Upstream sources of the Denmark Strait Overflow : observations from a high-resolution mooring array

© The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Deep Sea Research Part I: Oceanographic Research Papers 112 (2016): 94-112, doi:10.1016/j.dsr.2016.02.007.We present the first results from a densely instrumented mooring array upstream of the Denmark Strait sill, extending from the Iceland shelfbreak to the Greenland shelf. The array was deployed from September 2011 to July 2012, and captured the vast majority of overflow water denser than 27.8 kgm-3 approaching the sill. The mean transport of overflow water over the length of the deployment was 3.54 ± 0.16 Sv. Of this, 0.58 Sv originated from below sill depth, revealing that aspiration takes place in Denmark Strait. We confirm the presence of two main sources of overflow water: one approaching the sill in the East Greenland Current and the other via the North Icelandic Jet. Using an objective technique based on the hydrographic properties of the water, the transports of these two sources are found to be 2.54 ± 0.17 Sv and 1.00 ± 0.17 Sv, respectively. We further partition the East Greenland Current source into that carried by the shelfbreak jet (1.50 ± 0.16 Sv) versus that transported by a separated branch of the current on the Iceland slope (1.04 ± 0.15 Sv). Over the course of the year the total overflow transport is more consistent than the transport in either branch; compensation takes place among the pathways that maintains a stable total overflow transport. This is especially true for the two East Greenland Current branches whose transports vary out of phase with each other on weekly and longer time scales. We argue that wind forcing plays a role in this partitioning.The mooring and analysis work was supported by NSF OCE research grants OCE-0959381 and OCE-1433958, by the European Union 7th Framework Programme (FP7 2007-2013) under grant agreement n. 308299 NACLIM, and and by the Research Council of Norway through the Fram Centre Flaggship project 6606-299.2017-03-2

Upstream sources of the Denmark Strait Overflow : observations from a high-resolution mooring array

© The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Deep Sea Research Part I: Oceanographic Research Papers 112 (2016): 94-112, doi:10.1016/j.dsr.2016.02.007.We present the first results from a densely instrumented mooring array upstream of the Denmark Strait sill, extending from the Iceland shelfbreak to the Greenland shelf. The array was deployed from September 2011 to July 2012, and captured the vast majority of overflow water denser than 27.8 kgm-3 approaching the sill. The mean transport of overflow water over the length of the deployment was 3.54 ± 0.16 Sv. Of this, 0.58 Sv originated from below sill depth, revealing that aspiration takes place in Denmark Strait. We confirm the presence of two main sources of overflow water: one approaching the sill in the East Greenland Current and the other via the North Icelandic Jet. Using an objective technique based on the hydrographic properties of the water, the transports of these two sources are found to be 2.54 ± 0.17 Sv and 1.00 ± 0.17 Sv, respectively. We further partition the East Greenland Current source into that carried by the shelfbreak jet (1.50 ± 0.16 Sv) versus that transported by a separated branch of the current on the Iceland slope (1.04 ± 0.15 Sv). Over the course of the year the total overflow transport is more consistent than the transport in either branch; compensation takes place among the pathways that maintains a stable total overflow transport. This is especially true for the two East Greenland Current branches whose transports vary out of phase with each other on weekly and longer time scales. We argue that wind forcing plays a role in this partitioning.The mooring and analysis work was supported by NSF OCE research grants OCE-0959381 and OCE-1433958, by the European Union 7th Framework Programme (FP7 2007-2013) under grant agreement n. 308299 NACLIM, and and by the Research Council of Norway through the Fram Centre Flaggship project 6606-299.2017-03-2

Seizure-Related Gene 6 (Sez-6) in Amacrine Cells of the Rodent Retina and the Consequence of Gene Deletion

Background: Seizure-related gene 6 (Sez-6) is expressed in neurons of the mouse brain, retina and spinal cord. In the cortex, Sez-6 plays a role in specifying dendritic branching patterns and excitatory synapse numbers during development. Methodology/Principal Findings: The distribution pattern of Sez-6 in the retina was studied using a polyclonal antibody that detects the multiple isoforms of Sez-6. Prominent immunostaining was detected in GABAergic, but not in All glycinergic, amacrine cell subpopulations of the rat and mouse retina. Amacrine cell somata displayed a distinct staining pattern with the Sez-6 antibody: a discrete, often roughly triangular-shaped bright spot positioned between the nucleus and the apical dendrite superimposed over weaker general cytoplasmic staining. Displaced amacrines in the ganglion cell layer were also positive for Sez-6 and weaker staining was occasionally observed in neurons with the morphology of alpha ganglion cells. Two distinct Sez-6 positive strata were present in the inner plexiform layer in addition to generalized punctate staining. Certain inner nuclear layer cells, including bipolar cells, stained more weakly and diffusely than amacrine cells, although some bipolar cells exhibited a perinuclear "bright spot" similar to amacrine cells. In order to assess the role of Sez-6 in the retina, we analyzed the morphology of the Sez-6 knockout mouse retina with immunohistochemical markers and compared ganglion cell dendritic arbor patterning in Sez-6 null retinae with controls. The functional importance of Sez-6 was assessed by dark-adapted paired-flash electroretinography (ERG). Conclusions: In summary, we have reported the detailed expression pattern of a novel retinal marker with broad cell specificity, useful for retinal characterization in rodent experimental models. Retinal morphology, ganglion cell dendritic branching and ERG waveforms appeared normal in the Sez-6 knockout mouse suggesting that, in spite of widespread expression of Sez-6, retinal function in the absence of Sez-6 is not affected

Doublecortin and doublecortin-like are expressed in overlapping and non-overlapping neuronal cell population: implications for neurogenesis

We have characterized the expression of doublecortin-like (DCL), a microtubule-associated protein involved in embryonic neurogenesis that is highly homologous to doublecortin (DCX), in the adult mouse brain. To this end, we developed a DCL-specific antibody and used this to compare DCL expression with DCX. In the neurogenic regions of the adult brain like the subventricular zone (SVZ), the rostral migratory stream (RMS), the olfactory bulb (OB), and the hippocampus, DCL colocalizes with DCX in immature neuronal cell populations. In contrast to DCX, we also found high DCL expression in three other brain regions with suspected neurogenesis or neuronal plasticity. First, the radial glia-like, hypothalamic tanycytes show high DCL expression that partly colocalizes with the neural stem cell marker vimentin. Second, DCL expression is found in cells of the suprachiasmatic nucleus (SCN), which lacks expression of the adult neuron marker NeuN. Third, a novel region exhibiting DCL expression is part of the olfactory tubercle where DCL is found in the neuropil of the islands of Calleja (ICj). Our findings define DCL as a novel marker for specific aspects of adult neurogenesis, which partly overlap with DCX. In addition, we propose unique roles for DCL in adult neurogenesis and we suggest high levels of neuronal plasticity in tanycytes, SCN, and ICj

Silencing of Doublecortin-Like (DCL) Results in Decreased Mitochondrial Activity and Delayed Neuroblastoma Tumor Growth

Doublecortin-like (DCL) is a microtubule-binding protein crucial for neuroblastoma (NB) cell proliferation. We have investigated whether the anti-proliferative effect of DCL knockdown is linked to reduced mitochondrial activity. We found a delay in tumor development after DCL knockdown in vivo in doxycycline-inducible NB tumor xenografts. To understand the mechanisms underlying this tumor growth retardation we performed a series of in vitro experiments in NB cell lines. DCL colocalizes with mitochondria, interacts with the mitochondrial outer membrane protein OMP25/ SYNJ2BP and DCL knockdown results in decreased expression of genes involved in oxidative phosphorylation. Moreover, DCL knockdown decreases cytochrome c oxidase activity and ATP synthesis. We identified the C-terminal Serine/Proline-rich domain and the second microtubule-binding area as crucial DCL domains for the regulation of cytochrome c oxidase activity and ATP synthesis. Furthermore, DCL knockdown causes a significant reduction in the proliferation rate of NB cells under an energetic challenge induced by low glucose availability. Together with our previous studies, our results corroborate DCL as a key player in NB tumor growth in which DCL controls not only mitotic spindle formation and the stabilization of the microtubule cytoskeleton, but also regulates mitochondrial activity and energy availability, which makes DCL a promising molecular target for NB therapy

Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment

Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by a high level of molecular heterogeneity, and infiltration by various immune and stromal cell populations. Important advances have been made in deciphering the microenvironment of GBMs, but its association with existing molecular subtypes and its potential prognostic role remain elusive. We have investigated the abundance of infiltrating immune and stromal cells in silico, from gene expression profiles. Two cohorts, including in-house normal brain and glioma samples (n = 70) and a large sample set from TCGA (n = 393), were combined into a single exploratory dataset. A third independent cohort (n = 124) was used for validation. Tumors were clustered based on their microenvironment infiltration profiles, and associations with known GBM molecular subtypes and patient outcome were tested a posteriori in a multivariable setting. We identified a subset of GBM samples with significantly higher abundances of most immune and stromal cell populations. This subset showed increased expression of both immune suppressor and immune effector genes compared to other GBMs and was enriched for the mesenchymal molecular subtype. Survival analyses suggested that tumor microenvironment infiltration pattern was an independent prognostic factor for GBM patients. Among all, patients with the mesenchymal subtype with low immune and stromal infiltration had the poorest survival. By combining molecular subtyping with gene expression measures of tumor infiltration, the present work contributes with improving prognostic models in GBM