Childhood maltreatment is an important risk factor for adult depression and has been associated with changes in the hypothalamic pituitary adrenal (HPA) axis, including cortisol secretion and ...methylation of the
gene. Furthermore, associations between depression and HPA changes have been reported. This study investigated the associations of whole-blood
mRNA levels, serum cortisol levels, childhood maltreatment, and depressive symptoms with the whole-blood methylation status (assessed via target bisulfite sequencing) of 105 CpGs at the
locus using data from the general population-based Study of Health in Pomerania (SHIP) (
= 203). Both direct and interaction effects with the rs1360780 single-nucleotide polymorphism were investigated. Nominally significant associations of main effects on methylation of a single CpG site were observed at intron 3, intron 7, and the 3'-end of the gene. Additionally, methylation at two clusters at the 3'-end and intron 7 were nominally associated with childhood maltreatment × rs1360780 and depressive symptoms × rs1360780, respectively. The results add to the understanding of molecular mechanisms underlying the emergence of depression and could aid the development of personalised depression therapy and drug development.
Alzheimer's disease (AD) is a progressive neurodegenerative disease representing the most common type of dementia in older adults. The major risk factors include increased age, genetic predisposition ...and socioeconomic factors. Among the genetic factors, the apolipoprotein E (ApoE) ε4 allele poses the greatest risk. Growing evidence suggests that cerebrovascular dysfunctions, including blood-brain barrier (BBB) leakage, are also linked to AD pathology. Within the scope of this paper, we, therefore, look upon the relationship between ApoE, BBB integrity and AD. In doing so, both brain-derived and peripheral ApoE will be considered. Despite the considerable evidence for the involvement of brain-derived ApoE ε4 in AD, information about the effect of peripheral ApoE ε4 on the central nervous system is scarce. However, a recent study demonstrated that peripheral ApoE ε4 might be sufficient to impair brain functions and aggravate amyloid-beta pathogenesis independent from brain-based ApoE ε4 expression. Building upon recent literature, we provide an insight into the latest research that has enhanced the understanding of how ApoE ε4, secreted either in the brain or the periphery, influences BBB integrity and consequently affects AD pathogenesis. Subsequently, we propose a pathway model based on current literature and discuss future research perspectives.
Introduction
Sleep is increasingly recognized as a major risk factor for neurodegenerative disorders such as Alzheimer's disease (AD).
Methods
Using an magnetic resonance imaging (MRI)–based AD score ...based on clinical data from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) case‐control cohort, we investigated the associations between polysomnography‐based sleep macro‐architecture and AD‐related brain atrophy patterns in 712 pre‐symptomatic, healthy subjects from the population‐based Study of Health in Pomerania.
Results
We identified a robust inverse association between slow‐wave sleep and the AD marker (estimate: −0.019; 95% confidence interval: −0.03 to −0.0076; false discovery rate FDR = 0.0041), as well as with gray matter (GM) thicknesses in typical individual cortical AD‐signature regions. No effects were identified regarding rapid eye movement or non–rapid eye movement (NREM) stage 2 sleep, and NREM stage 1 was positively associated with GM thickness, mainly in the prefrontal cortical regions.
Discussion
There is a cross‐sectional relationship between AD‐related neurodegenerative patterns and the proportion of sleep spent in slow‐wave sleep.
Imbalance in the 3D structure of plants can be an important indicator of insufficient light or nutrient supply, as well as excessive wind, (formerly present) physical barriers, neighbor or storm ...damage. It can also be a simple means to detect certain illnesses, since some diseases like the apple proliferation disease, an infection with the barley yellow dwarf virus or plant canker can cause abnormal growth, like “witches' brooms” or burls, resulting in a deviating 3D plant architecture. However, quantifying imbalance of plant growth is not an easy task, and it requires a mathematically sound 3D model of plants to which imbalance indices can be applied. Current models of plants are often based on stacked cylinders or voxel matrices and do not allow for measuring the degree of 3D imbalance in the branching structure of the whole plant.
On the other hand, various imbalance indices are readily available for so-called graph-theoretical trees and are frequently used in areas like phylogenetics and computer science. While only some basic ideas of these indices can be transferred to the 3D setting, graph-theoretical trees are a logical foundation for 3D plant models that allow for elegant and natural imbalance measures.
In this manuscript, our aim is thus threefold: We first present a new graph-theoretical 3D model of plants and discuss desirable properties of imbalance measures in the 3D setting. We then introduce and analyze eight different 3D imbalance indices and their properties. Thirdly, we illustrate all our findings using a data set of 63 bush beans. Moreover, we implemented all our indices in the publicly available R-software package treeDbalance accompanying this manuscript. Using this software package, all presented 3D imbalance indices can be computed in linear time (depending on the size of the 3D plant model), and the package also provides an implementation of the algorithm to obtain a perfectly balanced version of a given 3D plant model (also in linear time).
Display omitted
•New graph-theoretical approach to 3D plant modeling.•Introduction and analysis of eight 3D imbalance indices.•Data set of 3D bean models (freely available).•Accompanying R-software package treeDbalance (freely available).
QUIDDICH: QUick IDentification of DIagnostic CHaracters Kühn, A. Luise; Haase, Martin
Journal of zoological systematics and evolutionary research,
February 2020, 2020-02-00, 20200201, Letnik:
58, Številka:
1
Journal Article
Recenzirano
Odprti dostop
With the advent of molecular genetic methods, an increasing number of morphologically cryptic taxa has been discovered. The majority of them, however, remains formally undescribed and without a ...proper name although their importance in ecology and evolution is increasingly being acknowledged. Despite suggestions to complement traditional descriptions with genetic characters, the taxonomic community appears to be reluctant to adopt this proposition. As an incentive, we introduce QUIDDICH, a tool for the QUick IDentification of DIgnostic CHaracters, which automatically scans a DNA or amino acid alignment for those columns that allow to distinguish taxa and classifies them into four different types of diagnostic characters. QUIDDICH is a system‐independent, fast and user‐friendly tool that requires few manual steps and provides a comprehensive output, which can be included in formal taxonomic descriptions. Thus, cryptic taxa do not have to remain in taxonomic crypsis and, bearing a proper name, can readily be included in biodiversity assessments and ecological and evolutionary analyses. QUIDDICH can be obtained from the comprehensive R archive network (CRAN, https://cran.r-project.org/package=quiddich).
To facilitate the incorporation of genetic characters into taxonomic descriptions, in particular of morphologically cryptic taxa, we developed QUIDDICH, an R package for the QUick IDentification of DIgnostic CHaracters. QUIDDICH identifies and tabs those columns in an alignment that allow to distinguish taxa and classifies them into four different types of diagnostic characters. Thus, cryptic taxa do not have to remain in taxonomic crypsis and, bearing a proper name, can be included in biodiversity assessments and ecological and evolutionary analyses.
Although the common pathology of Alzheimer's disease (AD) and white matter hyperintensities (WMH) is disputed, the gene
has been implicated in both conditions: its whole-blood gene expression was ...associated with WMH volume and its missense variant rs3747742 with AD risk. We re-examined those associations within one comprehensive dataset of the general population, additionally searched for cross-relations and illuminated the role of the apolipoprotein E (
) ε4 status in the associations. For our linear regression and linear mixed effect models, we used 1949 participants from the Study of Health in Pomerania (Germany). AD was assessed using a continuous pre-symptomatic MRI-based score evaluating a participant's AD-related brain atrophy. In our study, increased whole-blood
gene expression was significantly associated with reduced WMH volume but not with the AD score. Conversely, rs3747742-C was significantly associated with a reduced AD score but not with WMH volume. The
status did not influence the associations. In sum,
robustly associated with WMH volume and AD-related brain atrophy on different molecular levels. Our results thus underpin
's role in neurodegeneration, might point to its involvement in AD and WMH via different biological mechanisms, and highlight
as a worthwhile target for disentangling the two pathologies.
To analyse the prevalence, incidence and clinical relevance of pancreatic cysts detected as incidental finding in a population-based longitudinal study.
A total of 1077 participants (521 men, mean ...age 55.8±12.8 years) of 2333 participants from the population-based Study of Health in Pomerania (SHIP) underwent magnetic resonance cholangiopancreaticography (MRCP) at baseline (2008-2012). MRCP was analysed for pancreatic cysts with a diameter ≥2 mm. 676/1077 subjects received a 5-year follow-up (2014-2016). The prevalence and incidence of pancreatic cysts (weighted for study participation) were assessed in association to age, gender and suspected epidemiological risk factors. Mortality follow-up was performed in 2015 for all SHIP participants (mean follow-up period 5.9 years, range 3.2-7.5 years).
At baseline pancreatic cysts had a weighted prevalence of 49.1%, with an average number of 3.9 (95% CI 3.2 to 4.5) cysts per subject in the subgroup harbouring cysts. Cyst size ranged from 2 to 29 mm. Prevalence (p<0.001), number (p=0.001) and maximum size (p<0.001) increased significantly with age. The 5-year follow-up revealed a weighted incidence of 12.9% newly detected pancreatic cysts. 57.1% of the subjects initially harbouring pancreatic cysts showed an increase in number and/or maximum cyst size. Of all subjects undergoing MRCP, no participant died of pancreatic diseases within mortality follow-up.
The prevalence of pancreatic cysts in the general population is unexpectedly high, and their number and size increase with age. Overall, no pancreatic cancer was observed in this collective during a 5-year follow-up. Nevertheless, prospective follow-up imaging showed minimal progress in more than 50%. Only about 6% of cysts and 2.5% of the study group initially presented with cysts of more than 1 cm and thus might be clinically meaningful.
Purpose To quantify liver fat and liver iron content by measurement of confounder-corrected proton density fat fraction (PDFF) and R2* and to identify clinical associations for fatty liver disease ...and liver iron overload and their prevalence in a large-scale population-based study. Materials and Methods From 2008 to 2013, 2561 white participants (1336 women; median age, 52 years; 25th and 75th quartiles, 42 and 62 years) were prospectively recruited to the Study of Health in Pomerania (SHIP). Complex chemical shift-encoded magnetic resonance (MR) examination of the liver was performed, from which PDFF and R2* were assessed. On the basis of previous histopathologic calibration, participants were stratified according to their liver fat and iron content as follows: none (PDFF, ≤5.1%; R2*, ≤41.0 sec
), mild (PDFF, >5.1%; R2*, >41 sec
), moderate (PDFF, >14.1%; R2*, >62.5 sec
), high (PDFF: >28.0%; R2*: >70.1 sec
). Prevalence of fatty liver diseases and iron overload was calculated (weighted by probability of participation). Clinical associations were identified by using boosting for generalized linear models. Results Median PDFF was 3.9% (range, 0.6%-41.5%). Prevalence of fatty liver diseases was 42.2% (1082 of 2561 participants); mild, 28.5% (730 participants); moderate, 12.0% (307 participants); high content, 1.8% (45 participants). Median R2* was 34.4 sec
(range, 14.0-311.8 sec
). Iron overload was observed in 17.4% (447 of 2561 participants; mild, 14.7% 376 participants; moderate, 0.8% 20 participants; high content, 2.0% 50 participants). Liver fat content correlated with waist-to-height ratio, alanine transaminase, uric acid, serum triglycerides, and blood pressure. Liver iron content correlated with mean serum corpuscular hemoglobin, male sex, and age. Conclusion In a white German population, the prevalence of fatty liver diseases and liver iron overload is 42.2% (1082 of 2561) and 17.4% (447 of 2561). Whereas liver fat is associated with predictors related to the metabolic syndrome, liver iron content is mainly associated with mean serum corpuscular hemoglobin.
RSNA, 2017 Online supplemental material is available for this article.
Objectives
To identify a possible association between repeated intravenous administration of gadobutrol and increased signal intensity in the grey and white matter using voxel-based whole-brain ...analysis.
Methods
In this retrospective single-centre study, 217 patients with a clinically isolated syndrome underwent baseline brain magnetic resonance imaging and at least one annual follow-up examination with intravenous administration of 0.1 mmol/kg body weight of gadobutrol. Using the “Diffeomorphic Anatomical Registration using Exponentiated Lie algebra” (DARTEL) normalisation process, tissue templates for grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were calculated, as were GM-CSF and WM-CSF ratios. Voxel-based whole-brain analysis was used to calculate the signal intensity for each voxel in each data set. Paired t-test was applied to test differences to baseline MRI for significance.
Results
Voxel-based whole-brain analysis demonstrated no significant changes in signal intensity of grey and white matter after up to five gadobutrol administrations. There was no significant change in GM-CSF and grey WM-CSF ratios.
Conclusion
Voxel-based whole-brain analysis did not demonstrate increased signal intensity of GM and WM on unenhanced T1-weighted images after repeated gadobutrol administration. The molecular structure of gadolinium-based contrast agent preparations may be an essential factor causing SI increase on unenhanced T1-weighted images.
Key points
•
Repeated administration of gadobutrol does not lead to increased signal intensity.
•
Voxel-based whole-brain analysis allows assessment of subtle changes in signal intensity.
•
Macrocyclic contrast agents in a proven dosage are safe.
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