The first distribution, biomass and toxicity study of a newly established bloom of the colonial cyanobacteria Microcystis aeruginosa was conducted on October 15, 2003 in the upper San Francisco Bay Estuary. Microcystis aeruginosa was widely distributed throughout 180 km of waterways in the upper San Francisco Bay Estuary from freshwater to brackish water environments and contained hepatotoxic microcystins at all stations. Other cyanobacteria toxins were absent or only present in trace amounts. The composition of the microcystins among stations was similar and dominated by demethyl microcystin-LR followed by microcystin-LR. In situ toxicity computed for the >75 lm cell diameter size fraction was well below the 1 lg l )1 advisory level set by the World Health Organization for water quality, but the toxicity of the full population is unknown. The toxicity may have been greater earlier in the year when biomass was visibly higher. Toxicity was highest at low water temperature, water transparency and salinity. Microcystins from the bloom entered the food web and were present in both total zooplankton and clam tissue. Initial laboratory feeding tests suggested the cyanobacteria was not consumed by the adult copepod Eurytemora affinis, an important fishery food source in the estuary.

Intermittent saline intrusions are a common feature of many coastal lakes and wetlands. These ecosystems are often important sites of biodiversity, biological productivity, and ecosystem services such as the removal of sediment, nutrients, and contaminants from inflowing rivers. Predicted effects of global climate change, including sea level rise, are likely to intensify saline intrusions into such ecosystems. Analyses of taxonomic diversity and abundance of zooplankton at different salinities in Lake Waihola, South Island, New Zealand, are supported by results of laboratory studies of salinity tolerances of 3 crustacean taxa Gladioferens pectinatus, Boeckella hamata and Daphnia carinata obtained from the lake. The field and laboratory analyses show that severe perturbations of zooplankton community structure and abundance are caused by even minor saline intrusions into Lake Waihola that raise the salinity to >1.2 psu. Our analyses of Lake Waihola, and data from brackish ecosystems around the world, show that even relatively small increases in salinity levels can drive such systems to a state of depleted biodiversity and abundance, altering ecosystem functioning.KEY WORDS: Zooplankton diversity · Zooplankton abundance · Climate change · Community structure · Shallow lake · Salinity · Lake Waihola · Saline intrusion Resale or republication not permitted without written consent of the publisherMar Ecol Prog Ser 251: [181][182][183][184][185][186][187][188][189] 2003 a medium sized (surface area = 5.4 km 2 ), shallow (mean depth = 1.15 m), tidal (mean tidal range ca. 0.40 m) lake, connected to the sea via a 10 km reach of the Taieri River, ca. 30 km southwest of the city of Dunedin. The lake has a diverse fish community and a high catch per unit effort (CPUE) relative to other New Zealand lakes, though not relative to shallow Danish lakes (Jeppesen et al. 2000). Lake Waihola has a hydraulic residence time of 153 d, based on non-tidal, freshwater inflows (Schallenberg & Burns 2003). During drought conditions, when water levels in the Taieri River are low and when other freshwater inputs are small, intrusions of saline water enter the lake, as occurred in the austral summers 1997/98 and 1998/99. Global climate change is expected to affect New Zealand in ways similar to the El Niño climatic pattern, in which westerly and southerly airflows dominate and the east coast of New Zealand experiences dry (drought) conditions more frequently (Mullan 1996, NZMfE 2001. During dry summers, Lake Waihola often experiences saline intrusions which create strong temporal and spatial salinity gradients within the lake. Results of a calibrated hydrological model of the Taieri catchment, which was run using meteorological inputs based on downscaled global circulation models and 2 global climate change scenarios (NZMfE 2001), indicated that runoff in the Taieri catchment will decrease during summer months under both scenarios (B. Fitzharris unpubl. data). In addition to decreased summer freshwater inputs, Lake Waihola will ...

1. Daphnia carinata King, a freshwater cladoceran, occurs in Lake Waihola, a tidal lake with seasonal fluctuations in temperature (4–21 °C), and salinity (30–2000 mg L–1 Cl). We hypothesise that these fluctuations influence the seasonal changes in D. carinata abundance. 2. To test this hypothesis, adults and juveniles were exposed to combinations of temperature and salinity. We measured mortality of adults and juveniles, growth of juveniles over 20 days, and their age at first reproduction. 3. The salinity tolerance of adult D. carinata was temperature‐dependent. Juveniles were more sensitive to salinity, but more tolerant of temperature increases. 4. Growth rates were higher at elevated temperatures, but reduced by elevated salinities. The onset of reproduction was earlier at elevated temperatures. 5. We conclude that seasonal changes in temperature and salinity contribute to seasonal population changes of D. carinata.

The effects of a 185-min exposure to 48 degrees C db/33 degrees C wb, on intravascular volume and osmolarity and on intravascular electrolyte, aldosterone, and cortisol concentrations have been studied in five male subjects before and after acclimatization to heat. Changes in the hematocrit and plasma protein concentration indicated that a hemodilution occurred during the first 35 min of the heat exposures, and that this was followed by a hemoconcentration. Although these changes in intravascular volume were not affected by acclimatization, the plasma volume after heat acclimatization was 6.7% greater than before. This increase in plasma volume was associated with an elevation in the ratio [Na]/[K]. However, since plasma osmolarity decreased the intravascular expansion could not be explained in terms of elevated electrolyte levels. Plasma aldosterone and cortisol levels were not affected by heat acclimatization, although both were elevated following exercise in the heat. It is concluded that the adrenal cortex is not an important factor in maintaining a state of heat acclimatization once a salt balance has been achieved.

Monoclonal antibodies have recently started to deliver on their promise as highly specific and active drugs; however, a more effective, knowledge-based approach to the selection, design, and optimization of potential therapeutic antibodies is currently limited by the surprising lack of detailed structural information for complexes formed with target proteins. Here we show that complexes formed with minimal antigen binding single chain variable fragments (scFv) reliably reflect all the features of the binding interface present in larger Fab fragments, which are commonly used as therapeutics, and report the development of a robust, reliable, and relatively rapid approach to the determination of high resolution models for scFv-target protein complexes. This NMR spectroscopy-based approach combines experimental determination of the interaction surfaces and relative orientations of the scFv and target protein, with NMR restraint-driven, semiflexible docking of the proteins to produce a reliable and highly informative model of the complex. Experience with scFvs and Fabs targeted at a number of secreted regulatory proteins suggests that the approach will be applicable to many therapeutic antibodies targeted at proteins, and its application is illustrated for a potential therapeutic antibody targeted at the cytokine IL-1␤. The detailed structural information that can be obtained by this approach has the potential to have a major impact on the rational design and development of an increasingly important class of biological pharmaceuticals.The ability of antibodies to bind to an almost unlimited number of target proteins with high specificity makes them one of the fastest growing classes of therapeutics in the biological drugs market (1). Since the first description of monoclonal antibodies (2), dramatic progress has been made in the expression, engineering, humanization, and applications of antibodies as therapeutics. A wide variety of antibody fragments have been evaluated as potential therapeutics including the well characterized antigen binding fragment (Fab), which contains the light chain (V L and C L domains) and N-terminal portion of the heavy chain (V H and C H domains). The smallest fragment to retain full binding activity has also attracted considerable interest, with the so-called single chain variable fragment (scFv) 3 (3) consisting of the two variable domains joined by a short peptide.A detailed understanding of the interactions between candidate therapeutic antibodies and target proteins is key to further progress in rational design and humanization. Currently, identification of the binding sites for antibodies on target proteins is achieved via one or a combination of indirect methods such as protease protection, peptide scanning, site-directed mutagenesis, or analysis of backbone amide exchange (4 -6). Although providing valuable information, each of these approaches has drawbacks; in particular, they may not detect discontinuous epitopes and do not provide information on the spatial organization of ep...

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