| 1. |
- Molin, Anna-Maja, et al.
(author)
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A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features
- 2012
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In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 49:2, s. 104-109
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Journal article (peer-reviewed)abstract
- Background Congenital deletions affecting 3q11q23 have rarely been reported and only five cases have been molecularly characterised. Genotype. phenotype correlation has been hampered by the variable sizes and breakpoints of the deletions. In this study, 14 novel patients with deletions in 3q11q23 were investigated and compared with 13 previously reported patients. Methods Clinical data were collected from 14 novel patients that had been investigated by high resolution microarray techniques. Molecular investigation and updated clinical information of one cytogenetically previously reported patient were also included. Results The molecular investigation identified deletions in the region 3q12.3q21.3 with different boundaries and variable sizes. The smallest studied deletion was 580 kb, located in 3q13.31. Genotype. phenotype comparison in 24 patients sharing this shortest region of overlapping deletion revealed several common major characteristics including significant developmental delay, muscular hypotonia, a high arched palate, and recognisable facial features including a short philtrum and protruding lips. Abnormal genitalia were found in the majority of males, several having micropenis. Finally, a postnatal growth pattern above the mean was apparent. The 580 kb deleted region includes five RefSeq genes and two of them are strong candidate genes for the developmental delay: DRD3 and ZBTB20. Conclusion A newly recognised 3q13.31 microdeletion syndrome is delineated which is of diagnostic and prognostic value. Furthermore, two genes are suggested to be responsible for the main phenotype.
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| 4. |
- Parts, Leopold, et al.
(author)
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Revealing the genetic structure of a trait by sequencing a population under selection.
- 2011
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In: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 21:7, s. 1131-8
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Journal article (peer-reviewed)abstract
- One approach to understanding the genetic basis of traits is to study their pattern of inheritance among offspring of phenotypically different parents. Previously, such analysis has been limited by low mapping resolution, high labor costs, and large sample size requirements for detecting modest effects. Here, we present a novel approach to map trait loci using artificial selection. First, we generated populations of 10-100 million haploid and diploid segregants by crossing two budding yeast strains of different heat tolerance for up to 12 generations. We then subjected these large segregant pools to heat stress for up to 12 d, enriching for beneficial alleles. Finally, we sequenced total DNA from the pools before and during selection to measure the changes in parental allele frequency. We mapped 21 intervals with significant changes in genetic background in response to selection, which is several times more than found with traditional linkage methods. Nine of these regions contained two or fewer genes, yielding much higher resolution than previous genomic linkage studies. Multiple members of the RAS/cAMP signaling pathway were implicated, along with genes previously not annotated with heat stress response function. Surprisingly, at most selected loci, allele frequencies stopped changing before the end of the selection experiment, but alleles did not become fixed. Furthermore, we were able to detect the same set of trait loci in a population of diploid individuals with similar power and resolution, and observed primarily additive effects, similar to what is seen for complex trait genetics in other diploid organisms such as humans.
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| 5. |
- Grüne, L., et al.
(author)
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Event-based control
- 2014
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In: Control Theory of Digitally Networked Dynamic Systems. - Heidelberg : Springer International Publishing. - 9783319011318 - 9783319011301 ; , s. 169-261
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Book chapter (other academic/artistic)abstract
- Event-based control is a control methodology that is currently being developed as a means to reduce the communication between the sensors, the controller and the actuators in a control loop. The sampling instants are not determined periodically by a clock, but by an event generator, which adapts the information flow in the feedback loop to the current behavior of the closed-loop system. A communication among the components is invoked only after an event has indicated that the control error exceeds a tolerable bound.
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| 6. |
- Jakesevic, Maja, et al.
(author)
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Antioxidative protection of dietary bilberry, chokeberry and Lactobacillus plantarum HEAL19 in mice subjected to intestinal oxidative stress by ischemia-reperfusion
- 2011
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In: BMC Complementary and Alternative Medicine. - : Springer Science and Business Media LLC. - 1472-6882. ; 11
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Journal article (peer-reviewed)abstract
- Background: Ischemia-reperfusion (I/R) in the intestines is an inflammatory condition which activates leukocytes and reactive oxygen species (ROS) and leads to lipid peroxidation and DNA damage. Bilberry and chokeberry fruits are rich sources of polyphenols which may act as antioxidants and prevent lipid peroxidation. Lactic acid bacteria (LAB) may improve microbial status in the intestines and increase the metabolic activity towards polyphenolic degradation. The aim of the study was to clarify antioxidative effects of bilberry and chokeberry fruits alone and with addition of a LAB-strain, Lactobacillus plantarum HEAL19, in an I/R-model in mice. Methods: Male BALB/cJ mice were fed the experimental diets for 10 days. Diets consisted of standard chow supplemented with either bilberry (Vaccinium myrtillus) or chokeberry (Aronia x prunifolia) powder alone or in combination with the LAB-strain Lactobacillus plantarum HEAL19. I/R-injury was induced by holding superior mesenteric artery clamped for 30 minutes followed by reperfusion for 240 minutes. Thereafter, colonic and caecal tissues and contents were collected. Malondialdehyde (MDA) was used as indicator of lipid peroxidation and was measured by a calorimetric assay, lactobacilli were cultured on Rogosa agar plates and Enterobacteriaceae on VRBG agar plates, anthocyanins and phenolic acids were analysed by HPLC-DAD-ESI-MSn. Results: MDA was significantly decreased in the colon of groups fed bilberry alone (p = 0.030) and in combination with L. plantarum HEAL19 (p = 0.021) compared to the IR-control but not in chokeberry-fed groups. Supplementation with bilberry or chokeberry alone reduced the total number of lactobacilli on the mucosa. Higher concentrations of anthocyanins were found in the colon than in the caecum content of mice. A more varied composition of different anthocyanins was also observed in the colon content compared to the caecum of bilberry-fed mice. Phenolic acids formed by microbial degradation of the dietary polyphenols in the gut could be detected. More phenolic metabolites were found in the intestines of bilberry-fed mice than in the chokeberry-fed ones. Conclusions: Bilberry alone and in combination with L. plantarum HEAL19 exerts a better protection against lipid peroxidation than chokeberry. These dietary supplements may be used to prevent or suppress oxidative stress.
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| 7. |
- Lopes Pinto, Fernando A, et al.
(author)
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All Transcriptome Sequencing of Reciprocal Chicken Crosses to Explore Monoallelic Expression
- 2014
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Other publication (peer-reviewed)abstract
- The Virginia Tech high-growth and low-growth selection lines of White Plymouth Rock chickens have been developed by more than 50 generations of divergent selection for body weight at 56 days of age. These lines have been extensively used for QTL mapping in order to reveal the genetic basis for the huge selection response. In order to further clarify the mechanisms for how QTLs control phenotypic differences, we measured allelic RNA expression ratios to detect differential expression between alleles derived from the two lines. Using whole transcriptome sequencing, we set out to detect allelic imbalance in the RNA expression of 6 F1 progeny from reciprocal crosses between S54 parents from the high and low parental lines. The detection of allelic imbalance provides evidence for cis-acting regulatory QTLs. This experimental design also allows us to detect parent-of-origin specific differential expression. Using RNA samples extracted from liver, hypothalamus and pectoralis major, we generated circa 250 M (100 bp) RNA sequencing reads per F1 individual. The latter allows us to predict and test obligatory heterozygous loci in the F1 birds. The coverage exceeds the sequencing depth shown necessary to allow for the reliable measurement of mRNA expression across all genes in the chicken genome. The liver showed the strongest reciprocal difference in F1 birds with more than 700 differentially expressed genes. A dedicated bioinformatics pipeline was developed to identify allelic imbalance among F1 birds and the results from this analysis will be presented during the meeting.
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| 8. |
- Lopes Pinto, Fernando A, et al.
(author)
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Whole Transcriptome Sequencing in Reciprocal Crosses Suggests Parent-of-Origin Effects on Gene Expression in the Chicken Genome
- 2014
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Other publication (other academic/artistic)abstract
- The Virginia Tech body weight lines have undergone more than 50 generations of divergent selection for 56-day body weight. In this experiment we test for the preferential expression of alleles from certain lines (cisacting effects) or parents (parent-of-origin effects) in six F1 individuals from reciprocal crosses of generation 54 parents. Using RNA samples extracted from liver, hypothalamus and breast muscle (Pectoralis major), we generated circa 250 million RNA sequencing reads per F1 individual as well as a 25-fold coverage DNA sequence of each of the parents. We identified 11338 line-specific SNPs in the RNA across the three tissues. Allelic imbalance was biased for the SNP allele corresponding to the reference genome with ~65% of the SNPs showing a significant imbalance at P < 0.05. The number of SNPs with parent-of-origin effects without allelic imbalance was between 500 and 650 for each tissue.
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| 9. |
- Molin, Mikael, 1973, et al.
(author)
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Linking peroxiredoxin and vacuolar-ATPase functions in calorie restriction-mediated life span extension
- 2014
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In: International Journal of Cell Biology. - : Hindawi Limited. - 1687-8876 .- 1687-8884.
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Research review (peer-reviewed)abstract
- Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H 2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases. © 2014 Mikael Molin and Ayse Banu Demir.
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| 10. |
- Molin, Staffan, et al.
(author)
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Microbial risk assessment in heterogeneous aquifers : 2. Infection risk sensitivity
- 2010
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In: Water resources research. - 0043-1397 .- 1944-7973. ; 46, s. W05519-
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Journal article (peer-reviewed)abstract
- The entire chain of events of human disease transmitted through contaminated water, from pathogen introduction into the source (E. coli, rotavirus, and Hepatitis A), pathogen migration through the aquifer pathway, to ingestion via a supply well, and finally, the potential infection in the human host, is investigated. The health risk calculations are based on a relevant hazardous event with safe setback distances estimated by considering the infection risk from peak exposure in compliance with an acceptable level defined by a regulatory agency. A site-specific hypothetical scenario is illustrated for an aquifer with similar characteristics as the Cape Cod site, Massachusetts (United States). Relatively large variation of safe distances for the three index pathogens is found; individually, none of the index pathogens could predict the safe distance under the wide range of conditions investigated. It is shown that colloid filtration theory (CFT) with spatially variable attachment-detachment rates yields significantly different results from the effective CFT model (i.e., assuming spatially constant parameters).
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| 11. |
- Simard, J. F., et al.
(author)
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Pediatric Organ Transplantation and Risk of Premalignant and Malignant Tumors in Sweden
- 2011
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 11:1, s. 146-151
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Journal article (peer-reviewed)abstract
- Increased cancer risks are well documented in adult organ transplant recipients. However, the spectrum of malignancies and risk in the pediatric organ transplant population are less well described. We identified all solid organ transplanted patients aged < 18 in Sweden between 1970-2007 (n = 536) in the National Patient Register and linked to the Cancer Register. Nationwide rates were used to calculate standardized incidence rate ratios and 95% CI estimating the association between transplant and cancer during maximum 36 years of follow-up. Nearly 7% of pediatric solid organ transplant recipients developed a premalignant or malignant tumor during follow-up. Transplantation was associated with an increased risk of any cancer (n = 24, SIR = 12.5, 95% CI: 8.0-18.6): non-Hodgkin lymphoma (NHL) (n = 13, SIR = 127, 95% CI: 68-217), renal cell (n = 3, SIR = 105, 95% CI: 22-307), vulva/vagina (n = 3, SIR = 665, 95% CI: 137-1934) and nonmelanoma skin cancers (n = 2, SIR = 64.7, 95% CI: 7.8-233.8). NHL typically appeared during childhood, while other tumors were diagnosed during adulthood. Apart from short-term attention toward the potential occurrence of NHL, our results suggest cancer surveillance into adulthood with special attention to skin, kidneys and the female genitalia.
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| 12. |
- Tormo-Badia, Neivis, et al.
(author)
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Antibiotic treatment of pregnant non-obese diabetic (NOD) mice leads to altered gut microbiota and intestinal immunological changes in the offspring.
- 2014
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In: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 80:4, s. 250-260
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Journal article (peer-reviewed)abstract
- The intestinal microbiota is important for tolerance induction through mucosal immunological responses. The composition of the gut microbiota of an infant is affected by environmental factors like diet, disease and antibiotic treatment. However, already in utero these environmental factors can affect the immunological development of the fetus and influence the future gut microbiota of the infant. To investigate the effects of antibiotic treatment of pregnant mothers on the offspring's gut microbiome and diabetes development, we treated non-obese diabetic (NOD) mice with a cocktail of antibiotics during gestation and the composition of the gut microbiota, diabetes incidence and major gut-related T lymphocyte populations were investigated in the offspring. We observed a persistent reduction in the general diversity of the gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared to offspring from control mothers. In addition, by clustering the present bacterial taxa with principal component analysis we found a differential clustering of gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared to offspring from control mothers. Offspring from NOD mothers treated with antibiotics during gestation also showed some immunological alterations in the gut immune system, which could be related to the diversity of the gut microbiome and influence modulation of diabetes development at 20 weeks. Our data point out maternal derangement of the intestinal microbiota as a potential environmental risk factor for T1D development. This article is protected by copyright. All rights reserved.
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