Identification of novel and conserved microRNA and their expression in the gray mouse lemur, Microcebus murinus, a primate capable of daily torpor.

MicroRNA (miRNA) are endogenous small noncoding RNA gene products, on average 22 nt long, that play important regulatory roles in mediating gene expression by binding to and targeting mRNAs for degradation or translational repression. In this paper we identify both novel and conserved miRNA sequences present in the genome of the gray mouse lemur, Microcebus marinus. In total, 122 conserved and 44 novel miRNA were identified with high confidence from the lemur genome (Mmur_2.0) and were used for expression analysis. All conserved and novel miRNA were subjected to relative quantification by RT-qPCR in liver samples from control and torpid lemurs. A total of 26 miRNA (16 conserved and 10 novel) showed increased levels during primate torpor, whereas 31 (30 conserved and 1 novel) decreased. Additional in silico mapping of the predicted mRNA targets of torpor-responsive mature miRNA suggested that miRNA that increased during torpor were collectively involved in cell development and survival pathways, while miRNA that decreased were enriched in targeting immune function. Overall, the study suggests new regulatory mechanisms of primate torpor via miRNA action.

Regulation of cell cycle progression by Swe1p and Hog1p following hypertonic stress.

Exposure of yeast cells to an increase in external osmolarity induces a temporary growth arrest. Recovery from this stress is mediated by the accumulation of intracellular glycerol and the transcription of several stress response genes. Increased external osmolarity causes a transient accumulation of 1N and 2N cells and a concomitant depletion of S phase cells. Hypertonic stress triggers a cell cycle delay in G2 phase cells that appears distinct from the morphogenesis checkpoint, which operates in early S phase cells. Hypertonic stress causes a decrease in CLB2 mRNA, phosphorylation of Cdc28p, and inhibition of Clb2p-Cdc28p kinase activity, whereas Clb2 protein levels are unaffected. Like the morphogenesis checkpoint, the osmotic stress-induced G2 delay is dependent upon the kinase Swe1p, but is not tightly correlated with inhibition of Clb2p-Cdc28p kinase activity. Thus, deletion of SWE1 does not prevent the hypertonic stress-induced inhibition of Clb2p-Cdc28p kinase activity. Mutation of the Swe1p phosphorylation site on Cdc28p (Y19) does not fully eliminate the Swe1p-dependent cell cycle delay, suggesting that Swe1p may have functions independent of Cdc28p phosphorylation. Conversely, deletion of the mitogen-activated protein kinase HOG1 does prevent Clb2p-Cdc28p inhibition by hypertonic stress, but does not block Cdc28p phosphorylation or alleviate the cell cycle delay. However, Hog1p does contribute to proper nuclear segregation after hypertonic stress in cells that lack Swe1p. These results suggest a hypertonic stress-induced cell cycle delay in G2 phase that is mediated in a novel way by Swe1p in cooperation with Hog1p.

Shortened seasonal photoperiodic cycles accelerate aging of the diurnal and circadian locomotor activity rhythms in a primate.

The gray mouse lemur (Microcebus murinus), a prosimian primate, exhibits seasonal rhythms strictly controlled by photoperiodic variations. Previous studies indicated that longevity can be altered by long-term acceleration of seasonal rhythms, providing a model for assessing various aspects of aging. To assess the effect of aging and accelerated aging on the circadian system of this primate, we compared the circadian rhythm of the locomotor activity in adult mouse lemurs (2-4.5 years, n = 9), aged mouse lemurs (5-9 years, n = 10), and adult mouse lemurs that had been exposed from birth to a shortened seasonal photoperiodic cycle (2-4.5 years, n = 7). Compared to adult animals, aged mouse lemurs showed a significant increase in intradaily variability and an advanced activity onset. Aging was characterized by a decrease in amplitude, with both a decrease in nocturnal activity and an increase in daytime activity. When maintained in constant dim red light, aged animals exhibited a shortening of the free-running period (22.8 +/- 0.1 h) compared to adult animals (23.5 +/- 0.1 h). A 3- to 5-year exposure to an accelerated seasonal photoperiodic rhythm ("annual" duration of 5 months) in accelerated mouse lemurs produced disturbances of the locomotor activity rhythm that resembled those of aged mouse lemurs, whether animals were studied in entrained or in free-running conditions. The present study demonstrated a weakened and fragmented locomotor activity rhythm during normal aging in this primate. Increasing the number of expressed seasonal cycles accelerated aging of parameters related to circadian rhythmicity in adult animals.

Changes in olfactory inputs modify the energy balance response to short days in male gray mouse lemurs.

The role of olfaction/olfactory cues on photoperiodic responses was assessed in Malagasy primate, the gray mouse lemur. When exposed to short photoperiod (SP), this primate demonstrates rapid changes in energy balance as adaptive anticipatory response for winter survival. To follow early changes induced by SP exposure, body mass, food intake, resting metabolism (RMR) and free thyroxin levels in plasma (T4) were measured in males abruptly transferred to SP: six intact males (controls), eight males that underwent bilateral olfactory removal (BOX) and eight males exposed to male urinary cues (U-exposed). To assess the effect of SP exposure, two other groups were maintained for 6 weeks under LP: six controls and six BOX males. Whereas all studied parameters remained constant in controls and BOX males maintained under LP, exposure to SP led to different responses according to groups. In controls, SP exposure led to a regular increase in body mass and after 4 weeks under SP, plasma T4 levels, food consumption and RMR significantly decreased. Even if BOX males demonstrated hyperphagic patterns regardless of the photoperiod, an increase in body mass was also induced by SP exposure but without changes in RMR or food intake that were body mass-dependent. In U-exposed males, body mass gain was significantly reduced while food intake and RMR remained high. In both BOX and U-exposed males, SP exposure led to a transient but high increase in T4 levels compared to controls. These results suggest that olfaction/olfactory cues may delay the SP-mediated changes in energy balance.

Social inhibition of seasonal fattening in wild and captive gray mouse lemurs.

Due to their differential reproductive investment, males and females often exhibit high differences in energy management. The main hypothesis tested in this study is that short photoperiod-induced fattening in the small primate Microcebus murinus is strongly affected by social cues. Short photoperiod-induced changes in body mass, lean mass and thyroid hormone T4 plasma levels measurements were investigated in wild and captive animals. Individual housing showed that both males and females are able to fatten. Fattening was associated with a slight increase of lean mass that reached a plateau after 3 weeks. In contrast, social grouping led to an inhibition of fattening, even when direct interactions were prevented. This social inhibition was mainly observed in males, especially when housed with females, suggesting that their low weight gain in the wild is due to female dominance. Accordingly, wild and captive animals of both sexes exhibited a decrease in T4 plasma levels, revealing a decrease in energy expenditure. Moreover, testis recrudescence observed after 20 weeks of short photoperiod exposure did not lead to any inhibition of fattening, indicating that males take advantage of female hibernation late in the dry season to fatten and use their fat reserves for the mating competition. Therefore, seasonal fattening may be used by females to prepare for hibernation and by males to prepare for the mating competition.

Change in photoperiodic cycle affects life span in a prosimian primate (Microcebus murinus).

The lesser mouse lemur, a small prosimian primate, exhibits seasonal rhythms strictly controlled by photoperiodic variations. Exposure to day lengths shorter than 12 h results in complete sexual rest, fattening, lethargy, and reduced behavioral activities; whereas exposure to day lengths greater than 12 h induces sexual activity, an increase in behavioral activities, and high hormonal levels. The objective of this study was to test whether long-term acceleration of seasonal rhythms may affect survival and longevity of this primate. In captivity, acceleration of seasonal rhythms was obtained by exposing the animals to an accelerated photoperiodic regimen consisting of 5 months of long photoperiod followed by 3 months of short photoperiod. The age-specific survival rate in animals exposed from birth to accelerated photoperiodic conditions (n = 89) was compared to the age-specific survival rate of animals maintained under a natural photoperiod (n = 68). Independent of sexes, the mean life span (45.5 +/- 2.1 months) and maximal survival (79.3 +/- 3.3 months) were significantly (p < .01) shortened in mouse lemurs exposed to the accelerated photoperiodic cycle compared to those in animals living under annual photoperiod (63.2 +/- 2.5 and 98 +/- 3.9 months for mean life span and maximal survival, respectively). This reduction of about 30% of life span was not accompanied by a desynchronization of biological rhythms under photoperiodic control and was not related to an increase in reproduction or in duration of time spent in active conditions. However, when the number of seasonal cycles experienced by 1 individual is considered rather than chronological age, the mean life span was 5 seasonal cycles and maximum survival reached 9-10 cycles, independent of sex or of photoperiodic regimen. These results suggest that in mouse lemurs, as in other seasonal mammals, longevity may depend on the expression of a fixed number of seasonal cycles rather than on a fixed biological age.

Comparative distribution of mRNA encoding the growth hormone secretagogue-receptor (GHS-R) in Microcebus murinus (Primate, lemurian) and rat forebrain and pituitary.

The forebrain and pituitary sites of synthesis of growth hormone secretagogue-receptor mRNA were identified in four adult lemurs (Microcebus murinus) by in situ hybridisation performed with a radiolabeled cRNA probe transcribed from human Growth Hormone Secretagogue-Receptor cDNA. The cRNA sense and antisense probes were hybridised to cryostat sections containing structures extending from the rostral hypothalamus to its caudal limit as defined by the mammillary bodies. The pituitary gland and areas adjacent to the hypothalamus were also analyzed. For comparative purposes, sections from five adult rats containing these structures were hybridised with the same probes. The results point to a widespread distribution of Growth Hormone Secretagogue-Receptor mRNA in the hypothalamus, hippocampal formation, and cerebellar cortex of both lemurs and rats. As in the rat, specific hybridisation was particularly dense in the arcuate nucleus. Significant species differences were observed in the periventricular nucleus, the ventromedial nucleus, the lateral hypothalamic area, and the pituitary gland. In contrast to the rat, the lemur exhibited marked labelling in the infundibular nucleus, the periventricular nucleus and the pars tuberalis of the pituitary gland, whereas no labeling was detectable in the ventromedial nucleus and the lateral hypothalamic area. These results are discussed in terms of difference between the control of growth hormone secretion, feeding behaviour and seasonal rhythmicity among murine species and primates.

Predictive factors for late toxicity after endobronchial brachytherapy: a multivariate analysis.

PURPOSE: To determine the predictive factors associated with hemoptysis and radiation bronchitis after endobronchial brachytherapy by univariate and multivariate analyses METHODS AND MATERIALS: One hundred forty-nine patients underwent endobronchial brachytherapy and were divided into three therapeutic groups: group 1: patients treated with palliative intent (n=47); group 2: patients treated with curative intent (small endobronchial tumors without mediastinal or general dissemination: n=73); group 3: patients also receiving external irradiation (n=29). One hundred twelve patients had previously received external irradiation. Brachytherapy was delivered with a dose per fraction ranging from 4 to 7 Gy and a prescription point between 0.5 and 1.5 cm, usually 1 cm from the source center. Two to six fractions were delivered according to the therapeutic group and clinical situation. The influence of the following variables on the incidence of hemoptysis or radiation bronchitis was studied: age, sex, Karnofsky score, therapeutic group, histologic type, endoscopic tumor length, dose per fraction, total brachytherapy dose, total external beam irradiation dose, total dose (brachytherapy dose plus external irradiation dose), volumes of the 100% and 200% isodoses, and volumes of the 7 and 14 Gy isodoses. RESULTS: We observed 11 hemoptyses (7.4%), 10 were lethal. All but one occurred in patients with progressive disease. Two clinical factors were significantly associated with hemoptysis by univariate analysis: palliative group (p=0.009) and endobronchial tumor length (p=0.004). No technical factors seem to be implicated in the occurrence of hemoptysis. Only endobronchial tumor length remained in the multivariate model (p=0.02). Radiation bronchitis was observed in 13 cases (8.7%). By univariate analysis, a good Karnofsky score (p=0.02), curative treatment (p=0.02), and tumor location on trachea and main stem bronchus (p=0.002) were significantly associated with this complication. Two technical factors were also incriminated: the total dose (p=0.04) and the 100% isodose volume (p=0.02). By multivariate analysis, only the tumor location retained statistical significance (p=0.009). CONCLUSION: Hemoptysis is most likely due to disease progression, with the bleeding being facilitated by brachytherapy. Some rare cases could be a direct complication of brachytherapy itself, particularly when tumors are located in the upper lobes. In contrast, radiation bronchitis occurred more frequently in patients with controlled disease, and was significantly influenced by tumor location and technical factors (dose and volumes treated). Technical improvements should increase the therapeutic ratio.

Artificially accelerated aging by shortened photoperiod alters early gene expression (Fos) in the suprachiasmatic nucleus and sulfatoxymelatonin excretion in a small primate, Microcebus murinus.

In mammals, a number of anatomical and functional changes occur in the circadian timing system with aging. In certain species, aging can be modified by various factors which induce a number of pathological changes. In a small primate, the gray mouse lemur (Microcebus murinus), long-term acceleration of seasonal rhythms by exposing the animals to a shortened photoperiodic regime (up to 2.5 times the natural photoperiodic regime) alters longevity, based on survival curves and morphological changes. This provides a model for challenging the idea that modifications of the circadian pacemaker are related to chronological (years) versus biological (photoperiodic cycles) age. To assess the effect of aging and accelerated aging on the circadian pacemaker of this primate, we measured body weight variations, the daily rhythm in urine 6-sulfatoxymelatonin and the light-induced expression of the immediate early gene (Fos) in the suprachiasmatic nucleus of mouse lemurs that had been exposed to different photoperiodic cycles. Urine samples were collected throughout the day and urine 6-sulfatoxymelatonin levels were measured by radioimmunoassay. Light-induced Fos expression in the suprachiasmatic nucleus was studied by exposing the animals to a 15-min monochromatic pulse of light (500 nm) at saturating or sub-saturating levels of irradiance (10(11) or 10(14) photons/cm(2)/s) during the dark phase. The classical pattern of 6-sulfatoxymelatonin excretion was significantly altered in aged mouse lemurs which failed to show a nocturnal peak. Fos expression following exposure to low levels of irradiance was reduced by 88% in the suprachiasmatic nucleus of aged mouse lemurs. Exposure to higher irradiance levels showed similar results, with a reduction of 66% in Fos expression in the aged animals. Animals subjected to artificially accelerated aging demonstrated the same alterations in melatonin production and Fos response to light as animals that had been maintained in a routine photoperiodic cycle. Our data indicate that there are dramatic changes in melatonin production and in the cellular response to photic input in the suprachiasmatic nucleus of aged mouse lemurs, and that these alterations depend on the number of expressed seasonal cycles rather than on a fixed chronological age. These results provide new insights into the mechanisms underlying artificial accelerated aging at the level of the molecular mechanisms of the biological clock.

Plasma testosterone-binding globulin-binding capacity in the male lesser mouse lemur (Microcebus murinus): relationship to seasonal and social factors.

Plasma testosterone-binding globulin (TeBG)-binding capacity was determined by equilibrium dialysis in the lesser mouse lemur (Microcebus murinus), a prosimian which exhibits a clear photoperiod-dependent sexual cycle. Plasma TeBG-binding capacity showed significant seasonal changes which were inversely correlated to those of plasma testosterone concentrations. The capacity of TeBG was at its maximum (1.72 +/- 0.4 mumol/l) during the sexual rest period and decreased to 0.98 +/- 0.24 mumol/l during the breeding season when testosterone concentrations were about 200-280 nmol/l. In addition, when males developed a social hierarchy in groups, the decreased sexual function in non-dominant animals was associated with a higher TeBG-binding capacity. However, although TeBG-binding capacity increased when testosterone concentrations decreased either during sexual rest or under social dominance, a positive correlation was found between TeBG-binding capacity and testosterone levels during the breeding season in males with a normal reproductive cycle, i.e. in both isolated and dominant males. This suggests that factors other than sex steroids are involved in the changes in TeBG-binding capacity occurring under seasonal and social influences.

Role of prolactin in a pheromone-like sexual inhibition in the male lesser mouse lemur.

Sexual activity of the male lesser mouse lemur can be induced by a long photoperiod, and plasma testosterone concentrations increase from 20 to 220 nmol/l within 3 weeks of photoperiodic stimulation. When isolated males were exposed to the volatile compounds from the urine of an active dominant male for 4 weeks at the beginning of the long daylight period, they demonstrated a significant decrease in testosterone concentrations (134 +/- 11 nmol/l) compared with controls (210 +/- 26 nmol/l) within 2 weeks. Lowering concentrations of prolactin by daily injections of bromocriptine prevented the decrease in testosterone in males simultaneously exposed to the odorant stimulation. Increasing concentrations of prolactin by daily injections of sulpiride mimicked the effect of the odorant stimulation in males receiving only fresh non-odorized air. The decrease in testosterone was strengthened when sulpiride was administered concurrently with exposure to urine. These results support the conclusion that variations in the concentration of prolactin are involved in the neuroendocrinological process mediating the pheromone-like sexual inhibition in the male lesser mouse lemur. However, daily injections of bromocriptine in males which were photoperiodically stimulated but not exposed to dominant male urine odour, also induced a significant decrease in testosterone concentrations. This finding suggests that two different systems involving prolactin and leading to opposite effects might be implicated in the regulation by environmental factors of sexual activity in the male lesser mouse lemur.

Response to short photoperiod and spontaneous sexual recrudescence in the lesser mouse lemur: role of olfactory bulb removal.

The body weight and sexual activity of the male lesser mouse lemur, a prosimian primate, undergo cyclic changes that are photoperiod-dependent. Exposure to long daylength (LD; 14 h light/day) led to sustained sexual activity, fully developed testes and high plasma testosterone concentrations (228 +/- 25 nmol/l, n = 10). After 14 weeks under LD, a marked decrease in testosterone levels occurred. Gonadal regression was completed within 20 weeks under LD without concomitant changes in body weight. Exposure to short daylength (SD; 8 h light/day) reinforced the sexual quiescence and was associated with a high ponderal gain (from 60 to 110 g). However, independent of the date of gonadal arrest, the sexual activity of males spontaneously resumed at a fixed time after exposure to SD. The testes developed, testosterone concentrations increased to 155 nmol/l and the body weight decreased (from 110 to 80 g) within 20 weeks under SD exposure. The timing for refractoriness appeared very similar under inhibitory and stimulatory photoperiods. This is consistent with the hypothesis that the perception of a critical daylength is used to regulate the timing of the following sexual phase through a mechanism involving photorefractoriness. Contrary to cricetid rodents, a direct response to photoperiodic signals for both body weight and sexual activity were not prevented by olfactory bulb removal in male mouse lemurs. In bulbectomized males (n = 12), sexual activity was stimulated by LD and inhibited by SD. Their plasma testosterone levels, however, significantly differed from those of controls in both photoperiods. Likewise, ponderal cycles remained intact but the fattening phase was delayed and reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Sexual inhibition in a prosimian primate: a pheromone-like effect.

The effect of dominant urine odour on plasma levels of testosterone and cortisol was studied in the prosimian primate Microcebus murinus. This species shows a photoperiod-dependent cycle of sexual activity. In particular, mean testosterone levels vary from 15 nmol/l during the annual rest period to 245 nmol/l during the breeding season. When males of this solitary and territorial species are artificially grouped in captivity, they develop a social hierarchy which in turn results in physiological disorders, especially of reproductive function, in non-dominant individuals. Since olfactory behaviours appear to be important in the establishment and maintenance of the social structure, we have tested the effects of dominant odorant signals upon the sexual inhibition observed in male conspecifics. A preliminary experiment showed that a decrease in plasma testosterone concentrations could be induced by dominant scent marks. Furthermore, dominant urine odour alone was found to be sufficient to induce this modification. Plasma cortisol levels also increased in these animals. Conversely, when sexually inhibited males were olfactorily isolated from dominant urine odour, testosterone and cortisol concentrations returned to a normal seasonal level. These effects were observed even in males which had had no previous contact with the dominant urine donor. It is inferred from these results that a pheromone-like process could lead to sexual inhibition in male Microcebus murinus exposed to an odorant urinary signal produced by a dominant individual. Nevertheless, the endocrine response seems to vary according to the seasonal period of the sexual activity cycle which suggests that the social effect described is modulated by other external (e.g. photoperiodic) or internal (e.g. reproductive physiology) factors.

Age dependence of the T2-weighted MRI signal in brain structures of a prosimian primate (Microcebus murinus).

Mouse lemurs (Microcebus murinus) are prosimian primates described to be convenient models of brain aging. We observed very high correlations between the T2-weighted magnetic resonance imaging (MRI) signal decrease and the natural logarithm of age in the basal ganglia. The correlation coefficient was higher for the pallidum (r = 0.95, P < 0.0001) than for other structures. We suggest that the ratio of the pallidum intensity divided by the amygdala and temporal lobe intensity should be a valuable non-invasive marker of age and of cerebral aging. It should be particularly useful for the non-invasive assessment of interventions and drugs that affect the aging process.

The effect of adrenomedullin on the isolated heart.

A novel peptide found in human blood, adrenomedullin (ADM), has been shown to have systemic vasodepressor activity in the rat. However, the direct effects of ADM on cardiac function are unknown. Results of the present study demonstrate that ADM13-52 possesses marked systemic vasodepressor activity in the anesthetized rat. Although ADM13-52 modestly decreased peak systolic pressure (PSP) indicating mild negative inotropic activity, the present data suggest that bolus administration of ADM decreases systemic arterial pressure by dilating the systemic vasculature. The present data also suggest that only a portion of the ADM molecule is necessary to produce systemic vasodilation.

Photoperiod-induced changes in energy balance in gray mouse lemurs.

To cope with the 6-month dry winter occurring in its natural habitat, the gray mouse lemur (Microcebus murinus), a Malagasy prosimian primate, exhibits a pre-wintering fattening phase that has been previously demonstrated to be dependent on the photoperiod. To assess early changes in energy balance following a photoperiodic shift, food intake (FI), resting metabolic rate (RMR), plasma triglycerides, plasma thyroxine and urinary excretion of cortisol were measured in 12 males and 12 females for 8 weeks following a shift from short (SP: 10 h light/day) to long (LP: 14 h light/day) photoperiod or from LP to SP. Shift from LP to SP led to a high, linear body mass (BM) increase in both sexes, concomitant to an increase in plasma triglycerides and a decrease in plasma thyroxine, while no change in RMR occurred. FI significantly increased from 30 to 40 kcal/day as early as the first week following SP exposure but spontaneously decreased after 4 weeks, reaching minimal values (10 kcal/day) after 14 weeks of SP exposure. Shift from SP to LP led to a decrease in BM and an increase in FI, but both were slow and different between males and females. No change in RMR was observed except a significant increase in males during the first week of LP exposure. However, plasma thyroxine levels and cortisol excretion similarly increased in both sexes following LP exposure. These results suggest that autumnal fattening mainly proceed from changes in FI and in thyroxine secretion triggered by exposure to SP. In contrast, BM loss following LP exposure would be related to seasonal sexual activation rather than to a direct control by photoperiod.

Sexual responses to urinary chemosignals depend on photoperiod in a male primate.

In male lesser mouse lemurs, testicular size and plasma testosterone levels are controlled by photoperiodic variations but can be modified by urinary cues from conspecifics. To test whether urinary cues may have differential effects on testicular size and testosterone levels depending on the photoperiodic state of the receiver, isolated males were exposed for 4 wk to urinary cues from oestrous females or dominant males:--at the beginning of the breeding season induced by long photoperiod (LD),--during refractoriness to LD leading to spontaneous sexual regression and during sexual quiescence exhibited by males kept in short photoperiod (SD). Urinary chemosignals from females were always stimulatory producing significant increases in testosterone levels. By contrast, urinary cues from dominant males produced significant differential effects on reproductive function. They depressed sexual function only at the beginning of the breeding season. During SD or during refractoriness to LD, chemosignals were stimulatory leading to increases in testosterone levels and full development of testes. These results demonstrate that the same chemosignal may have opposite effect on sexual function of the receiver depending on endocrine mechanisms set up by photoperiod.

Age-related effects on reproductive function and sexual competition in the male prosimian primate, Microcebus murinus.

In the male lesser mouse lemur (Microcebus murinus), a polygamous long-day breeder of which the life span may reach 12-14 years, the effects of aging on socio-sexual relationships were studied on 44 captive animals of various ages. In this primate, new dominance relationships must be established at the beginning of each breeding season. During the breeding season induced by exposure to artificial long days, preoestrous females were introduced into cages of paired males to elicit sexual competition. Sexual behaviors, social interactions through chemical signals, and dominance relationships were recorded in paired males either of similar age (young or aged pairs), or of mixed ages. In all pairs, competition for priority access to females always occurred and dominance relationships were established unrelated to body weight. Although aged animals exhibited significantly less number of sexual and aggressive behaviors, they outranked younger males excepted when reaching oldest age. Independent of male's age, the typical pattern of seasonal rhythm of testosterone was observed, but aged males demonstrated a significant reduction in mean hormonal levels (25.5 +/- 2.8 ng/mL, n = 8) compared to young animals (50 +/- 2.7 ng/mL, n = 8). Moreover, their hormonal response to photoperiod was phase-shifted leading to reduced testosterone values when females entered oestrus. Despite the fact that testosterone levels and sexual behaviors decreased with aging in this primate, older males reached a dominant position, increasing thus their reproductive success.

Daily hypothermia in captive grey mouse lemurs (Microcebus murinus): effects of photoperiod and food restriction.

The grey mouse lemur (Microcebus murinus) is a small nocturnal primate exhibiting daily torpor. In constant ambient temperature (22-24 degrees C), body temperature (Tb) and locomotor activity were monitored by telemetry in animals exposed to short (SP: 10 h light/day) or long (LP: 14 light/day) photoperiods. They were first fed ad libitum for 8 days and then subjected to 80% restricted feeding for 8 more days. During ad libitum feeding, locomotor activity was significantly lower in SP-exposed animals than in LP-exposed animals. Whatever the photoperiod, animals entered daily hypothermia within the first hours following the light onset. Depth of daily hypothermia increased irregularly under SP exposure, whereas minimal daily Tb was constantly above 35 degrees C under LP exposure. After the transfer from long photoperiod to short photoperiod corresponding to the induction of seasonal fattening, locomotor activity and depth of controlled daily hypothermia did not change significantly. In contrast, food restriction led to a significant increase in locomotor activity and in frequency of daily torpor (Tb<33 degrees C) and body temperature reached minimum values averaging 25 degrees C. However, SP-exposed animals exhibited lower minimal daily Tb and higher torpor duration than LP exposed animals. Therefore, daily torpor appears as a rapid response to food restriction occurring whatever the photoperiod, although enhanced by short photoperiod.

[Endobronchial brachytherapy: the Saint-Louis Hospital experience]. / Curiethérapie endobronchique: l'expérience de l'hôpital Saint-Louis.

PURPOSE: During the evolution of lung cancer, bronchial obstruction is often noticed and is sometimes responsible for serious symptoms. Several methods of desobstruction can be proposed, including brachytherapy. MATERIALS AND METHODS: One hundred forty-nine patients presenting with endobronchial brachytherapy were included into the study. Seventy-three were treated with curative intent, 47 with palliative intent and 29 with a combination of external irradiation and brachytherapy. We usually delivered a series of two 7-Gy fractions (1 cm from the catheter), the treatment being repeated one, two or three times. RESULTS: When all symptoms were taken into account, respiratory function improvement was present in 79% of the patients. Among the 132 tumors that could be evaluated via a new endoscopy 2 months after treatment, 64 (48.5%) were in complete histological remission. The median survival was 14.4 months for the patients treated with curative intent. Eleven massive hemoptysies and 13 radiation bronchitis were observed. CONCLUSION: These results confirm the feasibility and good results related to endobronchial brachytherapy, though controlled studies are needed to better define its place in the therapeutic strategy of bronchial carcinomas.