The heteromeric 5-HT3A/B receptor:the effect of 5-HT3B subunits on receptor structure and ligand recognition

The 5-HT3 receptors are members of the cys-loop family of ligand-gated ion channels. Two functional subtypes are known, the homomeric 5HT3A and the heteromeric 5HT3A/B receptors, which exhibit distinct biophysical characteristics but are difficult to differentiate pharmacologically. Atomic force microscopy has been used to determine the stoichiometry and architecture of the heteromeric 5HT3A/B receptor. Each subunit was engineered to express a unique C-terminal epitope tag, together with six sequential histidine residues to facilitate nickel affinity purification. The 5-HT3 receptors, ectopically expressed in HEK293 cells, were solubilised, purified and decorated with antibodies to the subunit specific epitope tags. Imaging of individual receptors by atomic force microscopy revealed a pentameric arrangement of subunits in the order BBABA, reading anti-clockwise when viewed from the extracellular face. Homology models for the heteromeric receptor were then constructed using both the electron microscopic structure of the nicotinic acetylcholine receptor, from Torpedo marmorata, and the X-ray crystallographic structure of the soluble acetylcholine binding protein, from Lymnaea stagnalis, as templates. These homology models were used, together with equivalent models constructed for the homomeric receptor, to interpret mutagenesis experiments designed to explore the minimal recognition differences of both the natural agonist, 5-HT, and the competitive antagonist, granisetron, for the two human receptor subtypes. The results of this work revealed that the 5-HT3B subunit residues within the ligand binding site, for both the agonist and antagonist, are accommodating to conservative mutations. They are consistent with the view that the 5-HT3A subunit provides the principal and the 5-HT38 subunit the complementary recognition interactions at the binding interface.

Drug action on anxiety models with special reference to serotonergic mechanisms

A study has been made of drugs acting at 5-HT receptors on animal models of anxiety. An elevated X-maze was used as a model of anxiety for rats and the actions of various ligands for the 5-HT receptor, and its subtypes, were examined in this model. 5-HT agonists, with varying affinities for the 5-HT receptor subtypes, were demonstrated to have anxiogenic-like activity. The 5-HT2 receptor antagonists ritanserin and ketanserin exhibited an anxiolytic-like profile. The new putatuve anxiolytics ipsapirone and buspirone, which are believed to be selective for 5-HT1 receptors, were also examined. The former had an anxiolytic profile whilst the latter was without effect. Antagonism studies showed the anxiogenic response to 8-hydroxy-2-(Di-n-propylamino)tetralin (8-OH-DPAT) to be antagonised by ipsapirone, pindolol, alprenolol and para-chlorophenylalanine, but not by diazepam, ritanserin, metoprolol, ICI118,551 or buspirone. To confirm some of the results obtained in the elevated X-maze the Social Interaction Test of anxiety was used. Results in this test mirrored the effects seen with the 5-HT agonists, ipsapirone and pindolol, whilst the 5-HT2 receptor antagonists were without effect. Studies using operant conflict models of anxiety produced marginal and varying results which appear to be in agreement with recent criticisms of such models. Finally, lesions of the dorsal raphe nucleus (DRN) were performed in order to investigate the mechanisms involved in the production of the anxiogenic response to 8-OH-DPAT. Overall the results lend support to the involvement of 5-HT, and more precisely 5-HT1, receptors in the manifestation of anxiety in such animal models.

A study of the growth and differentiation of the human adenocarcinoma of the colon cell line HT-29

The HT-29 human colon adenocarcinoma cell line, like many epithelial cells, displays an undifferentiated phenotype when cultured on plastic substrata. Biochemical markers of differentiation, such as brush border associated enzymes and carcinoembryonic antigen were expressed at very low levels. The differentiation-inducing effects of the culture of HT-29 cells on collagen type I gels were evaluated, and were assessed by morphological appearance, brush border associated enzyme activities and the secretion of CEA. The effect that this more physiological environment had on their chemosensitivity to a panel of chemotherapeutic agents was determined, so as to indicate whether this system could be used to improve the selectivity of screening for novel anticancer agents. Initial studies were performed on HT-29 cells derived from cells seeded directly from plastic substrata onto the collagen gels (designated Non-PPC gels). Their time of exposure to the collagen was limited to the time course of a single experiment and the results suggested that a longer, more permanent exposure might produce a more pronounced differentiation. HT-29 cells were then passaged continuously on collagen gels for a minimum of 10 passages prior to experimentation (designated PPC gels). The same parameters were measured, and compared to those for the cells grown on plastic and on the non-passaged collagen gels (Non-PPC) from the original studies. Permanently passaged cells displayed a similar degree of morphological differentiation as the non-passaged cells, with both culture conditions resulting in a more pronounced differentiation than that achieved by culture on plastic. It was noted that the morphological differentiation observed was very heterogeneous, a situation also seen in xenografted tumours in vivo. The activity of alkaline phosphatase and the production of CEA was higher in the cells passaged on collagen (PPC) than the cells cultured on non-passaged collagen gel (Non-PPC) and plastic. The biochemical determination of aminopeptidase activity showed that collagen gel culture enhanced the activity in both non-passaged and passaged HT-29 cells above that of the cells cultured on plastic. However, immunocytochemical localization of aminopeptidase and sucrase-isomaltase of samples of cells grown on the various substrata for 7, 14, 21 and 28 days showed a reduction in both enzymes in the cells grown on collagen gels when compared to cells grown on plastic. The reason for the discrepancy between the two assays for aminopeptidase is at this stage unexplained. Although, there was evidence to suggest that the culture of HT-29 cells on collagen gels was capable of inducing morphological and biochemical markers of enterocytic differentiation, there were no differences in the chemosensitivity of the different cell groups to a panel of anticancer agents. Preliminary studies suggested that the ability of the cells to polarize by their culture on porous filter chambers without any exogenous ECM was sufficient to enhance HT-29 differentiation and the onset of differentiation was probably correlated with the production of ECM by the cells themselves.

Modulation of certain 5-HT-related behaviours by serotonergic and noradrenergic systems

The modulation of 5-hydroxytryptamine (5-HT)-related head-twitchbehaviour by antimigraine drugs and migraine triggers was examined inmice. The antimigraine drugs examined produced either inhibition or noeffect on 5-HT-related head-twitching. On the basis of these resultsit is suggested that 5-HT-related head-twitching is unlikely to beuseful in the preclinical screening and discovery of systemically-activeantimigraine agents. The migraine triggers examined, tyramineand beta-PEA initially produced a repeatable complex time-relatedeffect on 5-HT-related head-twitching, with both inhibition andpotentiation of this behaviour being observed, however, when furtherexamination of the effect of the migraine triggers on 5-HT-relatedhead-twitching was attempted some time later the effects seeninitially were no longer produced. The effect of (±)-1-<2, 5-dimethoxy-4-iodophenyl)-2-aminopropane,((±)DOl), on on-going behaviour of mice and rats was examined. Shakingbehaviour was observed in both species. In mice, excessive scratchingbehaviour was also present. (±)DOl-induced scratching and shakingbehaviour were found to be differentially modulated by noradrenergicand serotonergic agents, however, the fact that both behaviours wereblocked by ritanserin (5-HT2/5-HT1c receptor antagonist) and inhibitedby FLA-63 (a dopamine-beta-oxidase inhibitor which depletesnoradrenaline), suggests the pathways mediating these behaviours mustbe convergent in some manner, and that both behaviours require intact5-HT receptors, probably 5-HT2 receptors, for their production. Ingeneral, the behavioural profile of (±)DOI was as expected for anagent which exhibits high affinity binding to 5-HT2/5-HT1c receptors.Little sign of the 5-HTl-related '5-HT syndrome' was seen in eithermice or rats. The effect of a variety of noradrenergic agents on head-twitchinginduced by a variety of shake-inducing agents was examined. A patternof modulatory effect was seen whereby the modulatory effect of thenoradrenergic agents on 5-hydroxytryptophan <5-HTP) (and in some cases, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)) was found to be the opposite of that observed with quipazine and (±)DOI. The relationship between these effects, and their implications for understanding the pharmacology of centrally acting drugs is discussed.

Apoptotic and necrotic effects of hexanedione derivatives on the human neuroblastoma line SK-N-SH

The potential cytotoxicity of two hexanedione food additives (2,3 and 3,4 isomers) was evaluated in comparison with the neurotoxic hexane metabolite 2,5-hexanedione in the human SK-N-SH neuroblastoma line using the MTT assay to indicate mitochondrial dehydrogenase activity and flow cytometry to monitor the cell cycle over 48 h. The IC50s of the 2,3-hexanedione (3.3 ± 0.1 mM) and 3,4-hexanedione (3.5 ± 0.1 mM), indicated that the sensitivity of the cells was approximately seven-fold greater to these toxins compared with the 2,5 derivative (IC50 of 22.4 ± 0.2 mM). Comparison between the respective IC50s of the 2,3-hexanedione and 3,4-hexanedione revealed no difference between the two isomers in terms of their effects on MTT turnover. With flow cytometry analysis, all three hexanediones showed increases in apoptosis within their respective concentration ranges of toxicity shown previously by MTT. In the presence of 2,5-hexanedione, between 8.5 and 17 mM concentrations, there was a significant increase in apoptotic nucleoids which was accompanied by a significant fall in the percentage of nucleoids in the G0/G1 phase (72.4 ± 0.3-45.3 ± 0.6%,), and a rise in the numbers of cells in the G2/M phase. This is likely to indicate growth arrest at cell cycle G2/M checkpoint in response to toxin damage. G2/M accumulation was also shown with 3,4 and 2,3 HD, which was maximal at much lower concentrations (approximately 4 and 3 mM, respectively). Arrest at G1 and G2/M phase is indicative of inhibition of the cell cycle at the stages of DNA replication and chromosome segregation, respectively. It was also apparent that flow cytometry, rather than the MTT assay, did distinguish between the effects of the α-diketones 2,3-hexanedione and 3,4-hexanedione on the cell cycle. At a concentration of 5.8 mM 3,4-hexanedione, the percentage of apoptotic nucleoids was 10.9 ± 0.8% whilst apoptosis induced by 3,4-hexanedione had already reached a maximal level of 60.4 ± 0.5%. In summary, flow cytometry indicated that the 3,4-hexanedione derivative was more toxic than its 2,3 isomer and that both food additives caused interruption in the neuroblastoma cell cycle and further investigation may be required to assess if these α-diketones present in diets pose any possible risks to human health. © 2006 Elsevier Ireland Ltd. All rights reserved.

TiN-based coatings on fuel cladding tubes for advanced nuclear reactors

Titanium nitride (TiN) thin films are coated on HT-9 and MA957 fuel cladding tubes and bars to explore their mechanical strength, thermal stability, diffusion barrier properties, and thermal conductivity properties. The ultimate goal is to implement TiN as an effective diffusion barrier to prevent the inter-diffusion between the nuclear fuel and the cladding material, and thus lead to a longer lifetime of the cladding tubes. Mechanical tests including hardness and scratch tests for the samples before and after thermal cycle tests show that the films have a high hardness of 28GPa and excellent adhesion properties despite the thermal treatment. Thermal conductivity measurements demonstrate that the thin TiN films have very minimal impact on the overall thermal conductivity of the MA957 and HT-9 substrates, i.e., the thermal conductivity of the uncoated HT-9 and MA957 substrates was 26.25 and 28.44 W m-1 K-1, and that of the coated ones was 26.21 and 28.38W m-1 K-1, respectively. A preliminary Ce diffusion test on the couple of Ce/TiN/HT-9 suggests that TiN has excellent material compatibility and good diffusion barrier properties.

A comparison of the apoptotic and cytotoxic effects of hexanedione derivatives on human non-neuronal lines and the neuroblastoma line SH-SY5Y

The effects of the alpha-diketone derivatives 2,3- and 3,4-hexanediones were investigated in three non-neuronal cell lines (MCF7, HepG2 and CaCo-2) as well as in the neuroblastoma line, SH-SY5Y. The MTT reduction assay was employed to determine the necrotic effects of the alpha-diketones and the neurotoxin 2,5-hexanedione over 4, 24 and 48 hr exposures. Flow cytometry was also used to study the effects of the three isomers on the cell cycle of the SH-SY5Y line only. With 2,5-hexanedione, the mean MTT IC50 decreased more than 10-fold from 4 to 48 hr. The toxicities of both alpha-diketones were similar, with a more than 18-fold increase in sensitivity of the SH-SY5Y at 24 hr compared to that of 4 hr. With flow cytometry at 48 hr, SH-SY5Y apoptosis with 2,5-hexanedione rose throughout the concentration range evaluated (0-30 mM) while 2,3- and 3,4-hexanediones showed apoptosis over the concentration range 1-1.6 mM, with 3,4-hexanedione being the more potent compared to the 2,3-isomer. At 1.6 mM nearly all the cells had entered apoptosis in the presence of the 3,4-isomer, (94.9 ± 1.4%) but only 57.5 ±4.1% of the 2,3-isomer-treated cells had reached that stage. The 2,3-and 3,4-isomers in diets alone may not pose a serious threat to human health. Further studies may be necessary to evaluate the effects of other dietary components on their toxicity. These alpha-diketones also display a degree of toxic selectivity towards neuroblastoma cells, which may have therapeutic implications.

INFRAWEBS Semantic Web Service Development on the Base of Knowledge Management Layer

The paper gives an overview about the ongoing FP6-IST INFRAWEBS project and describes the main layers and software components embedded in an application oriented realisation framework. An important part of INFRAWEBS is a Semantic Web Unit (SWU) – a collaboration platform and interoperable middleware for ontology-based handling and maintaining of SWS. The framework provides knowledge about a specific domain and relies on ontologies to structure and exchange this knowledge to semantic service development modules. INFRAWEBS Designer and Composer are sub-modules of SWU responsible for creating Semantic Web Services using Case-Based Reasoning approach. The Service Access Middleware (SAM) is responsible for building up the communication channels between users and various other modules. It serves as a generic middleware for deployment of Semantic Web Services. This software toolset provides a development framework for creating and maintaining the full-life-cycle of Semantic Web Services with specific application support.

Mainstream media behavior analysis on Twitter:a case study on UK general election

With the development of social media tools such as Facebook and Twitter, mainstream media organizations including newspapers and TV media have played an active role in engaging with their audience and strengthening their influence on the recently emerged platforms. In this paper, we analyze the behavior of mainstream media on Twitter and study how they exert their influence to shape public opinion during the UK's 2010 General Election. We first propose an empirical measure to quantify mainstream media bias based on sentiment analysis and show that it correlates better with the actual political bias in the UK media than the pure quantitative measures based on media coverage of various political parties. We then compare the information diffusion patterns from different categories of sources. We found that while mainstream media is good at seeding prominent information cascades, its role in shaping public opinion is being challenged by journalists since tweets from them are more likely to be retweeted and they spread faster and have longer lifespan compared to tweets from mainstream media. Moreover, the political bias of the journalists is a good indicator of the actual election results. Copyright 2013 ACM.

Aspirin and aspirin analogs on esophageal cancer

Background: Esophageal cancer is the eighth most common cancer seen worldwide and is the sixth most common cause of death from cancer. The UK alone has over 8,000 new cases of esophageal cancer every year. Epidemiological studies have shown that low-dose daily intake of aspirin can decrease the incidence of esophageal cancer. However, its use as an anti-cancer drug has been restrained because of its side effects exerted through inhibition of cyclooxygenase (COX) enzymes. In our study, we have investigated the effects of a number of novel aspirin analogs on esophageal cancer cell lines. Methods: The effects of aspirin and its analogs on the viability of esophageal cancer cell lines were tested using the MTT assay. ApoSense and flow cytometric analysis were performed to examine whether aspirin analog-mediated tumor cell death is due to apoptosis or necrosis. Colorimetric assays measuring peroxidase component of cyclooxygenases were employed to screen aspirin analogs for COX inhibition. Results: Our data suggests that the anti-proliferative property of certain aspirin analogs is greater than that of aspirin itself. Benzoylsalicylates and fumaroyl diaspirin were more effective than aspirin against the oe21 squamous cell carcinoma cells and oe33 esophageal adenocarcinoma cells. Flo-1 esophageal adenocarcinoma cells showed resistance to aspirin and most of the aspirin analogs other than the benzoylsalicylates. Both diaspirin and benzoylsalicylates inhibited metabolic activity in all these esophageal cells. However, apoptosis was induced in only a small proportion. We have also shown that these aspirin analogs do not appear to inhibit COX enzymes. Conclusion: We have synthesized and characterized a number of novel aspirin analogs that are more effective against esophageal cancer cell lines than aspirin. These compounds do not exert their anti-proliferative effect through induction of apoptosis. Moreover, these analogs inability to inhibit COX enzymes suggests that they may cause fewer or no side effects compared to aspirin.

Three essays on corporate governance and meeting-beating or missing analyst forecasts

The beginning of the 21st century was plagued with unprecedented instances of corporate fraud. In an attempt to address apparent non-existent or “broken” corporate governance policies, sweeping measures of financial reporting reform ensued, having specific requirements relating to the composition of audit committees, the interaction between audit committees and external auditors, and procedures concerning auditors’ assessment of client risk. The purpose of my dissertation is to advance knowledge about “good” corporate governance by examining the association between meeting-or-beating analyst forecasts and audit fees, audit committee compensation, and audit committee tenure and “busyness”. Using regression analysis, I found the following: (1) the frequency of meeting-or-just beating (just missing) analyst forecasts is negatively (positively) associated with audit fees, (2) the extent by which a firm exceeds analysts’ forecasts is positively (negatively) associated with audit committee compensation that is predominately equity-based (cash-based), and (3) the likelihood of repeatedly meeting-or-just beating analyst forecasts is positively associated with audit committee tenure and “busyness”. These results suggest that auditors consider clients who frequently meet-or-just beat forecasts as being less “risky”, and clients that frequently just miss as being more “risky”. The results also imply that cash-based director compensation is more successful in preserving the effectiveness of the audit committee’s financial reporting oversight role, that equity-based compensation motivates independent audit committee directors to focus on short-term performance thereby aligning their interests with management, and that audit committee director tenure and the degree of director “busyness” can affect an audit committee member’s effectiveness in providing financial reporting oversight. Collectively, my dissertation provides additional insights regarding corporate governance practices and informs policy-makers for future relevant decisions.^

The Acute Effects of Whole Body Vibration on Muscular Power and Agility

Context: While research suggests whole body vibration (WBV) positively affects measures of neuromuscular performance in athletes, researchers have yet to address appropriate and effective vibration protocols. Objective: To identify the acute effects of continuous and intermittent WBV on muscular power and agility in recreationally active females. Design: We used a randomized 3-period cross-over design to observe the effects of 3 vibration protocols on muscular power and agility. Setting: Sports Science and Medicine Research Laboratory at Florida International University. Patients or Other Participants: Eleven recreationally active female volunteers (age=24.4±5.7y; ht=166.0±10.3cm; mass=59.7±14.3kg). Interventions: Each session, subjects stood on the Galileo WBV platform (Orthometrix, White Plains, NY) and received one of three randomly assigned vibration protocols. Our independent variable was vibration length (continuous, intermittent, or no vibration). Main Outcome Measures: An investigator blinded to the vibration protocol measured muscular power and agility. We measured muscular power with heights of squat and countermovement jumps. We measured agility with the Illinois Agility Test. Results: Continuous WBV significantly increased SJ height from 97.9±7.6cm to 98.5±7.5cm (P=0.019, β=0.71, η2 =0.07) but not CMJ height [99.1±7.4cm pretest and 99.4±7.4cm posttest (P=0.167, β=0.27)] or agility [19.2±2.1s pretest and 19.0±2.1s posttest (P=0.232, β=0.21)]. Intermittent WBV significantly enhanced SJ height from 97.6±7.7cm to 98.5±7.7cm (P=0.017, β=0.71, η2 =0.11) and agility 19.4±2.2s to 19.0±2.1s (P=0.001, β=0.98, η2=0.16), but did not effect CMJ height [98.7±7.7cm pretest and 99.3±7.3cm posttest (P=0.058, β=0.49)]. Conclusion: Continuous WBV increased squat jump height, while intermittent vibration enhanced agility and squat jump height. Future research should continue investigating the effect of various vibration protocols on athletic performance.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Fatores determinantes da near miss materna em uma unidade de terapia intensiva obstétrica: avaliação das competências profissionais da área médica

Objective: Evaluate the determinants of morbidity and mortality in an obstetric intensive care unit and professional medical skills of students/residents at a university hospital. Methods: observational cross - sectional with 492 pregnant/pue rperal women and 261 students/residents. Patients were admitted to the obstetric intensive care unit during a year, being informed about the proposals of the study and a questionnaire was applied. The analysis was performed using Microsoft Excel 2013 and G raphPad6. Chi - square tests were used to evaluate risk factors and student t test evaluates resident/students' skills concerning the cognitive test and the Mini - Cex. Results: the main risk factors to near miss were: non - white race (OR = 2.527; RR = 2.342) ; marital status(married women) (OR = 7.968; RR = 7.113) , schooling (primary) (OR = 3.177 ; RR = 2.829) , from country town (OR = 4.643 ; RR = 4.087), low income (OR = 7014 ; RR = 5.554) , gestational hypertensive disorders (OR = 16.35 ; RR = 13.27) , re alization of pre - natal (OR = 5.023 ; RR = 4.254) and C - section before labor(OR = 39.21 ; RR = 31.25). In cognitive/Mini - cex analysis were noted significant difference in the performance of students on the subject (3.75 ± 0.93, 4.03 ± 0.94 and 4.88 ± 0.35). We still observed the best performance of residents, when compared to graduation students (p < 0.01). Conclusions: the prevalence of near miss was associated with socioeconomic/clinics factors and care issues, revealing the importance of interventions to improve these indicators. In addition, we suggest a better curriculum insertion of this subject in the medical Course disciplines due the importance to avoid the near miss through of adequacy of medical education.

Paleoceanographic and paleoclimatic evolution of the Aegean Sea since the last interglacial (~130 ka BP) with special emphasis on sapropel formation

Five long piston cores collected from different subbasins of the Aegean Sea constitute the primary source of data for this PhD thesis. This study is the first to document a continuous paleoceanographic and paleoclimatic record of the Aegean Sea since the last interglacial. The chronostratigraphic reconstructions of the cored sediments based on organic carbon contents, stratigraphic position of known ash layers and oxygen isotopic curve matching collectively demonstrate the presence of sapropel S1 and MISS sapropels S3, S4 and S5 in the Aegean Sea subbasins. Generally, the organic carbon (TOC wt%) contents in sapropels range between 0.8% and 2% with highest concentrations of 9-13% in sapropels S4 and S5. Average sedimentation rates range between 4.7 and 11.8 cmlka with highest rates being observed in Euboea and North Ikaria basins (9.8 and 11.8 cm lka, respectively). The timing of the onset of sapropels S4 and S5 mostly predate those in the eastern Mediterranean with ages ranging from 106.4-105.6 and 128.6-128.4 ka BP, respectively. On the other hand, the initiation of the onset of sapropel S3 (i.e., 83.2-80.4 ka BP) seems to agree with its Mediterranean counterparts, which highlights the heterogeneity of the Aegean Sea subbasins in terms of rapid vs. lagged response to changing climatic conditions. The sapropel initiations appear to be synchronous across the Aegean Sea; whereas, the terminations display a wider temporal variability implying that the cessation of sapropels is controlled both by the amplitude of paleoclimatic changes and the physiography/location ofthe subbasins. Quantitative variations in the planktonic faunal assemblages exhibit a sequence of bioevents during the last -130,000 years which allow identification of four major biozones. The distributional patterns of the most significant taxa demonstrate similar trends among all core localities suggesting that the major changes in the planktonic foraminifera assemblages have taken place rather synchronously in the Aegean Sea. Sapropels S3, S4 and S5 were deposited under similar hydrographic conditions during which a distinct deep chlorophyll maximum (DCM) layer was established. This situation points to a stratified water column and increased export productivity during times of sapropel formation. On the other hand, the faunal contrast between Sl and older sapropels indicates that the former was developed in the absence of a DCM layer, lacking a deep phytoplankton assemblage. Under such conditions, oxygen advection via intermediate water flow must have been significantly reduced which implies significant stagnation. Sapropels are interpreted to have been deposited under normal marine conditions with temporary establishment of semi-euxinic bottom water conditions. Both marine and terrestrial organic matter contributed equally to MISS sapropels. In addition, organic carbon isotopic values across sapropels are more depleted than those in the eastern Mediterranean which, in tum, suggests enhanced riverine input during their deposition. Primary productivity calculations show that, particularly for sapropels with very high TOC values, both preservation and increased productivity are imperative in order to deposit sapropels with very high organic carbon contents (i.e., up to 13%).