Local and systemic oxidant/antioxidant status before and during lung cancer radiotherapy

To examine local and systemic oxidative status of lung cancer (LC) and oxidant effects of radiotherapy (RT), this study evaluated antioxidants and markers of oxidative and nitrosative stress in bronchoalveolar lavage (BAL) fluid and in the blood of 36 LC patients and 36 non-cancer controls at baseline and during and after RT for LC. LC patients had higher baseline serum urate, plasma nitrite and lower serum oxidized proteins than controls (p=0.016, p<0.001 and p=0.027, respectively), but BAL fluid oxidative stress markers were similar. RT tended to raise some antioxidants, however, significant increases were seen in serum urate, conjugated dienes and TBARS (p=0.044, p=0.034 and p=0.004, respectively) 3 months after RT. High urate at baseline may compensate against the oxidative stress caused by LC. RT shifts the oxidant/antioxidant balance towards lipid peroxidation, although the antioxidant defense mechanisms of the body appear to counteract the increased oxidative stress rather effectively.     

The laccase-catalyzed modification of lignin for enzymatic hydrolysis

The efficient use of cellulases in the hydrolysis of pretreated lignocellulosic biomass is limited due to the presence of lignin. Lignin is known to bind hydrolytic enzymes nonspecifically, thereby reducing their action on carbohydrate substrates. The composition and location of residual lignin therefore seem to be important for optimizing the enzymatic hydrolysis of lignocellulosic substrates. The use of lignin-modifying enzymes such as laccase may have potential in the modification or partial removal of lignin from the biomass. In this study, the effect of lignin modification by laccase on the hydrolysis of pretreated spruce (Picea abies) and giant reed (Arundo donax) was evaluated. The substrates were first treated with laccase and then hydrolyzed with commercial cellulases. Laccase modification improved the hydrolysis yield of spruce by 12%, but surprisingly had an adverse effect on giant reed, reducing the hydrolysis yield by 17%. The binding properties of cellulases on the untreated and laccase-treated lignins were further studied using isolated lignins. The laccase treatment reduced the binding of enzymes on modified spruce lignin, whereas with giant reed, the amount of bound proteins increased after laccase treatment. Further understanding of the reactions of laccase on lignin will help to control the unspecific-binding of cellulases on lignocellulosic substrates.     

Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen-activated protein kinase pathways

Introduction  

Adiponectin is an adipokine that regulates energy metabolism and insulin sensitivity, but recent studies have pointed also to a role in inflammation and arthritis. The purpose of the present study was to investigate the association and effects of adiponectin on inflammation and cartilage destruction in osteoarthritis (OA).     

The effect of small zooplankton on the microbial loop and edible algae during a cyanobacterial bloom

SUMMARY 1. We studied the effect of the small crustacean zooplankton on heterotrophic micro-organisms and edible phytoplankton in a eutrophic lake during a cyanobacterial bloom.
2. Small (15 L) enclosures were filled with natural or screened (100 μm) lake water and incubated for 5 days in the lake. Screening removed crustacean zooplankton but the initial density of rotifers and phytoplankton remained the same in control and removal treatments. Changes in the abundance and biomass of bacteria, autotrophic picoplankton (APP), heterotrophic nanoflagellates (HNF) and ciliates were measured daily.
3. The crustacean zooplankton, dominated by the small cladoceran Chydorus sphaericus , did not affect cyanobacteria, the main phytoplankton group during the experiment.
4. The removal of the crustacean zooplankton induced a higher abundance of ciliates and reduced that of the HNF, indicating the importance of ciliates in controlling HNF in this system.     

Role of <Emphasis Type="Italic">MAPT</Emphasis> mutations and haplotype in frontotemporal lobar degeneration in Northern Finland

Background

Frontotemporal lobar degeneration (FTLD) consists of a clinically and neuropathologically heterogeneous group of syndromes affecting the frontal and temporal lobes of the brain. Mutations in microtubule-associated protein tau (MAPT), progranulin (PGRN) and charged multi-vesicular body protein 2B (CHMP2B) are associated with familial forms of the disease. The prevalence of these mutations varies between populations. The H1 haplotype of MAPT has been found to be closely associated with tauopathies and with sporadic FTLD. Our aim was to investigate MAPT mutations and haplotype frequencies in a clinical series of patients with FTLD in Northern Finland.

Methods

MAPT exons 1, 2 and 9–13 were sequenced in 59 patients with FTLD, and MAPT haplotypes were analysed in these patients, 122 patients with early onset Alzheimer's disease (eoAD) and 198 healthy controls.

Results

No pathogenic mutations were found. The H2 allele frequency was 11.0% (P = 0.028) in the FTLD patients, 9.8% (P = 0.029) in the eoAD patients and 5.3% in the controls. The H2 allele was especially clustered in patients with a positive family history (P = 0.011) but did not lower the age at onset of the disease. The ApoE4 allele frequency was significantly increased in the patients with eoAD and in those with FTLD.

Conclusion

We conclude that although pathogenic MAPT mutations are rare in Northern Finland, the MAPT H2 allele may be associated with increased risks of FTLD and eoAD in the Finnish population.

     

Metapopulation dynamics of the bog fritillary butterfly: movements between habitat patches

Recent studies on metapopulation dynamics have emphasized the need for improved methods for quantifying individual movements between local populations and habitat patches. In this paper, we report on a 6-yr study in which a network of 12 habitat patches occupied by the bog fritillary, Proclossiana eunomia , was surveyed, with special focus on quantifying movements between the habitat patches. We applied the Virtual Migration model which has been designed to estimate survival and migration parameters in a metapopulation of several connected local populations. The model was parameterized using mark-release-recapture data collected during 6 yr. Generally, the estimated parameter values indicated a high level of movements, with roughly half of butterfly-days spent outside the natal patch. Mortality within patches was higher in males than in females. Females tended to be more mobile and spent more time outside their natal patch than males. Further analysis of the MRR data shows that in this protandrous species males tend to move very little between habitat patches before substantial numbers of females have emerged.     

META-X: Generic Software for Metapopulation Viability Analysis

The major tools used to make population viability analyses (PVA) quantitative are stochastic models of population dynamics. Since a specially tailored model cannot be developed for every threatened population, generic models have been designed which can be parameterised and analysed by non-modellers. These generic models compromise on detail so that they can be used for a wide range of species. However, generic models have been criticised because they can be employed without the user being fully aware of the concepts, methods, potentials, and limitations of PVA. Here, we present the conception of a new generic software package for metapopulation viability analysis, META-X. This conception is based on three elements, which take into account the criticism of earlier generic PVA models: (1) comparative simulation experiments; (2) an occupancy-type model structure which ignores details of local population dynamics (these details are integrated in external submodels); and (3) a unifying currency to quantify persistence and viability, the intrinsic mean time to extinction. The rationale behind these three elements is explained and demonstrated by exemplary applications of META-X in the three fields for which META-X has been designed: teaching, risk assessment in the field, and planning. The conception of META-X is based on the notion that PVA is a tool to deal with rather than to overcome uncertainty. The purpose of PVA is to produce relative, not absolute, assessments of extinction risk which support, but do not supplant, management decisions.     

Divergent effect of mometasone on human eosinophil and neutrophil apoptosis

Mometasone is a potent synthetic glucocorticoid, which is under development as an inhaled preparation for the treatment of asthma. Previous studies have suggested that glucocorticoids have direct effects on human eosinophil and neutrophil apoptosis. The present study was designed to characterize the effects of mometasone on constitutive apoptosis and cytokine-afforded survival in isolated human eosinophils and neutrophils. The isolated eosinophils or neutrophils were cultured in vitro, and apoptosis was assessed by flow cytometric analysis of relative DNA content, by annexin-V binding and morphological analysis. Mometasone enhanced constitutive human eosinophil apoptosis in a concentration-dependent manner. The maximal enhancement of eosinophil apoptosis was 2.1-fold with an EC(50) value of 5.63 +/- 2.33 nM. This enhancing effect was reversed by the glucocorticoid receptor antagonist, mifepristone. In the presence of added cytokines, mometasone reversed tumor necrosis factor -alpha-induced eosinophil survival but not that afforded by interleukin -5. In contrast, mometasone inhibited human neutrophil apoptosis in a concentration-dependent manner. The maximal inhibition of neutrophil apoptosis was 50% with an EC(50) value of 0.17 +/- 0.03 nM. The inhibitory effect was partly reversed by mifepristone. In the presence of added cytokines, mometasone further enhanced neutrophil survival induced by the granulocyte-macrophage colony-stimulating factor and leukotriene B(4). The present data suggests that mometasone has opposite effects on apoptosis of human eosinophils and neutrophils at clinically relevant drug concentrations via an effect on glucocorticoid receptor.     

Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein

Overexpression of human alpha-synuclein in model systems, including cultured neurons, drosophila and mice, leads to biochemical and pathological changes that mimic synucleopathies including Parkinson's disease. We have overexpressed both wild-type (WT) and mutant alanine53-->threonine (A53T) human alpha-synuclein by transgenic injection into Caenorhabditis elegans. Motor deficits were observed when either WT or A53T alpha-synuclein was overexpressed with a pan-neuronal or motor neuron promoter. Neuronal and dendritic loss were accelerated in all three sets of C. elegans dopaminergic neurons when human alpha-synuclein was overexpressed under the control of a dopaminergic neuron or pan-neuronal promoter, but not with a motor neuron promoter. There were no significant differences in neuronal loss between overexpressed WT and A53T forms or between worms of different ages (4 days, 10 days or 2 weeks). These results demonstrate neuronal and behavioral perturbations elicited by human alpha-synuclein in C. elegans that are dependent upon expression in specific neuron subtypes. This transgenic model in C. elegans, an invertebrate organism with excellent experimental resources for further genetic manipulation, may help facilitate dissection of pathophysiologic mechanisms of various synucleopathies.