Variegated silencing through epigenetic modifications of a large Xq region in a case of balanced X;2 translocation with Incontinentia Pigmenti-like phenotype

Molecular mechanisms underlying aberrant phenotypes in balanced X;autosome translocations are scarcely understood. We report the case of a de novo reciprocal balanced translocation X;2(q23;q33) presenting phenotypic alterations highly suggestive of Incontinentia Pigmenti (IP) syndrome, a genodermatosis with abnormal skin pigmentation and neurological failure, segregating as X-linked dominant disorder. Through molecular studies, we demonstrated that the altered phenotype could not be ascribed to chromosome microdeletions or to XIST-mediated inactivation of Xq24-qter. Interestingly, we found that the Xq24-qter region, which translocated downstream of the heterochromatic band 2q34, undergoes epigenetic silencing mediated by DNA methylation and histone alterations. Among the downregulated genes, we found the inhibitor of kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG/NEMO), the causative gene of IP. We hypothesize that a mosaic functional nullisomy of the translocated genes, through a Position Effect Variegation-like heterochromatization, might be responsible for the proband's phenotypic anomalies. Partial silencing of IKBKG may be responsible for the skin anomalies observed, thereby mimicking the IP pathological condition. In addition to its clinical relevance, this paper addresses fundamental issues related to the chromatin status and nuclear localization of a human euchromatic region translocated proximally to heterochromatin. In conclusion, the study provides new insight into long-range gene silencing mechanisms and their direct impact in human disease.     

Relationship between Periodontitis and Pre-Eclampsia: A Meta-Analysis

Background

Studies have suggested controversial results regarding a possible association between pre-eclampsia (PE) and periodontal disease (PD) and no meta-analysis has been performed to clarify this issue.

Methods

A literature search of electronic databases was performed for articles published through March 24, 2013, followed by a manual search of several dental and medical journals. The meta-analysis was conducted according to the recommendations of the Cochrane Collaboration and PRISMA. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed with the χ²-based Cochran Q test and I² statistic. The level of significance was set at P <0.05.

Results

Fifteen studies were included, including three cohort and 12 case-control studies. A positive association was found between PE and PD (OR 2.17, 95% CI 1.38–3.41, P = 0.0008). However, a high and significant heterogeneity was found (χ² = 62.42, P<0.00001, I² = 75%). In most cases, subgroup analysis had low power to detect significant differences between PE and non-PE groups.

Conclusion

Based on the findings of the meta-analysis, PD appears to be a possible risk factor for PE. However, given the important differences in the definitions and diagnoses of PD and PE among the studies, as well as their lack of good methodological quality, future trials are needed to confirm the results of the present meta-analysis.     

Identification of risk factors of severe hypersensitivity reactions in general anaesthesia

Background

Hypersensitivity reactions to anaesthetic agents are rare but often severe, with a mortality ranging from 4 to 9% in IgE-mediated events. Identification of the risk factors may contribute to limit the incidence of these reactions. The aim of our study was to search for possible risk factors of severe perioperative hypersensitivity reactions in our study population.

Methods

For this study we retrospectively reviewed data from 193 patients who experienced drug hypersensitivity reactions during general anaesthesia. The diagnostic protocol consisted of 1) history of the reaction, 2) measurement of serum baseline tryptase and specific IgE-assays for latex, beta-lactams and succinylcholine, 3) skin tests for the agents listed in the anaesthesia chart and for others likely to be safe for future use, latex, and others medications administered during the perioperative period (i.e. antibiotics), 4) subdivision of our patients on the basis of two criteria: a) grade of severity of clinical reactions according to the Ring and Messmer classification; b) results of skin tests and/or serum specific IgE-assays.

Results

One hundred of 193 patients had reactions of grade I, 32/193 patients had reactions of grade II, 55/193 patients had reactions of grade III and 6/193 patients had reactions of grade IV. A diagnosis of IgE-mediated reaction was established in 55 cases (28.50%); the most common causes were neuromuscular blocking agents, followed by latex and beta-lactams. Severe reactions were associated with older age (p = 0.025), asthma (p = 0.042), history of hypertension (p = 0.001), intake of serum angiotensin converting enzyme inhibitor medication (p = 0.012) or serum angiotensin II antagonist (p = 0.033), higher levels of basal tryptase (p = 0.0211). Cardiovascular symptoms (p = 0.006) and history of hypersensitivity to antibiotics (p = 0.029) were more frequently reported in IgE-mediated reactions.

Conclusions

We confirmed the relevance of several clinical features as risk factors for anaphylactic reactions induced by anaesthetic agents: older age, asthma, hypertension and antihypertensive drugs. We observed increased levels of serum basal tryptase in severe reactions: this finding may signify that this biomarker is useful for the identification of patients at risk.

Electronic supplementary material

The online version of this article (doi:10.1186/s12948-015-0017-9) contains supplementary material, which is available to authorized users.     

Mistletoe Infection in an Oak Forest Is Influenced by Competition and Host Size

Host size and distance from an infected plant have been previously found to affect mistletoe occurrence in woody vegetation but the effect of host plant competition on mistletoe infection has not been empirically tested. For an individual tree, increasing competition from neighbouring trees decreases its resource availability, and resource availability is also known to affect the establishment of mistletoes on host trees. Therefore, competition is likely to affect mistletoe infection but evidence for such a mechanism is lacking. Based on this, we hypothesised that the probability of occurrence as well as the abundance of mistletoes on a tree would increase not only with increasing host size and decreasing distance from an infected tree but also with decreasing competition by neighbouring trees. Our hypothesis was tested using generalized linear models (GLMs) with data on Loranthus europaeus Jacq., one of the two most common mistletoes in Europe, on 1015 potential host stems collected in a large fully mapped plot in the Czech Republic. Because many trees were multi-stemmed, we ran the analyses for both individual stems and whole trees. We found that the probability of mistletoe occurrence on individual stems was affected mostly by stem size, whereas competition had the most important effects on the probability of mistletoe occurrence on whole trees as well as on mistletoe abundance. Therefore, we confirmed our hypothesis that competition among trees has a negative effect on mistletoe occurrence.     

Need for Cognitive Closure Modulates How Perceptual Decisions Are Affected by Task Difficulty and Outcome Relevance

The aim of this study was to assess the extent to which Need for Cognitive Closure (NCC), an individual-level epistemic motivation, can explain inter-individual variability in the cognitive effort invested on a perceptual decision making task (the random motion task). High levels of NCC are manifested in a preference for clarity, order and structure and a desire for firm and stable knowledge. The study evaluated how NCC moderates the impact of two variables known to increase the amount of cognitive effort invested on a task, namely task ambiguity (i.e., the difficulty of the perceptual discrimination) and outcome relevance (i.e., the monetary gain associated with a correct discrimination). Based on previous work and current design, we assumed that reaction times (RTs) on our motion discrimination task represent a valid index of effort investment. Task ambiguity was associated with increased cognitive effort in participants with low or medium NCC but, interestingly, it did not affect the RTs of participants with high NCC. A different pattern of association was observed for outcome relevance; high outcome relevance increased cognitive effort in participants with moderate or high NCC, but did not affect the performance of low NCC participants. In summary, the performance of individuals with low NCC was affected by task difficulty but not by outcome relevance, whereas individuals with high NCC were influenced by outcome relevance but not by task difficulty; only participants with medium NCC were affected by both task difficulty and outcome relevance. These results suggest that perceptual decision making is influenced by the interaction between context and NCC.     

Characterization of the major allergen of plum as a lipid transfer protein

Background: Allergy to Prunoideae fruit (plum, peach, cherry and apricot) is one of the most frequent food allergies in southern Europe. All these fruits cross-react in vivo and in vitro, as they share their major allergen, a 9 kD lipid transfer protein (LTP). Objective: The aim of the study was the identification and molecular characterization of the major allergen of plum. Methods: The IgE pattern of reactivity to plums was investigated by SDS–PAGE and immunoblotting with the sera of 23 patients. The identified major allergen was purified by HPLC, using a cationic-exchange column followed by gel-filtration. Further characterization was achieved by periodic-Schiff stain, isoelectrofocusing and N-terminal amino acid sequencing. Results and conclusions: The major allergen of plum is a 9 kD lipid transfer protein, not glycosylated and with a basic character (pI>9), highly homologous to the major allergen of peach.