| 1. |
- Enroth, Stefan, et al.
(author)
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A strand specific high resolution normalization method for chip-sequencing data employing multiple experimental control measurements
- 2012
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In: Algorithms for Molecular Biology. - : Springer Science and Business Media LLC. - 1748-7188. ; 7, s. 2-
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Journal article (peer-reviewed)abstract
- Background: High-throughput sequencing is becoming the standard tool for investigating protein-DNA interactions or epigenetic modifications. However, the data generated will always contain noise due to e. g. repetitive regions or non-specific antibody interactions. The noise will appear in the form of a background distribution of reads that must be taken into account in the downstream analysis, for example when detecting enriched regions (peak-calling). Several reported peak-callers can take experimental measurements of background tag distribution into account when analysing a data set. Unfortunately, the background is only used to adjust peak calling and not as a preprocessing step that aims at discerning the signal from the background noise. A normalization procedure that extracts the signal of interest would be of universal use when investigating genomic patterns.Results: We formulated such a normalization method based on linear regression and made a proof-of-concept implementation in R and C++. It was tested on simulated as well as on publicly available ChIP-seq data on binding sites for two transcription factors, MAX and FOXA1 and two control samples, Input and IgG. We applied three different peak-callers to (i) raw (un-normalized) data using statistical background models and (ii) raw data with control samples as background and (iii) normalized data without additional control samples as background. The fraction of called regions containing the expected transcription factor binding motif was largest for the normalized data and evaluation with qPCR data for FOXA1 suggested higher sensitivity and specificity using normalized data over raw data with experimental background.Conclusions: The proposed method can handle several control samples allowing for correction of multiple sources of bias simultaneously. Our evaluation on both synthetic and experimental data suggests that the method is successful in removing background noise.
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| 2. |
- Gustafsson, Claes G. R., 1965, et al.
(author)
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Phylogenetic relationships among species of the neotropical genus Randia (Rubiaceae, Gardenieae) inferred from molecular and morphological data.
- 2002
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In: Taxon. ; 51:4, s. 661-674
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Journal article (peer-reviewed)abstract
- Relationships among 38 taxa of Randia (Rubiaceae, Gardenieae) are estimated using nuclear ribosomal internal transcribed spacers (ITS), the 5S non-transcribed spacer (5S-NTS), and six morphological characters. In addition to Randia, 13 species from eight related genera in Gardenieae (four African, four neotropical) formed the ingroup. Three species from three more distantly related genera in Gardenieae (one African, two neotropical) were chosen as the outgroup. Representatives of the African ingroup genera Calochone, Macrosphyra, Oligocodon and Preussiodora formed a well supported monophyletic group as did the neotropical genera Rosenbergiodendron, Sphinctanthus and Tocoyena. Only when including morphological characters did Randia form a monophyletic group corresponding approximately to contemporary circumscription of the genus, but in this analysis Casasia appears sister to a group of Mexican, Central American, and Antillean Randia. There is no strong jackknife support, however, for either Randia or Casasia to be monophyletic. It is concluded that Randia is comprised of several distinct groups, each with its own geographical distribution. One group of Mexican, Central American, and Antillean Randia, including the type species, can be recognized as Randia in a strict sense. Two other South American groups can be recognized as separate taxa. One of these groups comprises mainly lowland species, and the second is comprised of strictly Andean species.
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| 3. |
- Gustafsson, Karin L., 1987, et al.
(author)
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The role of membrane ER alpha signaling in bone and other major estrogen responsive tissues
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Estrogen receptor a (ER alpha) signaling leads to cellular responses in several tissues and in addition to nuclear ER alpha-mediated effects, membrane ER alpha (mER alpha) signaling may be of importance. To elucidate the significance, in vivo, of mER alpha signaling in multiple estrogen-responsive tissues, we have used female mice lacking the ability to localize ER alpha to the membrane due to a point mutation in the palmitoylation site (C451A), so called Nuclear-Only-ER (NOER) mice. Interestingly, the role of mER alpha signaling for the estrogen response was highly tissue-dependent, with trabecular bone in the axial skeleton being strongly dependent (>80% reduction in estrogen response in NOER mice), cortical and trabecular bone in long bones, as well as uterus and thymus being partly dependent (40-70% reduction in estrogen response in NOER mice) and effects on liver weight and total body fat mass being essentially independent of mER alpha (<35% reduction in estrogen response in NOER mice). In conclusion, mER alpha signaling is important for the estrogenic response in female mice in a tissue-dependent manner. Increased knowledge regarding membrane initiated ER alpha actions may provide means to develop new selective estrogen receptor modulators with improved profiles.
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| 4. |
- Movérare-Skrtic, Sofia, et al.
(author)
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The bone-sparing effects of estrogen and WNT16 are independent of each other
- 2015
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:48, s. 14972-14977
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Journal article (peer-reviewed)abstract
- Wingless-type MMTV integration site family (WNT)16 is a key regulator of bone mass with high expression in cortical bone, and Wnt16-/- mice have reduced cortical bone mass. As Wnt16 expression is enhanced by estradiol treatment, we hypothesized that the bone-sparing effect of estrogen in females isWNT16-dependent. This hypothesis was tested in mechanistic studies using two genetically modified mouse models with either constantly high osteoblastic Wnt16 expression or no Wnt16 expression. We developed a mouse model with osteoblast-specific Wnt16 overexpression (Obl-Wnt16). These mice had several-fold elevated Wnt16 expression in both trabecular and cortical bone compared with wild type (WT) mice. Obl- Wnt16 mice displayed increased total body bone mineral density (BMD), surprisingly caused mainly by a substantial increase in trabecular bone mass, resulting in improved bone strength of vertebrae L3. Ovariectomy (ovx) reduced the total body BMD and the trabecular bone mass to the same degree in Obl-Wnt16 mice and WT mice, suggesting that the bone-sparing effect of estrogen is WNT16-independent. However, these bone parameters were similar in ovx Obl- Wnt16 mice and sham operated WT mice. The role of WNT16 for the bone-sparing effect of estrogen was also evaluated in Wnt16-/- mice. Treatment with estradiol increased the trabecular and cortical bone mass to a similar extent in both Wnt16-/- and WT mice. In conclusion, the bone-sparing effects of estrogen and WNT16 are independent of each other. Furthermore, loss of endogenous WNT16 results specifically in cortical bone loss, whereas overexpression of WNT16 surprisingly increases mainly trabecular bone mass. WNT16- targeted therapies might be useful for treatment of postmenopausal trabecular bone loss.
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| 5. |
- Ohlsson, Claes, 1965, et al.
(author)
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The effects of estradiol are modulated in a tissue-specific manner in mice with inducible inactivation of ERα after sexual maturation.
- 2020
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 318:5, s. 646-654
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Journal article (peer-reviewed)abstract
- Mouse models with lifelong inactivation of estrogen receptor α (ERα) show that ERα is the main mediator of estrogenic effects in bone, thymus, uterus, and fat. However, ERα inactivation early in life may cause developmental effects that confound the adult phenotypes. To address the specific role of adult ERα expression for estrogenic effects in bone and other non-skeletal tissues, we established a tamoxifen-inducible ERα-inactivated model by crossing CAG-Cre-ER and ERαflox/flox mice. Tamoxifen-induced ERα-inactivation after sexual maturation substantially reduced ERα mRNA levels in cortical bone, trabecular bone, thymus, uterus, gonadal fat, and hypothalamus, in CAG-Cre-ERαflox/flox (inducible ERαKO) compared to ERαflox/flox (control) mice. 17β-estradiol (E2) treatment increased trabecular bone volume fraction (BV/TV), cortical bone area and uterine weight, while it reduced thymus weight and fat mass in ovariectomized control mice. The estrogenic responses were substantially reduced in inducible ERαKO mice compared to control mice on BV/TV (-67%), uterine weight (-94%), thymus weight (-70%), and gonadal fat mass (-94%). In contrast, the estrogenic response on cortical bone area was unaffected in inducible ERαKO compared to control mice. In conclusion, using an inducible ERαKO model, not confounded by lack of ERa during development, we demonstrate that ERα expression in sexually mature female mice is required for normal E2 responses in most, but not all tissues. The finding that cortical, but not trabecular bone, responds normally to E2 treatment in inducible ERαKO mice strengthens the idea of cortical and trabecular bone being regulated by estrogen via different mechanisms.
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| 6. |
- Scheffler, Julia M., et al.
(author)
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ER alpha Signaling in a Subset of CXCL12-Abundant Reticular Cells Regulates Trabecular Bone in Mice
- 2022
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In: JBMR Plus. - : Wiley. - 2473-4039. ; 6:8
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Journal article (peer-reviewed)abstract
- Estrogen has pronounced effects on the immune system, which also influences bone homeostasis. In recent years, stromal cells in lymphoid organs have gained increasing attention as they not only support the regulation of immune responses but also affect bone remodeling. A conditional knockout mouse model where estrogen receptor alpha (ER alpha) is deleted in CCL19-expressing stromal cells (Ccl19-Cre ER alpha(fl/fl) mice) was generated and bone densitometry was performed to analyze the importance of stromal cell-specific ER alpha signaling on the skeleton. Results showed that female Ccl19-Cre ER alpha(fl/fl) mice display reduced total bone mineral density and detailed X-ray analyses revealed that ER alpha expression in CCL19-expressing stromal cells is important for trabecular but not cortical bone homeostasis. Further analysis showed that the trabecular bone loss is caused by increased osteoclastogenesis. Additionally, the bone formation rate was reduced; however, the expression of osteoprogenitor genes was not altered. Analysis of the bone marrow stromal cell compartment revealed a deletion of ER alpha in a subgroup of CXCL12-abundant reticular (CAR) cells resulting in increased secretion of the pro-osteoclastogenic chemokine CXCL12. In conclusion, this study reveals the importance of ER alpha signaling in CAR cells for bone health. (c) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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| 7. |
- Abarenkov, Kessy, et al.
(author)
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Annotating public fungal ITS sequences from the built environment according to the MIxS-Built Environment standard – a report from a May 23-24, 2016 workshop (Gothenburg, Sweden)
- 2016
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In: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
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Journal article (peer-reviewed)abstract
- Recent molecular studies have identified substantial fungal diversity in indoor environments. Fungi and fungal particles have been linked to a range of potentially unwanted effects in the built environment, including asthma, decay of building materials, and food spoilage. The study of the built mycobiome is hampered by a number of constraints, one of which is the poor state of the metadata annotation of fungal DNA sequences from the built environment in public databases. In order to enable precise interrogation of such data – for example, “retrieve all fungal sequences recovered from bathrooms” – a workshop was organized at the University of Gothenburg (May 23-24, 2016) to annotate public fungal barcode (ITS) sequences according to the MIxS-Built Environment annotation standard (http://gensc.org/mixs/). The 36 participants assembled a total of 45,488 data points from the published literature, including the addition of 8,430 instances of countries of collection from a total of 83 countries, 5,801 instances of building types, and 3,876 instances of surface-air contaminants. The results were implemented in the UNITE database for molecular identification of fungi (http://unite.ut.ee) and were shared with other online resources. Data obtained from human/animal pathogenic fungi will furthermore be verified on culture based metadata for subsequent inclusion in the ISHAM-ITS database (http://its.mycologylab.org).
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| 8. |
- Aila Gustafsson, Sanna, et al.
(author)
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Characteristics measured by the Eating Disorder Inventory for children at risk and protective factors for disordered eating in adolescent girls
- 2010
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In: International Journal of Women's Health. - : Dove Medical Press. - 1179-1411. ; 2, s. 375-379
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Journal article (peer-reviewed)abstract
- Objective: The aim of this study was to examine longitudinally the role of characteristics measured by the Eating Disorder Inventory-Child version (EDI-C) to find early predictors that might constitute risk and protective factors in the development of disordered eating.Method: Participants were divided into three groups based on eating attitudes at T2: disordered eating (n = 49), intermediate eating concern (n = 260), and healthy eating attitudes (n = 120). EDI-C from T1 (four to five years earlier) was then analyzed to find predictors of group classification at T2.Results: Drive for thinness and body dissatisfaction emerged as risk factors at T1, while drive for thinness, body dissatisfaction, and interoceptive awareness emerged as protective factors after controlling for initial eating concerns and body mass index.Discussion: Eating disorders should not be seen as a result of a premorbid personality type. Rather we should take a more social-psychological perspective to explain how individual and sociocultural factors work together in the development of these conditions.
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| 10. |
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