Crop wild relative populations of Beta vulgaris allow direct mapping of agronomically important genes.

Rapid identification of agronomically important genes is of pivotal interest for crop breeding. One source of such genes are crop wild relative (CWR) populations. Here we used a CWR population of <200 wild beets (B. vulgaris ssp. maritima), sampled in their natural habitat, to identify the sugar beet (Beta vulgaris ssp. vulgaris) resistance gene Rz2 with a modified version of mapping-by-sequencing (MBS). For that, we generated a draft genome sequence of the wild beet. Our results show the importance of preserving CWR in situ and demonstrate the great potential of CWR for rapid discovery of causal genes relevant for crop improvement. The candidate gene for Rz2 was identified by MBS and subsequently corroborated via RNA interference (RNAi). Rz2 encodes a CC-NB-LRR protein. Access to the DNA sequence of Rz2 opens the path to improvement of resistance towards rhizomania not only by marker-assisted breeding but also by genome editing.

Cognitive interventions in mild Alzheimer's disease: a therapy-evaluation study on the interaction of medication and cognitive treatment.

BACKGROUND/AIMS: Many studies have shown that not only pharmacological treatment but also cognitive stimulation in the early stages of Alzheimer's disease (AD) improves language processing and (other) cognitive functions, stabilizes Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) functions and increases the subjective quality of life (wherein a combination of pharmacological intervention and cognitive stimulation could provide greater relief of clinical symptoms than either intervention given alone). Today, it is no longer the question of whether cognitive stimulation helps but rather what kind of stimulation helps more than others. METHODS: A sample of 42 subjects with mild AD (all medicated with an acetylcholinesterase inhibitor and well adjusted) underwent clinical and cognitive evaluation and participated in a 6-month study with 2 experimental groups (i.e. 'client-centered' global stimulation vs. cognitive training) and a control group. Since the test performance also depends on the individual test, we used a wide variety of tests; we z-transformed the results and then calculated the mean value for the global cognitive status (using the Mini-Mental State Examination) as well as for the single functional areas. RESULTS: Between-group differences were found, they were overall in favor of the experimental groups. Different functional areas led to different treatment and test patterns. Client-centered, global, cognitive therapy stimulated many cognitive functions and thus led to a better performance in language processing and ADL/IADL. The subjective quality of life increased as well. The cognitive training (of working memory) improved only the ADL/IADL performance (more, however, than client-centered, global, cognitive stimulation) and stabilized the level of performance in the other three functional areas. © 2013 S. Karger AG, Basel.

Risk and monitoring based indicators of receiving water status: alternative or complementary elements in IWRM?

The European Water Framework Directive (WFD) was enacted in the year 2000 with a stepwise approach. After legal implementation in the various member states large efforts were undertaken for the initial characterization of water bodies, risk assessment, to implement extensive monitoring schemes and to develop management plans at different aggregation levels by the year 2010. The initial characterization process and risk assessment had to be finalized by 2004 and delineated water bodies including a typological classification and identified the significant pressures and impacts in a screening procedure. In parallel, monitoring programmes and new biological indicator systems were developed in order to proof and refine the results of the risk assessment with an ecological indicator based assessment in a subsequent step which was finalized in 2009. Although the risk assessment for Germany was based on existing data that were originally collected for other purposes and came from a large variety of environmental or economical sectors, the results differ only slightly from the monitoring and indicator based information with respect to classifications of the 'ecological status' and 'chemical status'. From this result we conclude that a risk assessment based on a careful application and intelligent combination of existing data sources with proven quality allows the recognition of trends and the identification of priorities for action of measures already at an early stage of a management process. However, monitoring schemes and advanced sets of ecological indicators are essential in later management steps both for narrowing uncertainties remaining from the risk assessment and to allow for effect controls of implemented measures. Moreover, these monitoring indicators should differentiate the effects of multiple stressors more factor specific and with respect to ecosystem states and functions. In conclusion, we see risk and indicator based assessments as complementary elements in Integrated Water Resources Management (IWRM), which have to be linked in systematic and phased procedures.

Element patterns for particulate matter in stormwater effluent.

Particulate matter in stormwater deteriorates the quality of receiving water and sediment. Characterization of stormwater particulate matter by means of its particle-associated element pattern provides an aid to determining its impact on receiving surface waters. During a 6 month measurement campaign, we determined particle-associated concentrations of major pollutants and rare earths for three combined water/stormwater outlets in the town of Stassfurt. We differentiated the particle-associated constituents on the basis of a hierarchical cluster analysis. Repeating the cluster analysis on random subsets, we gained information about the variability of the element patterns between and within the sites. In general, constituents associated with sewage and sewer sediment behave differently compared with constituents associated with runoff. The degree to which associations can be established for element patterns from site to site is limited by the variability encountered within sample sets taken from individual sites. The latter variability depends on the complexity of the catchment.

Glucogenic blood sugar formation in an insect Manduca sexta L.: asymmetric synthesis of trehalose from 13C enriched pyruvate.

Gluconeogenesis and blood sugar formation were examined in Manduca sexta, fed carbohydrate- and fat-free diets with varying levels of casein. De novo carbohydrate synthesis was examined by nuclear magnetic resonance spectroscopy of the 13C enrichment in blood trehalose and alanine derived from (2-(13)C)pyruvate and (2,3-(13)C(2))pyruvate administered to 5th instar larvae. Gluconeogenic flux and blood trehalose concentration were positively correlated with protein consumption. On all diets, the 13C distribution in trehalose was asymmetric, with C6 more highly enriched than C1. The C6/C1 13C enrichment ratio, however, decreased with increased protein consumption and gluconeogenic flux. Although the asymmetric 13C enrichment pattern in trehalose is consistent with pentose cycling via the pentose phosphate pathway following de novo synthesis, experiments employing [2,3-(13)C(2)]pyruvate demonstrated that pentose cycling is not detected in insects under these nutritional conditions. Analysis of the multiplet NMR signal structure in trehalose due to spin-spin coupling between adjacent 13C enriched carbons showed the absence of uncoupling expected by pentose phosphate pathway activity. Here we suggest that the asymmetric 13C distribution in trehalose results from a disequilibrium of the triose phosphate isomerase-catalyzed reaction.

Dietary nutrient levels regulate protein and carbohydrate intake, gluconeogenic/glycolytic flux and blood trehalose level in the insect Manduca sexta L.

This study examined the effects of dietary casein and sucrose levels on nutrient intake, and distinguished the effects of carbohydrate and protein consumption on growth, fat content, pyruvate metabolism and blood trehalose level of 5th instar Manduca sexta larvae. Growth increased with increasing casein consumption but was unaffected by carbohydrate intake. Fat content also increased with carbohydrate consumption, but on carbohydrate-free diets fat content increased with increased protein consumption. Blood trehalose level and pyruvate metabolism were examined by nuclear magnetic resonance spectroscopy analysis of blood following administration of (3-(13)C)pyruvate. On diets containing sucrose, blood trehalose increased with increasing carbohydrate intake, and on most diets trehalose was synthesized entirely from dietary sucrose. Pyruvate cycling, indicated by the alanine C2/C3 (13)C enrichment ratio, increased with carbohydrate consumption reflecting increased glycolysis, and pyruvate decarboxylation exceeded carboxylation on all sucrose diets. Larvae that consumed <75 mg/day sucrose were gluconeogenic, based on the [2 (trehalose C6)(Glx C3/C2)]/alanine C2] (13)C enrichment ratio. On carbohydrate-free diets, blood trehalose levels were low and maintained entirely by gluconeogenesis. Blood trehalose level increased with increasing protein intake. Pyruvate cycling was very low, although many insects displayed higher levels of pyruvate decarboxylation than carboxylation. All gluconeogenic larvae displayed alanine (13)C enrichment ratios <0.35 and had blood trehalose levels <50 mM.

Identification of significant pressures and impacts upon receiving waters.

This study gives a review on the process of identification of significant pressures and impacts, which is an important part of river basin planning and in particular for implementing the EU Water Framework Directive (WFD) (2000/60/EC). The questions: what is a "significant pressure" in terms of the WFD? which sources and driving forces have to be regarded? which data can be used? which pressure on a water body is significant? and which implications and requirements result from the identification process?--should be considered. The European Commission requires reporting from all Member States about the status of the water bodies within a river basin district and about the risk of failing the environmental objectives by the end of 2004. Therefore, a number of prevailing projects across Europe aim to develop a guideline on a common understanding of the most effective approach towards the identification of significant anthropogenic pressures, and the analysis of potential impacts including the identification of appropriate tools and models. In such a guideline suitable and intelligent criteria have to be developed in order to enable a uniform assessment of the anthropogenic pressures within a river basin district.

The glucogenic response of a parasitized insect Manduca sexta L. is partially mediated by differential nutrient intake.

Induction of gluconeogenesis is accelerated in larvae of the insect Manduca sexta L. parasitized by Cotesia congregata (Say), maintaining the concentration of the blood sugar trehalose, an important nutrient for parasite development. Investigation has demonstrated that when host larvae are offered a choice of diets with varying levels of sucrose and casein, parasitized insects consume a different balance of these nutrients, principally due to a decrease in protein consumption. The result is metabolic homeostasis, with normal unparasitized and parasitized larvae exhibiting similar levels of gluconeogenesis and blood sugar level. In the present study, normal unparasitized and parasitized larvae were maintained on individual chemically defined diets having the balance of protein and carbohydrate consumed by each when offered a dietary choice. Total dietary nutrient, the sum of carbohydrate and protein, was provided at six levels, composed of three pairs of diets. Each diet pair consisting of diets having equivalent overall nutrient ratios of 2:1 and 1:1 casein/sucrose. Host growth and diet consumption were significantly affected by dietary nutrient level and the magnitude of these effects was influenced by parasitism. Due to the effects of dietary nutrient level on diet consumption, none of the unparasitized and parasitized larvae within any of the three diet pairs consumed protein and carbohydrate at the levels predicted by the earlier choice experiments. Among insects on all of the diets, however, two groups of unparasitized and parasitized larvae consumed the expected levels of protein and carbohydrate. In each case, gluconeogenesis, as measured by 13C nuclear magnetic resonance spectroscopy (NMR) analysis of pyruvate cycling and trehalose synthesis from [2-13C]pyruvate, was evident in unparasitized and parasitized insects, confirming the conclusions of the earlier experiments. Generally, all larvae that consumed less than approximately 250 mg of sucrose over the 3-day feeding period, were gluconeogenic, regardless of diet. Differential carbohydrate consumption, therefore, was an important factor in inducing gluconeogenesis in both unparasitized and parasitized insects. The selective 13C enrichment in trehalose displayed by non-gluconeogenic larvae on some diets demonstrated trehalose formation from [2]pyruvate. The absence of net carbohydrate synthesis in these insects was likely due to an elevation of glycolysis. There was no significant effect of diet consumption or parasitism on blood trehalose level. Parasitized larvae displayed higher levels of gluconeogenesis than did unparasitized insects, a finding consistent with the conclusion that blood sugar is rapidly sequestered by developing parasites. The parasite burden, the total number of parasites developing within host larvae, as well as the number of parasites emerging from host larvae to complete development, was significantly less at the lowest dietary nutrient level, but was otherwise similar at all dietary nutrient levels. Moreover, the number of parasites that emerged increased with increasing diet consumption as reflected by host final weight.

Functional characterization of beta-ketoacyl-CoA synthase genes from Brassica napus L.

Seed-specifically expressed beta-ketoacyl-CoA synthase genes of Brassica napus (Bn-FAE1.1 genes) were cloned from two cultivars, namely Askari, a high-erucic-acid type, and Drakkar, a low-erucic-acid type. The genes from the two cultivars were found to be nearly identical. They encode proteins of 507 amino acids, the sequences of which differ only at position 282. The Bn-FAE1.1 gene of Askari, unlike that of Drakkar, was functionally expressed in yeast cells suggesting that the single amino acid exchange effects the low erucic acid phenotype at the E1 gene locus. In yeast cells the beta-ketoacyl-CoA synthase of Askari elongated not only oleoyl but also palmitoleoyl groups as well as saturated acyl groups in such a way that monounsaturated acyl groups of 22 carbons and saturated ones of 26 carbons were formed as main products. A reporter gene fused to the promoter region of the Bn-FAE1.1 gene from Askari showed seed-specific expression in transgenic rapeseed plants. Over-expression of the coding region of the Askari gene in developing seeds of transgenic Drakkar plants resulted in a significant increase in the levels of eicosenoic acid and erucic acid esterified in the seed oil. On the other hand, in transgenic high-erucic-acid rapeseed plants the increase in erucic acid level was at most 60% although the chimeric Bn-FAE1.1 gene was co-expressed with an erucoyl-CoA-specific lysophosphatidate acyltransferase gene enabling trierucoyl glycerol to accumulate in the seed oil.

River Water Quality Model no. 1 (RWQM1): I. Modelling approach.

Successful river water quality modelling requires the specification of an appropriate model structure and process formulation. Both must be related to the compartment structure of running water ecosystems including their longitudinal, vertical, and lateral zonation patterns. Furthermore, the temporal variability of abiotic boundary conditions may be important and must be incorporated by an appropriate choice of model parameters. A six-step decision procedure is proposed to achieve these objectives. The steps address the determination of the following model features: (1) temporal representation (dynamic or steady-state); (2) model dimensionality; (3) mixing; (4) advection; (5) reaction terms; and (6) boundary conditions. Numerical criteria based on process time constants and length scales provide a basis for these decisions.

River Water Quality Model no. 1 (RWQM1): II. Biochemical process equations.

In this paper, biochemical process equations are presented as a basis for water quality modelling in rivers under aerobic and anoxic conditions. These equations are not new, but they summarise parts of the development over the past 75 years. The primary goals of the presentation are to stimulate communication among modellers and field-oriented researchers of river water quality and of wastewater treatment, to facilitate practical application of river water quality modelling, and to encourage the use of elemental mass balances for the derivation of stoichiometric coefficients of biochemical transformation processes. This paper is part of a series of three papers. In the first paper, the general modelling approach is described; in the present paper, the biochemical process equations of a complex model are presented; and in the third paper, recommendations are given for the selection of a reasonable submodel for a specific application.

River Water Quality Model no. 1 (RWQM1): III. Biochemical submodel selection.

The new River Water Quality Model no. 1 introduced in the two accompanying papers by Shanahan et al. and Reichert et al. is comprehensive. Shanahan et al. introduced a six-step decision procedure to select the necessary model features for a certain application. This paper specifically addresses one of these steps, i.e. the selection of submodels of the comprehensive biochemical conversion model introduced in Reichert et al. Specific conditions for inclusion of one or the other conversion process or model component are introduced, as are some general rules that can support the selection. Examples of simplified models are presented.

River Water Quality Model no. 1 (RWQM1): case study. I. Compartmentalisation approach applied to oxygen balances in the River Lahn (Germany).

A case study on the application of the River Water Quality Model No. 1 (RWQM1) is presented in order to illustrate the importance of modelling a sediment compartment for an ecologically meaningful assessment of the impact of wastewater effluents and combined sewer overflows. The focus of this case study is on the compartmentalisation approach of the RWQM1 that makes such a description possible. In contrast to this, a strongly simplified biochemical submodel is used that considers only oxygen and dissolved substrate. The object of the case study is the River Lahn, a moderately polluted 5th order stream in Germany, for which the connectivity of surface/subsurface flows and mass fluxes within river sediments have been intensively investigated. The hyporheic flow between a downwelling and upwelling zone of a riffle-pool sequence has been studied with the aid of tracer experiments and continuous records of water constituents. High diurnal fluctuations of oxygen travelled to considerable depth of the sediment and oxygen in the interstitial water decreased considerably while travelling through the riffle. Starting with the implementation of a strongly simplified version of the biochemical part of the RWQM1, but with the consideration of a sediment pore water compartment in addition to the water column compartment, a calibration procedure is performed using tracer data from the water column and the sediment. The calibrated model is then used to study the system response to wastewater treatment plant effluent and combined sewer overflow emissions. The modelling approach makes it possible to quantify the sediment oxygen demand and the spatial and temporal extent of sediment zones with oxygen depletion. However, the spatially averaged approach does not account for inhomogeneities in the sediment. It is shown that for this river with its alluvial coarse sediments even moderate emissions from sewerage systems may be high enough to drop sediment oxygen concentrations to low levels while those in the surface flow remain close to saturation. Similarly, it is demonstrated that combined sewer overflows may cause anoxic sediment oxygen conditions for extended time periods. The implications for ecologically sound river water quality modelling and for specific quality objectives are discussed.

PCR-based cloning and segregation analysis of functional gene homologues in Beta vulgaris.

To analyse genetic factors that potentially affect sugar quality and yield in Beta vulgaris, we designed primers based on 18 homologous ESTs and conserved regions of 32 heterologous ESTs encoding gene products that act in the Calvin cycle, the oxidative pentose phosphate cycle, photorespiration, synthesis, transport and degradation of sucrose, glycolysis, the citric acid cycle, nitrogen metabolism and osmoprotection. Data on the amplification of 54 gene homologues from B. vulgaris are presented. Among these are 35 homologues for which DNA sequence information from B. vulgaris is now available for the first time. For genetic mapping a PCR-based strategy using CAPS (cleaved amplified polymorphic sequence), DFLP (DNA fragment length polymorphism), SSCP (single-strand conformation polymorphism) and HD (heteroduplex) analysis was adopted. RFLP analysis was also used in some cases. The different techniques used for the detection of polymorphisms are evaluated with respect to their sensitivity and versatility. In all, 42 functional genes have been assigned to the nine linkage groups of sugar beet.

Arginine kinase and phosphoarginine, a functional phosphagen, in the rhabditoid nematode steinernema carpocapsae.

Moderate activity of arginine kinase was found in Steinernema carpocapsae, an entomopathogenic nematode. In the forward reaction, 4.60 and 3.12 micromol ATP/min/mg protein was produced in infectious third-stage juveniles (J3s) and adult nematodes, respectively. For the reverse reaction, 3.20 and 2.27 micromol phosphoarginine/min/mg protein was produced by J3s and adults, respectively. The K(m)s for phosphoarginine and ADP were 0.73 and 0.42 mM, respectively, in the forward reaction, whereas in the reverse reaction, the K(m)s were 0.37 and 2.35 mM for arginine and ATP, respectively, for the enzyme from J3s. The pH optimum for the forward reaction was 7.2 and 7.3 in J3s and adults, respectively. The pH optimum was elevated for the reverse reaction, 7.8 and 7.9-8.5 in J3s and adults, respectively. In the J3s, the in vitro optima for arginine kinase activity was correlated with the in vivo tissue pH in hypoxic (6.9) and aerobic (7.5) J3s estimated by in vivo flow 31P-NMR.

Effects of histone and diolein on the structure of phosphatidylcholine/phosphatidylserine or phosphatidylcholine/phosphatidylglycerol bilayers.

The effects of the PKC substrate histone 1 and the PKC activator diolein (Ole2Gro) on the structure of phosphatidylcholine (PtdCho)/phosphatidylserine (PtdSer), or PtdCho/phosphatidylglycerol (PtdGro) bilayers were studied using 2H-NMR. The results showed that in PtdCho/PtdSer bilayers, histone preferentially increased order parameters of the acyl chains of the PtdSer, but not the PtdCho lipid component. This effect was additive with the effect of Ole2Gro, which equally increased the ordering of the acyl chains of both PtdCho and PtdSer. The histone-induced change in the conformation of the PtdCho headgroups in PtdCho/PtdSer bilayers indicated that positively charged residues of the bound histone are located above the lipid-water interface and their location was altered by the presence of Ole2Gro. A different picture was observed in the case of PtdCho/PtdGro bilayers; although the effect of Ole2Gro on both the PtdCho or the PtdGro components was similar to the case of the PtdCho/PtdSer bilayers, histone did not significantly affect the order parameters of PtdCho or PtdGro in either the absence or presence of Ole2Gro. The results indicate that histone 1 induces clustering of PtdSer in PtdCho bilayers which may contribute to PKC activation. Moreover, the observed differences in the interactions of histone with PtdCho/PtdSer compared with PtdCho/PtdGro bilayers may explain the higher efficiency of PtdSer in activating PKC.

Genetic Structure of Setosphaeria turcica Populations in Tropical and Temperate Climates.

ABSTRACT Northern leaf blight, caused by Setosphaeria turcica, is a serious disease of maize in temperate and tropical environments. To examine the pathogen's population structure, we analyzed 264 isolates from four different continents with 70 random amplified polymorphic DNA markers and determined their mating types. Tropical populations (from Kenya, Mexico, and southern China) had an extremely high genotypic diversity, no or only weak gametic phase disequilibrium, and an even distribution of the two mating types, indicating frequent sexual recombination. Temperate populations (from Europe and northern China) had a much lower genotypic diversity, strong gametic phase disequilibrium, and an uneven distribution of mating types, indicating that sexual recombination has been rare. Populations in different continents were genetically isolated. They shared no haplotypes and carried several "private" alleles. The number of migrants between continents and between regions (between northern and southern China, western and central Kenya, and Europe west and east of the Alps) was estimated to be less than one per generation. Multivariate statistics suggested a greater relatedness of populations from the same continents than from different continents. Within agroecological zones, migration must be extensive. The potential within populations of S. turcica for adaptation should be regarded as very high, especially in tropical climates.

Endogenous natriuretic factors 6: the stereochemistry of a natriuretic gamma-tocopherol metabolite LLU-alpha.

2,7,8-Trimethyl-(S)-2-(beta-carboxyethyl)-6-hydroxy chroman (S-LLU-alpha) isolated from human uremic urine is apparently an oxidative side-chain degradation product of gamma-tocopherol. This compound exhibits natriuretic activity in vivo and it appears to mediate the inhibition of the 70 pS K+ channel in the apical membrane of the thick ascending limb of the nephron. The stereochemistry at the C-2 of LLU-alpha has been unequivocally established to be S(+) by X-ray crystallographic analysis of a diastereomeric amide derivative. It was also established that the chroman ring oxidation of S-LLU-alpha proceeded without racemization at C-2. This finding can be extended to nonepimerization at C-2 of alpha-delta tocopherols (Vitamin E) during side-chain oxidation and stereospecificity (retention or inversion) of oxidative opening of the chroman ring. The resolution of the enantiomers of the parent compound and derivatives was accomplished by chiral high-performance liquid chromatography. The stereospecific enzymatic hydrolysis by an array of commercially available enzymes of the racemic methyl ester of LLU-alpha was investigated. The lipase from Humicola languinosa appears to be the best enzyme for resolution by selective hydrolysis of the racemic methyl ester.

Spectroscopic evidence for preexisting T- and R-state insulin hexamer conformations.

The insulin hexamer is an allosteric protein exhibiting both positive and negative cooperative homotropic interactions and positive cooperative heterotropic interactions (C. R. Bloom et al., J. Mol. Biol. 245, 324-330, 1995). In this study, detailed spectroscopic analyses of the UV/Vis absorbance spectra of the Co(II)-substituted human insulin hexamer and the 1H NMR spectra of the Zn(II)-substituted hexamer have been carried out under a variety of ligation conditions to test the applicability of the sequential (KNF) and the half-site reactivity (SMB) models for allostery. Through spectral decomposition of the characteristic d-->d transitions of the octahedral Co(II)-T-state and tetrahedral Co(II)-R-state species, and analysis of the 1H NMR spectra of T- and R-state species, these studies establish the presence of preexisting T- and R-state protein conformations in the absence of ligands for the phenolic pockets. The demonstration of preexisting R-state species with unoccupied sites is incompatible with the principles upon which the KNF model is based. However, the SMB model requires preexisting T- and R-states. This feature, and the symmetry constraints of the SMB model make it appropriate for describing the allosteric properties of the insulin hexamer.

[Radiation protection through cytokine release by N-acetylcysteine]. / Radioprotektion durch Zytokinfreisetzung unter N-Acetylcystein.

BACKGROUND: Interleukin-1, tumornecrosisfactor-alpha and interferon-gamma endogenously provide protection of the hematopoietic system against radiation. Thiols have already been used successfully as radioprotective agents. In this study the effect von N-acetylcysteine (NAC) on the release of interleukin-1 alpha and beta (IL-1), interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and tumornecrosisfactor-alpha (TNF-alpha) was assessed in an in vitro assay. PATIENTS AND METHODS: Whole blood samples from 8 healthy volunteers were stimulated with 7.5 micrograms/ml PHA. NAC was added at concentrations of 0.6, 6, 12 and 24 mmol/l. Subsequently the samples were irradiated with a dose of 18 Gy according to preceding validation experiments. RESULTS: IL-1 alpha, IL-1 beta b and IL-2: In comparison to stimulation and radiation alone the addition of 0.6 and 6 mmol/l, with IL-2 also 12 mmol/l, NAC resulted in a significant increase of the cytokine-concentrations. The highest concentration of 24 mmol/l NAC, however, resulted in a decrease beyond control levels. IFN-gamma and TNF-alpha: Until 12 mmol/l NAC no changes were observed. 24 mmol/l NAC resulted in a significant decrease, too. CONCLUSION: N-acetylcysteine is capable to co-stimulate radioprotective cytokines like IL-1 alpha and IL-1 beta and to enhance IL-2 in vitro, whereas higher doses result in a suppression.