254 research outputs found

    Inner-shelf circulation and sediment dynamics on a series of shoreface-connected ridges offshore of Fire Island, NY

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    Locations along the inner-continental shelf offshore of Fire Island, NY, are characterized by a series of shoreface-connected ridges (SFCRs). These sand ridges have approximate dimensions of 10 km in length, 3 km spacing, and up to similar to 8 m ridge to trough relief and are oriented obliquely at approximately 30 degrees clockwise from the coastline. Stability analysis from previous studies explains how sand ridges such as these could be formed and maintained by storm-driven flows directed alongshore with a key maintenance mechanism of offshore deflected flows over ridge crests and onshore in the troughs. We examine these processes both with a limited set of idealized numerical simulations and analysis of observational data. Model results confirm that alongshore flows over the SFCRs exhibit offshore veering of currents over the ridge crests and onshore-directed flows in the troughs, and demonstrate the opposite circulation pattern for a reverse wind. To further investigate these maintenance processes, oceanographic instruments were deployed at seven sites on the SFCRs offshore of Fire Island to measure water levels, ocean currents, waves, suspended sediment concentrations, and bottom stresses from January to April 2012. Data analysis reveals that during storms with winds from the northeast, the processes of offshore deflection of currents over ridge crests and onshore in the troughs were observed, and during storm events with winds from the southwest, a reverse flow pattern over the ridges occurred. Computations of suspended sediment fluxes identify periods that are consistent with SFCR maintenance mechanisms. Alongshore winds from the northeast drove fluxes offshore on the ridge crest and onshore in the trough that would tend to promote ridge maintenance. However, alongshore winds from the southwest drove opposite circulations. The wind fields are related to different storm types that occur in the region (low-pressure systems, cold fronts, and warm fronts). From the limited data set, we identify that low-pressure systems drive sediment fluxes that tend to promote stability and maintain the SFCRs while cold front type storms appear to drive circulations that are in the opposite sense and may not be a supporting mechanism for ridge maintenance

    An extended window of opportunity for G-CSF treatment in cerebral ischemia

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    BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) is known as a powerful regulator of white blood cell proliferation and differentiation in mammals. We, and others, have shown that G-CSF is effective in treating cerebral ischemia in rodents, both relating to infarct size as well as functional recovery. G-CSF and its receptor are expressed by neurons, and G-CSF regulates apoptosis and neurogenesis, providing a rational basis for its beneficial short- and long-term actions in ischemia. In addition, G-CSF may contribute to re-endothelialisation and arteriogenesis in the vasculature of the ischemic penumbra. In addition to these trophic effects, G-CSF is a potent neuroprotective factor reliably reducing infarct size in different stroke models. RESULTS: Here, we have further delayed treatment and studied effects of G-CSF on infarct volume in the middle cerebral artery occlusion (MCAO) model and functional outcome in the cortical photothrombotic model. In the MCAO model, we applied a single dose of 60 μg/kg bodyweight G-CSF in rats 4 h after onset of ischemia. Infarct volume was determined 24 h after onset of ischemia. In the rat photothrombotic model, we applied 10 μg/kg bodyweight G-CSF daily for a period of 10 days starting either 24 or 72 h after induction of ischemia. G-CSF both decreased acute infarct volume in the MCAO model, and improved recovery in the photothrombotic model at delayed timepoints. CONCLUSION: These data further strengthen G-CSF's profile as a unique candidate stroke drug, and provide an experimental basis for application of G-CSF in the post-stroke recovery phase

    Reconstruction of Endometrium from Human Endometrial Side Population Cell Lines

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    Endometrial regeneration is mediated, at least in part, by the existence of a specialized somatic stem cell (SSC) population recently identified by several groups using the side population (SP) technique. We previously demonstrated that endometrial SP displays genotypic, phenotypic and the functional capability to develop human endometrium after subcutaneous injection in NOD-SCID mice. We have now established seven human endometrial SP (hESP) cell lines (ICE 1–7): four from the epithelial and three from the stromal fraction, respectively. SP cell lines were generated under hypoxic conditions based on their cloning efficiency ability, cultured for 12–15 passages (20 weeks) and cryopreserved. Cell lines displayed normal 46XX karyotype, intermediate telomerase activity pattern and expressed mRNAs encoding proteins that are considered characteristic of undifferentiated cells (Oct-4, GDF3, DNMT3B, Nanog, GABR3) and those of mesodermal origin (WT1, Cardiac Actin, Enolase, Globin, REN). Phenotype analysis corroborated their epithelial (CD9+) or stromal (vimentin+) cell origin and mesenchymal (CD90+, CD73+ and CD45−) attributes. Markers considered characteristic of ectoderm or endoderm were not detected. Cells did not express either estrogen receptor alpha (ERα) or progesterone receptor (PR). The hESP cell lines were able to differentiate in vitro into adipocytes and osteocytes, which confirmed their mesenchymal origin. Finally, we demonstrated their ability to generate human endometrium when transplanted beneath the renal capsule of NOD-SCID mice. These findings confirm that SP cells exhibit key features of human endometrial SSC and open up new possibilities for the understanding of gynecological disorders such as endometriosis or Asherman syndrome. Our cell lines can be a valuable model to investigate new targets for endometrium proliferation in endometriosis

    A Distinct Translation Initiation Mechanism Generates Cryptic Peptides for Immune Surveillance

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    MHC class I molecules present a comprehensive mixture of peptides on the cell surface for immune surveillance. The peptides represent the intracellular protein milieu produced by translation of endogenous mRNAs. Unexpectedly, the peptides are encoded not only in conventional AUG initiated translational reading frames but also in alternative cryptic reading frames. Here, we analyzed how ribosomes recognize and use cryptic initiation codons in the mRNA. We find that translation initiation complexes assemble at non-AUG codons but differ from canonical AUG initiation in response to specific inhibitors acting within the peptidyl transferase and decoding centers of the ribosome. Thus, cryptic translation at non-AUG start codons can utilize a distinct initiation mechanism which could be differentially regulated to provide peptides for immune surveillance

    Local Individual Preferences for Nest Materials in a Passerine Bird

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    Variation in the behavioural repertoire of animals is acquired by learning in a range of animal species. In nest-building birds, the assemblage of nest materials in an appropriate structure is often typical of a bird genus or species. Yet plasticity in the selection of nest materials may be beneficial because the nature and abundance of nest materials vary across habitats. Such plasticity can be learned, either individually or socially. In Corsican populations of blue tits Cyanistes caeruleus, females regularly add in their nests fragments of several species of aromatic plants during the whole breeding period. The selected plants represent a small fraction of the species present in the environment and have positive effects on nestlings.We investigated spatiotemporal variations of this behaviour to test whether the aromatic plant species composition in nests depends on 1) plant availability in territories, 2) female experience or 3) female identity. Our results indicate that territory plays a very marginal role in the aromatic plant species composition of nests. Female experience is not related to a change in nest plant composition. Actually, this composition clearly depends on female identity, i.e. results from individual preferences which, furthermore, are repeatable both within and across years. A puzzling fact is the strong difference in plant species composition of nests across distinct study plots.This study demonstrates that plant species composition of nests results from individual preferences that are homogeneous within study plots. We propose several hypotheses to interpret this pattern of spatial variation before discussing them in the light of preliminary results. As a conclusion, we cannot exclude the possibility of social transmission of individual preferences for aromatic plants. This is an exciting perspective for further work in birds, where nest construction behaviour has classically been considered as a stereotypic behaviour

    Cancer initiation and progression: an unsimplifiable complexity

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    BACKGROUND: Cancer remains one of the most complex diseases affecting humans and, despite the impressive advances that have been made in molecular and cell biology, how cancer cells progress through carcinogenesis and acquire their metastatic ability is still widely debated. CONCLUSION: There is no doubt that human carcinogenesis is a dynamic process that depends on a large number of variables and is regulated at multiple spatial and temporal scales. Viewing cancer as a system that is dynamically complex in time and space will, however, probably reveal more about its underlying behavioural characteristics. It is encouraging that mathematicians, biologists and clinicians continue to contribute together towards a common quantitative understanding of cancer complexity. This way of thinking may further help to clarify concepts, interpret new and old experimental data, indicate alternative experiments and categorize the acquired knowledge on the basis of the similarities and/or shared behaviours of very different tumours

    Investigation of the role of gas hydrates in continental slope stability west of Fiordland, New Zealand

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    Sediment weakening due to increased local pore fluid pressure is interpreted to be the cause of a submarine landslide that has been seismically imaged off the southwest coast of New Zealand. Data show a distinct and continuous bottom‐simulating reflection (BSR)—a seismic phenomena indicative of the presence of marine gas hydrate—below the continental shelf from water depths of c. 2400 m to c. 750 m, where it intersects the seafloor. Excess pore fluid pressure (EPP) generated in a free gas zone below the base of gas hydrate stability is interpreted as being a major factor in the slope's destabilisation. Representative sediment strength characteristics have been applied to limit‐equilibrium methods of slope stability analysis with respect to the Mohr‐Coulomb failure criterion to develop an understanding of the feature's sensitivity to EPP. EPP has been modelled with representative material properties (internal angle of friction, bulk soil unit weight and cohesion) to show the considerable effect it has on stability. The best estimate of average EPP being solely responsible for failure is 1700 kPa, assuming a perfectly elastic body above a pre‐defined failure surface in a static environment

    Incomplete Inhibition of Sphingosine 1-Phosphate Lyase Modulates Immune System Function yet Prevents Early Lethality and Non-Lymphoid Lesions

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    BACKGROUND: S1PL is an aldehyde-lyase that irreversibly cleaves sphingosine 1-phosphate (S1P) in the terminal step of sphingolipid catabolism. Because S1P modulates a wide range of physiological processes, its concentration must be tightly regulated within both intracellular and extracellular environments. METHODOLOGY: In order to better understand the function of S1PL in this regulatory pathway, we assessed the in vivo effects of different levels of S1PL activity using knockout (KO) and humanized mouse models. PRINCIPAL FINDINGS: Our analysis showed that all S1PL-deficient genetic models in this study displayed lymphopenia, with sequestration of mature T cells in the thymus and lymph nodes. In addition to the lymphoid phenotypes, S1PL KO mice (S1PL(-/-)) also developed myeloid cell hyperplasia and significant lesions in the lung, heart, urinary tract, and bone, and had a markedly reduced life span. The humanized knock-in mice harboring one allele (S1PL(H/-)) or two alleles (S1PL(H/H)) of human S1PL expressed less than 10 and 20% of normal S1PL activity, respectively. This partial restoration of S1PL activity was sufficient to fully protect both humanized mouse lines from the lethal non-lymphoid lesions that developed in S1PL(-/-) mice, but failed to restore normal T-cell development and trafficking. Detailed analysis of T-cell compartments indicated that complete absence of S1PL affected both maturation/development and egress of mature T cells from the thymus, whereas low level S1PL activity affected T-cell egress more than differentiation. SIGNIFICANCE: These findings demonstrate that lymphocyte trafficking is particularly sensitive to variations in S1PL activity and suggest that there is a window in which partial inhibition of S1PL could produce therapeutic levels of immunosuppression without causing clinically significant S1P-related lesions in non-lymphoid target organs
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