A simple mathematical model of the thermal death of microorganisms

This note is concerned with a simple mathematical model of how a population of bacterial spores decrease with time when subjected to a uniform temperature. The model assumes that there is a Boltzman distribution of energy among water or other molecules surrounding the assumed single lethal target in a spore; it assumes that repair is not possible; and that only molecules with energies above a critical level cause inactivation. The model provides new insight concerning the ‘kill-rate’ of spores during ultra heat treatment.     

Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

Background

Tamoxifen (TAM) is a well characterized breast cancer drug and selective estrogen receptor modulator (SERM) which also has been associated with a small increase in risk for uterine cancers. TAM's partial agonist activation of estrogen receptor has been characterized for specific gene promoters but not at the genomic level in vivo.Furthermore, reducing uncertainties associated with cross-species extrapolations of pharmaco- and toxicogenomic data remains a formidable challenge.

Results

A comparative ligand and species analysis approach was conducted to systematically assess the physiological, morphological and uterine gene expression alterations elicited across time by TAM and ethynylestradiol (EE) in immature ovariectomized Sprague-Dawley rats and C57BL/6 mice. Differential gene expression was evaluated using custom cDNA microarrays, and the data was compared to identify conserved and divergent responses. 902 genes were differentially regulated in all four studies, 398 of which exhibit identical temporal expression patterns.

Conclusion

Comparative analysis of EE and TAM differentially expressed gene lists suggest TAM regulates no unique uterine genes that are conserved in the rat and mouse. This demonstrates that the partial agonist activities of TAM extend to molecular targets in regulating only a subset of EE-responsive genes. Ligand-conserved, species-divergent expression of carbonic anhydrase 2 was observed in the microarray data and confirmed by real time PCR. The identification of comparable temporal phenotypic responses linked to related gene expression profiles demonstrates that systematic comparative genomic assessments can elucidate important conserved and divergent mechanisms in rodent estrogen signalling during uterine proliferation.     

Nitrogen vs. phosphorus limitation across an ecotonal gradient in a mangrove forest

Mangrove forests are characterized by distinctive tree-height gradientsthat reflect complex spatial, within-stand differences in environmentalfactors,including nutrient dynamics, salinity, and tidal inundation, across narrowgradients. To determine patterns of nutrient limitation and the effects ofnutrient availability on plant growth and within-stand nutrient dynamics, weused a factorial experiment with three nutrient treatment levels (control, N,P)and three zones along a tree-height gradient (fringe, transition, dwarf) onoffshore islands in Belize. Transects were laid out perpendicular to theshoreline across a mangrove forest from a fringe stand along the seaward edge,through a stand of intermediate height, into a dwarf stand in the interior ofthe island. At three sites, three trees were fertilized per zone for 2yr. Although there was spatial variability in response, growth byR. mangle was generally nitrogen (N) -limited in thefringe zone;phosphorus (P) -limited in the dwarf zone; and, N- and/or P-limited in thetransition zone. Phosphorus-resorption efficiency decreased in all three zones,and N-resorption efficiency increased in the dwarf zone in response to Penrichment. The addition of N had no effect on either P or N resorptionefficiencies. Belowground decomposition was increased by P enrichment in allzones, whereas N enrichment had no effect. This study demonstrated thatessential nutrients are not uniformly distributed within mangrove ecosystems;that soil fertility can switch from conditions of N to P limitation acrossnarrow ecotonal gradients; and, that not all ecological processes respondsimilarly to, or are limited by, the same nutrient.     

Patients’ Knowledge,Attitudes, Behaviour and Health Care Experiences on the Prevention,Detection, Management and Control of Hypertension in Colombia: A Qualitative Study

Hypertension is a leading cause of premature death worldwide and the most important modifiable risk factor for cardiovascular disease. Effective screening programs, communication with patients, regular monitoring, and adherence to treatment are essential to successful management but may be challenging in health systems facing resource constraints. This qualitative study explored patients’ knowledge, attitudes, behaviour and health care seeking experiences in relation to detection, treatment and control of hypertension in Colombia. We conducted in-depth interviews and focus group discussions with 26 individuals with hypertension and 4 family members in two regions. Few participants were aware of ways to prevent high blood pressure. Once diagnosed, most reported taking medication but had little information about their condition and had a poor understanding of their treatment regime. The desire for good communication and a trusting relationship with the doctor emerged as key themes in promoting adherence to medication and regular attendance at medical appointments. Barriers to accessing treatment included co-payments for medication; costs of transport to health care facilities; unavailability of drugs; and poor access to specialist care. Some patients overcame these barriers with support from social networks, family members and neighbours. However, those who lacked such support, experienced loneliness and struggled to access health care services. The health insurance scheme was frequently described as administratively confusing and those accessing the state subsidized system believed that the treatment was inferior to that provided under the compulsory contributory system. Measures that should be addressed to improve hypertension management in Colombia include better communication between health care professionals and patients, measures to improve understanding of the importance of adherence to treatment, reduction of co-payments and transport costs, and easier access to care, especially in rural areas.     

Response of macroinvertebrates to warming,nutrient addition and predation in large-scale mesocosm tanks

There is increasing concern about the effect of climate change on aquatic systems. We examined changes in macroinvertebrate communities caused by increased temperature (3°C above ambient during summer only and continuous 3°C above ambient all year round), influences of fish (Gasterosteus aculeatus L.) and addition of nutrients (nitrogen and phosphorus) in 48 large-scale (3000 l) tanks over a 2 year period. While numbers of Isopoda, Chaoborus, Corixidae, Ephemeroptera, Notonectidae and Odonata were reduced by the presence of fish, nutrient addition caused isopods, corixids, mayflies and odonates to increase in abundance. Impacts of temperature increase were surprisingly low, with only gastropods increasing in heated tanks, suggesting that, overall abundances of most macroinvertebrate taxa will not be severely affected by the predicted temperature rise. To determine if taxa were sampled representatively during the experiment, net sweep samples taken towards the end of the experiment were compared with final macroinvertebrate abundances when the complete contents of each tank were harvested. We found that net sweeping is an appropriate semi-quantitative method for most taxa in mesocosm tanks. However, mites, coleopteran adults and larvae, dipterans and Chaoborus were not adequately sampled. This might explain why we could not detect any treatment effects of temperature, fish or nutrients on mites, coleopterans and dipterans and calls for different sampling techniques for these taxa, especially in ponds with vegetation stands.     

Measurements of tooth wear among Australian aborigines: II. Intrapopulational variation in patterns of dental attrition

The possible implications of variations in dental attrition patterns have necessitated a detailed assessment of the types, ranges, and causes of tooth wear. Hear we employ measurements of postcanine occlusal wear facets from a sample population of extant Australian aborigines. A principal components analysis was applied as a tool in determining common types of attritional patterns. It was concluded that the range of intrapopulational variation in dental wear patterns must be attributed to a multiplicity of sources in addition to such commonly cited causes as dietary variations, gender, age, and developmental eruption sequences.     

Investigating small molecules to inhibit germinal center kinase-like kinase (GLK/MAP4K3) upstream of PKCθ phosphorylation: Potential therapy to modulate T cell dependent immunity

Germinal center kinase-like kinase (GLK, also known as MAP4K3) has been hypothesized to have an effect on key cellular activities, including inflammatory responses. GLK is required for activation of protein kinase C-θ (PKCθ) in T cells. Controlling the activity of T helper cell responses could be valuable for the treatment of autoimmune diseases. This approach circumvents previous unsuccessful approaches to target PKCθ directly. The use of structure based drug design, aided by the first crystal structure of GLK, led to the discovery of several inhibitors that demonstrate potent inhibition of GLK biochemically and in relevant cell lines.