A Structured Avian Influenza Model with Imperfect Vaccination and Vaccine-Induced Asymptomatic Infection

We introduce a model of avian influenza in domestic birds with imperfect vaccination and age-since-vaccination structure. The model has four components: susceptible birds, vaccinated birds (stratified by vaccination age), asymptomatically infected birds, and infected birds. The model includes reduction in the probability of infection, decreasing severity of disease of vaccinated birds and vaccine waning. The basic reproduction number, \(\mathcal R_0\) , is calculated. The disease-free equilibrium is found to be globally stable under certain conditions when \({\mathcal {R}}_0<1\) . When \({\mathcal {R}}_0>1\) , existence of an endemic equilibrium is proved (with uniqueness for the ODE case and local stability under stricter conditions) and uniform persistence of the disease is established. The inclusion of reduction in susceptibility of vaccinated birds, reduction in infectiousness of asymptomatically infected birds and vaccine waning can have important implications for disease control. We analytically and numerically demonstrate that vaccination can paradoxically increase the total number of infected, resulting in the “silent spread” of the disease. We also study the effects of vaccine efficacy on disease prevalence and the minimum critical vaccination coverage, a threshold value for vaccination coverage to avoid an increase in total disease prevalence due to asymptomatic infection.     

The BAR domain protein PICK1 regulates cell recognition and morphogenesis by interacting with Neph proteins

Neph proteins are evolutionarily conserved membrane proteins of the immunoglobulin superfamily that control the formation of specific intercellular contacts. Cell recognition through these proteins is essential in diverse cellular contexts such as patterning of the compound eye in Drosophila melanogaster, neuronal connectivity in Caenorhabditis elegans, and the formation of the kidney filtration barrier in mammals. Here we identify the PDZ and BAR domain protein PICK1 (protein interacting with C-kinase 1) as a Neph-interacting protein. Binding required dimerization of PICK1, was dependent on PDZ domain protein interactions, and mediated stabilization of Neph1 at the plasma membrane. Moreover, protein kinase C (PKCα) activity facilitated the interaction through releasing Neph proteins from their binding to the multidomain scaffolding protein zonula occludens 1 (ZO-1), another PDZ domain protein. In Drosophila, the Neph homologue Roughest is essential for sorting of interommatidial precursor cells and patterning of the compound eye. RNA interference-mediated knockdown of PICK1 in the Drosophila eye imaginal disc caused a Roughest destabilization at the plasma membrane and a phenotype that resembled rst mutation. These data indicate that Neph proteins and PICK1 synergistically regulate cell recognition and contact formation.     

Serum Levels of Trace Elements and Heavy Metals in Patients with Acute Hemorrhagic Stroke

Trace elements are essential components of biological structures, but alternatively, they can be toxic at concentrations beyond those necessary for their biological functions. Changes in the concentration of essential trace elements and heavy metals may affect acute hemorrhagic stroke. The aim of this study was to measure serum levels of essential trace elements [iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), and magnesium (Mg)] and heavy metals [cobalt (Co), cadmium (Cd), and lead (Pb)] in patients with acute hemorrhagic stroke. Twenty-six patients with acute hemorrhagic stroke and 29 healthy controls were enrolled. Atomic absorption spectrophotometry (UNICAM-929) was used to measure serum Fe, Cu, Pb, Cd, Zn, Co, Mn and Mg concentrations. Serum Cd, Pb and Fe levels were significantly higher in patients with acute hemorrhagic stroke than controls (p < 0.001), while serum Cu, Zn, Mg and Mn levels were significantly lower (all p < 0.001). However, there was no significant difference between the groups with respect to serum Co levels (p > 0.05). We first demonstrate increased Cd, Pb, and Fe levels; and decreased Cu, Zn, Mg, and Mn levels in patients with acute hemorrhagic stroke. These findings may have diagnostic and prognostic value for acute hemorrhagic stroke. Further studies are required to elucidate the roles of trace elements and heavy metals in patients with acute hemorrhagic stroke.     

Effective asymmetric Michael addition of anthrone to nitroalkenes using chiral tetraoxacalix[2]arene[2]triazines as organocatalysts

Novel chiral secondary amines bearing a tetraoxacalix[2]arene[2]triazine scaffold were created and used for catalytic asymmetric Michael reaction of anthrone with nitroalkenes. The relevant adducts were obtained in good to excellent yields (82%‐98%) and enantioselectivities (75%‐98%).     

Design,synthesis and application of chiral tetraoxacalix[2]arene[2]triazine‐based organocatalysts in asymmetric Michael addition reactions

A novel type of oxacalix[2]arene[2]triazine‐based organocatalysts for asymmetric Michael reactions are reported for the first time. Chiral subunits were attached to the heteroatom‐bridged calixaromatic platform by a reaction of (R)‐ and (S)‐1‐aminotetraline with tetraoxacalix[2]arene[2]triazine in both enantiomeric forms. To evaluate the catalytic efficiency of the novel organocatalysts, isobutyraldehyde reacted with various substituted and unsubstituted aromatic trans‐β‐nitrostyrenes in tetrahydrofuran (THF), leading to Michael adducts in excellent yields and enantioselectivites (up to 97% yield and 99% ee).     

Enhanced production of recombinant Staphylococcus simulans lysostaphin using medium engineering

Abstract

Staphylococcus aureus, among other staphylococcal species, developed multidrug resistance and causes serious health risks that require complex treatments. Therefore, the development of novel and effective strategies to combat these bacteria has been gaining importance. Since Staphylococcus simulans lysostaphin is a peptidoglycan hydrolase effective against staphylococcal species, the enzyme has a significant potential for biotechnological applications. Despite promising results of lysostaphin as a bacteriocin capable of killing staphylococcal pathogens, it is still not widely used in healthcare settings due to its high production cost. In this study, medium engineering techniques were applied to improve the expression yield of recombinant lysostaphin in E. coli. A new effective inducible araBAD promoter system and different mediums were used to enhance lysostaphin production. Our results showed that the composition of autoinduction media enhanced the amount of lysostaphin production 5-fold with the highest level of active lysostaphin at 30?°C. The production cost of 1000?U of lysostaphin was determined as 4-fold lower than the previously proposed technologies. Therefore, the currently developed bench scale study has a great potential as a large-scale fermentation procedure to produce lysostaphin efficiently.     

Relation between insulin resistance and serum concentrations of IL-6 and TNF-alpha in overweight or obese women with early stage breast cancer

Insulin resistance (IR) and obesity may be risk factors for breast cancer. The mechanism of IR in patients with cancer has not been fully clarified yet. This study was conducted to evaluate the possible role of circulating cytokines; tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) in inducing IR in 20 overweight or obese patients with early stage breast cancer and to compare their levels with that of body mass index matched 20 healthy controls. IR was calculated by homeostasis model assessment (HOMA) method. Four groups were formed according to a 2.7 HOMA-IR cut-off value as breast cancer with or without IR and controls with or without IR. IL-6 and HOMA-IR values were found to be higher in breast cancer patients with IR compared to other groups. There was no significant difference in TNF-alpha levels between groups. HOMA-IR values correlated with estradiol and IL-6 levels in all breast cancer patients but not TNF-alpha. HOMA-IR values, serum insulin, estradiol and IL-6 levels in the receptor positive group were significantly higher than those of the receptor negative group. These results suggested a possible contribution of endogenous IL-6 production and hyperinsulinemia to the development of breast cancer in overweight or obese patients with prominent IR.