Occurrence of an Intersexual Blacktip Shark in the Northern Gulf of Mexico, with Notes on the Standardization of Classifications for This Condition in Elasmobranchs

An intersexual Blacktip Shark Carcharhinus limbatus with a testis, immature female reproductive tracts (embedded), and claspers was caught in the Gulf of Mexico. Histology of the single gonad revealed that all stages of spermatogenesis were occurring; however, the absence of ovaries and a male duct system suggests that neither sex would have been functional in this individual. Intersexuality has been reported in 17 families and 36 species of elasmobranchs. The degree to which the different sexes are present in a given individual is often difficult to categorize by normal hermaphroditic standards, as this is typically an anomalous presentation in elasmobranchs. Therefore, this report provides three categories for classification (basic, incomplete, and complete intersexuality) to standardize terminology and allow for more precise comparisons to be made among elasmobranch examples. Basic intersexuals have gonadal tissue of only one sex and a combination of other male and female characters with neither or only one sex being complete. Incomplete intersexuals have gonadal tissue of both sexes and a combination of other male and female characters; however, neither or only one sex is complete. Complete intersexuals have claspers as well as gonadal tissue and tracts for both sexes. The majority of the reported intersexual elasmobranchs, including the shark described here, are basic intersexuals

Cirrhipèdes

Contiene: Cirrhipèdes, par M. Gruvel (p. 1-180) ; Némertiens, par L. Joubin (p. 181-220) ; Ophistobranches, par A. Vayssière (p. 221-272) ; Holoturies, par R. Perrier (p. 273-540

Postglacial changes in fuvial morphologies of the upstream Loire catchment and the middle Cher river valley

International audienceThe present study aims to provide new insights of fluvial metamorphosis associated with postglacial environmental changes. Investigations were conducted on different points upstream to downstream of the Loire catchment (Loire itself, Dore river and Cher river). This work allows the role of catchment size to be discussed regarding sensitivity of fluvial environments to climate changes. Topography of the alluvial plain was analyzed using LiDAR DEM. Such datasets show topographic variations highlighting postglacial fluvial patterns and their relative chronology. Boreholes and electrical imaging survey help to estimate the geometry of former channels. Cores collected in palaeochannels provide organic materials suitable for radiocarbon dating and multiproxy analyses. In Dore valley, incision of Pleniglacial deposits and the building of the Holocene floodplain occur after 23136-23958 Cal. BP., the youngest date obtained from organic filling sampled in palaeochannels. The oldest dates obtained in the Holocene deposits take place around 8000 Cal. BP. On Burgundian Loire, Pleniglacial deposits are incised around 17 000 Cal. B.P. The fluvial pattern is then characterized by a braided system evolving to a meandering pattern probably active until 14 0000 Cal. B.P., when a new incision occurs and another braided system reworks previous deposits until 12 000 Cal. B.P. In the Cher river valley, some inherited landforms correspond to wide and straight palaeochannels interpreted as transitional multichannel system following a braided fluvial pattern. They might be associated with an incision of the Pleniglacial floodplain and their cutoff are dated from 15 000 to 13 500 Cal. BP. The beginning of the Lateglacial period is characterized by a significant incision occurring at different times. If this phenomenon is not unknown within postglacial alluvial deposits, such results can lead to a better knowledge of diversity and complexity of fluvial responses observed during the Lateglacial period on key positions of a fluvial network

Lifespan cerebral grey matter changes in the marmoset monkey

International audienceLifespan cerebral grey matter changes in the marmoset monkeyF. Rémy, N. Vayssière, F. Bazzi, D. Mateo, A. Sadoun, P. Girard, M. Mescam, C. FontaIn the research field of nervous system aging, the common marmoset monkey Callithrix Jacchus may reveal a model of great interest. With its short lifespan (10 years on average), a life-long assessment of cerebral changes in an individual is made feasible in laboratory settings. Moreover, similar to humans, cognitive deficits spontaneously occur at old age and are highly variable between individuals (Sadoun et al 2019, Neurobiology of Aging 74:1-14). Here, we aimed at characterizing marmoset brain structural aging in a cross-sectional MRI study performed on 48 individuals of all ages (6 months to 14 years old, with 21 individuals above 8 years). High-resolution (0.35 × 0.35 × 0.35 mm3) T1-weighted anatomical scans were acquired on a 3T MRI system using a human wrist coil. Scans were processed in SPM12 using the voxel-based morphometry (VBM) pipeline. All images were co-registered to a home-made T1 template (average of 12 individual scans). The image segmentation used Tissue Probability Maps (TPMs) of grey matter (GM), white matter (WM), cerebrospinal fluid (CSF) and head/background, which were derived from the creation of a study-specific template using the SPM12 DARTEL procedure. GM images were then spatially normalized to the DARTEL template and smoothed. VBM of grey matter evidenced linear age-related decreases mainly in the prefrontal cortex, anterior cingulate region and hippocampus, in both hemispheres (figure). This is in line with age-related cortical changes observed in humans. Further analyses, using cortical regions-of-interest derived from the marmoset digital atlas developed in our group (Risser et al 2019, Brain Struct Funct 224(5):1957-1969) are currently underway and could be linked to behavioral performances of these animals in various tasks

Age effects on the neural processing of object-context associations in briefly flashed natural scenes

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FGF1 C-terminal domain and phosphorylation regulate intracrine FGF1 signaling for its neurotrophic and anti-apoptotic activities

International audienceFibroblast growth factor 1 (FGF1) is a prototypic member of the FGFs family overexpressed in various tumors. Contrarily to most FGFs, FGF1 lacks a secretion peptide signal and acts mainly in an intracellular and nuclear manner. Intracellular FGF1 induces cell proliferation, differentiation and survival. We previously showed that intracellular FGF1 induces neuronal differentiation and inhibits both p53- and serum-free-medium-induced apoptosis in PC12 cells. FGF1 nuclear localization is required for these intracellular activities, suggesting that FGF1 regulates p53-dependent apoptosis and neuronal differentiation by new nuclear pathways. To better characterize intracellular FGF1 pathways, we studied the effect of three mutations localized in the C-terminal domain of FGF1 (i.e., FGF1(K132E), FGF1(S130A) and FGF1(S130D)) on FGF1 neurotrophic and anti-apoptotic activities in PC12 cells. The change of the serine 130 to alanine precludes FGF1 phosphorylation, while its mutation to aspartic acid mimics phosphorylation. These FGF1 mutants kept both a nuclear and cytosolic localization in PC12 cells. Our study highlights for the first time the role of FGF1 phosphorylation and the implication of FGF1 C-terminal domain on its intracellular activities. Indeed, we show that the K132E mutation inhibits both the neurotrophic and anti-apoptotic activities of FGF1, suggesting a regulatory activity for FGF1 C terminus. Furthermore, we observed that both FGF1(S130A) and FGF1(S130D) mutant forms induced PC12 cells neuronal differentiation. Therefore, FGF1 phosphorylation does not regulate FGF1-induced differentiation of PC12 cells. Then, we showed that only FGF1(S130A) protects PC12 cells against p53-dependent apoptosis, thus phosphorylation appears to inhibit FGF1 anti-apoptotic activity in PC12 cells. Altogether, our results show that phosphorylation does not regulate FGF1 neurotrophic activity but inhibits its anti-apoptotic activity after p53-dependent apoptosis induction, giving new insight into the poorly described FGF1 intracrine/nuclear pathway. The study of nuclear pathways could be crucial to identify key regulators involved in neuronal differentiation, tumor progression and resistances to radio- and chemo-therapy

p53 can promote mitochondria- and caspase-independent apoptosis

International audienceThe tumour suppressor p53 plays a pivotal role in suppressing tumorigenesis by inducing cell cycle arrest or apoptosis. Cell cycle arrest is mediated by transcriptional induction of genes whose products inhibit cell cycle progression. Conversely, the molecular events that lead to p53-dependent apoptosis are less clear. Transcriptional activation is commonly implicated but growing evidences show that transrepression and transcription-independent functions can also play a central role in p53-dependent apoptosis. 1 At the cellular level, all studies converge to the crucial role of both the mitochondrial pathway (cytochrome c release, 2 ROS production or/and DCm drop) 3 and caspase activation in p53-induced apopto-sis. 4 In this way, the Bcl-2 antiapoptotic protein as well as caspase inhibition were shown to protect cells from p53-induced apoptosis. We previously showed in rat embryo fibroblasts (e.g. the REtsAF cell line) expressing a temperature-sensitive mutant (tsA58) of the simian virus 40 large tumour antigen (LT) that LT inactivation leads to p53-mediated apoptosis. Moreover, we reported that while bcl-2 overexpression inhibits apopto-sis, caspase inhibition surprisingly accelerates apoptosis and moreover abolishes the protective effect of Bcl-2. 5 These data led us to postulate that caspase inhibition would unmask an alternative route for p53-induced cell death signal, which would lead to a caspase-independent and Bcl-2-insensitive cell death process. In order to ascertain that this new cell death process observed in the presence of ZVAD is dependent on p53 activity, REtsAF cells were transiently transfected with genes encoding temperature-sensitive dominant-negative mutants of p53 (p53 val135 and p53 ala143). 6,7 At restrictive temperature, these mutants are defective in their DNA binding domain and consequently loss their sequence-specific transactivation and transrepression properties. We observed that overexpression of either p53 val135 or p53 ala143 led to a decreased rate of apoptosis in the absence or in the presence of ZVAD (Figure 1a), demonstrating that active p53 is required for these two cell death pathways. Next, we controlled that this unexpected effect of ZVAD on p53-induced cell death could be reproduced in a more physiological model. For this purpose, we induced a p53-dependent apoptosis in primary rat embryo fibroblasts (RE) by addition of 100 mM etoposide, in the absence or in the presence of ZVAD. As observed in REtsAF cells, ZVAD treatment accelerated commitment to death of RE cells. As control, ZVAD reduced staurosporine-induced apoptosis of RE cells, showing its usual protector effect against this p53-independent cell death (Figure 1b). These results argue for a physiological relevance of the proapoptotic effect of ZVAD on p53-mediated apoptosis. In order to characterise the pattern of the p53-induced death of REtsAF cells in the presence of ZVAD, we examined the associated nuclear and cytological alterations. In the absence of ZVAD, the earliest morphological changes observed are the rounding up, the brightening phase, the shrinkage of the cells as well as the blebbing of the plasma membrane (Figure 1c). These events are associated with typical apoptotic chromatin compaction and fragmentation in globular, crescent-shaped figures (stage II chromatin condensation), and they preceded the breaking up of the cells into fragments as well as the fragmentation of DNA, as judged by the flow cytometric analysis of TUNEL-stained cells. In the presence of ZVAD, light microscopy observation showed that some typical morphological features of apoptosis such as loss of adherence and condensed cytoplasm were evident in dying REtsAF cells. Further fluorescence microscopy examination revealed chromatin condensed in lumps (stage I chromatin condensation), and rounded cells without microvilli or protu-sions on the surface (Figure 1c). However, specific events of the final degradation phase such as the nucleus and cell fragmentation do not occur whereas cells completely detached from the substratum. These observations indicate that p53 can promote two cell death pathways showing apoptotic features, one that is caspase-dependent and another that is independent of caspases. Recent data suggest that noncaspase proteases including calpains, cathepsins or serine proteases can also mediate cell death and bring about many of the morphological changes characteristic of apoptosis in a caspase-independent manner. 8 We investigated the possible involvement of these proteases in the novel route by which p53 signal cell death through the use of specific inhibitors: serine protease inhibitors (TPCK, TLCK), calpain protease inhibitors (ALLN, MDL), cysteine protease inhibitors (Lactacystine, Z-FA-fmk). Microscopic studies of cell morphology did not show notable differences in the amount of Z-VAD-dependent cellular death whether the cells were cultured in the presence or in the absence of the drugs. These results suggest that none of the tested proteases are involved in p53-induced apoptosis of REtsAF cells in the presence of ZVAD. Inasmuch as the mitochondrial pathway plays a central role in many models of p53-dependent apoptosis, we investigate

Differential effects of Bcl-2 and caspases on mitochondrial permeabilization during endogenous or exogenous reactive oxygen species-induced cell death: A comparative study of H 2 O 2 , paraquat, t-BHP, etoposide and TNF-α-induced cell death

International audienceIn this study, we have compared several features of cell death triggered by classical inducers of apoptotic pathways (etoposide and tumour necrosis factor (TNF)-α) versus exogenous reactive oxygen species (ROS; hydrogen peroxide (H 2 O 2), tert-butyl hydroper-oxide (t-BHP)) or a ROS generator (paraquat). Our aim was to characterize relationships that exist between ROS, mitochondrial perturbations, Bcl-2 and caspases, depending on source and identity of ROS. First, we have found that these five inducers trigger oxidative stress, mitochondrial membrane permeabilization (MMP), cy-tochrome c (cyt c) release from mitochondria and cell death. In each case, cell death could be inhibited by several antioxidants, showing that it is primarily ROS dependent. Second, we have highlighted that during etoposide or TNF-α treatments, intracellular ROS level, MMP and cell death are all regulated by caspases and Bcl-2, with caspases acting early in the process. Third, we have demonstrated that H 2 O 2-induced cell death shares many of these characteristics with etoposide and TNF-α, whereas t-BHP induces both caspase-dependent and caspase-independent cell death. Surprisingly , paraquat-induced cell death, which harbours some characteristics of apoptosis such as cyt c release and caspase-3 activation, is not modulated by Bcl-2 and caspase inhibitors, suggesting that paraquat also triggers non-apoptotic cell death signals. On the one hand, these results show that endogenous or exogenous ROS can trigger multiple cell death pathways with Bcl-2 and caspases acting differentially. On the other hand, they suggest that H 2 O 2 could be an important mediator of etoposide and TNF-α-dependent cell death since these inducers trigger similar phenotypes