Toward optimized temperature sum parameterizations for forecasting the start of the pollen season

The start date of flowering of allergenic species is of great interest in the context of allergy. Such forecasts can help to plan the therapy and design the medical treatment. For this purpose, temperature sum models are usually employed. Designing temperature sum models requires the selection of different parameters such as the base temperature and the start date for the temperature sum. However, the optimal parameterization is often unknown and varies depending on location and species. The purpose of this study was to systematically test parameterizations of temperature sum models based on 12 Swiss pollen stations. The examined taxa include Corylus, Alnus, Fraxinus, Betula, and Poaceae. We tested the simple thermal model type (forcing-only model hereafter) which relies solely on forcing temperatures and the sequential model type that includes also chilling temperatures. The mean absolute error was used to assess the performance of the models. Our study shows that the sequential model could not achieve a discernible reduction of the (statistical) error compared to the forcing-only model for all taxa. The mean absolute error lies roughly between 2 and 4 days with the lowest values for Betula. The optimized parameterizations in combination with temperature forecast and the climatological mean were used during the 2012 pollen season to provide daily updated forecasts of the start of flowering for all five taxa. Improvements of the models could possibly be achieved by testing additional temperature parameters as well as other meteorological factors such as precipitation or irradiation. Identification of a process-oriented model with high statistical performance for all stations would facilitate the implementation in numerical pollen dispersion models.     

The Mood-Stabilizer Lithium Prevents Hippocampal Apoptosis and Improves Spatial Memory in Experimental Meningitis

Pneumococcal meningitis is associated with high morbidity and mortality rates. Brain damage caused by this disease is characterized by apoptosis in the hippocampal dentate gyrus, a morphological correlate of learning deficits in experimental paradigms. The mood stabilizer lithium has previously been found to attenuate brain damage in ischemic and inflammatory diseases of the brain. An infant rat model of pneumococcal meningitis was used to investigate the neuroprotective and neuroregenerative potential of lithium. To assess an effect on the acute disease, LiCl was administered starting five days prior to intracisternal infection with live Streptococcus pneumoniae. Clinical parameters were recorded, cerebrospinal fluid (CSF) was sampled, and the animals were sacrificed 42 hours after infection to harvest the brain and serum. Cryosections of the brains were stained for Nissl substance to quantify brain injury. Hippocampal gene expression of Bcl-2, Bax, p53, and BDNF was analyzed. Lithium concentrations were measured in serum and CSF. The effect of chronic lithium treatment on spatial memory function and cell survival in the dentate gyrus was evaluated in a Morris water maze and by quantification of BrdU incorporation after LiCl treatment during 3 weeks following infection. In the hippocampus, LiCl significantly reduced apoptosis and gene expression of Bax and p53 while it increased expression of Bcl-2. IL-10, MCP-1, and TNF were significantly increased in animals treated with LiCl compared to NaCl. Chronic LiCl treatment improved spatial memory in infected animals. The mood stabilizer lithium may thus be a therapeutic alternative to attenuate neurofunctional deficits as a result of pneumococcal meningitis.     

Mining the human autoantibody repertoire: Isolation of potent IL17A-neutralizing monoclonal antibodies from a patient with thymoma

Anti-cytokine autoantibodies have been widely reported to be present in human plasma, both in healthy subjects and in patients with underlying autoimmune conditions, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or thymic epithelial neoplasms. While often asymptomatic, they can cause or facilitate a wide range of diseases including opportunistic infections. The potential therapeutic value of specific neutralizing anti-cytokine autoantibodies has not been thoroughly investigated. Here we used mammalian cell display to isolate IL17A-specific antibodies from a thymoma patient with proven high-titer autoantibodies against the same. We identified 3 distinct clonotypes that efficiently neutralized IL17A in a cell-based in vitro assay. Their potencies were comparable to those of known neutralizing antibodies, including 2, AIN457 (secukinumab) and ixekizumab that are currently in clinical development for the treatment of various inflammatory disorders. These data clearly demonstrate that the human autoantibody repertoire can be mined for antibodies with high therapeutic potential for clinical development.     

ONE TWO WE—life cycle management in canteens together with suppliers,customers and guests

Purpose

Private food consumption accounts for 30 % of total environmental impacts caused by the final consumption of Swiss households. The private expenses for gastronomy and hotels account for another 6 %. Therefore, it is necessary to investigate and better understand the environmental impacts of food consumption and the possibilities for a reduction of these impacts. This was the starting point for the collaboration between the canteen operator SV Group, the life cycle assessment (LCA) consultancy ESU-services, the energy supplier ewz and the World Wide Fund for Nature (WWF) in Switzerland focusing on food consumption in canteens.

Methods

In a first step, an LCA study was used to analyse the environmental impacts of about 20 million meals served in 240 canteens in 2011. LCA data for 160 food items were linked to the food amounts of about 10,000 articles purchased in this year. This was supplemented by data on canteen operation and resulted in a full organisational LCA.

Results and discussion

The impacts of food purchases are about four times higher than the direct impacts due to the operation of the canteens. The most important product groups are meat and dairy products. Improvement potentials have been identified within 14 different themes by the project group. They include measures in the canteen operation (e.g. reduction of food waste or energy-efficient appliances); measures in the supply chain, e.g. a reduction of vegetables grown in heated greenhouses; or the abandonment of air-transported products. But also dietary choices such as a reduction of the average amount of meat per meal are considered as an option. The results and recommendations of the detailed LCA as well as information by other partners have been used by the SV Group to develop the programme ONE TWO WE. It assists the customers (companies who commission the operation of canteens in their premises) to reach improved levels of environmental performance. The programme aims for a 20 % cut on GHG emissions after full implementation in the participating canteens.

Conclusions

The programme started successfully with many customers positively convinced by the proposed changes in the provision of canteen meals. An initial reduction of greenhouse gas emissions compared to the baseline was achieved. This LCA study is a good example for the value of calculating a full organisational environmental footprint for a company in the gastronomy sector and for using the results of such a study to bring down the overall environmental impacts.

     

Regulation of rat ovarian cell growth and steroid secretion

A cultured rat ovarian cell line (31 A-F(2)) was used to study the effect of growth factors (epidermal growth factor [EGF] and fibroblast growth factor [FGF]), a survival factor (ovarian growth factor [OGF]), a hormone (insulin), and an iron-binding protein (transferring) on cell proliferation and steroid production under defined culture conditions. EGF and insulin were shown to be mitogenic (half-maximal response at 0.12 nM and 0.11 muM, respectively) for 31A-F(2) cells incubated in serum-free medium. EGF induced up to three doublings in the cell population, whereas insulin induced an average of one cell population doubling. FGF, OGF, and transferrin were found not to have any prominent effect on cell division when incubated individually with 31A-F(2) cells in serum-free medium. However, a combination of EGF, OGF, insulin, and transferrin stimulated cell division to the same approximate extent as cells incubated in the presence of 5 percent fetal calf serum. EGF or insulin did not significantly affect total cell cholesterol levels (relative to cells incubated in serum-free medium) when incubated individually with 31A-F(2) cells. However, cell cholesterol levels were increased by the addition of OGF (250 percent), FGF (370 percent), or a combination of insulin and EGF (320 percent). Progesterone secretion from 31A-F(2) cells was enhanced by EGF (25 percent), FGF (80 percent), and insulin (115 percent). However, the addition of a mitogenic mixture of EGF, OGF, insulin, and transferrin suppressed progesterone secretion 150 percent) below that of control cultures. These studies have permitted us to determine that EGF and insulin are mitogenic factors that are required for the growth of 31A-F(2) cells and that OGF and transferrin are positive cofactors that enhance growth. Also, additional data suggest that cholesterol and progesterone production in 31A-F(2) cells can be regulated by peptide growth factors and the hormone insulin.     

Infectious salmon anaemia virus (ISAV) isolated from the ISA disease outbreaks in Chile diverged from ISAV isolates from Norway around 1996 and was disseminated around 2005, based on surface glycoprotein gene sequences

Background

All viruses in the family Bunyaviridae possess a tripartite genome, consisting of a small, a medium, and a large RNA segment. Bunyaviruses therefore possess considerable evolutionary potential, attributable to both intramolecular changes and to genome segment reassortment. Hantaviruses (family Bunyaviridae, genus Hantavirus) are known to cause human hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome. The primary reservoir host of Sin Nombre virus is the deer mouse (Peromyscus maniculatus), which is widely distributed in North America. We investigated the prevalence of intramolecular changes and of genomic reassortment among Sin Nombre viruses detected in deer mice in three western states.

Methods

Portions of the Sin Nombre virus small (S) and medium (M) RNA segments were amplified by RT-PCR from kidney, lung, liver and spleen of seropositive peromyscine rodents, principally deer mice, collected in Colorado, New Mexico and Montana from 1995 to 2007. Both a 142 nucleotide (nt) amplicon of the M segment, encoding a portion of the G2 transmembrane glycoprotein, and a 751 nt amplicon of the S segment, encoding part of the nucleocapsid protein, were cloned and sequenced from 19 deer mice and from one brush mouse (P. boylii), S RNA but not M RNA from one deer mouse, and M RNA but not S RNA from another deer mouse.

Results

Two of 20 viruses were found to be reassortants. Within virus sequences from different rodents, the average rate of synonymous substitutions among all pair-wise comparisons (π_s) was 0.378 in the M segment and 0.312 in the S segment sequences. The replacement substitution rate (π_a) was 7.0 × 10^-4 in the M segment and 17.3 × 10^-4 in the S segment sequences. The low π_a relative to π_s suggests strong purifying selection and this was confirmed by a Fu and Li analysis. The absolute rate of molecular evolution of the M segment was 6.76 × 10^-3 substitutions/site/year. The absolute age of the M segment tree was estimated to be 37 years. In the S segment the rate of molecular evolution was 1.93 × 10^-3 substitutions/site/year and the absolute age of the tree was 106 years. Assuming that mice were infected with a single Sin Nombre virus genotype, phylogenetic analyses revealed that 10% (2/20) of viruses were reassortants, similar to the 14% (6/43) found in a previous report.

Conclusion

Age estimates from both segments suggest that Sin Nombre virus has evolved within the past 37–106 years. The rates of evolutionary changes reported here suggest that Sin Nombre virus M and S segment reassortment occurs frequently in nature.     

A comparison of univariate and multivariate gene selection techniques for classification of cancer datasets

Background  

Gene selection is an important step when building predictors of disease state based on gene expression data. Gene selection generally improves performance and identifies a relevant subset of genes. Many univariate and multivariate gene selection approaches have been proposed. Frequently the claim is made that genes are co-regulated (due to pathway dependencies) and that multivariate approaches are therefore per definition more desirable than univariate selection approaches. Based on the published performances of all these approaches a fair comparison of the available results can not be made. This mainly stems from two factors. First, the results are often biased, since the validation set is in one way or another involved in training the predictor, resulting in optimistically biased performance estimates. Second, the published results are often based on a small number of relatively simple datasets. Consequently no generally applicable conclusions can be drawn.     

Apoptosis in ventricular myocytes: the role of tumor suppressor proteins

Apoptosis or programmed cell death is an important physiologic event crucial for the selective removal of damaged or unwanted cells from body tissues. In the cardiovascular system, apoptosis has been observed in the vasculature and myocardium. Untimely or inappropriate myocardial cell loss through an apoptotic process may contribute to ventricular remodeling and the ultimate demise of ventricular function following injury. Therapeutic interventions designed to modulate or prevent myocardial apoptotic cell loss may therefore prove beneficial in maintaining cardiac function. Incite into the molecular mechanisms that govern apoptosis in mammalian cells has led to the identification of several key factors that promote or prevent the apoptotic process. In this report, we discuss putative regulators of cardiac cell apoptosis with specific reference to the tumor suppressor proteins, p53 and Rb. The interplay between these factors, as well as the anti-apoptotic molecules related to the Bcl-2 the family are discussed in the context of the heart under normal and disease conditions.