Combined Chondroitinase and KLF7 Expression Reduce Net Retraction of Sensory and CST Axons from Sites of Spinal Injury

Axon regeneration in the central nervous system is limited both by inhibitory extracellular cues and by an intrinsically low capacity for axon growth in some CNS populations. Chondroitin sulfate proteoglycans (CSPGs) are well-studied inhibitors of axon growth in the CNS, and degradation of CSPGs by chondroitinase has been shown to improve the extension of injured axons. Alternatively, axon growth can be improved by targeting the neuron-intrinsic growth capacity through forced expression of regeneration-associated transcription factors. For example, a transcriptionally active chimera of Krüppel-like Factor 7 (KLF7) and a VP16 domain improves axon growth when expressed in corticospinal tract neurons. Here we tested the hypothesis that combined expression of chondroitinase and VP16-KLF7 would lead to further improvements in axon growth after spinal injury. Chondroitinase was expressed by viral transduction of cells in the spinal cord, while VP16-KLF7 was virally expressed in sensory neurons of the dorsal root ganglia or corticospinal tract (CST) neurons. After transection of the dorsal columns, both chondroitinase and VP16-KLF7 increased the proximity of severed sensory axons to the injury site. Similarly, after complete crush injuries, VP16-KLF7 expression increased the approach of CST axons to the injury site. In neither paradigm however, did single or combined treatment with chondroitinase or VP16-KLF7 enable regenerative growth distal to the injury. These results substantiate a role for CSPG inhibition and low KLF7 activity in determining the net retraction of axons from sites of spinal injury, while suggesting that additional factors act to limit a full regenerative response

Detection of Salinity by the Lobster, Homarus americanus

Changes in the heart rates of lobsters (Homarus americanus) were used as an indicator that the animals were capable of sensing a reduction in the salinity of the ambient seawater. The typical response to a gradual (1 to 2 ppt/min) reduction in salinity consisted of a rapid increase in heart rate at a mean threshold of 26.6 ± 0.7 ppt, followed by a reduction in heart rate when the salinity reached 22.1 ± 0.5 ppt. Animals with lesioned cardioregulatory nerves did not exhibit a cardiac response to changes in salinity. A cardiac response was elicited from lobsters exposed to isotonic chloride-free salines but not to isotonic sodium-, magnesium- or calcium-free salines. There was little change in the blood osmolarity of lobsters when bradycardia occurred, suggesting that the receptors involved are external. Furthermore, lobsters without antennae, antennules, or legs showed typical cardiac responses to low salinity, indicating the receptors are not located in these areas. Lobsters exposed to reductions in the salinity of the ambient seawater while both branchial chambers were perfused with full-strength seawater did not display a cardiac response until the external salinity reached 21.6 ± 1.8 ppt. In contrast, when their branchial chambers were exposed to reductions in salinity while the external salinity was maintained at normal levels, changes in heart rate were rapidly elicited in response to very small reductions in salinity (down to 29.5 ± 0.9 ppt in the branchial chamber and 31.5 ± 0.3 ppt externally). We conclude that the primary receptors responsible for detecting reductions in salinity in H. americanus are located within or near the branchial chambers and are primarily sensitive to chloride ions

Earliest Holocene south Greenland ice sheet retreat within its late Holocene extent

Early Holocene summer warmth drove dramatic Greenland ice sheet (GIS) retreat. Subsequent insolation-driven cooling caused GIS margin readvance to late Holocene maxima, from which ice margins are now retreating. We use 10Be surface exposure ages from four locations between 69.4°N and 61.2°N to date when in the early Holocene south to west GIS margins retreated to within these late Holocene maximum extents. We find that this occurred at 11.1 ± 0.2 ka to 10.6 ± 0.5 ka in south Greenland, significantly earlier than previous estimates, and 6.8 ± 0.1 ka to 7.9 ± 0.1 ka in southwest to west Greenland, consistent with existing 10Be ages. At least in south Greenland, these 10Be ages likely provide a minimum constraint for when on a multicentury timescale summer temperatures after the last deglaciation warmed above late Holocene temperatures in the early Holocene. Current south Greenland ice margin retreat suggests that south Greenland may have now warmed to or above earliest Holocene summer temperatures

A statistical study of variation in the catch of plankton nets

Staternent of the Problern.----In a previous communication, Winsor and Walford (1936) analyzed the results of repeated vertical hauls of different types of plankton nets, making use of data available in the literature. They concluded that the observed results could be accounted for reasonably well on the assumptions that (a) the organisms were randomly distributed in the medium and (b) that the volume of medium effectively sampled varied from haul to haul. From this result it follows that as the total catch is increased (as by increasing the net size) the reliability of a population estimate is ultimately limited by variation in volume sampled; and that where such conditions hold, it is useless to attempt greater accuracy by increasing either the total catch or the fraction counted much beyond the point where 100 organisms of the kind in question are counted

The Tumor Suppressor HHEX Inhibits Axon Growth when Prematurely Expressed in Developing Central Nervous System Neurons

Neurons in the embryonic and peripheral nervoussystem respond to injury by activating transcriptional programs supportive of axon growth, ultimately resulting in functional recovery. In contrast, neurons in the adult central nervous system (CNS) possess a limited capacity to regenerate axons after injury, fundamentally constraining repair. Activating pro-regenerative gene expression in CNS neurons is a promising therapeutic approach, but progress is hampered by incomplete knowledge of the relevant transcription factors. An emerging hypothesis is that factors implicated in cellular growth and motility outside the nervous system may also control axon growth in neurons. We therefore tested sixty-nine transcription factors, previously identified as possessing tumor suppressive or oncogenic properties in non-neuronal cells, in assays of neurite outgrowth. This screen identified YAP1 and E2F1 as enhancers of neurite outgrowth, and PITX1, RBM14, ZBTB16, and HHEX as inhibitors. Follow-up experiments are focused on the tumor suppressor HHEX, one of the strongest growth inhibitors. HHEX is widely expressed in adult CNS neurons, including corticospinal tract neurons after spinal injury, but is present only in trace amounts in immature cortical neurons and adult peripheral neurons. HHEX overexpression in early postnatal cortical neurons reduced both initial axonogenesis and the rate of axon elongation, and domain deletion analysis strongly implicated transcriptional repression as the underlying mechanism. These findings suggest a role for HHEX in restricting axon growth in the developing CNS, and substantiate the hypothesis that previously identified oncogenes and tumor suppressors can play conserved roles in axon extension

The St. Lawrence polynya and the Bering shelf circulation : new observations and a model comparison

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 111 (2006): C09023, doi:10.1029/2005JC003268.Using 14 year-long instrumented moorings deployed south of St. Lawrence Island, along with oceanographic drifters, we investigate the circulation over the central Bering shelf and the role of polynyas in forming and disseminating saline waters over the shelf. We focus also on evaluating the Gawarkiewicz and Chapman [1995] model of eddy production within coastal polynyas. Principal results include: 1) The northern central shelf near-surface waters exhibit westward flow carrying low-salinity waters from the Alaskan coast in fall and early winter, with consequences for water mass formation and biological production. 2) Within the St. Lawrence polynya, the freshening effect of winter advection is about half as large as the salting effect of surface brine flux resulting from freezing. 3) Brine production over the Bering shelf occurs primarily offshore, rather than within coastal polynyas, even though ice production per unit area is much larger within the polynyas. 4) We find little evidence for the geostrophic flow adjustment predicted by recent polynya models. 5) In contrast to the theoretical prediction that dense water from the polynya is carried offshore by eddies, we find negligible cross-shelf eddy density fluxes within and surrounding the polynya and very low levels of eddy energy that decreased from fall to winter, even though dense water accumulated within the polynya and large cross-shore density gradients developed. 6) It is possible that dense polynya water was advected downstream of our array before appreciable eddy fluxes materialized.This work was supported by National Science Foundation grant OCE9730697 to the University of Alaska and grant OCE9730823 to the University of Washington. S. M. acknowledges the support of the National Science Foundation under OCE9811097 and of NASA under grant NNG04GM69G. The University of Hamburg contributions were funded by the Bundesminister für Bildung und Wissenschaft. Funding for the drifter deployment was made possible by the North Pacific Research Board, grant NPMRI T2130. Manuscript preparation was additionally supported by Office of Naval Research grants N00014-99-1-0345 and N00014-02-1-0305 to the University of Washington

Pressure Induced Topological Phase Transitions in Membranes

Some highly unusual features of a lipid-water liquid crystal are revealed by high pressure x-ray diffraction, light scattering and dilatometric studies of the lamellar (bilayer $L_{\alpha}$) to nonlamellar inverse hexagonal ($H_{II}$) phase transition. (i) The size of the unit cell of the $H_{II}$ phase increases with increasing pressure. (ii) The transition volume, $\Delta V_{bh}$, decreases and appears to vanish as the pressure is increased. (iii) The intensity of scattered light increases as $\Delta V_{bh}$ decreases. Data are presented which suggest that this increase is due to the formation of an intermediate cubic phase, as predicted by recent theoretical suggestions of the underlying universal phase sequence.Comment: 12 pages, typed using REVTEX 2.

Pseudomonas Genome Database: facilitating user-friendly, comprehensive comparisons of microbial genomes

Pseudomonas aeruginosa is a well-studied opportunistic pathogen that is particularly known for its intrinsic antimicrobial resistance, diverse metabolic capacity, and its ability to cause life threatening infections in cystic fibrosis patients. The Pseudomonas Genome Database (http://www.pseudomonas.com) was originally developed as a resource for peer-reviewed, continually updated annotation for the Pseudomonas aeruginosa PAO1 reference strain genome. In order to facilitate cross-strain and cross-species genome comparisons with other Pseudomonas species of importance, we have now expanded the database capabilities to include all Pseudomonas species, and have developed or incorporated methods to facilitate high quality comparative genomics. The database contains robust assessment of orthologs, a novel ortholog clustering method, and incorporates five views of the data at the sequence and annotation levels (Gbrowse, Mauve and custom views) to facilitate genome comparisons. A choice of simple and more flexible user-friendly Boolean search features allows researchers to search and compare annotations or sequences within or between genomes. Other features include more accurate protein subcellular localization predictions and a user-friendly, Boolean searchable log file of updates for the reference strain PAO1. This database aims to continue to provide a high quality, annotated genome resource for the research community and is available under an open source license

Pseudomonas Genome Database: improved comparative analysis and population genomics capability for Pseudomonas genomes

Pseudomonas is a metabolically-diverse genus of bacteria known for its flexibility and leading free living to pathogenic lifestyles in a wide range of hosts. The Pseudomonas Genome Database (http://www.pseudomonas.com) integrates completely-sequenced Pseudomonas genome sequences and their annotations with genome-scale, high-precision computational predictions and manually curated annotation updates. The latest release implements an ability to view sequence polymorphisms in P. aeruginosa PAO1 versus other reference strains, incomplete genomes and single gene sequences. This aids analysis of phenotypic variation between closely related isolates and strains, as well as wider population genomics and evolutionary studies. The wide range of tools for comparing Pseudomonas annotations and sequences now includes a strain-specific access point for viewing high precision computational predictions including updated, more accurate, protein subcellular localization and genomic island predictions. Views link to genome-scale experimental data as well as comparative genomics analyses that incorporate robust genera-geared methods for predicting and clustering orthologs. These analyses can be exploited for identifying putative essential and core Pseudomonas genes or identifying large-scale evolutionary events. The Pseudomonas Genome Database aims to provide a continually updated, high quality source of genome annotations, specifically tailored for Pseudomonas researchers, but using an approach that may be implemented for other genera-level research communities

The Wrangel Island Polynya in early summer : trends and relationships to other polynyas and the Beaufort Sea High

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 39 (2012): L05503, doi:10.1029/2011GL050691.Polynyas, regions of reduced sea ice concentration relative to their surroundings, are important features of the polar climate system in which enhanced fluxes of heat, moisture, and momentum can occur between the atmosphere and ocean. As such, they play a significant role in many atmospheric, oceanographic and biological processes. There are concerns that in a warming climate, in which there is a trend towards a reduction in sea ice cover, that the location, size and duration of many polynyas may change resulting in climatological and ecological impacts. In this paper, we identify an early summer manifestation of the Wrangel Island polynya that forms in the western Chuckchi Sea. We show that over the past 30 years there has been an increased frequency of occurrence as well as a doubling in the size of the polynya. The polynya is shown to form when there is an enhanced easterly flow over the Chukchi Sea that is associated with an anomalously intense Beaufort Sea High (BSH), a closed anti-cyclonic atmospheric circulation that forms over the Beaufort Sea. We also show that there has been a concomitant trend towards a more intense BSH over the same time period and we propose that this trend is responsible for the observed changes in the Wrangel Island polynya. Given its large and increasing size, the early summer polynya may also play an important and unaccounted role in the physical and biological oceanography of the western Chukchi Sea.GWKM was supported by the Natural Science and Engineering Research Council of Canada. RSP was supported by the NOAA project NA08-OAR4320895.2012-09-1