Macrofossils in Raraku Lake (Easter Island) integrated with sedimentary and geochemical records towards a palaeoecological synthesis for the last 34,000 years

Macrofossil analysis of a composite 19 m long sediment core from Rano Raraku Lake (Easter Island)was related to litho-sedimentary and geochemical features of the sediment. Strong stratigraphical patterns are shown by indirect gradient analyses of the data. The good correspondence between the stratigraphical patterns derived from macrofossil (Correspondence Analysis) and sedimentary and geochemical data (Principal Component Analysis) shows that macrofossil associations provide sound palaeolimnological information in conjunction with sedimentary data. The main taphonomic factors in fluencing the macrofossil assemblages are run-off from the catchment, the littoral plant belt, and the depositional environment within the basin. Five main stages during the last 34,000 calibrated years BP (cal yr BP) are characterised from the lithological, geochemical, and macrofossil data. From 34 to 14.6 cal kyr BP (last glacial period) the sediments were largely derived from the catchment, indicating a high energy lake environment with much erosion and run-off bringing abundant plant trichomes, lichens, and mosses into the centre of Raraku Lake.

Study of Johnsons Glacier (Livingston Island, Antarctica) by means of shallow ice cores and their tephra and by analysis of 137Cs content

With the aim of monitoring the dynamics of the Livingston Island ice cap, the Departament de Geodinàmica i Geofísica of the Universitat de Barcelona began ye a r ly surveys in the austral summer of 1994-95 on Johnsons Glacier. During this field campaign 10 shallow ice cores were sampled with a manual ve rtical ice-core drilling machine. The objectives were: i) to detect the tephra layer accumulated on the glacier surface, attributed to the 1970 Deception Island pyroclastic eruption, today interstratified; ii) to verify wheter this layer might serve as a reference level; iii) to measure the 1 3 7Cs radio-isotope concentration accumulated in the 1965 snow stratum; iv) to use the isochrone layer as a mean of verifying the age of the 1970 tephra layer; and, v) to calculate both the equilibrium line of the glacier and average mass balance over the last 28 years (1965-1993). The stratigr a p hy of the cores, their cumulative density curves and the isothermal ice temperatures recorded confi rm that Johnsons Glacier is a temperate glacier. Wi n d, solar radiation heating and liquid water are the main agents controlling the ve rtical and horizontal redistribution of the volcanic and cryoclastic particles that are sedimented and remain interstratified within the g l a c i e r. It is because of this redistribution that the 1970 tephra layer does not always serve as a ve ry good reference level. The position of the equilibrium line altitude (ELA) in 1993, obtained by the 1 3 7Cs spectrometric analysis, varies from about 200 m a.s.l. to 250 m a.s.l. This indicates a rising trend in the equilibrium line altitude from the beginning of the 1970s to the present day. The va rying slope orientation of Johnsons Glacier relative to the prevailing NE wind gives rise to large local differences in snow accumulation, which locally modifies the equilibrium line altitude. In the cores studied, 1 3 7Cs appears to be associated with the 1970 tephra laye r. This indicates an intense ablation episode throughout the sampled area (at least up to 330 m a.s.l), which probably occurred synchronically to the 1970 tephra deposition or later. A rough estimate of the specific mass balance reveals a considerable accumulation gradient related to the increase with altitude.

N-acetylcysteine treatment ameliorates the skeletal phenotype of a mouse model of diastrophic dysplasia.

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by mutations in SLC26A2, a cell membrane sulfate-chloride antiporter. Sulfate uptake impairment results in low cytosolic sulfate, leading to cartilage proteoglycan (PG) undersulfation. In this work, we used the dtd mouse model to study the role of N-acetyl-l-cysteine (NAC), a well-known drug with antioxidant properties, as an intracellular sulfate source for macromolecular sulfation. Because of the important pre-natal phase of skeletal development and growth, we administered 30 g/l NAC in the drinking water to pregnant mice to explore a possible transplacental effect on the fetuses. When cartilage PG sulfation was evaluated by high-performance liquid chromatography disaccharide analysis in dtd newborn mice, a marked increase in PG sulfation was observed in newborns from NAC-treated pregnancies when compared with the placebo group. Morphometric studies of the femur, tibia and ilium after skeletal staining with alcian blue and alizarin red indicated a partial rescue of abnormal bone morphology in dtd newborns from treated females, compared with pups from untreated females. The beneficial effect of increased macromolecular sulfation was confirmed by chondrocyte proliferation studies in cryosections of the tibial epiphysis by proliferating cell nuclear antigen immunohistochemistry: the percentage of proliferating cells, significantly reduced in the placebo group, reached normal values in dtd newborns from NAC-treated females. In conclusion, NAC is a useful source of sulfate for macromolecular sulfation in vivo when extracellular sulfate supply is reduced, confirming the potential of therapeutic approaches with thiol compounds to improve skeletal deformity and short stature in human DTD and related disorders.

Contribution of estrogen and GluN2B subunit to the HtraKO mouse phenotype

Htr1a is one of the most widespread serotonin receptor across the brain, strongly expressed in CAI region of hippocampus. Our laboratory studies the phenotypic alteration in 5HTla- deficient mice (Htr1aK0), characterized an abnormal anxious-like behavior. Our aim is to evaluate the regulation of this cognitive process by understanding the circuitry involved. This phenotype sets up early during development and has durable effect in adulthood. Our laboratory showed that adult Htr1aK0 male mice displaying exuberant dendritic growth of oblique dendrites in a specific layer of a CAI pyramidal neurons, the stratum radiatum. Application of drugs in organotypic cultures and by in vivo injections revealed that GluN2B, a subunit of NMDA receptor highly expressed during development, is responsible for this dendritic exuberance. Immunohistochemistry highlighted in particular a synaptic enrichment of GluN2B in stratum radiatum of Htr1aK0 CAI pyramidal neurons at puberty. Finally, original analysis of Htr1aK0 mouse behavior showed a different response to anxiety between male and female. Htr1a activation down-regulates the CaMKII activity in the CAI pyramidal neurons. CaMKII directly favors the membrane conductance and stability of GluN2B at the synapse. In the context of the Htr1aK0 mouse, GluN2B is the final common pathway of our phenotype. This subunit is well known to regulate the threshold of LTD/LTP and the dendritogenesis during development. In my thesis, I establish a link between the gender differences in the morphology and the physiology in the Htr1aK0 mice during development to understand how these characteristics shape the circuit with prominent cognitive impacts in adulthood. My study highlighted that during development, Htr1aK0 male mice show a constant increase of the dendritic growth of oblique dendrites from early ages until adulthood associated with an increased physiological impact of altered GluN2A/GluN2B ratio. Whereas during puberty, synaptic contribution of GluN2B to NMDA response is higher in Htr1aK0 compared to WT male mice, this ratio comes back to normal values towards adulthood. However, this recovery of the ratio of GluN2A/GluN2B located at the synaptic level is concomitant with the lateral diffusion of excess GluN2B subunits, leading to extrasynaptic enrichment. The main impact was a lowering of the LTP threshold characterized by strong increased potentiation of synaptic strength after 5 Hz low frequency stimulation. Moreover, the extrasynaptic GluN2B overexpression leads to a shift of the maturation phase switch explaining the exuberant morphology. However, Htr1aK0 females characterized during the 3 first weeks of development by an increase of the dendritic growth of oblique dendrites showed starting at puberty that the dendrite arborization returns progressively to WT values. The physiological impact of GluN2B was investigated and directly linked to this morphology, since Htr1aK0 female mice does not show alteration of the synaptic strength during development. These observations show a compensation occurring in Htr1aK0 female, responsible for a rescue of the phenotype morphologically, physiologically and to be tested behaviorally. We highlighted then the biological processes underlying this compensation. During development, sexual hormones such as testosterone and estrogen are responsible to induce sexual differentiation of specific brain regions. I demonstrated that estrogen, but not testosterone, was able to reduce both in vitro and in vivo the dendritic arborization early during development, through activation of GPER-1, a G-coupled protein estrogen receptor, which phenocopy the activation of Htr1a by reducing GluN2B conductance and stability. I then identified a pathway, parallel to Htr1a, able to regulate GluN2B and responsible for the morphological and physiological phenotype in Htr1aK0 female mice. The specific rise of estrogen occurring at puberty in female is responsible for the compensation observed and induces a late rescue of the Htr1aK0 phenotype by activation GPER-1. -- Htr1a est un des récepteurs à la sérotonine les plus répandus dans le cerveau, fortement exprimé dans la région CAI de l'hippocampe. Notre laboratoire étudie les altérations phénotypiques de souris déficientes pour ce récepteur (Htr1aK0), caractérisées par un comportement avec des traits anxieux. Notre objectif est d'évaluer la régulation de ces processus cognitifs en comprenant les connexions nerveuses impliquées. Ce phénotype se met en place tôt au cours du développement et présente un effet durable à l'âge adulte. Notre laboratoire a montré que les souris Htr1aK0 mâles adultes se caractérisent par une croissance exubérante des dendrites obliques dans une couche spécifique des neurones pyramidaux du CAI, le stratum radiatum. L'application de drogues sur cultures organotypiques et par injections in vivo ont révélé que GluN2B, une sous-unité du récepteur NMDA fortement exprimée au cours du développement, est responsable de cette exubérance dendritique. Des expériences d'immunohistochimie ont notamment mis en évidence un enrichissement synaptique de GluN2B durant la puberté dans le stratum radiatum des neurones de la région CAI des souris Htr1aK0. Finalement, l'analyse originale du comportement des souris Htr1aK0 a montré une différence de réponse à l'anxiété entre mâles et femelles. L'activation de Htr1a diminue l'activité de la CaMKII dans les neurones pyramidaux du CAI. La CaMKII favorise directement la conductance et la stabilité de la sous-unité GluN2B à la synapse. Dans le contexte de la souris Htr1aK0, GluN2B est le « médiateur » de notre phénotype. Cette sous-unité est particulièrement connue pour réguler le seuil de LTD-LTP ainsi que la dendritogénèse durant le développement. Dans ma thèse, j'ai établi le lien entre les différences dépendant du genre dans la morphologie et physiologie des souris Htr1aK0 au cours du développement pour comprendre comment ces caractéristiques modulent le circuit accompagnés d'impacts cognitifs visibles à l'âge adulte. Mon étude a mis en évidence que durant le développement, les souris mâles Htr1aK0 montrent une constante augmentation de la croissance des dendrites obliques entre les premières semaines et l'âge adulte associée à une augmentation de l'impact physiologique du ratio GluN2A/GluN2B altéré. Alors que durant la puberté, la contribution synaptique de GluN2B à la réponse NMDA est plus haute chez la souris mâle Htr1aK0 que le WT, ce ratio revient à des valeurs normales à l'âge adulte. Cependant, cette récupération de l'expression du récepteur au niveau synaptique est concomitante avec la diffusion des sous-unités GluN2B excédantes, amenant alors à un enrichissement extrasynaptique. Le principal impact est une diminution du seuil de la LTP caractérisée par une forte potentiation de la plasticité après une stimulation basse fréquence à 5 Hz. De plus, la surexpression des GluN2B extrasynaptiques conduit à un décalage de la bascule à la phase de maturation, expliquant la morphologie dendritique exubérante. Cependant, les femelles Htr1aK0 initialement caractérisées pendant les 3 premières semaines du développement par une augmentation de la croissance des dendrites obliques montrent à partir de la puberté que cette arborisation dendritique retourne à des valeurs WT. L'impact physiologique de GLuN2B a été investigué et mis en lien avec cette morphologie, étant donné que les femelles Htr1aK0 ne montrent pas d'altération de la plasticité durant le développement. Ces observations montrent une compensation se produisant chez la femelle Htr1aK0, responsable d'une récupération du phénotype morphologique, physiologique et peut-être comportemental. Nous avons souligné les processus biologiques sous-jacent à cette compensation. Au cours du développement, les hormones sexuelles telles que la testostérone et l'estrogène sont responsables de la différentiation sexuelle de régions du cerveau spécifiques. J'ai démontré que l'estrogène, mais pas la testostérone, était capable de réduire in vitro et in vivo l'arborisation dendritique tôt dans le développement au travers de l'activation du récepteur GPER-1, un récepteur aux estrogènes couplés à un protéine G, qui phénocopie l'activation de Htr1a en réduisant la conductance et la stabilité de GluN2B à la membrane. J'ai identifié une voie de signalisation parallèle à celle de Htr1a, capable de réguler GluN2B et responsable du phénotype morphologique et physiologique de la souris femelle Htr1aK0. La montée spécifique d'estrogène se déroulant à la puberté chez la femelle est responsable de cette compensation et implique une récupération tardive du phénotype Htr1aK0 par l'activation de GPER-1.

A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion

Deletions in the 2p16.3 region that includes the neurexin (NRXN1) gene are associated with intellectual disability and various psychiatric disorders, in particular, autism and schizophrenia. We present three unrelated patients, two adults and one child, in whom we identified an intragenic 2p16.3 deletion within the NRXN1 gene using an oligonucleotide comparative genomic hybridization array. The three patients presented dual diagnosis that consisted of mild intellectual disability and autism and bipolar disorder. Also, they all shared a dysmorphic phenotype characterized by a long face, deep set eyes, and prominent premaxilla. Genetic analysis of family members showed two inherited deletions. A comprehensive neuropsychological examination of the 2p16.3 deletion carriers revealed the same phenotype, characterized by anxiety disorder, borderline intelligence, and dysexecutive syndrome. The cognitive pattern of dysexecutive syndrome with poor working memory and reduced attention switching, mental flexibility, and verbal fluency was the same than those of the adult probands. We suggest that in addition to intellectual disability and psychiatric disease, NRXN1 deletion is a risk factor for a characteristic cognitive and dysmorphic profile. The new cognitive phenotype found in the 2p16.3 deletion carriers suggests that 2p16.3 deletions might have a wide variable expressivity instead of incomplete penetrance

Impaired aldehyde dehydrogenase 1 subfamily member 2A-dependent retinoic acid signaling is related with a mesenchymal-like phenotype and an unfavorable prognosis of head and neck squamous cell carcinoma.

BACKGROUND: An inverse correlation between expression of the aldehyde dehydrogenase 1 subfamily A2 (ALDH1A2) and gene promoter methylation has been identified as a common feature of oropharyngeal squamous cell carcinoma (OPSCC). Moreover, low ALDH1A2 expression was associated with an unfavorable prognosis of OPSCC patients, however the causal link between reduced ALDH1A2 function and treatment failure has not been addressed so far. METHODS: Serial sections from tissue microarrays of patients with primary OPSCC (n = 101) were stained by immunohistochemistry for key regulators of retinoic acid (RA) signaling, including ALDH1A2. Survival with respect to these regulators was investigated by univariate Kaplan-Meier analysis and multivariate Cox regression proportional hazard models. The impact of ALDH1A2-RAR signaling on tumor-relevant processes was addressed in established tumor cell lines and in an orthotopic mouse xenograft model. RESULTS: Immunohistochemical analysis showed an improved prognosis of ALDH1A2(high) OPSCC only in the presence of CRABP2, an intracellular RA transporter. Moreover, an ALDH1A2(high)CRABP2(high) staining pattern served as an independent predictor for progression-free (HR: 0.395, p = 0.007) and overall survival (HR: 0.303, p = 0.002), suggesting a critical impact of RA metabolism and signaling on clinical outcome. Functionally, ALDH1A2 expression and activity in tumor cell lines were related to RA levels. While administration of retinoids inhibited clonogenic growth and proliferation, the pharmacological inhibition of ALDH1A2-RAR signaling resulted in loss of cell-cell adhesion and a mesenchymal-like phenotype. Xenograft tumors derived from FaDu cells with stable silencing of ALDH1A2 and primary tumors from OPSCC patients with low ALDH1A2 expression exhibited a mesenchymal-like phenotype characterized by vimentin expression. CONCLUSIONS: This study has unraveled a critical role of ALDH1A2-RAR signaling in the pathogenesis of head and neck cancer and our data implicate that patients with ALDH1A2(low) tumors might benefit from adjuvant treatment with retinoids.

Environmental influence on the phenotype of ant workers revealed by common garden experiment

Many organism traits vary along environmental gradients. Common garden experiments provide powerful means to disentangle the role of intrinsic factors, such as genetic or maternal effects, from extrinsic environmental factors in shaping phenotypic variation. Here, we investigate body size and lipid content variation in workers of the socially polymorphic ant Formica selysi along several independent elevation gradients in Switzerland. We compare field-collected workers and workers sampled as eggs from the same colonies but reared in common laboratory conditions. Overall, field-collected workers from high elevation are larger than those from low elevation, but the trend varies substantially among valleys. The same pattern is recovered when the eggs are reared in a common garden, which indicates that body size variation along elevation gradients and valleys is partly explained by genetic or maternal effects. However, both body size and lipid content exhibit significantly greater variation in field-collected workers than in laboratory-reared workers. Hence, much of the phenotypic variation results from a plastic response to the environment, rather than from genetic differences. Eggs from different elevations also show no significant difference in development time in the common garden. Overall, selection on individual worker phenotypes is unlikely to drive the altitudinal distribution of single- and multiple-queen colonies in this system, as phenotypic variation tends to be plastic and can be decoupled from social structure. This study provides insights into the interplay between individual phenotypic variation and social organization and how the two jointly respond to differing environmental conditions.

A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.

Seventy-five percent of breast cancers are estrogen receptor α positive (ER(+)). Research on these tumors is hampered by lack of adequate in vivo models; cell line xenografts require non-physiological hormone supplements, and patient-derived xenografts (PDXs) are hard to establish. We show that the traditional grafting of ER(+) tumor cells into mammary fat pads induces TGFβ/SLUG signaling and basal differentiation when they require low SLUG levels to grow in vivo. Grafting into the milk ducts suppresses SLUG; ER(+) tumor cells develop, like their clinical counterparts, in the presence of physiological hormone levels. Intraductal ER(+) PDXs are retransplantable, predictive, and appear genomically stable. The model provides opportunities for translational research and the study of physiologically relevant hormone action in breast carcinogenesis.

Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells.

Tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily members play essential roles in the development of the different phases of the immune response. Mouse LIGHT (TNFSF14) is a type II transmembrane protein with a C-terminus extracellular TNF homology domain (THD) that assembles in homotrimers and regulates the course of the immune responses by signaling through 2 receptors, the herpes virus entry mediator (HVEM, TNFSFR14) and the lymphotoxin β receptor (LTβR, TNFSFR3). LIGHT is a membrane-bound protein transiently expressed on activated T cells, natural killer (NK) cells and immature dendritic cells that can be proteolytically cleaved by a metalloprotease and released to the extracellular milieu. The immunotherapeutic potential of LIGHT blockade was evaluated in vivo. Administration of an antagonist of LIGHT interaction with its receptors attenuated the course of graft-versus-host reaction and recapitulated the reduced cytotoxic activity of LIGHT-deficient T cells adoptively transferred into non-irradiated semiallogeneic recipients. The lack of LIGHT expression on donor T cells or blockade of LIGHT interaction with its receptors slowed down the rate of T cell proliferation and decreased the frequency of precursor alloreactive T cells, retarding T cell differentiation toward effector T cells. The blockade of LIGHT/LTβR/HVEM pathway was associated with delayed downregulation of interleukin-7Rα and delayed upregulation of inducible costimulatory molecule expression on donor alloreactive CD8 T cells that are typical features of impaired T cell differentiation. These results expose the relevance of LIGHT/LTβR/HVEM interaction for the potential therapeutic control of the allogeneic immune responses mediated by alloreactive CD8 T cells that can contribute to prolong allograft survival.

Populations of breeding birds in Byers Peninsula, Livingston Island, South Shetland Islands

Data about breeding populations of birds in the Antarctica are rare and fragmented. Thus, information about the status of the breeding populations of Antarctic birds is crucial given the current scenario of climate change, which is particularly acute in Antarctica. This paper presents new information about the populations of the Antarctic tern Sterna vittata, the kelp gull Larus dominicanus, the southern giant petrel Macronectes giganteus, the Antarctic skua Catharacta antarctica lonnbergi, the chinstrap penguin Pygoscelis antarctica and the gentoo penguin Pygoscelis papua on Byers Peninsula (Livingston Island, South Shetland Islands). We used line transects counts to estimate both densities and numbers of nests of the different species. We estimate that there are 398.96 birds km-2 of southern giant petrels (2793 individuals), 62.4 birds km-2 of Antarctic tern (3746 individuals) and 269.1 birds km-2 of kelp gull (1884 individuals). Furthermore, we found 15 nests of Antarctic skua in 25 km2, from which we can estimate that 6091 birds must breed on Byers Peninsula. We also censused two colonies of gentoo penguins (3000 and 1200 pairs) and 50 pairs of chinstrap. Compared to previous estimates, gentoo penguins seem to have increased whereas chinstrap penguin have decreased. Finally, the populations of Antarctic tern, southern giant petrel and kelp gull have stabilized or slightly increased.

Back to the island of calm: mallorcan human traditional medicine and ethnobotany

This study reveals that a successful ethnobotanical survey can take place still nowadays, even close to one of the hotspots of tourism in the Mediterranean coast. This is the first approach in this field entirely based on interviews with local people in Mallorca. An amount of 235 informants has been inquired from all the 53 municipalities of the island. The data collected have been analyzed from the botanical and ethnographical points of view, and managed using the online platform of our research team (details at www.etnobiofic.cat). The Mallorcan ethnopharmacopoeia includes 255 plant taxa referring more than 150 medicinal use categories. Ethnomedical queries as the one here presented contribute to the knowledge of the traditional use of plants of the island and appreciate the benefits of this knowledge, applied to the present and future of its society.

Back to the island of calm: Mallorcan human traditional medicine and ethnobotany

This study reveals that a successful ethnobotanical survey can take place still nowadays, even close to one of the hotspots of tourism in the Mediterranean coast. This is the first approach in this field entirely based on interviews with local people in Mallorca. An amount of 235 informants has been inquired from all the 53 municipalities of the island. The data collected have been analyzed from the botanical and ethnographical points of view, and managed using the online platform of our research team (details at www.etnobiofic.cat). The Mallorcan ethnopharmacopoeia includes 255 plant taxa referring more than 150 medicinal use categories. Ethnomedical queries as the one here presented contribute to the knowledge of the traditional use of plants of the island and appreciate the benefits of this knowledge, applied to the present and future of its society.

Coral Island : for soprano and orchestra

Digitoitu 10. 6. 2008.