Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV: Structure-based drug design,synthesis, and biological evaluation

A novel series of potent thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV was discovered using structure-based drug design. Synthesis, structure–activity relationship, and optimization of physicochemical properties are described. Low nanomolar potency was achieved, and selected compounds with improved thermodynamic solubility showed promising in vitro inhibition of carbonic anhydrase activity in rabbit iris ciliary body homogenate.     

Interspecific Associations between Cycloneda sanguinea and Two Aphid Species (Aphis gossypii and Hyadaphis foeniculi) in Sole-Crop and Fennel-Cotton Intercropping Systems

Aphids cause significant damage to crop plants. Studies regarding predator-prey relationships in fennel (Foeniculum vulgare Mill.) and cotton (Gossypium hirsutum L.) crops are important for understanding essential ecological interactions in the context of intercropping and for establishing pest management programs for aphids. This study evaluated the association among Hyadaphis foeniculi (Passerini) (Hemiptera: Aphididae), Aphis gossypii Glover (Hemiptera: Aphididae) and Cycloneda sanguinea (L.) (Coleoptera: Coccinellidae) in cotton with coloured fibres, fennel and cotton intercropped with fennel. Association analysis was used to investigate whether the presence or absence of prey and predator species can indicate possible interactions between aphids and ladybugs. Significant associations among both apterous and alate H. foeniculi and C. sanguinea were observed in both the fennel and fennel-cotton intercropping systems. The similarity analysis showed that the presence of aphids and ladybugs in the same system is significantly dependent on the type of crop. A substantial amount of evidence indicates that the presence of the ladybug C. sanguinea, is associated with apterous or alate A. gossypii and H. foeniculi in fennel-cotton intercropping system. We recommend that future research vising integrated aphid management taking into account these associations for take decisions.     

Can Observation Skills of Citizen Scientists Be Estimated Using Species Accumulation Curves?

Volunteers are increasingly being recruited into citizen science projects to collect observations for scientific studies. An additional goal of these projects is to engage and educate these volunteers. Thus, there are few barriers to participation resulting in volunteer observers with varying ability to complete the project’s tasks. To improve the quality of a citizen science project’s outcomes it would be useful to account for inter-observer variation, and to assess the rarely tested presumption that participating in a citizen science projects results in volunteers becoming better observers. Here we present a method for indexing observer variability based on the data routinely submitted by observers participating in the citizen science project eBird, a broad-scale monitoring project in which observers collect and submit lists of the bird species observed while birding. Our method for indexing observer variability uses species accumulation curves, lines that describe how the total number of species reported increase with increasing time spent in collecting observations. We find that differences in species accumulation curves among observers equates to higher rates of species accumulation, particularly for harder-to-identify species, and reveals increased species accumulation rates with continued participation. We suggest that these properties of our analysis provide a measure of observer skill, and that the potential to derive post-hoc data-derived measurements of participant ability should be more widely explored by analysts of data from citizen science projects. We see the potential for inferential results from analyses of citizen science data to be improved by accounting for observer skill.     

Documenting Differences between Early Stone Age Flake Production Systems: An Experimental Model and Archaeological Verification

This study investigates morphological differences between flakes produced via “core and flake” technologies and those resulting from bifacial shaping strategies. We investigate systematic variation between two technological groups of flakes using experimentally produced assemblages, and then apply the experimental model to the Cutting 10 Mid -Pleistocene archaeological collection from Elandsfontein, South Africa. We argue that a specific set of independent variables—and their interactions—including external platform angle, platform depth, measures of thickness variance and flake curvature should distinguish between these two technological groups. The role of these variables in technological group separation was further investigated using the Generalized Linear Model as well as Linear Discriminant Analysis. The Discriminant model was used to classify archaeological flakes from the Cutting 10 locality in terms of their probability of association, within either experimentally developed technological group. The results indicate that the selected independent variables play a central role in separating core and flake from bifacial technologies. Thickness evenness and curvature had the greatest effect sizes in both the Generalized Linear and Discriminant models. Interestingly the interaction between thickness evenness and platform depth was significant and played an important role in influencing technological group membership. The identified interaction emphasizes the complexity in attempting to distinguish flake production strategies based on flake morphological attributes. The results of the discriminant function analysis demonstrate that the majority of flakes at the Cutting 10 locality were not associated with the production of the numerous Large Cutting Tools found at the site, which corresponds with previous suggestions regarding technological behaviors reflected in this assemblage.     

Canopy Openness Enhances Diversity of Ant–Plant Interactions in the Brazilian Amazon Rain Forest

In closed‐canopy tropical forest understory, light availability is a significant determinant of habitat diversity because canopy structure is highly variable in most tropical forests. Consequently, variation in canopy cover affects the composition and distribution of plant species via creating variable light environments. Nevertheless, little is known about how variation in canopy openness structures patterns of plant–animal interactions. Because of the great diversity and dominance of ants in tropical environments, we used ant–plant interactions as a focal network to evaluate how variation in canopy cover influences patterns of plant–insect interactions in the Brazilian Amazon rain forest. We observed that small increases in canopy openness are associated with increased diversity of ant–plant interactions in our study area, and this change is independent of plant or ant species richness. Additionally, we found smaller niche overlap for both ants and plants associated with greater canopy openness. We hypothesize that enhanced light availability increases the breadth of ant foraging sources because variation in light availability gives rise to plant resources of different quality and amounts. Moreover, greater light availability promotes vegetative growth in plants, creating ant foraging ‘bridges’ between plants. In sum, our results highlight the importance of environmental heterogeneity as a determinant of ant–plant interaction diversity in tropical environments.     

Hybrid computational phantoms for medical dose reconstruction

As outlined in NCRP Report No. 160 of the US National Council on Radiation Protection and Measurements (NCRP), the average value of the effective dose to exposed individuals in the United States has increased by a factor of 1.7 over the time period 1982–2006, with the contribution of medical exposures correspondingly increasing by a factor of 5.7. At present, medical contributors to effective dose include computed tomography (50% of total medical exposure), nuclear medicine (25%), interventional fluoroscopy (15%), and conventional radiography and diagnostic fluoroscopy (10%). An increased awareness of medical exposures has led to a gradual shift in the focus of radiation epidemiological studies from traditional occupational and environmental exposures to those focusing on cohorts of medical patients exposed to both diagnostic and therapeutic sources. The assignment of organ doses to patients in either a retrospective or a prospective study has increasingly relied on the use of computational anatomic phantoms. In this paper, we review the various methods and approaches used to construct patient models to include anthropometric databases, cadaver imaging, prospective volunteer imaging studies, and retrospective image reviews. Phantom format types—stylized, voxel, and hybrid—as well as phantom morphometric categories—reference, patient-dependent, and patient-specific—are next defined and discussed. Specific emphasis is given to hybrid phantoms—those defined through the use of combinations of polygon mesh and non-uniform rational B-spline (NURBS) surfaces. The concept of a patient-dependent phantom is reviewed, in which phantoms of non-50th percentile heights and weights are designed from population-based morphometric databases and provided as a larger library of phantoms for patient matching and lookup of refined values of organ dose coefficients and/or radionuclide S values. We close with two brief examples of the use of hybrid phantoms in medical dose reconstruction—diagnostic nuclear medicine for pediatric subjects and interventional fluoroscopy for adult patients.     

All-codon scanning identifies p53 cancer rescue mutations

In vitro scanning mutagenesis strategies are valuable tools to identify critical residues in proteins and to generate proteins with modified properties. We describe the fast and simple All-Codon Scanning (ACS) strategy that creates a defined gene library wherein each individual codon within a specific target region is changed into all possible codons with only a single codon change per mutagenesis product. ACS is based on a multiplexed overlapping mutagenesis primer design that saturates only the targeted gene region with single codon changes. We have used ACS to produce single amino-acid changes in small and large regions of the human tumor suppressor protein p53 to identify single amino-acid substitutions that can restore activity to inactive p53 found in human cancers. Single-tube reactions were used to saturate defined 30-nt regions with all possible codon changes. The same technique was used in 20 parallel reactions to scan the 600-bp fragment encoding the entire p53 core domain. Identification of several novel p53 cancer rescue mutations demonstrated the utility of the ACS approach. ACS is a fast, simple and versatile method, which is useful for protein structure–function analyses and protein design or evolution problems.