Correlation of changes in cardiac calcium channels with hemodynamics in Syrian hamster cardiomyopathy and heart failure

We compared hemodynamics with [3H]nitrendipine (calcium channel) binding to cardiac membranes from Bio 14.6 cardiomyopathic Syrian hamsters at 4 and 10 months with their F1B controls. A 50% increase in the number (Bmax) of nitrendipine binding sites (calcium channels) was seen only in the 4 month old myopathic vs controls (Bmax = 468 +/- 11 vs 309 +/- 10 fmol/mg prot with no change in affinity (KD) (KD = .65 +/- .12 vs .75 +/- .14 nM), while no differences in Bmax or KD were seen at 10 months (Bmax = 375 +/- 9 vs 362 +/- 7 fmol/mg prot/KD = .82 +/- .18 vs .89 +/- .17 nM) myopathic vs control respectively. Hemodynamic studies revealed no significant differences in cardiac output, cardiac index, stroke volume, heart rate, mean arterial pressure, peripheral resistance, body weight, heart weight at 4 months, but a significant decrease in peripheral resistance (1120 +/- 360 vs 2080 +/- 240) increase in body weight (118 +/- 2 vs 94 +/- 2 grams) and heart weight (97 +/- 5 vs 78 +/- 2 gms/100 gms body weight) in 10 month myopathic vs control animals. We conclude that the onset of cardiomyopathy at 4 months is associated with a selective increase in calcium channel binding sites and heart failure at 10 months is associated with a relative decrease in these sites.     

Differential inhibition of sclerotial germination in Whetzelinia sclerotiorum

A number of diverse compounds including divalent metal ions, simple sugars, and common counterions, buffers, and fungicides were surveyed in the laboratory with regard to ability to inhibit germination of field-collected sclerotia from Whetzelinia sclerotiorum. Many compounds were inhibitory and several were comparable in effectiveness to benomyl and other commercial fungicides. Different levels of a given inhibitor were needed to prevent stipe formation, apothecial formation or mycelial germination. Inhibition was not correlated with ionic strength or related to pH.     

A differential scanning calorimetric study of the bovine lens crystallins

Differential scanning calorimetry was performed on the five major lens crystallin fractions [HM-alpha, alpha, beta H, beta L, and (beta s + gamma)] of the bovine lens as well as on more purified forms of alpha- and gamma-crystallins. All were found to be relatively thermally stable although the alpha-crystallin were found to at least partially unfold at an approximately 10 degrees C lower temperature than the beta and gamma fractions. Increasing protein concentration had little effect on gamma-crystallin thermograms but had marked effects on those of the alpha- and beta-crystallins. Increases in the thermal stability with increasing protein concentration for the beta-crystallins can be explained most simply by the known beta L/beta H equilibrium, but, in the case of the alpha-crystallins, excluded volume effects may be an important factor. In both cases, the increased stability at high concentrations could be of physiological relevance. As well as the expected endothermic unfolding transitions, all of the lens crystallins revealed exothermic peaks that correlate with protein precipitation. Interestingly, this phenomenon occurs only after extensive structural alteration in the case of the alpha-crystallins but is present very early in the initial stages of structural perturbation of the beta- and gamma-crystallins.     

A new species of Late Pleistocene rail (Aves: Rallidae) from Abaco, the Bahamas

We describe a new species of rail from the Sawmill Sink blue hole on Abaco Island in the northern Bahamas. Known from abundant, beautifully preserved Late Pleistocene fossils, Rallus cyanocavi sp. nov. was a medium-sized, flightless species that probably was endemic to the Little Bahama Bank, which is a carbonate platform surrounded by deeper water. We are uncertain whether R. cyanocavi survived into the Holocene, when higher sea levels transformed the Little Bahama Bank from a single large, Late Pleistocene island (ca. 12000 km²) to the scattering of smaller islands seen today, the largest of which is Abaco (1681 km²). Fossils of additional extinct, flightless species of Rallus probably await discovery on some of the 21 other carbonate banks that span the Bahamian Archipelago.     

The discovery of the benzazepine class of histamine H3 receptor antagonists

This Letter describes the discovery of a novel series of H₃ receptor antagonists. The initial medicinal chemistry strategy focused on deconstructing and simplifying an early screening hit which rapidly led to the discovery of a novel series of H₃ receptor antagonists based on the benzazepine core. Employing an H₃ driven pharmacodynamic model, the series was then further optimised through to a lead compound that showed robust in vivo functional activity and possessed overall excellent developability properties.     

Mississippians in motion? A population genetic analysis of interregional gene flow in West-Central Illinois

Population genetic and biological distance studies of Late Woodland and Mississippian populations from west-central Illinois have provided insight into a number of prehistoric demographic processes at the regional level. However, a formal analysis of diachronic interregional gene flow has not been attempted within a population genetics framework. In this study, cranial measurements of 489 individuals from 13 skeletal samples across the central and lower Illinois valleys are analyzed to address two central issues. First, the potential impact of Cahokia's decline and associated demographic events on the population structure of west-central Illinois Mississippians is examined. Second, the Mississippian and Late Woodland interregional migration patterns are compared to determine if geographic and/or cultural boundaries affected local population structure. Following Relethford and Blangero ([1990] Hum Biol 62:5-25), R matrix methods are utilized to calculate observed and expected phenotypic variances, minimum genetic distances, and F(ST) values in order to detect patterns of differential external gene flow over time. The results indicate that Late Woodland peoples had a larger sphere of biological interaction than Mississippians. In the Mississippian period, culturally imposed barriers paralleled geographic boundaries between regions such that the geographic distribution of biological variation closely adheres to a classic isolation-by-distance model. Further, intraregional population movement was a more significant contributor to Mississippian population structure than interregional gene flow, even during periods of sociopolitical strife. Small-scale intraregional shuffling is consistent with other recent studies of prehistoric Mississippian biocultural and geographic landscapes in the southeast United States.     

Autoclave method for rapid preparation of bacterial PCR-template DNA

An autoclave method for preparing bacterial DNA for PCR template is presented, it eliminates the use of detergents, organic solvents, and mechanical cellular disruption approaches, thereby significantly reducing processing time and costs while increasing reproducibility. Bacteria are lysed by rapid heating and depressurization in an autoclave. The lysate, cleared by microcentrifugation, was either used directly in the PCR reaction, or concentrated by ultrafiltration. This approach was compared with seven established methods of DNA template preparation from four bacterial sources which included boiling Triton X-100 and SDS, bead beating, lysozyme/proteinase K, and CTAB lysis method components. Bacteria examined were Enterococcus and Escherichia coli, a natural marine bacterial community and an Antarctic cyanobacterial-mat. DNAs were tested for their suitability as PCR templates by repetitive element random amplified polymorphic DNA (RAPD) and denaturing gradient gel electrophoresis (DGGE) analysis. The autoclave method produced PCR amplifiable template comparable or superior to the other methods, with greater reproducibility, much shorter processing time, and at a significantly lower cost.     

Changing Exploitation of Terrestrial Vertebrates During the Past 3000 Years on Tobago, West Indies

On the southern Caribbean island of Tobago, we excavated two archaeological deposits, the preceramic (ca. 2900 years old) Milford 1 site (TOB-3) and the ceramic (ca. 1200 to 900 years old) Golden Grove site (TOB-13). The non-fish bone assemblages from these sites are very different, with an emphasis at TOB-3 on sea turtles (which seldom nest today on Tobago) and the collared peccary Tayassu tajacu, a large (17–30 kg) mammal extremely rare now on Tobago. TOB-3 also yielded bones of two somewhat smaller mammals that are extinct on Tobago, the red howler monkey Alouatta seniculus and paca Agouti paca. The non-fish species at TOB-3 comprise only four reptiles and seven mammals, whereas they are more diverse (29 species) at TOB-13 and mostly represent small- to medium-sized vertebrates (<10 kg, often <1 kg), such as a toad, lizards, snakes, birds, opossum, armadillo, and eight species of rodents, as well as sea turtle and peccary, although the latter is uncommon. We interpret these differences as possibly being due to a local or island-wide scarcity of big game (peccaries) in ceramic times, which would have promoted diversification of hunting practices. Related to this may have been a more sedentary way of life for Tobago's ceramic peoples, with increased agriculture leading to more hunting near the site and less time being devoted to longer distance big-game hunting. While prehistoric anthropogenic extinction or population reduction of vertebrates is well documented on Caribbean islands to the north, our data from Tobago show that such depletions probably occurred as well on continental, land-bridge islands with more diverse faunas. Models of post-Pleistocene faunal relaxation toward a lower value for species richness should not ignore human-caused losses, which may be impossible to distinguish from non-anthropogenic losses.