Biologically inspired sensing: infrared spectroscopic analysis of cell responses to an inhalation health hazard

This work describes the development of a biologically based sensing technique to quantify chemical agents that pose inhalation health hazards. The approach utilizes cultured epithelial cells (A549 human type II pneumocytes) of the lung, exposed to potential toxins and monitored through the noninvasive means of infrared spectroscopy to quantify changes to cell physiology and function. Cell response to Streptolysin O, a cholesterol-binding cytolysin, is investigated here. Infrared spectra display changes in cell physiology indicative of membrane damage, altered proteins, and some nucleic acid damage. Methods to improve cell adhesion through modification of support surface properties are detailed. This spectroscopic approach not only provides a robust means to detect potential toxins but also provides information on modes of damage and mechanisms of cellular response.     

Book Reviews

Book reviewed in this article:
NORTH AMERICA: Camp, Clan, and Kin among the Cow Creek Seminole of Florida , Alexander Spoehr.
NORTH AMERICA: Kinship System of the Seminole. Alexander Spoehr.
NORTH AMERICA: The Florida Seminole Camp. Alexander Spoehr.
NORTH AMERICA: Changing Kinship Systems. Alexander Spoehr.     

BioCaster: detecting public health rumors with a Web-based text mining system

SUMMARY: BioCaster is an ontology-based text mining system for detecting and tracking the distribution of infectious disease outbreaks from linguistic signals on the Web. The system continuously analyzes documents reported from over 1700 RSS feeds, classifies them for topical relevance and plots them onto a Google map using geocoded information. The background knowledge for bridging the gap between Layman's terms and formal-coding systems is contained in the freely available BioCaster ontology which includes information in eight languages focused on the epidemiological role of pathogens as well as geographical locations with their latitudes/longitudes. The system consists of four main stages: topic classification, named entity recognition (NER), disease/location detection and event recognition. Higher order event analysis is used to detect more precisely specified warning signals that can then be notified to registered users via email alerts. Evaluation of the system for topic recognition and entity identification is conducted on a gold standard corpus of annotated news articles. AVAILABILITY: The BioCaster map and ontology are freely available via a web portal at http://www.biocaster.org.     

Dopaminergic and brain-derived neurotrophic factor signalling in inbred mice exposed to a restricted feeding schedule

Increased physical activity and decreased motivation to eat are common features in anorexia nervosa. We investigated the development of these features and the potential implication of brain-derived neurotrophic factor (BDNF) and dopaminergic signalling in their development in C57BL/6J and A/J inbred mice, using the 'activity-based anorexia' model. In this model, mice on a restricted-feeding schedule are given unlimited access to running wheels. We measured dopamine receptor D2 and BDNF expression levels in the caudate putamen and the hippocampus, respectively, using in situ hybridization. We found that in response to scheduled feeding, C57BL/6J mice reduced their running wheel activity and displayed food anticipatory activity prior to food intake from day 2 of scheduled feeding as an indication of motivation to eat. In contrast, A/J mice increased running wheel activity during scheduled feeding and lacked food anticipatory activity. These were accompanied by increased dopamine receptor D2 expression in the caudate putamen and reduced BDNF expression in the hippocampus. Consistent with human linkage and association studies on BDNF and dopamine receptor D2 in anorexia nervosa, our study shows that dopaminergic and BDNF signalling are altered as a function of susceptibility to activity-based anorexia. Differences in gene expression and behaviour between A/J and C57BL/6J mice indicate that mouse genetic mapping populations based on these progenitor lines are valuable for identifying molecular determinants of anorexia-related traits.     

The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor

Recent events have created an urgent need for new therapeutic strategies to treat anthrax. We have applied a mixture-based peptide library approach to rapidly determine the optimal peptide substrate for the anthrax lethal factor (LF), a metalloproteinase with an important role in the pathogenesis of the disease. Using this approach we have identified peptide analogs that inhibit the enzyme in vitro and that protect cultured macrophages from LF-mediated cytolysis. The crystal structures of LF bound to an optimized peptide substrate and to peptide-based inhibitors provide a rationale for the observed selectivity and may be exploited in the design of future generations of LF inhibitors.     

A quantitative study of the interactions of Bacillus anthracis edema factor and lethal factor with activated protective antigen

Bacillus anthracis secretes three proteins, which associate in binary combinations to form toxic complexes at the surface of mammalian cells. Receptor-bound protective antigen (PA) is proteolytically activated, yielding a 63 kDa fragment (PA(63)). PA(63) oligomerizes into heptamers, which bind edema factor (EF) or lethal factor (LF) to form the toxic complexes. We undertook a quantitative analysis of the interactions of EF with PA(63) by means of surface plasmon resonance (SPR) measurements. Heptameric PA(63) was covalently bound by amine coupling to an SPR chip, or noncovalently bound via a C-terminal hexahistidine tag on the protein to Ni(2+)nitrilotriacetate groups on the chip. Values of k(on) and k(off) for EF at 23 degrees C were approximately 3 x 10(5) M(-)(1) s(-)(1) and (3-5) x 10(-)(4) s(-)(1), respectively, giving a calculated K(d) of (1-2) x 10(-)(9) M. A similar value of K(d) (7 x 10(-)(10) M) was obtained when we measured the binding of radiolabeled EF to receptor-bound PA(63) on the surface of L6 cells (at 4 degrees C). Each of these analyses was also performed with LF and LF(N) (the N-terminal 255 residues of LF), and values obtained were comparable to those for EF. The similarity in the dissociation constants determined by SPR and by measurements on the cell surface suggests that the presence of the receptor does not play a large role in the interaction between PA(63) and EF/LF.     

Do Leptin Levels Predict Weight Gain?—A 5-Year Follow-Up Study in Mauritius

Objective : To investigate whether relative baseline leptin levels predict long-term changes in adiposity and/or its distribution. Research Methods and Procedures : In a longitudinal study of 2888 nondiabetic Mauritians aged 25 years to 74 years who participated in population-based surveys in 1987 and 1992, changes in body mass index (BMI), waist/hip ratio (WHR), and waist circumference were compared between “hyperleptinemic,” “normoleptinemic,” and “hypoleptinemic” groups. “Relative leptin levels” were calculated as standardized residuals from the regression of log₁₀ leptin on baseline BMI to provide a leptin measure independent of BMI. Analyses were performed within each sex. A linear regression model was used to assess the effect of standardized residuals on changes in BMI, WHR, and waist circumference, independent of baseline BMI, age, fasting insulin, and ethnicity. Results : After adjusting for age and baseline BMI by analysis of covariance, there was no difference in changes in BMI, WHR, or waist circumference between men with low, normal, or high relative leptin levels. Among women, there was a significant difference in ΔWHR across leptin groups, such that the largest increase occurred in the “normal” leptin group. For both men and women, the linear regression models explained ?10% of variation in dependent variables, and the only significant independent variables were age, BMI, and being of Chinese origin, compared with Indian origin. Discussion : These findings do not support a role for leptin concentration in predicting weight gain or changes in fat distribution in adults over a 5-year period.     

Genetic mapping of 14 short tandem repeat polymorphisms on human chromosome 22

We have constructed a linkage map of 14 short tandem repeat polymorphisms (11 with heterozygosity > 70%) on the long arm of human chromosome 22 using 23 non-CEPH pedigrees. Twelve of the markers could be positioned uniquely with a likelihood of at least 1,000:1, and distributed at an average distance of 6.62 cM (range 1.5–16.1 cM). The sex-combined map covers a total of 79.6 cM, the female map 93.2 cM and the male map 64.6 cM. Based on comparisons between physical maps and other genetic maps, we estimate that our map covers 70%–80% of the chromosome. The map integrates markers from previous genetic maps and uniquely positions one marker (D22S307). Data from physical mapping on the location of four genetic markers correlates well with our linkage map, and provides information on an additional marker (D22S315). This map will facilitate high resolution mapping of additional polymorphic loci and disease genes on chromosome 22, and act as a reference for building and verifying physical maps.     

Spotlight surveys for white-tailed deer: Monitoring panacea or exercise in futility?

Many monitoring programs for white-tailed deer (Odocoileus virginianus) on both private and public lands across the United States have long relied on the use of road-based spotlight surveys for monitoring population size and trends. Research has suggested spotlight surveys are ineffective and that road-based surveys for deer are biased because of highly variable detection rates. To evaluate variability in detection rates relative to the assumption that repeated surveys along roads will provide reliable trend data for use in calculating deer density estimates, we collected 5 years of thermal-imager and spotlight survey data using a multiple-observer, closed-capture approach. Using a Huggin's closed capture model, data bootstrapping, and variance components analyses, our results suggest that density estimates for white-tailed deer generated from data collected during road-based spotlight surveys are likely not reflective of the standing deer population. Detection probabilities during individual spotlight surveys ranged from 0.00 to 0.80 (median = 0.45) across all surveys, and differed by observer, survey, management unit, and survey transect replicate. Mean spotlight detection probability (0.41) and process standard deviation (0.12) estimates indicated considerable variability across surveys, observers, transects, and years, which precludes the generation of a correction factor or use of spotlight data to evaluate long-term trends at any scale. Although recommended by many state, federal, and non-governmental agencies, our results suggest that the benefit of spotlight survey data for monitoring deer populations is limited and likely represents a waste of resources with no appreciable management information gained. © 2012 The Wildlife Society.