Mutagenic bypass of the butadiene-derived 2'-deoxyuridine adducts by polymerases eta and zeta

Butadiene is a ubiquitous environmental chemical carcinogen that when activated to its monoepoxide intermediate can react with the N3 position of cytosine, resulting in two stereoisomeric adducted bases that rapidly deaminate to N3 2′-deoxyuridine lesions. We have previously shown that replication of DNAs containing these adducts through mammalian cells resulted in 97% mutagenicity, predominantly C to T transitions. Since replicative DNA polymerases were blocked by these lesions in vitro, translesional polymerases were assessed for their ability to bypass these adducts. While polymerases ι, κ and ζ were significantly blocked one nucleotide prior to the lesion, pol η incorporated nucleotides opposite the adducts with a preference for insertion of a G or A. Following polymerase dissociation and reassociation, pol η was also able to extend primers with mispaired termini opposite the lesions, with extensions from the A and T mismatched primer termini being the most efficient. Pol ζ was also able to extend primers containing all mismatched nucleotides opposite the lesions, with the most efficient extension occurring off of the A mismatched primer.     

Sustained oscillations via coherence resonance in SIR

Sustained oscillations in a stochastic SIR model are studied using a new multiple scale analysis. It captures the interaction of the deterministic and stochastic elements together with the separation of time scales inherent in the appearance of these dynamics. The nearly regular fluctuations in the infected and susceptible populations are described via an explicit construction of a stochastic amplitude equation. The agreement between the power spectral densities of the full model and the approximation verifies that coherence resonance is driving the behavior. The validity criteria for this asymptotic approximation give explicit expressions for the parameter ranges in which one expects to observe this phenomenon.     

Functional connections between auditory cortical fields in humans revealed by Granger causality analysis of intra-cranial evoked potentials to sounds: comparison of two methods

Knowledge of neural interactions amongst cortical sites is important for understanding higher brain function. We studied such interactions using Granger causality (GC) to analyze auditory event-related potentials (ERPs) recorded directly and simultaneously from two physiologically identified and functionally interconnected auditory areas of cerebral cortex in human neurosurgical patients. Two methods of GC analysis were used and the results compared. Both approaches involved adaptive autoregressive modeling but differed from each other in other ways. Results obtained by using the two methods also differed. Fewer false-positive results were obtained using the method that suppressed the ERP non-stationarity and that expressed the GC as the sum of model coefficients, which suggests that this is the more appropriate approach for analyzing ERPs recorded directly from the human cortex.     

Replication of <Emphasis Type="Italic">Legionella pneumophila</Emphasis> in Floating Biofilms

Biofilms are a major source of human pathogenic Legionella pneumophila in aquatic systems. In this study, we investigated the capacity of L. pneumophila to colonize floating biofilms and the impact of Acanthamoeba castellanii on the replication of biofilm-associated Legionella. Biofilms were grown in Petri dishes and consisted of Aeromonas hydrophila, Escherichia coli, Flavobacterium breve, and Pseudomonas aeruginosa. Six hours following inoculation, Legionella were detected in floating biofilms in mean concentrations of 1.4 × 10⁴ cells/cm² (real-time polymerase chain reaction) and 8.3 × 10² CFU/cm² (culture). Two-way analysis of variance tests and fluorescent in situ hybridization clearly proved that increased biofilm-associated L. pneumophila concentrations were the result of intracellular replication in A. castellanii. Forty-eight hours after the introduction of A. castellanii in the Petri dishes, 90 ± 0.8% of the amoebae (infection rate) were completely filled with highly metabolic active L. pneumophila (mean infection intensity).     

Immunomodulatory effects of bovine colostrum in human peripheral blood mononuclear cells

Human and bovine colostrum (BC) contain a remarkable amount of bioactive substances, including antibodies towards many common pathogens of the intestinal and respiratory tract as well as growth factors, vitamins, cytokines and other proteic, lipidic and glucidic factors. In this study we investigated whether BC had any immunomodulatory effect on human peripheral blood mononuclear cells (PBMC) from healthy donors. To this aim we focused on the production of IL-12 and IFN-gamma, cytokines involved in the Th1 polarization required for a successful immune response towards intracellular pathogens, such as bacteria and viruses. BC induced a dose-dependent production of IL-12 by CD14+ monocytes, but was unable to induce IFN-gamma production. However, BC differentially affected stimuli-induced IFN-gamma production: it enhanced IFN-gamma in response to weak antigenic stimulation and it inhibited IFN-gamma in response to strong antigenic stimulation. These effects were not dose-dependent. We also measured PBMC proliferation, which was substantially unaffected by BC. Our data suggest that the Th1-promoting activity of BC could contribute, together with the antibodies, to the protective effect of BC on the offspring. BC could also represent an inexpensive therapeutic tool in prevention and treatment of several human microbial infections, including influenza.     

Soil-vegetation relationships in hyperseasonal cerrado, seasonal cerrado, and wet grassland in Emas National Park (central Brazil)

In South America, the largest savanna region is the Brazilian cerrado, in which there are few areas that become waterlogged in the rainy season. However, we found a small cerrado area in which the soil is poorly drained and becomes waterlogged at the end of the rainy season, allowing the appearance of a hyperseasonal cerrado. We investigated the soil–vegetation relationships in three vegetation forms: hyperseasonal cerrado, seasonal cerrado, and wet grassland. We collected vegetation and soil samples in these three vegetation forms and submitted obtained data to a canonical correspondence analysis. Our results showed a distinction among hyperseasonal cerrado, seasonal cerrado and wet grassland, which presented different floristic compositions and species abundances. The edaphic variables best related to the hyperseasonal and seasonal cerrados were sand, base saturation, pH, and magnesium. The wet grassland was related to higher concentrations of clay, organic matter, aluminium saturation, aluminium, phosphorus, and potassium. Although it is not possible to infer causal relationships based on our results, we hypothesize that the duration of waterlogging in the hyperseasonal cerrado may not be long enough to alter most of its soil characteristics, such as organic matter, phosphorus, and potassium, but may be long enough to alter some, such as pH and base saturation, as the soils under both cerrados were more similar to one another than to the soil under the wet grassland. Since waterlogging may alter soil characteristics and since these characteristics were enough to explain the plant community variation, we may conclude that water excess—permanent or seasonal—is one of the main factors to distinguish the three vegetation forms, which presented different floristic compositions and species abundances.     

Interactions between strains of Staphylococcus xylosus and Kocuria varians isolated from fermented meats

AIMS: To evaluate the interactions of Staphylococcus xylosus on Kocuria varians strains isolated from fermented meat products. Methods and Results: Interactions were assessed in vitro by agar spot test, agar well diffusion assay and spectrophotometric assay. The growth of K. varians (five strains) alone was compared with that in the presence of growing cells of S. xylosus (50 strains) or in the presence of heat-treated or untreated supernatants of S. xylosus. Sixteen strains stimulated the growth of K. varians K4, while four strains inhibited the K4 strain. Heated cell-free supernatants of S. xylosus did not have any effect on K. varians. The proteolytic activity of single strains or their combinations was assessed in vitro and in vivo by sodiumdodecylsulfate-polyacrylamide gel electrophoresis of sarcoplasmic protein extracts. Combinations of stimulatory strains of S. xylosus and K. varians showed a higher proteolytic activity compared with that of S. xylosus or K. varians alone. CONCLUSIONS: The interactions between strains may influence both the growth of the co-cultured strains and proteolysis, technologically relevant characteristics. SIGNIFICANCE AND IMPACT OF THE STUDY: The study of interactions between coagulase-negative cocci may guide the formulation of mixed strain starters for the production of fermented sausages.     

Feeding habits of <Emphasis Type="Italic">Bathydraco marri</Emphasis> (Pisces,Notothenioidei, Bathydraconidae) from the Ross Sea,Antarctica

In comparison with other bathydraconids, all species of the genus Bathydraco are poorly known from an ecological perspective. The diet of juvenile Bathydraco marri Norman, 1938 was studied for the first time in specimens collected in the southwestern Ross Sea during summer 1998. Fish were collected in a single otter trawl catch at 330–340 m depth. The stomach content analysis showed that this species fed exclusively on crustaceans. Overall, 20 prey taxa were identified to genus or species level. Mysids, amphipods and copepods were the most important prey in decreasing order of importance. Other prey, such as Euphausia superba, isopods and tanaids were eaten occasionally and in very small amounts. A multivariate analysis was applied to feeding data to assess ontogenetic or sex-related changes in diet. No difference was detected between sexes, whereas diet of small and large fish differed in some degree. An ontogenetic shift from small and pelagic crustaceans such as copepods to benthic–benthopelagic prey such as amphipods and mysids was observed. Relating present results with published data on physiological characteristics of B. marri, it was possible to infer their feeding behaviour and mode of life. Like other bathydraconids, this species appeared to be an inactive and sluggish fish, which relied on more or less motile benthic or epibenthic prey adopting a “sit and wait” feeding strategy. On the other hand, smaller fish seem to be more active, feeding also on pelagic prey such as copepods that can be seasonally abundant, thus reducing the intraspecific competition for food.     

Evolution of a pulmonary insulin delivery system (Exubera) for patients with diabetes

Many patients with diabetes fail to meet recommended glycemic goals regardless of the recognition of optimal glycemic control as a key component for improving clinical outcomes and quality of life in patients with diabetes. Patient- and physician-related barriers to the adoption of insulin therapy include fear and anxiety about injecting insulin, concerns about side effects, and personal health beliefs in regard to the use of insulin. There is an unmet need for an alternative insulin therapy that provides optimal glycemic control, is well tolerated, and improves patient adherence. Of the several inhaled insulin devices that are in various stages of development, the Exubera (INH) formulation is the first to be approved for use in the United States and in Europe. Exubera is a novel, rapid-acting inhaled human insulin formulation that has been developed for prandial insulin use. Clinical studies have shown that INH consistently improves glycemic control, in combination with longer-acting subcutaneous (SC) insulin regimens in patients with type 1 or type 2 diabetes, or is used to supplement or replace oral antidiabetic therapy in patients with type 2 diabetes. INH has demonstrated long-term safety and tolerability, with a risk for hypoglycemia similar to that of SC insulin, and no clinically meaningful changes in pulmonary function have been noted with its use. Patients treated with INH in clinical studies reported high levels of satisfaction with treatment, and many patients with diabetes choose inhaled insulin when it is offered as a treatment option. Taken together, these findings suggest that INH represents an important new development in the treatment of diabetes that may improve glycemic control in many patients with diabetes.