Chronic periodontal disease is associated with single-nucleotide polymorphisms of the human TLR-4 gene

Periodontitis is an inflammatory disease affecting the connective tissue surrounding the teeth leading to tooth loss. Pathogens associated with periodontitis interact with Toll-like receptors (TLRs) to induce cytokines causing and aggravating disease. We screened 197 individuals suffering from generalized periodontitis for the presence of Asp299Gly and Thr399Ile of TLR-4 as well as Arg753Gln of TLR-2 in comparison to matched controls. Single-nucleotide polymorphisms (SNPs) of TLR-4 were elevated among patients (odd's ratio 3.650, 95% CI 1.573-8.467, P < or = 0.0001), while no difference was observed for TLR-2. TLR-4 SNPs were correlated with chronic periodontitis (odd's ratio 5.562, 95% CI 2.199-14.04, P < or = 0.0001), but not with aggressive periodontitis. This observation was confirmed employing a group of periodontally healthy probands over 60 years of age. These data demonstrate that genetic variants of TLR-4 may act as risk factors for the development of generalized chronic periodontitis in humans.     

TLR8 and TLR7 are involved in the host's immune response to human parechovirus 1

Toll-like receptors (TLR) have a key role in regulating immunity against microbial agents. Engagement of TLR by bacterial, viral or fungal components leads to the production and release of inflammatory cytokines. In this study we show that mainly TLR8 and also TLR7 act as the host sensors for human parechovirus 1, a single-stranded RNA (ssRNA) virus. Furthermore, we see that the viral ssRNA genome is detected in endosomal compartments by these TLR, which activate signalling that lead to the synthesis of pro-inflammatory molecules by the host.     

The influence of skull-conductivity misspecification on inverse source localization in realistically shaped finite element head models

Summary The electric conductivities of different tissues are important parameters of the head model and their precise knowledge appears to be a prerequisite for the localization of electric sources within the brain. To estimate the error in source localization due to errors in assumed conductivity values, parameter variations on skull conductivities are examined. The skull conductivity was varied in a wide range and, in a second part of this paper, the effect of a nonhomogeneous skull conductivity was examined. An error in conductivity of lower than 20% appears to be acceptable for fine finite element head models with average discretization errors down to 3mm. Nonhomogeneous skull conductivities, e.g., sutures, yield important mislocalizations especially in the vincinty of electrodes and should be modeled.The authors wish to thank the VW — Foundation for financial support.     

A target sample of adolescents and reward processing: same neural and behavioral correlates engaged in common paradigms?

Adolescence is a transition period that is assumed to be characterized by increased sensitivity to reward. While there is growing research on reward processing in adolescents, investigations into the engagement of brain regions under different reward-related conditions in one sample of healthy adolescents, especially in a target age group, are missing. We aimed to identify brain regions preferentially activated in a reaction time task (monetary incentive delay (MID) task) and a simple guessing task (SGT) in a sample of 14-year-old adolescents (N?=?54) using two commonly used reward paradigms. Functional magnetic resonance imaging was employed during the MID with big versus small versus no win conditions and the SGT with big versus small win and big versus small loss conditions. Analyses focused on changes in blood oxygen level?Cdependent contrasts during reward and punishment processing in anticipation and feedback phases. We found clear magnitude-sensitive response in reward-related brain regions such as the ventral striatum during anticipation in the MID task, but not in the SGT. This was also true for reaction times. The feedback phase showed clear reward-related, but magnitude-independent, response patterns, for example in the anterior cingulate cortex, in both tasks. Our findings highlight neural and behavioral response patterns engaged in two different reward paradigms in one sample of 14-year-old healthy adolescents and might be important for reference in future studies investigating reward and punishment processing in a target age group.     

Semicrystalline Macromolecular Design by Nitroxide‐Mediated Polymerization

The syntheses of PODA‐b‐PMA and PODA‐grad‐PMA copolymers using NMP are reported for the first time. The gradient copolymerization of ODA and MA was performed in a semi‐batch system with a continuous addition of MA during ODA polymerization. The results showed that the semi‐batch NMP proceeded in a living fashion, producing well‐defined copolymers with narrow polydispersities and controlled molecular weights. The potentially semicrystalline copolymers were characterized by techniques such as ¹H NMR, SEC and DSC. Their surface crystallization has also been studied by AFM.

     

A novel miniaturized multimodal bioreactor for continuous in situ assessment of bioartificial cardiac tissue during stimulation and maturation

Stem cell-based cardiac tissue engineering is a promising approach for regenerative therapy of the injured heart. At present, the small number of stem cell-derived cardiomyocytes that can be obtained using current culture and enrichment techniques represents one of the key limitations for the development of functional bioartificial cardiac tissue (BCT). We have addressed this problem by construction of a novel bioreactor with functional features of larger systems that enables the generation and in situ monitoring of miniaturized BCTs. BCTs were generated from rat cardiomyocytes to demonstrate advantages and usefulness of the bioreactor. Tissues showed spontaneous, synchronized contractions with cell orientation along the axis of strain. Cyclic stretch induced cardiomyocyte hypertrophy, demonstrated by a shift of myosin heavy chain expression from the alpha to beta isoform, together with elevated levels of atrial natriuretic factor. Stretch led to a moderate increase in systolic force (1.42?±?0.09?mN vs. 0.96?±?0.09?mN in controls), with significantly higher forces observed after β-adrenergic stimulation with noradrenalin (2.54?±?0.11?mN). Combined mechanical and β-adrenergic stimulation had no synergistic effect. This study demonstrates for the first time that mechanical stimulation and direct real-time contraction force measurement can be combined into a single multimodal bioreactor system, including electrical stimulation of excitable tissue, perfusion of the culture chamber, and the possibility of (fluorescence) microscopic assessment during continuous cultivation. Thus, this bioreactor represents a valuable tool for monitoring tissue development and, ultimately, the optimization of stem cell-based tissue replacement strategies in regenerative medicine.     

Age at onset of psychotic disorder: Cannabis,BDNF Val66Met,and sex‐specific models of gene–environment interaction

Discovering modifiable predictors for age at onset may help to identify predictors of transition to psychotic disorder in the “at‐risk mental state.” Inconsistent effects of sex, BDNF Val66Met (rs6265), and cannabis use on age of onset were previously reported. BDNF Val66Met and cannabis use before illness onset were retrospectively assessed in a sample of 585 patients with schizophrenia and their association with age at onset was evaluated. Cannabis use was significantly associated with earlier age at onset of psychotic disorder (AOP; average difference 2.7 years, P < 0.001), showing dose–response effects with higher frequency and earlier age at first use. There was a weak association between BDNF Val66Met genotype and AOP (difference 1.2 years; P = 0.050). No evidence was found for BDNF × cannabis interaction (interaction χ²(1) = 0.65, P = 0.420). However, a significant BDNF × cannabis × sex interaction was found (interaction χ²(1) = 4.99, P = 0.026). In female patients, cannabis use was associated with earlier AOP in BDNF Met‐carriers (difference 7 years), but not in Val/Val‐genotypes. In male patients, cannabis use was associated with earlier AOP irrespective of BDNF Val66Met genotype (difference 1.3 years). BDNF Val66Met genotype in the absence of cannabis use did not influence AOP, neither in female or male patients with psychotic disorder. Complex interactions between cannabis and BDNF may shape age at onset in female individuals at risk of psychotic disorder. No compelling evidence was found that BDNF genotype is associated with age at onset of psychotic disorder in the absence of cannabis use. © 2011 Wiley‐Liss, Inc.