Marine Protected Areas: An Overview

Some Members of Congress are among the many people who are interested in considering limiting human activity in some areas of the marine environment as one response to mounting evidence of deteriorating conditions and declining populations of living resources. The purposes of proposed additional limits would be to both stem the decline and permit the rehabilitation of these environments and populations. One method of implementing this concept is to designate areas where activity would be limited, often referred to as marine protected areas (MPAs)

Quantum Information Processing and Relativistic Quantum Fields

It is shown that an ideal measurement of a one-particle wave packet state of a relativistic quantum field in Minkowski spacetime enables superluminal signalling. The result holds for a measurement that takes place over an intervention region in spacetime whose extent in time in some frame is longer than the light-crossing time of the packet in that frame. Moreover, these results are shown to apply not only to ideal measurements but also to unitary transformations that rotate two orthogonal one-particle states into each other. In light of these observations, possible restrictions on the allowed types of intervention are considered. A more physical approach to such questions is to construct explicit models of the interventions as interactions between the field and other quantum systems such as detectors. The prototypical Unruh-DeWitt detector couples to the field operator itself and so most likely respects relativistic causality. On the other hand, detector models which couple to a finite set of frequencies of field modes are shown to lead to superluminal signalling. Such detectors do, however, provide successful phenomenological models of atom-qubits interacting with quantum fields in a cavity but are valid only on time scales many orders of magnitude larger than the light-crossing time of the cavity.Comment: 16 pages, 2 figures. Improved abstract and discussion of 'ideal' measurements. References to previous work adde

Ocean Commissions: Ocean Policy Review and Outlook

This report includes information regarding ocean commissions. Ocean policy review, further outlook, and legislation are among topics discussed in this report

A unique role of GATA1S in down syndrome acute megakaryocytic leukemia biology and therapy

Background: Acute megakaryocytic leukemia (AMkL) in Down syndrome (DS) children is uniformly associated with somatic GATA1 mutations, which result in the synthesis of a shorter protein (GATA1s) with altered transactivation activity compared to the wild-type GATA1. It is not fully established whether leukemogenesis and therapeutic responses in DS AMkL patients are due to loss of the wild-type GATA1 or due to a unique function of GATA1s. Methodology: Stable clones of CMK cells with decreased GATA1s or Bcl-2 levels were generated by using GATA1- or BCL-2-specific lentivirus shRNAs. In vitro ara-C, daunorubicin, and VP-16 cytotoxicities of the shRNA stable clones were determined by using the Cell Titer-blue reagent. Apoptosis and cell cycle distribution were determined by flow cytometry analysis. Changes in gene transcript levels were determined by gene expression microarray and/or real-time RT-PCR. Changes in protein levels were measured by Western blotting. In vivo binding of GATA1s to IL1A promoter was determined by chromatin immunoprecipitation assays. Results: Lentivirus shRNA knockdown of the GATA1 gene in the DS AMkL cell line, CMK (harbors a mutated GATA1 gene and only expresses GATA1s), resulting in lower GATA1s protein levels, promoted cell differentiation towards the megakaryocytic lineage and repressed cell proliferation. Increased basal apoptosis and sensitivities to ara-C, daunorubicin, and VP-16 accompanied by down-regulated Bcl-2 were also detected in the CMK GATA1 shRNA knockdown clones. Essentially the same results were obtained when Bcl-2 was knocked down with lentivirus shRNA in CMK cells. Besides Bcl-2, down-regulation of GATA1s also resulted in altered expression of genes (e.g., IL1A, PF4, and TUBB1) related to cell death, proliferation, and differentiation. Conclusion: Our results suggest that GATA1s may facilitate leukemogenesis and potentially impact therapeutic responses in DS AMkL by promoting proliferation and survival, and by repressing megakaryocytic lineage differentiation, potentially by regulating expression of Bcl-2 protein and other relevant genes. © 2011 Xavier et al

Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatoses

ABSTRACT Background: Human Polyomavirus 6 (HPyV6) and Human Polyomavirus 7 (HPyV7) are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. Objective: We determined whether biopsies showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. Methods: We screened biopsies showing "peacock plumage" histology by PCR for human polyomaviruses. Cases positive for HPyV 6 or 7 were then analyzed by immunohistochemistry, electron microscopy (EM), immunofluorescence, quantitative PCR, and complete sequencing, including unbiased, next generation sequencing (NGS). Results: We identified three additional cases of HPyV6 or 7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared to normal skin and the identification of intact virions by both EM and NGS support a role for active viral infections in these skin diseases. Limitation: This was a small case-series of archived materials. Conclusion: We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a unique histologic pattern and describe this entity as "HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatosis (H6PD and H7PD).

How open science helps researchers succeed

Open access, open data, open source, and other open scholarship practices are growing in popularity and necessity. However, widespread adoption of these practices has not yet been achieved. One reason is that researchers are uncertain about how sharing their work will affect their careers. We review literature demonstrating that open research is associated with increases in citations, media attention, potential collaborators, job opportunities, and funding opportunities. These findings are evidence that open research practices bring significant benefits to researchers relative to more traditional closed practices

Uncoupling of ATP-Mediated Calcium Signaling and Dysregulated Interleukin-6 Secretion in Dendritic Cells by Nanomolar Thimerosal

Dendritic cells (DCs), a rare cell type widely distributed in the soma, are potent antigen-presenting cells that initiate primary immune responses. DCs rely on intracellular redox state and calcium (Ca(2+)) signals for proper development and function, but the relationship between these two signaling systems is unclear. Thimerosal (THI) is a mercurial used to preserve vaccines and consumer products, and is used experimentally to induce Ca(2+) release from microsomal stores. We tested adenosine triphosphate (ATP)-mediated Ca(2+) responses of DCs transiently exposed to nanomolar THI. Transcriptional and immunocytochemical analyses show that murine myeloid immature DCs (IDCs) and mature DCs (MDCs) express inositol 1,4,5-trisphosphate receptor (IP(3)R) and ryanodine receptor (RyR) Ca(2+) channels, known targets of THI. IDCs express the RyR1 isoform in a punctate distribution that is densest near plasma membranes and within dendritic processes, whereas IP(3)Rs are more generally distributed. RyR1 positively and negatively regulates purinergic signaling because ryanodine (Ry) blockade a) recruited 80% more ATP responders, b) shortened ATP-mediated Ca(2+) transients > 2-fold, and c) produced a delayed and persistent rise (≥ 2-fold) in baseline Ca(2+). THI (100 nM, 5 min) recruited more ATP responders, shortened the ATP-mediated Ca(2+) transient (≥ 1.4-fold), and produced a delayed rise (≥ 3-fold) in the Ca(2+) baseline, mimicking Ry. THI and Ry, in combination, produced additive effects leading to uncoupling of IP(3)R and RyR1 signals. THI altered ATP-mediated interleukin-6 secretion, initially enhancing the rate of cytokine secretion but suppressing cytokine secretion overall in DCs. DCs are exquisitely sensitive to THI, with one mechanism involving the uncoupling of positive and negative regulation of Ca(2+) signals contributed by RyR1

Tumor-associated endothelial cells display GSTP1 and RARβ2 promoter methylation in human prostate cancer

BACKGROUND: A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment. METHODS: Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RARβ2 promoters via the QMS-PCR method. RESULTS: Comparing GSTP1 and RARβ2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas. CONCLUSION: We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature

Comprehensive analysis of chemical and biological problems associated with browning agents used in aquatic studies

Inland waters receive and process large amounts of colored organic matter from the terrestrial surroundings. These inputs dramatically affect the chemical, physical, and biological properties of water bodies, as well as their roles as global carbon sinks and sources. However, manipulative studies, especially at ecosystem scale, require large amounts of dissolved organic matter with optical and chemical properties resembling indigenous organic matter. Here, we compared the impacts of two leonardite products (HuminFeed and SuperHume) and a freshly derived reverse osmosis concentrate of organic matter in a set of comprehensive mesocosm- and laboratory-scale experiments and analyses. The chemical properties of the reverse osmosis concentrate and the leonardite products were very different, with leonardite products being low and the reverse osmosis concentrate being high in carboxylic functional groups. Light had a strong impact on the properties of leonardite products, including loss of color and increased particle formation. HuminFeed presented a substantial impact on microbial communities under light conditions, where bacterial production was stimulated and community composition modified, while in dark potential inhibition of bacterial processes was detected. While none of the browning agents inhibited the growth of the tested phytoplankton Gonyostomum semen, HuminFeed had detrimental effects on zooplankton abundance and Daphnia reproduction. We conclude that the effects of browning agents extracted from leonardite, particularly HuminFeed, are in sharp contrast to those originating from terrestrially derived dissolved organic matter. Hence, they should be used with great caution in experimental studies on the consequences of terrestrial carbon for aquatic systems

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology