columns and corresponds to a dimer. The dimerization domain is localized in the same part of the molecule as the catalytic domain and the portion responsible for membrane localization. The biological relevance of dimerization is still an open question, however by allowing heterodimerization with Sdc25p it could permit a more complex combinatorial regulation of ras in yeast.

Membrane-anchoring domains of Cdc25p, a Saccharomyces cerevisiae ras exchange factor.

The CDC25 gene product from Saccharomyces cerevisiae, the prototype of the family of ras guanine nucleotide exchange factors, is expressed as a 180-kDa polypeptide, tightly bound to a membrane fraction. The ability to complement a cdc25 defect is located in the 3' part of the gene (codons 877-1589). Sequence analysis reveals only a short hydrophobic domain (residues 1459-1471) and no consensus sequence for post-translational acylation. The SH3 domain present in the N-terminal part of Cdc25p is not involved nor required for membrane localization, since the N-terminal part of Cdc25p did not fractionate with a membrane pellet. In contrast, the C-terminal part was attached to a 18000 g pellet after subcellular fractionation and immunoblotting. This subcellular localization was conserved in a ras1 ras2 double disruption mutant and in a ira2 disruption mutant. Immunofluorescence analysis showed a patchy staining, mainly at the periphery of the cells. These patches were quite distinct from actin patches by double immunolabeling. By analysing a set of truncated derivatives, the elements required for a particulate localization were restricted to residues 1441-1552.

The glyceraldehyde-3-phosphate dehydrogenase binds in vitro to the SH3 domain of Saccharomyces cerevisiae Cdc25p.

In order to isolate yeast proteins able to bind to the SH3 domain of the Cdc25p exchange factor, a biochemical approach was used. The SH3 (src homolog type 3) domain of yeast Cdc25p, fused both to a tail of 6 histidine (His) and to glutathione-S-transferase (GST), was purified and then, using His affinity for Ni2+ ions, bound to a Ni-NTA column. This column was used for isolating yeast proteins which have affinity for the yeast SH3-Cdc25p domain. The major protein thus isolated, was sequenced and identified as a yeast glyceraldehyde-3-phosphate dehydrogenase (GAP3DH).

Hydrolytic degradation of devices based on poly(DL-lactic acid) size-dependence.

The hydrolytic degradation of aliphatic polyesters derived from lactic and glycolic acids (PLA/GA polymers) has been previously shown to proceed heterogeneously in the case of large size devices, the rate of degradation being greater inside than at the surface. A qualitative model based on diffusion-reaction phenomena was proposed which accounts for the formation of the more stable outer layer. However, this model also suggested that devices with dimensions smaller than the thickness of the outer layer should degrade less rapidly than larger ones. In an attempt to check this hypothesis, 15 x 10 x 2 mm compression moulded plates, millimetric beads and submillimetric microspheres and cast films, derived from the same batch of poly (DL-lactic acid) polymer were allowed to age comparatively in isoosmolar 0.13 M phosphate buffer, pH 7.4, at 37 degrees C. Ageing of the various devices was monitored by measuring water absorption, weight loss, L-lactic acid formation, pH and molar mass changes. As expected, large size plates and millimetric beads degraded heterogeneously and much faster than homogeneously degraded submillimetric films and particles.

[Yeast and the control of RAS by exchange factors]. / La levure et le contrôle de RAS par les facteurs d'échange.

Two isofunctional ras genes are present in the yeast Saccharomyces cerevisiae. Albeit their targets differ between mammals and yeast, they have conserved their regulators. The study of their positive regulators, guanine nucleotide exchange factors, have provided routes to the discovery of their regulatory elements in mammals. Ras are signal transducing proteins involved in the activation of the adenylate cyclase in yeast. They are activated by Cdc25p which has been shown to contain a Guanine Exchange Factor domain (GEF). SDC25, a gene partially homologous to CDC25, also contains a GEF domain but seems to be under a different regulation. It has been used to demonstrate the first guanine exchange activity on ras in vitro and was shown to be active by gene transfer in mammalian cells. Both Cdc25p and Sdc25p are associated to membrane and contain SH3 domains which are supposed to bind still unidentified proteins. Cdc25p is an unstable protein which contains a cyclin destruction box. Therefore activating effect on ras could be regulated by its level of expression. We have contributed to the isolation of a mammalian CDC25 homolog and we are analysing by directed mutagenesis key positions for ras activation of the human homolog HGRF55. That was performed by complementation analysis of yeast mutants as well as by use of two hybrid system. These approaches led us to the discovery of residues involved in ras interaction.

Attempts to map the structure and degradation characteristics of aliphatic polyesters derived from lactic and glycolic acids.

During the past 5 years, important advances have been accomplished in the understanding of the fate of aliphatic polyesters derived from lactic acid (LA) and glycolic acid (GA) in aqueous media. Hydrolysis of solid LA/GA polymers is now regarded as dependent upon a diffusion-reaction mechanism. Faster central degradation, degradation-induced composition, and morphology changes are three of the most important findings which appeared to be composition-dependent as deduced from the behavior of different LA/GA polymers. An attempt is made to generalize these findings to the whole family and to elaborate a map which could be used to predict degradation characteristics of LA/GA polymers from their initial composition and morphology.