New reactions in clavulanic acid biosynthesis

Clavulanic acid is only a modestly effective antibiotic against bacterial infections in humans, but a potent inhibitor/inactivator of beta-lactamase enzymes that confer bacterial resistance. The biosynthetic pathway to clavulanic acid is considerably more complex than that to the structurally related penicillins and cephalosporins and has revealed several interesting reactions.     

Synthesis and evaluation of 7-substituted-3-cyclobutylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide derivatives as K(ATP) channel agonists

A series of 7-substituted-3-cyclobutylamino-4H-1,2,4-benzothiadiazine-1,1-dioxide derivatives has been synthesized and evaluated as K(ATP) channel agonists using the inside-out excised patch clamp technique. The most active compounds were approximately 20-fold more potent than diazoxide in opening K(ATP) channels. A linear relationship exists between the potency of the compound and the sigma value of the 7-substituent with electron-withdrawing groups exhibiting higher activity. These compounds may be useful in modulating insulin release from pancreatic beta-cells and in diseases associated with hyperinsulinemia.     

Identification of novel and potent isoquinoline aminooxazole-based IMPDH inhibitors

Screening of our in-house compound collection led to the discovery of 5-bromo-6-amino-2-isoquinoline 1 as a weak inhibitor of IMPDH. Subsequent optimization of 1 afforded a series of novel 2-isoquinolinoaminooxazole-based inhibitors, represented by 17, with single-digit nanomolar potency against the enzyme.     

Shamanism: Traditional and Contemporary Approaches to the Mastery of Spirits and Healing

Shamanism: Traditional and Contemporary Approaches to the Mastery of Spirits and Healing. Merete Demant Jakobsen. New York: Berghahn Books, 1999. 274 pp.     

Modeling distributions of disjunct populations of the Sierra Madre Sparrow

ABSTRACT Sierra Madre Sparrows (Xenospiza baileyi) are among the least known of all bird species in Mexico. Recent surveys have discovered previously unknown populations and the current known distribution of Sierra Madre Sparrows consists of two populations separated by >800 km. We used available distributional information to develop ecological niche models that (1) predict much of the distribution potential of the species, (2) establish that the broad disjunction separating the two populations has ecological correlates that appear to be important to the distributional of these sparrows, and (3) illustrate the extremely restricted ecological distribution of the species. We used two sets of climatic and topographic variables, with one including all 22 variables available and the second with only six variables that were positively related to quality of distributional models. Although indications of differences between the two sets of populations were found based on the full 22‐dimensional environmental dataset, such a highly dimensional analysis is vulnerable to over‐fitting; models based on the reduced dataset indicated that the two populations occur in areas with similar ecological conditions. Our models also suggest that southern population of Sierra Madre Sparrows covers most of their potential range in that region. The potential range of the northern population, however, extends beyond known points of occurrence. To clarify the distribution of Sierra Madre Sparrows and evaluate their status and conservation opportunities, detailed searches for additional populations in areas identified by the model are needed.     

Dispersal limitation and geographical distributions of mammal species

Aim To relate the dispersal limitation of endemic terrestrial mammals in Mexico to species life‐history traits and latitude. Location Mexico. Methods We modelled species ecological niches projected as potential distributions (P) using point occurrence data and 19 environmental variables for 89 endemic mammal species, and compared the areas covered by these ecological niche models with maps of species actual distributions (R) based on minimum convex polygons connecting marginal records based on museum specimens. We correlated body mass, food habits (herbivore, omnivore, insectivore, frugivore/granivore), volant and non‐volant (fossorial, arboreal, terrestrial) habits and mean latitude to the proportion of occupancy of species potential distributional areas (R/P). Results R and P were significantly positively correlated, with an overall average R/P ratio of 0.49. Less than half of the endemics (41 species) had a high occupancy (R/P values ranging from 0.50 to 0.90); a few (four species) showed full occupancy (> 0.90). Body mass and food habits were not correlated with R/P, but latitude showed significant correlations with R/P; volant mammals tended to show higher R/P values than non‐volant mammals. Main conclusions Few species filled most of the spatial extent of their ecological niches. Life‐history traits were generally poor predictors of proportional occupancy of species potential distributions. Endemics occurring at higher latitudes showed higher occupancy, suggesting that abiotic factors are likely to limit their distributions. Conversely, species at lower latitudes showed lower occupancy, suggesting that their distributions are limited by biotic factors and/or by geographical or historical barriers that prevent dispersal. The dispersal abilities of volant compared with non‐volant endemics can explain the higher occupancy in species potential distributions in the former group. These trends provide a baseline for exploring the importance of life‐history traits and abiotic versus biotic factors in limiting species distributions.     

Longitudinal Intergenerational Birth Cohort Designs: A Systematic Review of Australian and New Zealand Studies

Background

The longitudinal birth cohort design has yielded a substantial contribution to knowledge of child health and development. The last full review in New Zealand and Australia in 2004 identified 13 studies. Since then, birth cohort designs continue to be an important tool in understanding how intrauterine, infant and childhood development affect long-term health and well-being. This updated review in a defined geographical area was conducted to better understand the factors associated with successful quality and productivity, and greater scientific and policy contribution and scope.

Methods

We adopted the preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach, searching PubMed, Scopus, Cinahl, Medline, Science Direct and ProQuest between 1963 and 2013. Experts were consulted regarding further studies. Five inclusion criteria were used: (1) have longitudinally tracked a birth cohort, (2) have collected data on the child and at least one parent or caregiver (3) be based in Australia or New Zealand, (4) be empirical in design, and (5) have been published in English.

Results

10665 records were initially retrieved from which 23 birth cohort studies met the selection criteria. Together these studies recruited 91,196 participants, with 38,600 mothers, 14,206 fathers and 38,390 live births. Seventeen studies were located in Australia and six in New Zealand. Research questions initially focused on the perinatal period, but as studies matured, longer-term effects and outcomes were examined.

Conclusions

This review demonstrates the significant yield from this effort both in terms of scientific discovery and social policy impact. Further opportunities have been recognised with cross-study collaboration and pooling of data between established and newer studies and international studies to investigate global health determinants.     

NicheA: creating virtual species and ecological niches in multivariate environmental scenarios

Robust methods by which to generate virtual species are needed urgently in the emerging field of distributional ecology to evaluate performance of techniques for modeling ecological niches and species distributions and to generate new questions in biogeography. Virtual species provide the opportunity to test hypotheses and methods based on known and unbiased distributions. We present Niche Analyst (NicheA), a toolkit developed to generate virtual species following the Hutchinsonian approach of an n‐multidimensional space occupied by the species. Ecological niche models are generated, analyzed, and visualized in an environmental space, and then projected to the geographic space in the form of continuous or binary species distribution models. NicheA is implemented in a stable and user‐friendly Java platform. The software, online manual, and user support are freely available at < http://nichea.sourceforge.net >.     

The Heat Is On! Using Particle Models to Change Students' Conceptions of Heat and Temperature

Elementary, middle-level, and high school science teachers commonly find their students have misconceptions about heat and temperature. Unfortunately, student misconceptions are difficult to modify or change and can prevent students from learning the accurate scientific explanation. In order to improve our students' understanding of heat and temperature, we created a three-part instructional activity designed to engage them in the development of kinetic particle models. First, the students use household materials—food coloring and water—to investigate and create particle models depicting motion at the molecular level. Second, the students complete a similar activity designed to help them visualize the connections between heat and particle motion. Third, the students build a thermometer, observe it in action, and create particle models explaining how the thermometer works. By the end of the series of activities, the students are able develop their own definitions for heat and temperature. Through this hands-on and minds-on series of activities, students learn to define and differentiate the concepts of heat and temperature.