Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages

Carbon nanotubes (CNTs) have promised a range of applications in biomedicine. Although influenced by the dispersants used, CNTs are recognized by the innate immune system, predominantly by the classical pathway of the complement system. Here, we confirm that complement activation by the CNT used continues up to C3 and C5, indicating that the entire complement system is activated including the formation of membrane-attack complexes. Using recombinant forms of the globular regions of human C1q (gC1q) as inhibitors of CNT-mediated classical pathway activation, we show that C1q, the first recognition subcomponent of the classical pathway, binds CNTs via the gC1q domain. Complement opsonisation of CNTs significantly enhances their uptake by U937 cells, with concomitant downregulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines in both U937 cells and human monocytes. We propose that CNT-mediated complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response. From the Clinical Editor: This study highlights the importance of the complement system in response to carbon nanontube administration, suggesting that the ensuing complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response

Does neurocognitive training have the potential to improve dietary self-care in type 2 diabetes? Study protocol of a double blind randomised controlled trial

Dietary self-care is a key element of self-management in type 2 diabetes. It is also the most difficult aspect of diabetes self-management. Adhering to long-term dietary goals and resisting immediate food desires requires top-down inhibitory control over subcortical impulsive and emotional responses to food. Practising simple neurocognitive tasks can improve inhibitory control and health behaviours that depend on inhibitory control, such as resisting alcohol consumption. It is yet to be investigated, however, whether neurocognitive training can improve dietary self-care in people with type 2 diabetes. The aim of this randomised controlled trial is to investigate whether web-based neurocognitive training can improve the ability of people with type 2 diabetes to resist tempting foods and better adhere to a healthy dietary regime

Integrative Network Biology: Graph Prototyping for Co-Expression Cancer Networks

Network-based analysis has been proven useful in biologically-oriented areas, e.g., to explore the dynamics and complexity of biological networks. Investigating a set of networks allows deriving general knowledge about the underlying topological and functional properties. The integrative analysis of networks typically combines networks from different studies that investigate the same or similar research questions. In order to perform an integrative analysis it is often necessary to compare the properties of matching edges across the data set. This identification of common edges is often burdensome and computational intensive. Here, we present an approach that is different from inferring a new network based on common features. Instead, we select one network as a graph prototype, which then represents a set of comparable network objects, as it has the least average distance to all other networks in the same set. We demonstrate the usefulness of the graph prototyping approach on a set of prostate cancer networks and a set of corresponding benign networks. We further show that the distances within the cancer group and the benign group are statistically different depending on the utilized distance measure

Multivariate Analysis of Dopaminergic Gene Variants as Risk Factors of Heroin Dependence

BACKGROUND: Heroin dependence is a debilitating psychiatric disorder with complex inheritance. Since the dopaminergic system has a key role in rewarding mechanism of the brain, which is directly or indirectly targeted by most drugs of abuse, we focus on the effects and interactions among dopaminergic gene variants. OBJECTIVE: To study the potential association between allelic variants of dopamine D2 receptor (DRD2), ANKK1 (ankyrin repeat and kinase domain containing 1), dopamine D4 receptor (DRD4), catechol-O-methyl transferase (COMT) and dopamine transporter (SLC6A3) genes and heroin dependence in Hungarian patients. METHODS: 303 heroin dependent subjects and 555 healthy controls were genotyped for 7 single nucleotide polymorphisms (SNPs) rs4680 of the COMT gene; rs1079597 and rs1800498 of the DRD2 gene; rs1800497 of the ANKK1 gene; rs1800955, rs936462 and rs747302 of the DRD4 gene. Four variable number of tandem repeats (VNTRs) were also genotyped: 120 bp duplication and 48 bp VNTR in exon 3 of DRD4 and 40 bp VNTR and intron 8 VNTR of SLC6A3. We also perform a multivariate analysis of associations using Bayesian networks in Bayesian multilevel analysis (BN-BMLA). FINDINGS AND CONCLUSIONS: In single marker analysis the TaqIA (rs1800497) and TaqIB (rs1079597) variants were associated with heroin dependence. Moreover, -521 C/T SNP (rs1800955) of the DRD4 gene showed nominal association with a possible protective effect of the C allele. After applying the Bonferroni correction TaqIB was still significant suggesting that the minor (A) allele of the TaqIB SNP is a risk component in the genetic background of heroin dependence. The findings of the additional multiple marker analysis are consistent with the results of the single marker analysis, but this method was able to reveal an indirect effect of a promoter polymorphism (rs936462) of the DRD4 gene and this effect is mediated through the -521 C/T (rs1800955) polymorphism in the promoter

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

The Effects of the Monoamine Stabilizer (-)-OSU6162 on Binge-Like Eating and Cue-Controlled Food-Seeking Behavior in Rats.

Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats. OSU6162 significantly reduced binge-like intake of chocolate-flavored sucrose pellets without affecting prior chow intake. Furthermore, OSU6162 significantly reduced the cue-controlled seeking of chocolate-flavored sucrose pellets under a second-order schedule of reinforcement before, but not after, the delivery and ingestion of reward, indicating a selective effect on incentive motivational processes. In contrast, the dopamine D2/D3 receptor antagonist raclopride reduced the seeking of chocolate-flavored sucrose pellets both pre- and post reward ingestion and also reduced responding under simpler schedules of seeking behavior. The D1/5 receptor antagonist SCH23390 had no effect on instrumental behavior under any reinforcement schedule tested. Finally, local administration of OSU6162 into the nucleus accumbens core, but not dorsolateral striatum, selectively reduced cue-controlled sucrose seeking. In conclusion, the present results show that OSU6162 reduces binge-like eating behavior and attenuates the impact of cues on seeking of palatable food. This indicates that OSU6162 might serve as a novel BED medication.These studies were financially supported by a grant from the Swedish Society of Medicine (SLS-253061) to PS and JA, and a Medical Research Council Programme Grant (no. G1002231) to BJE. The Behavioural and Clinical Neuroscience Institute is cofunded by the Medical Research Council and the Welcome Trust. JA was supported by the Swedish Pharmaceutical Society and the Swedish Research Council (350-2012-230). A travel grant from the Swedish Society for Medical Research enabled KF to participate in this collaboration. PS was supported by the Swedish Research Council (2015-03525)

Variability of air temperature in the Bystrzyckie Mountains during the vegetative season of 2001

Celem tego artykułu jest przedstawienie wyników badań dotyczących zróżnicowania temperatury powietrza w okresie 4 IV 2001-18 X 2001, przeprowadzonych za pomocą mikrotermografów na siedmiu stanowiskach pomiarowych, położonych na obszarze Gór Bystrzyckich. Z badań tych wynika, że czynnikami wpływającymi na zróżnicowanie termiczne omawianego obszaru są: wysokość bezwzględna, rodzaj formy terenu oraz pokrywa roślinna i glebowa. W czasie pogody cyklonalnej największe znaczenie ma wysokość bezwzględna - najniższe wartości temperatury odnotowano na stanowiskach położonych najwyżej. W czasie pogody antycyklonalnej czynnikiem dominującym jest rodzaj formy terenu, co skutkuje znacznymi spadkami temperatury w nocy, nierzadko również występowaniem przymrozków w obrębie dolin. Fakt, że na znacznym obszarze badanego terenu przymrozki odnotowywane były nawet w czerwcu i sierpniu, ma duże znaczenie dla gospodarki leśnej tego regionu. Wyniki badań przeprowadzonych w czasie okresu wegetacyjnego mogą być ważnym źródłem informacji w przypadku planowania upraw leśnych.This article shows spatial and temporal variability of temperature during the period 4 IV 2001-18 X 2001. Analyses took place in part of the Bystrzyckie Mountains where seven sites were located in order to measure air temperature with the use of microthermographs. Results show that the most important factors which influenced thermal variability were: altitude, land form, vegetation and soil. Altitude was the most important factor during cyclonic weather when the lowest temperature was measured in the highest areas. In the case of anticyclonic weather, the head factor was terrain relief. As a result the lowest nocturnal temperature was observed in sites located at the bottom of concave landforms. Such cases are often accompanied by frost events. Frequent frosts that happen during the vegetative period exert significant influence on forest economy. Results of the study can be an important source of information on places vulnerable to frosts, therefore they can be a very useful tool in forestry planning

Analysis of filtration coefficient in the aspect of possibilities for application of alternative materials in building separation screens in landfills

In the case of insufficiently tight natural geological barrier, the area of landfills should be protected by special artificial barriers (separation screens). The use of natural mineral materials for building the separation screens (loamy minerals, such as a variety of clays) requires their extraction from local deposits, which inevitably generates waste from extraction and treatment of the minerals, causes changes in hydrographic conditions and soil quality in the neighbourhood of the excavations, degraded landscape and additional costs, including the energy and examination of mineral usefulness. Therefore, it seems purposeful to search for replacement materials which are technologically and economically competitive, such as fine grain waste minerals and/or by-products from industrial activity. A fundamental parameter of the separation screen which ensures its efficiency in terms of stopping migration of pollutants outside the landfill is the adequate level of filtration coefficient, which according to legal regulation cannot be greater than 1 10-9 m/s. The aim of the present study was to analyse the filtration coefficient obtained as a result of the mixtures prepared from fine grain mineral waste and by-products from industrial activities under conditions of their maximum densification in order to find the material which shows the best tightness to match the requirements of separation screens for landfill applications. The following minerals were used in the study: coal dust from water and dust circulation system in the Sobieski mine in Jaworzno, Poland, fly ash from combustion of brown coal from Bełchatów power plant, fly ashes from combustion of black coal in conventional and fluidized bed furnaces in Łagisza power plant in Będzin, Poland, post-flotation from Zn-Pb ore dressing from inactive settler in the area of the city of Bytom and barren rock clays from brown coal deposits in the Bełchatów mine. These materials were used for preparation of 8 mixtures with various share of individual components with coal dust as the main component of the matrix, with participation of 50 wt%. Before the determination of filtration coefficient for each of the mixture began, the optimum humidity and maximum bulk density of the soil matrix was measured. In the most of the mixtures, the optimum humidity ranged from 25 to 27.5%, whereas in the case of the mixtures with bottom ash from fluidized bed and fly ash from the conventional furnace it was lower than 20%. Determination of the filtration coefficient was carried out on the specially designed stand under condition of fluid flow from the bottom to the upper part of the sample, with variable hydraulic gradient and i>30. Stabilization of the filtration coefficient was observed for the most of the mixtures after ca. 10–11 days from the beginning of the experiment, at the level typical of the particular mixture. The highest, unstable filtration coefficient of 1.6–2 10-8 m/s was observed for the mixture of coal dust with the ashes from brown coal, which makes it impossible to be used as proposed. Nevertheless, application of another addition to this mixture (floatation waste and clays) considerably improved the coefficient of filtration, which reached the value of ca. 2–2,5 10-9m/s. The most favourable coefficient was obtained for the mixtures of coal dust with ashes from combustion of hard coal in fluidized bed furnaces, modified with an addition of clays. The value of filtration coefficient ranged from 3 to 6.5 10-10 m/s. The results of the investigations confirmed the ability of achieving the alternative material for building the separation screen which is the mixture of waste and by-products from industrial activities with over-additive properties. It is necessary to continue the research in the area of modification of the mixtures, particularly in the aspect of increased fraction of coal dust in order to optimize filtration coefficient and obtain the screen with satisfactory degree of tightness