Macrofaunal response to artificial enrichments and depressions in a deep-sea habitat

To test whether colonizing macrofauna specialize on different types of small-scale patches of food and disturbance in the deep sea, sediment tray and artificial depression colonization experiments were conducted on the deep-sea floor at 900-m depth, south of St. Croix, U.S. Virgin Islands. Trays and depressions were unenriched (Unenriched Controls) or enriched with either Thalassiosira sp. or Sargassum sp. Concurrent deployment of different types of enrichment and disturbance made it possible to evaluate whether macrofauna specialize on different patches, and thus avoid species interactions that might lead to competitive exclusion. Depressions create a hydrodynamic regime that traps passive particles, allowing tests of the relative importance of active selection of different patch types versus passive deposition for abundant colonizers. After 23 d, total densities and densities of the four abundant colonizers (Capitella spp., Nereimyra punctata, Cumella sp. and Nebalia sp.) were extremely high in enriched trays, despite relatively low ambient densities. Densities in Unenriched Control Trays were very low, and did not attain ambient densities. After 24 d, total densities in all depression treatments were considerably lower than in enriched tray treatments, and only Sargassum Depression densities exceeded those in the ambient environment. Lower densities of organisms in depression treatments compared with trays and differences in densities among depression treatments suggest that the dominant colonizers were highly active and selective, and were not passively entrained in depressions. Faunal analysis indicated that trays and depressions were very different, and Sargassum Depression fauna was very different from other depression types. A strong difference was not observed between fauna in ambient sediments and Thalassiosira sp. or Unenriched Control Depressions, perhaps because Thalassiosira sp. was dropped in depressions on the sediment surface and may have been more readily available to consumers and more rapidly consumed than in trays. Thalassiosira Trays were colonized by a lower diversity fauna than Sargassum Trays, and Unenriched Control Trays were colonized by very low densities of a fauna that was comparable in diversity to the ambient community. Diversity in Sargassum Depressions was higher than in enriched trays but lower than in other artificial depressions and the ambient fauna. Thalassiosira Depressions and Unenriched Control Depressions were comparable in diversity to ambient fauna and natural depressions, which were highly diverse. These experiments suggest that fauna may respond quickly and selectively to artificial food patches and disturbance, and this fauna is different from that observed in the ambient sediment. Thus, a patch mosaic may be part of the reason for the high species diversity that is observed in deep-sea ecosystems. The different, highly diverse, fauna observed in natural depressions compared with flat ambient sediment suggests that natural analogs of these experiments have unique faunas that may contribute to the species richness of deep-sea habitats

The role of colonization in establishing patterns of community composition and diversity in shallow-water sedimentary communities

To determine whether pattern and diversity in benthic sedimentary communities are set primarily at colonization or by post-settlement biological interactions, we collected faunal cores and conducted reciprocal sediment transplant experiments at a sandy and a muddy site at 12 m depth, ~3 km apart off New Jersey. Multivariate analyses of cores collected at these sites in September 1994 indicated differences in the taxa determining local pattern, with the bivalve Spisula solidissima and the polychaete Polygordius sp. being dominant at the sandy site, and oligochaetes, several polychaete species and the bivalve Nucula annulata dominant at the muddy site. Individual cores from the sandy site were significantly less diverse than those at the muddy site. Short-term experiments (3-5 d) were deployed by divers at three different times (August-September, 1994). Replicate trays (100 cm2) filled with azoic sand or mud were placed flush with the ambient seafloor at both sites. Multivariate comparisons indicated that sediment treatment in trays played a greater role in determining colonization patterns in the first experiment, site played a greater role in the second, and both variables contributed in the third. This pattern suggests that larval settlement and habitat choice played an important role in the first and third experiments, and that local transport of recently settled juveniles from the surrounding sediments was important in the second and third experiments. Sandy-site trays had significantly lower diversity than muddy-site trays, but there was no effect of sediment type in trays on diversity of colonizers. These experiments focused on small spatial scales and three short time periods, but they demonstrate that species patterns in some environments may be set by habitat selection by larvae and by juvenile colonization from the surrounding community. Post-colonization processes such as predation and competition likely play a major role for some species, but patterns of initial colonization corresponded well with those in the local community

Guiding Brain Tumor Resection Using Surface-Enhanced Raman Scattering Nanoparticles and a Hand-Held Raman Scanner

The current difficulty in visualizing the true extent of malignant brain tumors during surgical resection represents one of the major reasons for the poor prognosis of brain tumor patients. Here, we evaluated the ability of a hand-held Raman scanner, guided by surface-enhanced Raman scattering (SERS) nanoparticles, to identify the microscopic tumor extent in a genetically engineered RCAS/tv-a glioblastoma mouse model. In a simulated intraoperative scenario, we tested both a static Raman imaging device and a mobile, hand-held Raman scanner. We show that SERS image-guided resection is more accurate than resection using white light visualization alone. Both methods complemented each other, and correlation with histology showed that SERS nanoparticles accurately outlined the extent of the tumors. Importantly, the hand-held Raman probe not only allowed near real-time scanning, but also detected additional microscopic foci of cancer in the resection bed that were not seen on static SERS images and would otherwise have been missed. This technology has a strong potential for clinical translation because it uses inert gold-silica SERS nanoparticles and a hand-held Raman scanner that can guide brain tumor resection in the operating room

Filamin A Binds to CCR2B and Regulates Its Internalization

The chemokine (C-C motif) receptor 2B (CCR2B) is one of the two isoforms of the receptor for monocyte chemoattractant protein-1 (CCL2), the major chemoattractant for monocytes, involved in an array of chronic inflammatory diseases. Employing the yeast two-hybrid system, we identified the actin-binding protein filamin A (FLNa) as a protein that associates with the carboxyl-terminal tail of CCR2B. Co-immunoprecipitation experiments and in vitro pull down assays demonstrated that FLNa binds constitutively to CCR2B. The colocalization of endogenous CCR2B and filamin A was detected at the surface and in internalized vesicles of THP-1 cells. In addition, CCR2B and FLNa were colocalized in lamellipodia structures of CCR2B-expressing A7 cells. Expression of the receptor in filamin-deficient M2 cells together with siRNA experiments knocking down FLNa in HEK293 cells, demonstrated that lack of FLNa delays the internalization of the receptor. Furthermore, depletion of FLNa in THP-1 monocytes by RNA interference reduced the migration of cells in response to MCP-1. Therefore, FLNa emerges as an important protein for controlling the internalization and spatial localization of the CCR2B receptor in different dynamic membrane structures

Modified Cav1.4 Expression in the Cacna1fnob2 Mouse Due to Alternative Splicing of an ETn Inserted in Exon 2

The Cacna1fnob2 mouse is reported to be a naturally occurring null mutation for the Cav1.4 calcium channel gene and the phenotype of this mouse is not identical to that of the targeted gene knockout model. We found two mRNA species in the Cacna1fnob2 mouse: approximately 90% of the mRNA represents a transcript with an in-frame stop codon within exon 2 of CACNA1F, while approximately 10% of the mRNA represents a transcript in which alternative splicing within the ETn element has removed the stop codon. This latter mRNA codes for full length Cav1.4 protein, detectable by Western blot analysis that is predicted to differ from wild type Cav1.4 protein in a region of approximately 22 amino acids in the N-terminal portion of the protein. Electrophysiological analysis with either mouse Cav1.4wt or Cav1.4nob2 cDNA revealed that the alternatively spliced protein does not differ from wild type with respect to activation and inactivation characteristics; however, while the wild type N-terminus interacted with filamin proteins in a biochemical pull-down experiment, the alternatively spliced N-terminus did not. The Cacna1fnob2 mouse electroretinogram displayed reduced b-wave and oscillatory potential amplitudes, and the retina was morphologically disorganized, with substantial reduction in thickness of the outer plexiform layer and sprouting of bipolar cell dendrites ectopically into the outer nuclear layer. Nevertheless, the spatial contrast sensitivity (optokinetic response) of Cacna1fnob2 mice was generally similar to that of wild type mice. These results suggest the Cacna1fnob2 mouse is not a CACNA1F knockout model. Rather, alternative splicing within the ETn element can lead to full-length Cav1.4 protein, albeit at reduced levels, and the functional Cav1.4 mutant may be incapable of interacting with cytoskeletal filamin proteins. These changes, do not alter the ability of the Cacna1fnob2 mouse to detect and follow moving sine-wave gratings compared to their wild type counterparts

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.https://deepblue.lib.umich.edu/bitstream/2027.42/144529/1/12967_2018_Article_1552.pd

Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis

PURPOSE: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. METHODS: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. RESULTS: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. CONCLUSION: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence

Comparative Composition, Diversity and Trophic Ecology of Sediment Macrofauna at Vents, Seeps and Organic Falls

Sediments associated with hydrothermal venting, methane seepage and large organic falls such as whale, wood and plant detritus create deep-sea networks of soft-sediment habitats fueled, at least in part, by the oxidation of reduced chemicals. Biological studies at deep-sea vents, seeps and organic falls have looked at macrofaunal taxa, but there has yet to be a systematic comparison of the community-level attributes of sediment macrobenthos in various reducing ecosystems. Here we review key similarities and differences in the sediment-dwelling assemblages of each system with the goals of (1) generating a predictive framework for the exploration and study of newly identified reducing habitats, and (2) identifying taxa and communities that overlap across ecosystems. We show that deep-sea seep, vent and organic-fall sediments are highly heterogeneous. They sustain different geochemical and microbial processes that are reflected in a complex mosaic of habitats inhabited by a mixture of specialist (heterotrophic and symbiont-associated) and background fauna. Community-level comparisons reveal that vent, seep and organic-fall macrofauna are very distinct in terms of composition at the family level, although they share many dominant taxa among these highly sulphidic habitats. Stress gradients are good predictors of macrofaunal diversity at some sites, but habitat heterogeneity and facilitation often modify community structure. The biogeochemical differences across ecosystems and within habitats result in wide differences in organic utilization (i.e., food sources) and in the prevalence of chemosynthesis-derived nutrition. In the Pacific, vents, seeps and organic-falls exhibit distinct macrofaunal assemblages at broad-scales contributing to ß diversity. This has important implications for the conservation of reducing ecosystems, which face growing threats from human activities

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known