John T. Finn

Streamflow Regulation and Fish Community Structure

Many regulated streams are characterized by high variable and unpredictable flow regimes. Since changes in streamflow directly modify physical habitat, streams with such highly variable flows provide highly unstable aquatic habitats. We evaluated the effect of artificial streamflow fluctuations on stream fish communities by comparing fish densities, in species and habitat groups, between two rivers differing in daily flow regime: on with with a natural flow, and one with highly regulated flows. We developed a simple model describing the relationship between available streams habitat and its use by 15 species or size classes of fish in the natural river. Species and size classes that used a specific set of microhabitat conditions were identified by comparing habitat characteristics for samples with and without each type of fish; for fish that used a particular type of microhabitat, we grouped species and size classes according to similarity in microhabitat use. Next, we categorized stream habitat samples in both the natural and regulated rivers into groups on the basis of fish habitat use criteria. Fish densities for each fish and habitat group were ten individually compared between the two rivers. An abundant (>90% of all fish) and diverse (nine species) group of small—fish species and size classes were restricted to microhabitat that was characterized as shallow in depth, slow in current velocity, and concentrated along stream margins. This group of fish was reduced in abundance in the regulated river and absent at the study site with the greatest flow fluctuation. Another fish group included species and size classes that used either a broad range of habitat or a microhabitat that was deep, fast, or both, and was concentrated in midstream areas. The density of fish in this group was higher in the regulated river and peaked at the sites with the greatest fluctuations in flow. Highly variable and unpredictable flow regimes appear to be a high—frequency disturbance that effects fish differently depending on the way they use stream habitat and acts to reduce community complexity.

Structural basis for bisphosphonate-mediated inhibition of isoprenoid biosynthesis

Farnesyl pyrophosphate synthetase (FPPS) synthesizes farnesyl pyrophosphate through successive condensations of isopentyl pyrophosphate with dimethylallyl pyrophosphate and geranyl pyrophosphate. Nitrogen-containing bisphosphonate drugs used to treat osteoclast-mediated bone resorption and tumor-induced hypercalcemia are potent inhibitors of the enzyme. Here we present crystal structures of substrate and bisphosphonate complexes of FPPS. The structures reveal how enzyme conformational changes organize conserved active site residues to exploit metal-induced ionization and substrate positioning for catalysis. The structures further demonstrate how nitrogen-containing bisphosphonates mimic a carbocation intermediate to inhibit the enzyme. Together, these FPPS complexes provide a structural template for the design of novel inhibitors that may prove useful for the treatment of osteoporosis and other clinical indications including cancer.

Flow Analysis of Models of the Hubbard Brook Ecosystem

Several models of energy and nutrient flow on the Hubbard Brook Ecosystem, New Hampshire, USA, were analyzed for the pattern of flow through the models, cycling index CI, path length PL, and straight—though path length PLs. CI represents the proportion of flow that cycles through components of the system. PL is the average number of components that a unit of flow passes through on its way from inflow to outflow. PLs is that portion of PL attributable to flow passing straight through the system without cycling at all. The energy model had low values for PL, PLs, and CI, compared to nutrient models. Flow measures for nutrients varied greatly. The order of the elements in terms of CI and K > Na > N > Ca > P > Mg > S. This could be explained by the mobility and biological role of each element, although Na is somewhat anomalous. PL was very large for K (24.3) but small for S (5.2). PLs was near 4 for all elements but Na (2.6) and S (2.5). This was a reflection of different flow patterns for Na, which flows primarily between available nutrients and belowground biomass, and S, which flows primarily between available nutrients, and below— and aboveground biomass. Sulfur returns to available nutrients via stemflow and throughflow, bypassing the forest floor. The remaining elements cycle between above— and belowground biomass, forest floor, and available nutrients. Three different models of Ca flow were compared. When all three models were analyzed using the same nutrient flux data, flow measures become very close, despite structural differences in the models. For these models, flow values were more important than the architecture of the models in determining cycling and flow characteristics.

Development and validation of an estuarine biotic integrity index

We tested hypotheses about how estuarine fish assemblages respond to habitat degradation and then integrated these responses into an overall index, the Estuarine Biotic Integrity Index (EBI), which summarized observed changes. Fish assemblages (based on trawl catches) and habitat quality were measured monthly or biweekly at nine sites in two estuaries from March 1988 to June 1990. Submerged aquatic vegetation habitats were classified as low or medium quality based on year-round measurements of chemical and physical characteristics (phytoplankton blooms; macroalgae; dissolved oxygen; nutrients; dredged channels). We tested 15 metrics and selected 8 for inclusion in the EBI: total number of species, dominance, fish abundance (number or biomass), number of nursery species, number of estuarine spawning species, number of resident species, proportion of benthic-associated fishes, and proportion abnormal or diseased. Fish assemblages in low-quality sites had lower number of species, density, biomass, and dominance compared with medium-quality sites. Fish abundance peaked in July and August, and was lowest in January to March. The seasonal cycle in low-quality sites was damped compared with medium-quality sites. Abundances of fishes using estuaries as a spawning and nursery area and of benthic species were lower in low-quality sites compared to medium-quality sites. The individual metrics and the overall index correlated with habitat degradation. The EBI based on biomass did not do better than the EBI based on number, indicating that the extra effort to obtain biomass may not be warranted. We suggest the EBI is a useful indicator of estuarine ecosystem status because it reflects the relationship between anthropogenic alterations in estuarine ecosystems and the status of higher trophic levels.

A Quantitative Method for Sampling Riverine Microhabitats by Electrofishing

Abstract An electrofishing device and sampling procedure was developed to sample lotic microhabitats. The device consists of a rectangular electrode frame powered by an alternating current generator. The device was very effective in immobilizing fish within the electrode frame. A time delay between setting and sampling electrode frames permitted a period without disturbance prior to sampling. No significant correlations were found between capture rates and time delays greater than 11 minutes. Consistent results were obtained in repeated sampling of a variety of microhabitats within a single stream reach. The device and sampling procedure allows multispecies abundances to be quantified with regard to discrete units of microhabitat and a priori sampling designs to be used.

Greenway planning: developing a landscape ecological network approach

Greenway planning has steadily grown in popularity in the planning and design professions as an efficient and socially desirable approach to open space planning. The purpose of this paper is to present a theoretical and methodological approach to greenway planning that accounts for regional biodiversity and systematizes the selection of greenway links. The approach used in this paper is based on the premise that a network of wildlife reserves and corridors should serve as the skeletal framework of a comprehensive greenway system. The paper draws from the knowledge bases of landscape ecology, conservation biology, network theory, and landscape planning. A case study is presented to demonstrate the approach using a forested region of Central New England.

Use of the average mutual information index in evaluating classification error and consistency

Abstract An information theory measure of shared information, average mutual information (AMI), is applied to the comparison of thematic maps. The use of a posteriori entropies for one map, given the class identity from the second map, allows evaluation of individual class performance. Examples are presented using classification error matrices and overlays of maps with different themes. AMI measures a different aspect of the problem than does either Percentage Correct or Kappa, measuring ‘consistency’ rather than ‘correctness’. Because of their different viewpoints in comparing classifications, and the potential for spotting mislabelling problems, one should use a combination of Kappa and AMI to assess error matrices. AMI provides a means of assessing the similarity of maps with different themes.

Discovery of a potent and selective series of pyrazole bacterial methionyl-tRNA synthetase inhibitors.

Starting with a micromolar lead identified from high-throughput screening, a series of pyrazoles were discovered with significantly improved potency on bacterial methionyl-tRNA synthetase and selectivity over human methionyl-tRNA synthetase.

Tricyclic GyrB/ParE (TriBE) inhibitors: a new class of broad-spectrum dual-targeting antibacterial agents.

Increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. The bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. However, growing resistance to fluoroquinolones, frequently mediated by mutations in the drug-binding site, is increasingly limiting the utility of this antibiotic class, prompting the search for other inhibitor classes that target different sites on the topoisomerase complexes. The highly conserved ATP-binding subunits of DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as excellent candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential. However, to date, no natural product or small molecule inhibitors targeting these sites have succeeded in the clinic, and no inhibitors of these enzymes have yet been reported with broad-spectrum antibacterial activity encompassing the majority of Gram-negative pathogens. Using structure-based drug design (SBDD), we have created a novel dual-targeting pyrimidoindole inhibitor series with exquisite potency against GyrB and ParE enzymes from a broad range of clinically important pathogens. Inhibitors from this series demonstrate potent, broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens of clinical importance, including fluoroquinolone resistant and multidrug resistant strains. Lead compounds have been discovered with clinical potential; they are well tolerated in animals, and efficacious in Gram-negative infection models.

Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE), Part II: development of inhibitors with broad spectrum, Gram-negative antibacterial activity.

The structurally related bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as prime candidates for the development of broad spectrum antibacterial agents. However, GyrB/ParE targeting antibacterials with spectrum that encompasses robust Gram-negative pathogens have not yet been reported. Using structure-based inhibitor design, we optimized a novel pyrrolopyrimidine inhibitor series with potent, dual targeting activity against GyrB and ParE. Compounds were discovered with broad antibacterial spectrum, including activity against Pseudomonas aeruginosa, Acinetobacter baumannii and Escherichia coli. Herein we describe the SAR of the pyrrolopyrimidine series as it relates to key structural and electronic features necessary for Gram-negative antibacterial activity.