Land Mollusks of Northeastern United States and Southeastern Canada

An illustrated key and description of the land snails and slugs of Northeastern United States and Southeastern CanadaOpe

Inhibition of DUSP6 sensitizes ovarian cancer cells to chemotherapeutic agents via regulation of ERK signaling response genes

Dual specificity phosphatase 6 (DUSP6) is a protein phosphatase that deactivates extracellular-signal-regulated kinase (ERK). Since the ovarian cancer biomarker human epididymis protein 4 (HE4) interacts with the ERK pathway, we sought to determine the relationship between DUSP6 and HE4 and elucidate DUSP6’s role in epithelial ovarian cancer (EOC). Viability assays revealed a significant decrease in cell viability with pharmacological inhibition of DUSP6 using (E/Z)-BCI hydrochloride in ovarian cancer cells treated with carboplatin or paclitaxel, compared to treatment with either agent alone. Quantitative PCR was used to evaluate levels of ERK pathway response genes to BCI in combination with recombinant HE4 (rHE4), carboplatin, and paclitaxel. Expression of EGR1, a promoter of apoptosis, was higher in cells co-treated with BCI and paclitaxel or carboplatin than in cells treated with chemotherapeutic agents alone, while expression of the proto-oncogene c-JUN was decreased with co-treatment. The effect of BCI on the expression of these two genes opposed that of rHE4. Pathway focused quantitative PCR also revealed suppression of ERBB3 in cells co-treated with BCI plus carboplatin or paclitaxel. Finally, expression levels of DUSP6 in EOC tissue were evaluated by immunohistochemistry, revealing significantly increased levels of DUSP6 in serous EOC tissue compared to adjacent normal tissue. A positive correlation between HE4 and DUSP6 levels was determined by Spearman Rank correlation. In conclusion, DUSP6 inhibition sensitizes ovarian cancer cells to chemotherapeutic agents and alters gene expression of ERK response genes, suggesting that DUSP6 could plausibly function as a novel therapeutic target to reduce chemoresistance in EOC

Temporal development and neutralising potential of antibodies against SARS-CoV-2 in hospitalised COVID-19 patients: An observational cohort study

Antibody responses are important in the control of viral respiratory infection in the human host. What is not clear for SARS-CoV-2 is how rapidly this response occurs, or when antibodies with protective capability evolve. Hence, defining the events of SARS-CoV-2 seroconversion and the time frame for the development of antibodies with protective potential may help to explain the different clinical presentations of COVID-19. Furthermore, accurate descriptions of seroconversion are needed to inform the best use of serological assays for diagnostic testing and serosurveillance studies. Here, we describe the humoral responses in a cohort of hospitalised COVID-19 patients (n = 19) shortly following the onset of symptoms. Commercial and ‘in-house’ serological assays were used to measure IgG antibodies against different SARS-CoV-2 structural antigens–Spike (S) S1 sub-unit and Nucleocapsid protein (NP)–and to assess the potential for virus neutralisation mediated specifically by inhibition of binding between the viral attachment protein (S protein) and cognate receptor (ACE-2). Antibody response kinetics varied amongst the cohort, with patients seroconverting within 1 week, between 1–2 weeks, or after 2 weeks, following symptom onset. Anti-NP IgG responses were generally detected earlier, but reached maximum levels slower, than anti-S1 IgG responses. The earliest IgG antibodies produced by all patients included those that recognised the S protein receptor-binding domain (RBD) and were capable of inhibiting binding to ACE-2. These data revealed events and patterns of SARS-CoV-2 seroconversion that may be important predictors of the outcome of infection and guide the delivery of clinical services in the COVID-19 response

Social Value of Marine and Coastal Protected Areas in England and Wales.

The U.K. government is committed to establishing a coherent network of marine protected areas by 2012 and the recentMarine and Coastal Access Act, 2009 will designate marine conservation zones and provide wider access rights to the coast. To fulfill these goals, this article argues the need for a clearer, shared understanding of the social value of protected areas in creating new designations and managing existing ones. Although marine and coastal environments attract many people and are vitally important in terms of realized and potential social value, the majority of the public in the United Kingdom lacks understanding and awareness regarding them. Combined with this, the social value of marine and coastal protected areas (MCPAs) have been largely ignored relative to conservation and economics, with the latter invariably taking precedence in environmental policymaking. Social value reflects the complex, individual responses that people experience in a given place. Many reasons determine why one area is valued above another, and this research investigates the social value of MCPAs from a practitioner’s perspective through a series of interviews. Understanding why we “socially” value MCPAs will ultimately equip managers with an informed understanding of these spaces, influence management decisions, and, potentially, policymaking. This article defines social value in the context of MCPAs in England and Wales from a practitioner perspective, explores key concepts, and suggests possible improvements in decision-making

Wide-Angle Seismic Imaging of Two Modes of Crustal Accretion in Mature Atlantic Ocean Crust

We present a high‐resolution 2‐D P‐wave velocity model from a 225‐km‐long active seismic profile, collected over ~60–75 Ma central Atlantic crust. The profile crosses five ridge segments separated by a transform and three nontransform offsets. All ridge discontinuities share similar primary characteristics, independent of the offset. We identify two types of crustal segment. The first displays a classic two‐layer velocity structure with a high gradient Layer 2 (~0.9 s$^{−1}$) above a lower gradient Layer 3 (0.2 s$^{−1}$). Here, PmP coincides with the 7.5 km s$^{−1}$ contour, and velocity increases to >7.8 km s$^{−1}$ within 1 km below. We interpret these segments as magmatically robust, with PmP representing a petrological boundary between crust and mantle. The second has a reduced contrast in velocity gradient between the upper and lower crust and PmP shallower than the 7.5 km s$^{−1}$ contour. We interpret these segments as tectonically dominated, with PmP representing a serpentinized (alteration) front. While velocity‐depth profiles fit within previous envelopes for slow‐spreading crust, our results suggest that such generalizations give a misleading impression of uniformity. We estimate that the two crustal styles are present in equal proportions on the floor of the Atlantic. Within two tectonically dominated segments, we make the first wide‐angle seismic identifications of buried oceanic core complexes in mature (>20 Ma) Atlantic Ocean crust. They have a ~20‐km‐wide “domal” morphology with shallow basement and increased upper crustal velocities. We interpret their midcrustal seismic velocity inversions as alteration and rock‐type assemblage contrasts across crustal‐scale detachment faults

Human Epididymis Secretory Protein 4 (HE4) Compromises Cytotoxic Mononuclear Cells via Inducing Dual Specificity Phosphatase 6

While selective overexpression of serum clinical biomarker Human epididymis secretory protein 4 (HE4) is indicative of ovarian cancer tumorigenesis, much is still known about the mechanistic role of the HE4 gene or gene product. Here, we examine the role of the secretory glycoprotein HE4 in ovarian cancer immune evasion. Through modified subtractive hybridization analyses of human peripheral blood mononuclear cells (PBMCs), we have characterized gene targets of HE4 and established a preliminary mechanism of HE4-mediated immune failure in ovarian tumors. Dual specificity phosphatase 6 (DUSP6) emerged as the most upregulated gene in PBMCs upon in vitro exposure to HE4. DUSP6 was found to be upregulated in CD8+ cells and CD56+ cells. HE4 exposure reduced Erk1/2 phosphorylation specifically in these cell populations and the effect was erased by co-incubation with a DUSP6 inhibitor, (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI). In co-culture with PBMCs, HE4-silenced SKOV3 human ovarian cancer cells exhibited enhanced proliferation upon exposure to external HE4, while this effect was partially attenuated by adding BCI to the culture. Additionally, the reversal effects of BCI were erased in the co-culture with CD8+ / CD56+ cell deprived PBMCs. Taken together, these findings show that HE4 enhances tumorigenesis of ovarian cancer by compromising cytotoxic CD8+ and CD56+ cells through upregulation of self-produced DUSP6

Novel Protein-Protein Interactions Inferred from Literature Context

We have developed a method that predicts Protein-Protein Interactions (PPIs) based on the similarity of the context in which proteins appear in literature. This method outperforms previously developed PPI prediction algorithms that rely on the conjunction of two protein names in MEDLINE abstracts. We show significant increases in coverage (76% versus 32%) and sensitivity (66% versus 41% at a specificity of 95%) for the prediction of PPIs currently archived in 6 PPI databases. A retrospective analysis shows that PPIs can efficiently be predicted before they enter PPI databases and before their interaction is explicitly described in the literature. The practical value of the method for discovery of novel PPIs is illustrated by the experimental confirmation of the inferred physical interaction between CAPN3 and PARVB, which was based on frequent co-occurrence of both proteins with concepts like Z-disc, dysferlin, and alpha-actinin. The relationships between proteins predicted by our method are broader than PPIs, and include proteins in the same complex or pathway. Dependent on the type of relationships deemed useful, the precision of our method can be as high as 90%. The full set of predicted interactions is available in a downloadable matrix and through the webtool Nermal, which lists the most likely interaction partners for a given protein. Our framework can be used for prioritizing potential interaction partners, hitherto undiscovered, for follow-up studies and to aid the generation of accurate protein interaction maps

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies

Nothing New in the (North) East? Interpreting the Rhetoric and Reality of Japanese Corporate Governance

Japan finally seems to be pulling itself out of its lost decade (and a half) of economic stagnation. Some grudgingly or triumphantly attribute this to micro-economic reforms, freeing up arthritic markets, although there is also evidence that macro-economic policy failures have been a major cause of poor performance since the 1990s. Many point to overlapping transformations in corporate governance, broadly defined to cover relationships among managers and employees as well as between firms and outside shareholders, creditors, and other stakeholders. These relationships are in flux, with moves arguably favouring shareholders and more market-driven control mechanisms. It has certainly been a found decade for law reform in Japan, particularly in corporate law, with a plethora of legislative amendments commencing around 1993 and culminating in the enactment of a consolidated Company Law in 2005. This modernisation project, particularly since 2001, is reportedly aimed at (i) securing better corporate governance, (ii) bringing the law into line with a highly-developed information society, (iii) liberalising fundraising measures, (iv) bringing corporate law into line with the internationalization of corporate activity, and (v) modernizing terms and consolidating corporate law. Because the suite of revisions has moved away from strict mandatory rules set out originally in Japan\u27s Commercial Code of 1899, modeled primarily on German law, another growing perception is that Japanese corporate law and practice is or will soon be converging significantly on US models. However, assessments remain divided as to whether these moves in corporate governance and capitalism more generally in Japan amount to a new paradigm or regime shift . Focusing primarily on quite influential commentary in English, Part I of this paper outlines two pairs of views. It concludes that the most plausible assessment is of significant but gradual transformation towards a more market-driven approach, evident also in other advanced political economies. Drawing more generally from these often virulently divided views, Part II sets out five ways forward through the proliferating literature and source material on corporate governance in Japan. Particular care must be taken in: (i) selecting the temporal timeframe, (ii) selecting countries to compare, (iii) balancing black-letter law and broader socio-economic context, (iv) reflecting on and disclosing normative preferences, and (v) giving weight to processes as well as outcomes, when assessing change in Japan - and any other country\u27s governance system. Part III ends with a call for further research particularly on law- and policy-producing processes, rather than mainly outcomes. It also outlines the usefulness of this analytical framework for analysing the broader field of Corporate Social Responsibility, now emerging as the next major area of debate and transformation in Japan - as elsewhere

Interlaboratory study of a method for determining nonvolatile organic carbon in aquifer materials

The organic carbon fraction in aquifer materials exerts a major influence on the subsurface mobilities of organic and organic-associated contaminants. The spatial distribution of total organic carbon (TOC) in aquifer materials must be determined before the transport of hydrophobic organic pollutants in aquifers can be modeled accurately. Previous interlaboratory studies showed that it is difficult to measure TOC concentrations 1%. We have tested a new analytical method designed to improve the accuracy and precision of nonvolatile TOC quantitation in geologic materials that also contain carbonate minerals. Four authentic aquifer materials and one NIST standard reference material were selected as test materials for a blind collaborative study. Nonvolatile TOC in these materials ranged from 0.05 to 1.4%, while TIC ranged from 0.46 to 12.6%. Sample replicates were digested with sulfurous acid, dried at 40°C, and then combusted at 950°C using LECO or UIC instruments. For the three test materials that contained >2% TIC, incomplete acidification resulted in a systematic positive bias of TOC values reported by five of the six laboratories that used the test method. Participants did not have enough time to become proficient with the new method before they analyzed the test materials. A seventh laboratory successfully used an alternative method that analyzed separate liquid and solid fractions of the acidified sample residues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46768/1/254_2004_Article_BF00770471.pd