Late Barremian-Early Aptian palaeoenvironmental change: the Cassis-La Bedoule section (SE France)

The well-dated section of Cassis-La Bédoule in the South Provencal Basin (southern France) allows for a detailed reconstruction of palaeoenvironmental change during the latest Barremian and Early Aptian. For this study, phosphorus (P) and clay-mineral contents, stable-isotope ratios on carbonate (δ13Ccarb) and organic matter (δ13Corg), and redox-sensitive trace elements (RSTE: V, U, As, Co, and Mo) have been measured in this historical stratotype. The base of the section consists of rudist limestone, which is attributed to the Urgonian platform. The presence of low P and RSTE content, and content of up to 30% kaolinite indicate deposition under oligotrophic and oxic conditions, and the presence of warm, humid climatic conditions on the adjacent continent. The top of the Urgonian succession is marked by a hardground with encrusted brachiopods and bivalves, which is interpreted as a drowning surface. The section continues with a succession of limestone and marl containing the first occurrence of planktonic foraminifera. This interval includes several laminated, organic-rich layers recording RSTE enrichments and high Corg:Ptot ratios. The deposition of these organic-rich layers was associated with oxygen-depleted conditions and a large positive excursion in δ13Corg. During this interval, a negative peak in the δ13Ccarb record is observed, which dates as latest Barremian. This excursion is coeval with negative excursions elsewhere in Tethyan platform and basin settings and is explained by the increased input of light dissolved inorganic carbon by rivers and/or volcanic activity. In this interval, an increase in P content, owing to reworking of nearshore sediments during the transgression, is coupled with a decrease in kaolinite content, which tends to be deposited in more proximal areas. The overlying hemipelagic sediments of the Early Aptian Deshayesites oglanlensis and D. weissi zones indicate rather stable palaeoenvironmental conditions with low P content and stable δ13C records. A change towards marl-dominated beds occurs close to the end of the D. weissi zone. These beds display a long decrease in their δ13Ccarb and δ13Corg records, which lasted until the end of the Deshayesites deshayesi subzone (corresponding to C3 in Menegatti et al., 1998). This is followed by a positive shift during the Roloboceras hambrovi and Deshayesites grandis subzones, which corresponds in time to oceanic anoxic event (OAE) 1a interval. This positive shift is coeval with two increases in the P content. The marly interval equivalent to OAE 1a lacks organic-rich deposits and RSTE enrichments indicating that oxic conditions prevailed in this particular part of the Tethys ocean. The clay mineralogy is dominated by smectite, which is interpreted to reflect trapping of kaolinite on the surrounding platforms rather than indicating a drier climate.

Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model

Gastrointestinal (GI) models that mimic physiological conditions in vitro are important tools for developing and optimizing biopharmaceutical formulations. Oral administration of live attenuated bacterial vaccines (LBV) can safely and effectively promote mucosal immunity but new formulations are required that provide controlled release of optimal numbers of viable bacterial cells, which must survive gastrointestinal transit overcoming various antimicrobial barriers. Here, we use a gastro-small intestine gut model of human GI conditions to study the survival and release kinetics of two oral LBV formulations: the licensed typhoid fever vaccine Vivotif comprising enteric coated capsules; and an experimental formulation of the model vaccine Salmonella Typhimurium SL3261 dried directly onto cast enteric polymer films and laminated to form a polymer film laminate (PFL). Neither formulation released significant numbers of viable cells when tested in the complete gastro-small intestine model. The poor performance in delivering viable cells could be attributed to a combination of acid and bile toxicity plus incomplete release of cells for Vivotif capsules, and to bile toxicity alone for PFL. To achieve effective protection from intestinal bile in addition to effective acid resistance, bile adsorbent resins were incorporated into the PFL to produce a new formulation, termed BR-PFL. Efficient and complete release of 4.4x107 live cells per dose was achieved from BR-PFL at distal intestinal pH, with release kinetics controlled by the composition of the enteric polymer film, and no loss in viability observed in any stage of the GI model. Use of this in vitro GI model thereby allowed rational design of an oral LBV formulation to maximize viable cell release.