A Keller-Segel model for C elegans L1 aggregation

We describe a mathematical model for the aggregation of starved first-stage C elegans larvae (L1s). We propose that starved L1s produce and respond chemotactically to two labile diffusible chemical signals, a short-range attractant and a longer range repellent. This model takes the mathematical form of three coupled partial differential equations, one that describes the movement of the worms and one for each of the chemical signals. Numerical solution of these equations produced a pattern of aggregates that resembled that of worm aggregates observed in experiments. We also describe the identification of a sensory receptor gene, srh–2, whose expression is induced under conditions that promote L1 aggregation. Worms whose srh–2 gene has been knocked out form irregularly shaped aggregates. Our model suggests this phenotype may be explained by the mutant worms slowing their movement more quickly than the wild type.     

Physical Activity and Reduced Intra‐abdominal Fat in Midlife African‐American and White Women

The purpose of our study was to determine whether self‐reported physical activity (PA), including recreational, household, and exercise activities, is associated with intra‐abdominal fat (IAF) in community‐dwelling white and black midlife women. We performed a cross‐sectional study of 369 women from the Chicago site of the Study of Women's Health Across the Nation (SWAN) ancillary study, the SWAN Fat Patterning Study. PA level was the independent variable, and IAF, assessed by computerized tomography (CT) scan, was the dependent variable. Measures were obtained at SWAN Fat Patterning Baseline visit between August 2002 and December 2005. Linear regression models explored the association between PA and IAF. The first model included IAF as the outcome and total score PA as the main predictor, adjusting for total percent fat mass, age, and ethnicity. The second model included education, parity, sex hormone–binding globulin (SHBG) level, and depressive symptoms, measured by Center for Epidemiological Studies‐Depression (CES‐D) scale. Each 1‐point higher total PA score was associated with a 4.0 cm² lower amount of IAF (P = 0.004), independent of total percent fat mass, age, ethnicity, SHBG level, educational level, CES‐D, and parity. Associations did not differ between white and black women. This study demonstrates a significant negative association between PA and IAF independent of multiple covariates in midlife women. Our findings suggest that motivating white and black women to increase PA during midlife may lessen IAF, which may have a positive impact on subsequent development of diabetes and cardiovascular disease.     

Endocytic recycling proteins EHD1 and EHD2 interact with fer-1-like-5 (Fer1L5) and mediate myoblast fusion

The mammalian ferlins are calcium-sensing, C2 domain-containing proteins involved in vesicle trafficking. Myoferlin and dysferlin regulate myoblast fusion and muscle membrane resealing, respectively. Correspondingly, myoferlin is most highly expressed in singly nucleated myoblasts, whereas dysferlin expression is increased in mature, multinucleated myotubes. Myoferlin also mediates endocytic recycling and participates in trafficking the insulin-like growth factor receptor. We have now characterized a novel member of the ferlin family, Fer1L5, because of its high homology to dysferlin and myoferlin. We found that Fer1L5 protein is expressed in small myotubes that contain only two to four nuclei. We also found that Fer1L5 protein binds directly to the endocytic recycling proteins EHD1 and EHD2 and that the second C2 domain in Fer1L5 mediates this interaction. Reduction of EHD1 and/or EHD2 inhibits myoblast fusion, and EHD2 is required for normal translocation of Fer1L5 to the plasma membrane. The characterization of Fer1L5 and its interaction with EHD1 and EHD2 underscores the complex requirement of ferlin proteins and mediators of endocytic recycling for membrane trafficking events during myotube formation.     

Spermatinamine, the first natural product inhibitor of isoprenylcysteine carboxyl methyltransferase, a new cancer target

Isoprenylcysteine methyltransferase (Icmt) catalyzes the carboxyl methylation of oncogenic proteins in the final step of a series of post-translational modifications. The inhibition of Icmt provides an attractive and novel anticancer target. A natural product high-throughput screening campaign was conducted to discover inhibitors of Icmt. The Australian marine sponge, Pseudoceratina sp., yielded spermatinamine, a novel alkaloid with a bromotyrosyl-spermine-bromotyrosyl sequence, as the bioactive constituent. Its structure was determined by 1D and 2D NMR spectroscopy. Spermatinamine is the first natural product inhibitor of Icmt.     

Is propagule size the critical factor in predicting introduction outcomes in passeriform birds?

Influential analyses of the propagule pressure hypothesis have been based on multiple bird species introduced to one region (e.g. New Zealand). These analyses implicitly assume that species-level and site-level characteristics are less important than the number of individuals released. In this study we compared records of passerine introductions with propagule size information across multiple regions (New Zealand, Australia, and North America). We excluded species introduced to just one of the three regions or with significant uncertainty in the historical record, as well as species that succeeded or failed in all regions. Because it is often impossible to attribute success to any single event or combination of events, our analysis compared randomly selected propagule sizes of unsuccessful introductions with those of successful introductions. Using Monte Carlo repeated sampling we found no statistical support for the propagule pressure hypothesis, even when using assumptions biased toward showing an effect.     

3-Alkylthio-1,2,4-triazine dimers with potent antimalarial activity

We report on the discovery of 3-alkylthio-1,2,4-triazine dimers that are potently toxic to Plasmodium falciparum, with single digit nanomolar activity, and up to several thousand-fold lower toxicity to mammalian cells. They are equipotent against chloroquine-resistant strains of P. falciparum.     

Caesium accumulation by microorganisms: uptake mechanisms,cation competition,compartmentalization and toxicity

Summary The continued release of caesium radioisotopes into the environment has led to a resurgence of interest in microbe-Cs interactions. Caesium exists almost exclusively as the monovalent cation Cs⁺ in the natural environment. Although Cs⁺ is a weak Lewis acid that exhibits a low tendency to form complexes with ligands, its chemical similarity to the biologically essential alkali cation K⁺ facilitates high levels of metabolism-dependent intracellular accumulation. Microbial Cs⁺ (K⁺) uptake is generally mediated by monovalent cation transport systems located on the plasma membrane. These differe widely in specificity for alkali cations and consequently microorganisms display large differences in their ability to accumulate Cs⁺; Cs⁺ appears to have an equal or greater affinity than K⁺ for transport in certain microorganisms. Microbial Cs⁺ accumulation is markedly influenced by the presence of external cations, e.g. K⁺, Na⁺, NH₄ ⁺ and H⁺, and is generally accompanied by an approximate stoichiometric exchange for intracellular K⁺. However, stimulation of growth of K⁺-starved microbial cultures by Cs⁺ is limited and its has been proposed that it is not the presence of Cs⁺ in cells that is growth inhibitory but rather the resulting loss of K⁺. Increased microbial tolerance to Cs⁺ may result from sequestration of Cs⁺ in vacuoles or changes in the activity and/or specificity of transport systems mediating Cs⁺ uptake. The precise intracellular target(s) for Cs⁺-induced toxicity has yet to be clearly defined, although certain internal structures, e.g. ribosomes, become unstable in the presence of Cs⁺ and Cs⁺ is known to substitute poorly for K⁺ in the activation of many K⁺-requiring enzymes.     

High CO2 and silicate limitation synergistically increase the toxicity of Pseudo-nitzschia fraudulenta

Anthropogenic CO(2) is progressively acidifying the ocean, but the responses of harmful algal bloom species that produce toxins that can bioaccumulate remain virtually unknown. The neurotoxin domoic acid is produced by the globally-distributed diatom genus Pseudo-nitzschia. This toxin is responsible for amnesic shellfish poisoning, which can result in illness or death in humans and regularly causes mass mortalities of marine mammals and birds. Domoic acid production by Pseudo-nitzschia cells is known to be regulated by nutrient availability, but potential interactions with increasing seawater CO(2) concentrations are poorly understood. Here we present experiments measuring domoic acid production by acclimatized cultures of Pseudo-nitzschia fraudulenta that demonstrate a strong synergism between projected future CO(2) levels (765 ppm) and silicate-limited growth, which greatly increases cellular toxicity relative to growth under modern atmospheric (360 ppm) or pre-industrial (200 ppm) CO(2) conditions. Cellular Si:C ratios decrease with increasing CO(2), in a trend opposite to that seen for domoic acid production. The coastal California upwelling system where this species was isolated currently exhibits rapidly increasing levels of anthropogenic acidification, as well as widespread episodic silicate limitation of diatom growth. Our results suggest that the current ecosystem and human health impacts of toxic Pseudo-nitzschia blooms could be greatly exacerbated by future ocean acidification and 'carbon fertilization' of the coastal ocean.     

The air-borne distribution of zoonotic agents from livestock waste spreading and microbiological risk to fresh produce from contaminated irrigation sources

Aims:  To assess the risks of zoonotic agents in dissemination of livestock wastes into the environment by airborne distribution. To subsequently assess the survival time of zoonotic agents, introduced in irrigation water, on the phylloplane of produce.
Methods and Results:  An Escherichia coli marker was introduced into pig slurry which was spread using a rain gun sprayer. Air sampling was undertaken to determine the distance reached by the marker. No recoveries were observed at a distance of 250 m. Borehole water, contaminated with zoonotic agents, was used to irrigate field plots sown with lettuce and spinach. Decline in bacterial numbers on the phylloplane was observed with time. After initial rapid decreases, we were unable to detect any pathogen from the phylloplane, 1 month after contamination.
Conclusions:  These preliminary results suggest that the risks to public health from the aerosolized spread of bacteria during slurry spreading by rain gun are low. Although, zoonotic agents on crop phylloplanes perish quickly, the risks of overhead irrigation of fresh produce 3 weeks before harvest should still be considered.
Significance and Impact of the Study:  These preliminary results improve our understanding on the fate of zoonotic agents in the environment. Spreading liquid livestock wastes by an airborne mechanism may not pose a significant public health risk. Detection of zoonotic agents 3 weeks after contamination of lettuce and spinach means that consideration should be given by the farmers until the time of harvest, when irrigating fresh produce with water that may have been directly or indirectly contaminated by livestock wastes.     

Self-selected resistance training intensity in healthy women: the influence of a personal trainer

The purpose of the present investigation was to examine the influence of resistance training with a personal trainer versus unsupervised resistance training on the self-selected intensities used by women during resistance exercise. Forty-six resistance-trained women (age = 26.6 +/- 6.4 years; body mass = 64.2 +/- 10.9 kg) who either trained individually (n = 27; No PT) or with a personal trainer (n = 19; PT) were carefully instructed to select a weight they used in their own resistance training workouts that enabled the completion of 10 repetitions for the chest press (CP), leg press (LP), seated row (SR), and leg extension (LE) exercises. Each participant was subsequently tested for one repetition-maximum (1RM) strength on each exercise, and the self-selected intensity was calculated based on a percent of each 1RM value. For self-selected relative intensity, the PT group selected significantly greater intensities for LP (50% vs. 41%), CP (57.4% vs. 48%), and SR (56% vs. 42%) whereas a trend (p = 0.10) was observed for LE (43% vs. 38%) compared with No PT. Overall, the average self-selected intensity for all exercises was approximately 51.4% in PT group and approximately 42.3% in the No PT group. 1RM values for LP, LE, and SR were greater in the PT than No PT group. Ratings of perceived exertion values were significantly greater in the PT compared with the No PT group for CP, LE, and SR but not LP. These results indicate that resistance training under the supervision of a personal trainer leads to greater initial 1RM strength values, self-selection of greater workout intensities, and greater ratings of perceived exertion values during resistance exercise.