The Biogeochemical Cycling of Dissolved Organic Carbon in the Iberian Margin Upwelling System (NE Atlantic Ocean

Merged with duplicate record 10026.1/2368 on 14.03.2017 by CS (TIS)Dissolved organic carbon (DOC) is the quantitatively most important organic carbon reservoir in the world's oceans and its determination at ocean margins, where the exchange of terrestrial and oceanic organic matter occurs, is important for estimating cross-slope fluxes to deep waters. With the increased accuracy and precision (-1%) of analytical methodologies, small changes in the DOC pool can be detected (i.e. 1- 2uM-C). This study investigated the biogeochemical cycling of DOC at the Iberian Margin upwelling system (42-43°N, --9-10°W), where contrasting seasonal hydrologic phenomena occur (e.g. summer upwelling, winter poleward current). Spatial and temporal DOC distributions were determined using high temperature catalytic oxidation (HTCO) techniques. DOC concentrations generally decreased with distance from the continental shelf and with increasing depth, although localised accumulation was observed in surface as well as in deep waters with a mean excess of up to 16 uM-C over background concentrations (57 uM-C). DOC concentrations in surface waters were closely associated with bacterial productivity and dissolved organic nitrogen (DON) production was facilitated by photosynthetic extra-cellular release from phytoplankton. There was no marked difference in DOC concentrations between the summer and winter seasons due to increased mineralization during the summer and lateral inputs during the winter. DOC production exceeded removal rates in summer upwelled surface waters following enhanced biological activity, in the winter surface poleward current and in deep waters that contained high levels of suspended particulates. DOC from terrestrial run-off was recycled rapidly at the coast before it could be exported to the shelf Cross-slope export of accumulated DOC was generally hindered by the net onshore velocity component during both winter and summer seasons and by the presence of water masses travelling along-slope.Plymouth Marine Laborator

Cytosolic delivery of mutant forms of toxin B from Clostridium difficile facilitates characterization of the intracellular activities of large clostridal toxins.

Clostridia are gram-positive spore-forming organisms responsible for a variety of diseases in both humans and animals Three species of Clostridia- Clostridium difficile, Clostridium sordellii and Clostridium novyi- produce a unique class of toxins termed large clostridial toxins (LCTs). These toxins inactivate members of the Ras superfamily of mammalian GTPases by glycosylation. LCTs are important in a variety of diseases, for example, Toxin A (TcdA) and toxin B (TcdB) are the major virulence factors in C. difficile associated diarrhea and pseudomembranous colitis. Whereas Clostridium sordellii lethal toxin (TcsL) and Clostridium novyi alpha toxin (Tcnalpha) have been implicated in gas gangrene infections. In addition to their roles in disease, TcdB and TcsL have been extensively used to decipher the effects of inactivating Ras proteins in mammalian cells. In order to better understand the role of these toxins in inactivating Ras proteins, we have undertaken the molecular characterization of intoxication by two LCTs, TcsL and TcdB. A chimeric fusion protein consisting of the TcdB enzymatic domain fused to the binding and translocation regions of anthrax lethal toxin (LFnTcdB1-556) was able to confer cytopathic effects on tissue culture cells and in a mouse, when delivered with the protective antigen (PA) component of anthrax toxin. Fusions containing mutants in the enzymatic domain of TcdB (LFnTcdB1-500, LFnTcdB 1-420 LFnTcdB1-170, LFnTcdB35-556, LFnTcdB 67-556, LFnTcdBC365S, LFnTcdBC365W LFnTcdB W102A) were inactive for glucosylation and CPE on cells, with the exception of LFnTcdBC365S and LFnTcdB1-170. The fusion proteins attenuated in enzymatic activity acted as inhibitors of TcdB both in vivo and in vitro. LFnTcdB1-500 was also able to inhibit the activity of TcsL and slowed cell rounding in transformed mammalian cells expressing the enzymatic domain of TcdB indicating the competition was occurring inside the cytosol. A combination of the lysosomotropic agent Bafilomycin A1 and the LFnTcdB1-500 inhibitor was used to determine the time required for cytosolic entry and irreversible cytopathic effects after treatment with TcdB. Furthermore, the time required for TcsL cytosolic entry was found to be considerably slower than that of TcdB accounting for the lower CPE of TcsL compared to TcdB

Concert recording 2019-11-17

[Track 1]. Introduction -- [Track 2]. Joy / Frank Ticheli -- [Track 3]. On a hymnsong of Philip Bliss / David Holsinger -- [Track 4]. Flashing winds / Jan Van der Roost -- Closing remarks -- [Track 5]. The Kappa Kappa Psi Fraternity hymn / Scott Jeffrey Heckstall, Jr. arranged by Lortie

Concert recording 2019-04-11

[Track 1]. Concert etude / Alexander Goedicke -- [Track 2]. Sonata VIII. I. Prelude: Largo II. Allemande: Allegro / Arcangelo Corelli -- [Track 3]. Oliver\u27s birthday / Bruce Broughton -- [Track 4]. Concerto [abridged] / Alexander Arutunian -- [Track 5]. Aria con variazioni / Georg Frederic Handel -- [Track 6]. Sonata for trumpet and piano. I. Lento, Allegro molto / Eric Ewazen -- [Track 7]. Concerto in E♭. I. Allegro / J.B.G. Neruda -- [Track 8]. Suite. II. Air [Track 9]. I. Prelude / William P. Latham

The Toxicology Investigators Consortium 2020 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology in 2010. The registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultation will be entered. This eleventh annual report summarizes the Registry\u27s 2020 data and activity with its additional 6668 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2020. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.6% cases in females, 48.4% in males, and 1.0% identifying as transgender. Non-opioid analgesics were the most commonly reported agent class, followed by opioid and antidepressant classes. Acetaminophen was once again the most common agent reported. There were 80 fatalities, comprising 1.2% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years\u27 reports. Sub-analyses were conducted to describe race and ethnicity demographics and exposures in the registry, telemedicine encounters, and cases related to the COVID-19 pandemic

Actin Crosslinking Toxins of Gram-Negative Bacteria

Actin crosslinking toxins produced by Gram-negative bacteria represent a small but unique class of bacterial protein toxins. For each of these toxins, a discrete actin crosslinking domain (ACD) that is a distant member of the ATP-dependent glutamine synthetase family of protein ligases is translocated to the eukaryotic cell cytosol. This domain then incorporates a glutamate-lysine crosslink between actin monomers, resulting in destruction of the actin cytoskeleton. Recent studies argue that the function of these toxins during infection is not destruction of epithelial layers, but rather may specifically target phagocytic cells to promote survival of bacteria after the onset of innate immune defenses. This review will summarize key experiments performed over the past 10 years to reveal the function of these toxins

Biogeochemical relationships between ultrafiltered dissolved organic matter and picoplankton activity in the Eastern Mediterranean Sea

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 57 (2010): 1460-1477, doi:10.1016/j.dsr2.2010.02.015.We targeted the warm, subsurface waters of the Eastern Mediterranean Sea (EMS) to investigate processes that are linked to the chemical composition and cycling of dissolved organic carbon (DOC) in seawater. The apparent respiration of semi-labile DOC accounted for 27 ± 18% of oxygen consumption in EMS mesopelagic and bathypelagic waters; this value is higher than that observed in the bathypelagic open ocean, so the chemical signals that accompany remineralization of DOC may thus be more pronounced in this region. Ultrafiltered dissolved organic matter (UDOM) collected from four deep basins at depths ranging from 2 to 4350 m exhibited bulk chemical (1H-NMR) and molecular level (amino acid and monosaccharide) abundances, composition, and spatial distribution that were similar to previous reports, except for a sample collected in the deep waters of the N. Aegean Sea that had been isolated for over a decade. The amino acid component of UDOM was tightly correlated with apparent oxygen utilization and prokaryotic activity, indicating its relationship with remineralization processes that occur over a large range of timescales. Principal component analyses of relative mole percentages of monomers revealed that oxygen consumption and prokaryotic activity were correlated with variability in amino acid distributions but not well correlated with monosaccharide distributions. Taken together, this study elucidates key relationships between the chemical composition of DOM and heterotrophic metabolism.TBM and AG acknowledge funding from the Hellenic GSRT/European Union (non-EU Grant No180) and SESAME Project (European Commission's Sixth Framework Program, EC Contract No GOCE-036949). TY was supported by the Japanese Society for the Promotion of Science (JSPS) Postdoctoral Fellowship for research abroad and DDC received a fellowship of the University of Groningen. Microbial laboratory work and molecular analyses were supported by a grant of the Earth and Life Science Division of the Dutch Science Foundation (ARCHIMEDES project, 835.20.023) to GJH. DJR and TBM were supported by grants from the Gordon and Betty Moore Foundation and from the C-MORE organization of NSF

A Novel and Lethal De Novo LQT-3 Mutation in a Newborn with Distinct Molecular Pharmacology and Therapeutic Response

SCN5A encodes the alpha-subunit (Na(v)1.5) of the principle Na(+) channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT syndrome (LQTS) variant 3 (LQT-3) in adults by disrupting inactivation of the Na(v)1.5 channel. Pharmacological targeting of mutation-altered Na(+) channels has proven promising in developing a gene-specific therapeutic strategy to manage specifically this LQTS variant. SCN5A mutations that cause similar channel dysfunction may also contribute to sudden infant death syndrome (SIDS) and other arrhythmias in newborns, but the prevalence, impact, and therapeutic management of SCN5A mutations may be distinct in infants compared with adults.Here, in a multidisciplinary approach, we report a de novo SCN5A mutation (F1473C) discovered in a newborn presenting with extreme QT prolongation and differential responses to the Na(+) channel blockers flecainide and mexiletine. Our goal was to determine the Na(+) channel phenotype caused by this severe mutation and to determine whether distinct effects of different Na(+) channel blockers on mutant channel activity provide a mechanistic understanding of the distinct therapeutic responsiveness of the mutation carrier. Sequence analysis of the proband revealed the novel missense SCN5A mutation (F1473C) and a common variant in KCNH2 (K897T). Patch clamp analysis of HEK 293 cells transiently transfected with wild-type or mutant Na(+) channels revealed significant changes in channel biophysics, all contributing to the proband's phenotype as predicted by in silico modeling. Furthermore, subtle differences in drug action were detected in correcting mutant channel activity that, together with both the known genetic background and age of the patient, contribute to the distinct therapeutic responses observed clinically.The results of our study provide further evidence of the grave vulnerability of newborns to Na(+) channel defects and suggest that both genetic background and age are particularly important in developing a mutation-specific therapeutic personalized approach to manage disorders in the young

Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells

Toxoplasma gondii is a wide spread pathogen that can cause severe and even fatal disease in fetuses and immune-compromised hosts. As an obligate intracellular parasite, Toxoplasma must alter the environment of its host cell in order to establish its replicative niche. This is accomplished, in part, by secretion of factors into the host cell that act to modulate processes such as transcription. Previous studies demonstrated that genes encoding transcription factors such as c-jun, junB, EGR1, and EGR2 were amongst the host genes that were the most rapidly upregulated following infection. In cells stimulated with growth factors, these genes are regulated by a transcription factor named Serum Response Factor. Serum Response Factor is a ubiquitously expressed DNA binding protein that regulates growth and actin cytoskeleton genes via MAP kinase or actin cytoskeletal signaling, respectively. Here, we report that Toxoplasma infection leads to the rapid activation of Serum Response Factor. Serum Response Factor activation is a Toxoplasma-specific event since the transcription factor is not activated by the closely related protozoan parasite, Neospora caninum. We further demonstrate that Serum Response Factor activation requires a parasite-derived secreted factor that signals via host MAP kinases but independently of the host actin cytoskeleton. Together, these data define Serum Response Factor as a host cell transcription factor that regulates immediate early gene expression in Toxoplasma-infected cells