Quantity, composition, and source of sediment collected in sediment traps along the fringing coral reef off Molokai, Hawaii

This paper is not subject to U.S. copyright. The definitive version was published in Marine Pollution Bulletin 52 (2006): 1034-1047, doi:10.1016/j.marpolbul.2006.01.008.Sediment traps were used to evaluate the frequency, cause, and relative intensity of sediment mobility/resuspension along the fringing coral reef off southern Molokai (February 2000–May 2002). Two storms with high rainfall, floods, and exceptionally high waves resulted in sediment collection rates > 1000 times higher than during non-storm periods, primarily because of sediment resuspension by waves. Based on quantity and composition of trapped sediment, floods recharged the reef flat with land-derived sediment, but had a low potential for burying coral on the fore reef when accompanied by high waves. The trapped sediments have low concentrations of anthropogenic metals. The magnetic properties of trapped sediment may provide information about the sources of land-derived sediment reaching the fore reef. The high trapping rate and low sediment cover indicate that coral surfaces on the fore reef are exposed to transient resuspended sediment, and that the traps do not measure net sediment accumulation on the reef surface

Environmental assessment of metal exposure to corals living in Castle Harbour, Bermuda

This paper is not subject to U.S. copyright. The definitive version was published in Marine Chemistry 154 (2013): 55–66, doi:10.1016/j.marchem.2013.05.002.Environmental contamination in Castle Harbour, Bermuda, has been linked to the dissolution and leaching of contaminants from the adjacent marine landfill. This study expands the evidence for environmental impact of leachate from the landfill by quantitatively demonstrating elevated metal uptake over the last 30 years in corals growing in Castle Harbour. Coral Pb/Ca, Zn/Ca and Mn/Ca ratios and total Hg concentrations are elevated relative to an adjacent control site in John Smith's Bay. The temporal variability in the Castle Harbour coral records suggests that while the landfill has increased in size over the last 35 years, the dominant input of metals is through periodic leaching of contaminants from the municipal landfill and surrounding sediment. Elevated contaminants in the surrounding sediment suggest that resuspension is an important transport medium for transferring heavy metals to corals. Increased winds, particularly during the 1990s, were accompanied by higher coral metal composition at Castle Harbour. Coupled with wind-induced resuspension, interannual changes in sea level within the Harbour can lead to increased bioavailability of sediment-bound metals and subsequent coral metal assimilation. At John Smith's Bay, large scale convective mixing may be driving interannual metal variability in the coral record rather than impacts from land-based activities. Results from this study provide important insights into the coupling of natural variability and anthropogenic input of contaminants to the nearshore environment.This work was supported by a grant from a postdoctoral scholarship to N.G. Prouty from the Woods Hole Oceanographic Institution and grants from the NSF (OCE-0402728; K. Hughen) and the Cove Point Foundation (C. Lamborg)

The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells

In this paper we report on the cloning and characterization of mouse CCR8. Like its human homologue, it is predominantly expressed in the thymus. In the periphery, murine CCR8 mRNA was found most abundantly expressed in activated Th2-polarized cells and in NK1.1+ CD4+ T cells. Human CCR8 is also preferentially expressed in human Th2-polarized cells and clones. This pattern of expression suggests that CCR8 is part of a Th2-specific gene expression program. The CCR8 ligands I-309 and its mouse homologue T cell activation gene 3 (TCA-3) are potent chemoattractants for Th2-polarized cells. Taken together, these observations strongly suggest that CCR8 plays a role in the control of Th2 responses, and may represent a potential target for treatment of allergic diseases

t(15;21) translocations leading to the concurrent downregulation of RUNX1 and its transcription factor partner genes SIN3A and TCF12 in myeloid disorders.

Through a combined approach integrating RNA-Seq, SNP-array, FISH and PCR techniques, we identified two novel t(15;21) translocations leading to the inactivation of RUNX1 and its partners SIN3A and TCF12. One is a complex t(15;21)(q24;q22), with both breakpoints mapped at the nucleotide level, joining RUNX1 to SIN3A and UBL7-AS1 in a patient with myelodysplasia. The other is a recurrent t(15;21)(q21;q22), juxtaposing RUNX1 and TCF12, with an opposite transcriptional orientation, in three myeloid leukemia cases. Since our transcriptome analysis indicated a significant number of differentially expressed genes associated with both translocations, we speculate an important pathogenetic role for these alterations involving RUNX1

Therapeutic implications of intratumor heterogeneity for TP53 mutational status in Burkitt lymphoma

Therapeutic implications of intra-tumor heterogeneity are still undefined. In this study we report a genetic and functional analysis aimed at defining the mechanisms of chemoresistance in a 43-year old woman affected by stage IVB Burkitt lymphoma with bulky abdominal masses and peritoneal effusion. The patient, despite a transient initial response to chemotherapy with reduction of the bulky masses, rapidly progressed and died of her disease. Targeted TP53 sequencing found that the bulky mass was wild-type whereas peritoneal fluid cells harbored a R282W mutation. Functional studies on TP53 mutant cells demonstrated an impaired p53-mediated response, resistance to ex vivo doxorubicin administration, overexpression of DNA damage response (DDR) activation markers and high sensitivity to pharmacologic DDR inhibition. These findings suggest that intra-tumor heterogeneity for TP53 mutational status may occur in MYC-driven cancers, and that DDR inhibitors could be effective in targeting hidden TP53 mutant clones in tumors characterized by genomic instability and prone to intra-tumor heterogeneity

Quantifying the Coastal Hazard Risk Reduction Benefits of Coral Reef Restoration in the U.S. Virgin Islands

Coastal habitat restoration, especially of coral reef ecosystems, can significantly reduce the exposure of coastal communities to natural hazards and, consequently, the risk of wave-driven flooding. Likewise, reef degradation can increase coastal flood risks to people and property. In this study, the valuation of coral reefs in the United States Virgin Islands (USVI), along the coasts of St. Croix, St. John, and St. Thomas, demonstrated the social and economic benefits provided by these natural defenses. Across the territory, more than 481 people and 31.2 million of infrastructure were estimated to receive protection from coral reefs per year (2010 U.S. dollars). In 2017, Hurricanes Irma and Maria significantly damaged coral reefs throughout the archipelago. By combining engineering, ecological, geospatial, social, and economic data and tools, this study provided a rigorous valuation of where potential coral reef restoration projects could help rebuild these damaged habitats and decrease the risks from coastal hazards faced by USVI’s reef-fronted communities. Multiple restoration scenarios were considered in the analysis, two of which are detailed in this report. These include (1) ‘Ecological’ restoration, where restoration creates a structure that is 0.25 m high and 25-m-wide reef, and (2) ‘Hybrid’ restoration, where restoration creates a structure that is 1.25 m high and 5 m wide. There are many ways that such structures could be developed. In the hydrodynamic analyses, there are no assumptions about how the restoration is developed. Many practitioners of both coral (and oyster reef) restoration consider that a reef height of 0.25 m might be delivered from planting corals alone and that 1.25 m might require a combination of artificial structures and coral planting. In a third scenario, the analysis investigated the reduction of protection benefits that would occur through the reduction of 1 meter of naturally occurring reef height due to reef degradation. The reduction of protection due to the loss of reefs can also be interpreted as the protection value of the existing reefs. In all studied restoration scenarios, it was assumed that the planting of corals would enhance hydrodynamic roughness, effectively dissipating incident wave energy and reducing the potential for coastal flooding. A standardized approach was employed to strategically locate potential restoration projects along the entire linear extent of existing reefs bordering the USVI, and to identify where coral reef restoration could offer valuable benefits in flood reduction. Potential restoration projects were only located within the existing distribution of reefs across the region, even though numerous sites were positioned far offshore (2-3 km), and some were at relatively deep depths (up to 7 m). Risk-based valuation approaches were followed to delineate flood zones at a 10 m2 resolution along the entire region's reef-lined shorelines for all the potential coral reef restoration scenarios. These were subsequently compared to flood zones without coral reef restoration. The potential reduction in coastal flood risk provided by coral reef restoration, and the protection value of existing reefs, were quantified utilizing the latest information available at the time of analysis from the U.S. Census Bureau, Federal Emergency Management Agency (FEMA), and Bureau of Economic Analysis for return-interval storm events. The change in Expected Annual Damages (EAD), a metric indicating the annual protection gained due to coral reef restoration, was calculated based on the damages associated with each storm probability. The findings suggest that the benefits of reef restoration are spatially variable within the USVI. In some areas, the analysis showed limited benefits from reef restoration, which may be attributed to the depth or offshore distances of proposed restoration sites. However, there were a number of key areas where reef restoration could have substantial benefits for flood risk reduction. The annual flood risk reduction attributed to potential ‘ecological’ coral reef restoration in the USVI was 99 people and 6.1 million (2010 U.S. dollars). The Benefit-to-Cost Ratio (BCR) for this restoration approach was found to be larger than 1 (i.e., cost-effective) along 11% of the St. Croix coastline, 4.9% of the St. John coastline, and 8.7% of the St. Thomas coastline. This analysis offers stakeholders and decision-makers a spatially explicit and rigorous evaluation that illustrates how, where, and when potential coral reef restoration efforts in St. Croix, St. John, and St. Thomas could be instrumental to reducing coastal storm-induced flooding. Understanding areas where reef management, recovery, and restoration could effectively reduce climate hazard-related risks is crucial to protect and enhance the resilience of coastal communities in USVI

Effect of MYC and PARP Inhibitors in Ovarian Cancer Using an In Vitro Model

Figures and Data: https://ar.iiarjournals.org/content/44/5/1817/tab-figures-dataBackground/Aim: The 8q24 chromosomal region, which contains the MYC and PVT1 candidate oncogenes, is amplified in carcinomas. Both genes have been involved in the etiopathogenesis of ovarian cancer (OC). In this study, we used an in vitro OC model with a known 8q24 copy number increase and in silico tools to investigate the expression of MYC/PVT1 loci and copy number variation in OC. We also assessed the effects of rucaparib (a PARP inhibitor) in the presence or absence of 10058F4 (a MYC inhibitor) on the expression of MYC/linear PVT1/circular PVT1. Materials and Methods: Tissue culture, chromosome preparation, RNA extraction, RT-qPCR, FISH, and wound healing assays were employed. OncoDB, cBioportal, UALKAN, and ROC Plotter in silico tools were also utilized. Results: Although PVT1 and MYC expression levels remained unaltered in OC, putative copy number alterations across all cancers showed a marked difference between the two genes, particularly in gain and amplification for MYC. PVT1 expression demonstrated prognostic value for the treatment of patients with serous and endometrioid OC. Both genes correlated with PARP10, FAM83H, and DEPTOR. The use of rucaparib in the presence or absence of the MYC inhibitor (10058F4) in vitro, led to a significant down-regulation in the expression of MYC, linear, and circular PVT1. Conclusion: Our data provide a novel insight into the potential interactions of MYC and PVT1 with other genes. Moreover, we identified a new PARP inhibition mechanism down-regulating MYC, as well as the linear and circular PVT1 transcripts. Future work should expand on clinical studies to better understand the prognostic role of PVT1 in OC.Cancer Treatment & Research Trust (CTRT); Global Thesis Program 2017-2018 (University of Bari Aldo Moro)

Principles of meiotic chromosome assembly revealed in S. cerevisiae

During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

Frequent NRG1 fusions in Caucasian pulmonary mucinous adenocarcinoma predicted by Phospho-ErbB3 expression

NRG1 fusions were recently reported as a new molecular feature of Invasive Mucinous Adenocarcinoma (IMA) of the lung. The NRG1 chimeric ligand acts as a strong inductor of phosphorylation and tyrosine kinase activity of the ErbB2/ErbB3 heterodimer, thus enhancing the PI3K–AKT/MAPK pathways. The NRG1 fusions were widely investigated in Asian IMA cohorts, whereas just anecdotal information are available about the occurrence of NRG1 fusions in IMA Caucasian population. Here we firstly explored a large Caucasian cohort of 51 IMAs and 34 non-IMA cases for the occurrence of NRG1 rearrangements by fluorescent in situ hybridization (FISH) and RNA target sequencing. FISH results were correlated to the immunohistochemical expression of phosphorylated-ErbB3 (pErbB3) receptor and the mutational status of KRAS, EGFR and ALK genes. The NRG1 rearrangements were detected in 31% IMAs and 3% non-IMAs and the CD74-NRG1 fusion transcript variant was characterized in 4 NRG1-positive IMAs. Moreover, pErbB3 expression was found to be strictly associated to the mucinous pattern (p = 0.012, Chi-square test) and all IMA cases showing aberrant expression of pErbB3 demonstrated NRG1 rearrangements. No significant correlation between NRG1 rearrangements and EGFR, KRAS or ALK mutations respectively, was observed. We report for the first time that NRG1 fusions are driver alterations clearly associated with mucinous lung adenocarcinoma subtype of Caucasian patients and not exclusive of Asiatic population. pErbB3 immunostaining may represent a strong predictor of NRG1 fusions, pointing out the detection of pErbB3 by IHC as a rapid and effective pre-screening method to select the NRG1-positive patients