Physical limits on kinesin-5–mediated chromosome congression in the smallest mitotic spindles

A characteristic feature of mitotic spindles is the congression of chromosomes near the spindle equator, a process mediated by dynamic kinetochore microtubules. A major challenge is to understand how precise, submicrometer-scale control of kinetochore micro­tubule dynamics is achieved in the smallest mitotic spindles, where the noisiness of microtubule assembly/disassembly will potentially act to overwhelm the spatial information that controls microtubule plus end–tip positioning to mediate congression. To better understand this fundamental limit, we conducted an integrated live fluorescence, electron microscopy, and modeling analysis of the polymorphic fungal pathogen Candida albicans, which contains one of the smallest known mitotic spindles (<1 μm). Previously, ScCin8p (kinesin-5 in Saccharomyces cerevisiae) was shown to mediate chromosome congression by promoting catastrophe of long kinetochore microtubules (kMTs). Using C. albicans yeast and hyphal kinesin-5 (Kip1p) heterozygotes (KIP1/kip1∆), we found that mutant spindles have longer kMTs than wild-type spindles, consistent with a less-organized spindle. By contrast, kinesin-8 heterozygous mutant (KIP3/kip3∆) spindles exhibited the same spindle organization as wild type. Of interest, spindle organization in the yeast and hyphal states was indistinguishable, even though yeast and hyphal cell lengths differ by two- to fivefold, demonstrating that spindle length regulation and chromosome congression are intrinsic to the spindle and largely independent of cell size. Together these results are consistent with a kinesin-5–mediated, length-dependent depolymerase activity that organizes chromosomes at the spindle equator in C. albicans to overcome fundamental noisiness in microtubule self-assembly. More generally, we define a dimensionless number that sets a fundamental physical limit for maintaining congression in small spindles in the face of assembly noise and find that C. albicans operates very close to this limit, which may explain why it has the smallest known mitotic spindle that still manifests the classic congression architecture.     

Changes in ventilation in response to ramp changes in treadmill exercise load

These experiments examined the changes in ventilation during a 40-s ramp increase in exercise load, produced by increasing either the speed of the treadmill or the grade, to equivalent end-points of oxygen uptake. Six subjects underwent five trials each for grade and speed, while ventilation was monitored breath-by-breath. For each subject, ventilation versus time for all five of the speed trials was plotted on a single graph and fitted by linear regression. The data for the grade trials were similarly treated. For all subjects, the slope of the regression line for the speed plots was found to be significantly (P < 0.05) greater than that for the grade plots. We concluded that these experimental results support the hypothesis that the neural drive to ventilation persists as exercise continues and is proportionately related to the frequency of limb movement.     

Influence of light on plant allelochemicals: A synergistic defense in higher plants

Plant phototoxins are broad-spectrum biocides which adversely affect an array of potential plant enemies, including among others disease-causing pathogens, nematodes, insect herbivores, and competing plant species. Thus far, plants which contain these broad-spectrum allelochemicals have been found to occur in open habitats (i.e., in full sunlight) where a defensive mechanism mediated by light would seem to operate most effectively. The levels of available light in shaded environments, although considerably lower than full sun (1–10% of full sun), are equivalent to the intensities of light used to kill phototoxin-treated insects in laboratory studies. This suggests that phototoxic reactions might mediate important organismal interactions in shaded environments as well. In this study, more than 230 Costa Rican rainforest plants were bioassayed for phototoxic metabolites in an effort to ascertain their prevalence among plants growing in moderate to extreme shade. Microbial bioassays, employing Bacillus cereus (a gram positive bacterium), Escherichia coli (a gram negative bacterium), and Saccharomyces cerevisiae (a yeast) were used to rapidly and sensitively indicate phototoxic action and potential for insecticidal action. Tissue extracts from 12 plant families tested positive for phototoxins. This is the first report of phototoxins occurring in eight of those families (Acanthaceae, Campanulaceae, Gesnariaceae, Loganiaceae, Malpigaceae, Phytolaccaceae, Piperaceae, and Sapotaceae). The presence of phototoxins in rainforest plants suggests that phototoxic plant allelochemicals may function as important defenses in low-light, as well as high-light, environments.     

Hazard Ranking Methodology for Assessing Health Impacts of Unconventional Natural Gas Development and Production: The Maryland Case Study

The recent growth of unconventional natural gas development and production (UNGDP) has outpaced research on the potential health impacts associated with the process. The Maryland Marcellus Shale Public Health Study was conducted to inform the Maryland Marcellus Shale Safe Drilling Initiative Advisory Commission, State legislators and the Governor about potential public health impacts associated with UNGDP so they could make an informed decision that considers the health and well-being of Marylanders. In this paper, we describe an impact assessment and hazard ranking methodology we used to assess the potential public health impacts for eight hazards associated with the UNGDP process. The hazard ranking included seven metrics: 1) presence of vulnerable populations (e.g. children under the age of 5, individuals over the age of 65, surface owners), 2) duration of exposure, 3) frequency of exposure, 4) likelihood of health effects, 5) magnitude/severity of health effects, 6) geographic extent, and 7) effectiveness of setbacks. Overall public health concern was determined by a color-coded ranking system (low, moderately high, and high) that was generated based on the overall sum of the scores for each hazard. We provide three illustrative examples of applying our methodology for air quality and health care infrastructure which were ranked as high concern and for water quality which was ranked moderately high concern. The hazard ranking was a valuable tool that allowed us to systematically evaluate each of the hazards and provide recommendations to minimize the hazards.     

Osteopathology in Rhinocerotidae from 50 Million Years to the Present

Individual elements of many extinct and extant North American rhinocerotids display osteopathologies, particularly exostoses, abnormal textures, and joint margin porosity, that are commonly associated with localized bone trauma. When we evaluated six extinct rhinocerotid species spanning 50 million years (Ma), we found the incidence of osteopathology increases from 28% of all elements of Eocene Hyrachyus eximius to 65–80% of all elements in more derived species. The only extant species in this study, Diceros bicornis, displayed less osteopathologies (50%) than the more derived extinct taxa. To get a finer-grained picture, we scored each fossil for seven pathological indicators on a scale of 1–4. We estimated the average mass of each taxon using M1-3 length and compared mass to average pathological score for each category. We found that with increasing mass, osteopathology also significantly increases. We then ran a phylogenetically-controlled regression analysis using a time-calibrated phylogeny of our study taxa. Mass estimates were found to significantly covary with abnormal foramen shape and abnormal bone textures. This pattern in osteopathological expression may reflect a part of the complex system of adaptations in the Rhinocerotidae over millions of years, where increased mass, cursoriality, and/or increased life span are selected for, to the detriment of long-term bone health. This work has important implications for the future health of hoofed animals and humans alike.     

Unaltered metabolism of taurolithocholic acid with changes in composition of rat intestinal microflora

Changes in composition of both total aerobes and anaerobes of rat intestinal microflora do not appear to affect the metabolism of taurolithocholic acid.