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  1. Article ; Online: Isoform-resolved genome annotation enables mapping of tissue-specific betalain regulation in amaranth.

    Winkler, Tom S / Vollmer, Susanne K / Dyballa-Rukes, Nadine / Metzger, Sabine / Stetter, Markus G

    The New phytologist

    2024  

    Abstract: Betalains are coloring pigments produced in some families of the order Caryophyllales, where they replace anthocyanins as coloring pigments. While the betalain pathway itself is well studied, the tissue-specific regulation of the pathway remains mostly ... ...

    Abstract Betalains are coloring pigments produced in some families of the order Caryophyllales, where they replace anthocyanins as coloring pigments. While the betalain pathway itself is well studied, the tissue-specific regulation of the pathway remains mostly unknown. We enhance the high-quality Amaranthus hypochondriacus reference genome and produce a substantially more complete genome annotation, incorporating isoform details. We annotate betalain and anthocyanin pathway genes along with their regulators in amaranth and map the genetic control and tissue-specific regulation of the betalain pathway. Our improved genome annotation allowed us to identify causal mutations that lead to a knock-out of red betacyanins in natural accessions of amaranth. We reveal the tissue-specific regulation of flower color via a previously uncharacterized MYB transcription factor, AhMYB2. Downregulation of AhMYB2 in the flower leads to reduced expression of key betalain enzyme genes and loss of red flower color. Our improved amaranth reference genome represents the most complete genome of amaranth to date and is a valuable resource for betalain and amaranth research. High similarity of the flower betalain regulator AhMYB2 to anthocyanin regulators and a partially conserved interaction motif support the co-option of anthocyanin regulators for the betalain pathway as a possible reason for the mutual exclusiveness of the two pigments.
    Language English
    Publishing date 2024-04-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 208885-x
    ISSN 1469-8137 ; 0028-646X
    ISSN (online) 1469-8137
    ISSN 0028-646X
    DOI 10.1111/nph.19736
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  2. Article ; Online: Elevated expression of ACE2 in tumor-adjacent normal tissues of cancer patients.

    Winkler, Tom / Ben-David, Uri

    International journal of cancer

    2020  Volume 147, Issue 11, Page(s) 3264–3266

    MeSH term(s) Betacoronavirus ; COVID-19 ; China ; Coronavirus Infections ; Humans ; Neoplasms ; Pandemics ; Peptidyl-Dipeptidase A ; Pneumonia, Viral ; SARS-CoV-2 ; Severe Acute Respiratory Syndrome
    Chemical Substances Peptidyl-Dipeptidase A (EC 3.4.15.1)
    Keywords covid19
    Language English
    Publishing date 2020-07-17
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.33145
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    Zs.A 478: Show issues Location:
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    Zs.MO 576: Show issues

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  3. Article: Transcriptome Profiling of Osteoblasts in a Medaka (

    Liu, Ranran / Imangali, Nurgul / Ethiraj, Lalith Prabha / Carney, Tom James / Winkler, Christoph

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 775512

    Abstract: Matrix metalloproteases (MMPs) play crucial roles in extracellular matrix (ECM) modulation during osteoclast-driven bone remodeling. In the present study, we used transcriptome profiling of bone cells in a medaka model for osteoporosis and bone ... ...

    Abstract Matrix metalloproteases (MMPs) play crucial roles in extracellular matrix (ECM) modulation during osteoclast-driven bone remodeling. In the present study, we used transcriptome profiling of bone cells in a medaka model for osteoporosis and bone regeneration to identify factors critical for bone remodeling and homeostasis. This identified
    Language English
    Publishing date 2022-02-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.775512
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  4. Book ; Online: Programmatic Strategy Synthesis

    Batz, Kevin / Biskup, Tom Jannik / Katoen, Joost-Pieter / Winkler, Tobias

    Resolving Nondeterminism in Probabilistic Programs

    2023  

    Abstract: We consider imperative programs that involve both randomization and pure nondeterminism. The central question is how to find a strategy resolving the pure nondeterminism such that the so-obtained determinized program satisfies a given quantitative ... ...

    Abstract We consider imperative programs that involve both randomization and pure nondeterminism. The central question is how to find a strategy resolving the pure nondeterminism such that the so-obtained determinized program satisfies a given quantitative specification, i.e., bounds on expected outcomes such as the expected final value of a program variable or the probability to terminate in a given set of states. We show how memoryless and deterministic (MD) strategies can be obtained in a semi-automatic fashion using deductive verification techniques. For loop-free programs, the MD strategies resulting from our weakest precondition-style framework are correct by construction. This extends to loopy programs, provided the loops are equipped with suitable loop invariants - just like in program verification. We show how our technique relates to the well-studied problem of obtaining strategies in countably infinite Markov decision processes with reachability-reward objectives. Finally, we apply our technique to several case studies.
    Keywords Computer Science - Logic in Computer Science ; Computer Science - Programming Languages
    Subject code 005
    Publishing date 2023-11-12
    Publishing country us
    Document type Book ; Online
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  5. Article ; Online: Elevated expression of ACE2 in tumor-adjacent normal tissues of cancer patients

    Winkler, Tom / Ben-David, Uri

    bioRxiv

    Abstract: The rapidly developing COVID-19 pandemic has raised a concern that cancer patients may have increased susceptibility to SARS-CoV-2 infection. This discussion has mostly focused on therapy-induced immune suppression. Here, we examined the expression ... ...

    Abstract The rapidly developing COVID-19 pandemic has raised a concern that cancer patients may have increased susceptibility to SARS-CoV-2 infection. This discussion has mostly focused on therapy-induced immune suppression. Here, we examined the expression patterns of ACE2, the receptor through which SARX-CoV2 enters human cells, and found that ACE2 mRNA levels are elevated in tumor-adjacent normal tissues of cancer patients, including in normal-adjacent lung tissues of lung cancer patients. These observations raise the possibility that the elevated COVID-19 risk of cancer patients may not be limited to those undergoing immune-suppressing treatment.
    Keywords covid19
    Language English
    Publishing date 2020-04-25
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.04.25.061200
    Database COVID19

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  6. Article ; Online: Elevated expression of ACE2 in tumor-adjacent normal tissues of cancer patients

    Winkler, Tom / Ben-David, Uri

    bioRxiv

    Abstract: The rapidly developing COVID-19 pandemic has raised a concern that cancer patients may have increased susceptibility to SARS-CoV-2 infection. This discussion has mostly focused on therapy-induced immune suppression. Here, we examined the expression ... ...

    Abstract The rapidly developing COVID-19 pandemic has raised a concern that cancer patients may have increased susceptibility to SARS-CoV-2 infection. This discussion has mostly focused on therapy-induced immune suppression. Here, we examined the expression patterns of ACE2, the receptor through which SARX-CoV2 enters human cells, and found that ACE2 mRNA levels are elevated in tumor-adjacent normal tissues of cancer patients, including in normal-adjacent lung tissues of lung cancer patients. These observations raise the possibility that the elevated COVID-19 risk of cancer patients may not be limited to those undergoing immune-suppressing treatment.
    Keywords covid19
    Publisher BioRxiv; WHO
    Document type Article ; Online
    DOI 10.1101/2020.04.25.061200
    Database COVID19

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  7. Article ; Online: Colorimetric and fluorescent TRAP assays for visualising and quantifying fish osteoclast activity.

    Ethiraj, Lalith Prabha / Fong, En Lei Samuel / Liu, Ranran / Chan, Madelynn / Winkler, Christoph / Carney, Tom James

    European journal of histochemistry : EJH

    2022  Volume 66, Issue 2

    Abstract: Histochemical detection of tartrate-resistant acid phosphatase (TRAP) activity is a fundamental technique for visualizing osteoclastic bone resorption and assessing osteoclast activity status in tissues. This approach has mostly employed colorimetric ... ...

    Abstract Histochemical detection of tartrate-resistant acid phosphatase (TRAP) activity is a fundamental technique for visualizing osteoclastic bone resorption and assessing osteoclast activity status in tissues. This approach has mostly employed colorimetric detection, which has limited quantification of activity in situ and co-labelling with other skeletal markers. Here we report simple colorimetric and fluorescent TRAP assays in zebrafish and medaka, two important model organisms for investigating the pathogenesis of bone disorders. We show fluorescent TRAP staining, utilising the ELF97 substrate, is a rapid, robust and stable system to visualise and quantify osteoclast activity in zebrafish, and is compatible with other fluorescence stains, transgenic lines and antibody approaches. Using this approach, we show that TRAP activity is predominantly found around the base of the zebrafish pharyngeal teeth, where osteoclast activity state appears to be heterogeneous.
    MeSH term(s) Acid Phosphatase/analysis ; Animals ; Colorimetry ; Isoenzymes ; Osteoclasts/chemistry ; Tartrate-Resistant Acid Phosphatase/analysis ; Zebrafish
    Chemical Substances Isoenzymes ; Acid Phosphatase (EC 3.1.3.2) ; Tartrate-Resistant Acid Phosphatase (EC 3.1.3.2)
    Language English
    Publishing date 2022-03-24
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 1109511-8
    ISSN 2038-8306 ; 0391-7258 ; 1121-4201 ; 1121-760X
    ISSN (online) 2038-8306
    ISSN 0391-7258 ; 1121-4201 ; 1121-760X
    DOI 10.4081/ejh.2022.3369
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 739: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  8. Article ; Online: Cognitive, Behavioral, and Circadian Rhythm Interventions for Insomnia Alter Emotional Brain Responses.

    Leerssen, Jeanne / Aghajani, Moji / Bresser, Tom / Rösler, Lara / Winkler, Anderson M / Foster-Dingley, Jessica C / Van Someren, Eus J W

    Biological psychiatry. Cognitive neuroscience and neuroimaging

    2023  Volume 9, Issue 1, Page(s) 60–69

    Abstract: Background: The highest risk of depression is conveyed by insomnia. This risk can be mitigated by sleep interventions. Understanding brain mechanisms underlying increased emotional stability following insomnia treatment could provide insight relevant to ...

    Abstract Background: The highest risk of depression is conveyed by insomnia. This risk can be mitigated by sleep interventions. Understanding brain mechanisms underlying increased emotional stability following insomnia treatment could provide insight relevant to the prevention of depression. Here, we investigated how different sleep interventions alter emotion-related brain activity in people with insomnia at high risk of developing depression.
    Methods: Functional magnetic resonance imaging was used to assess how the amygdala response to emotional stimuli (negative facial expression) in 122 people with insomnia disorder differed from 36 control subjects and how the amygdala response changed after 6 weeks of either no treatment or internet-based circadian rhythm support (CRS), cognitive behavioral therapy for insomnia (CBT-I), or their combination (CBT-I+CRS). Effects on depression, insomnia and anxiety severity were followed up for 1 year.
    Results: Only combined treatment (CBT-I+CRS) significantly increased the amygdala response, compared with no treatment, CBT-I, and CRS. Individual differences in the degree of response enhancement were associated with improvement of insomnia symptoms directly after treatment (r = -0.41, p = .021). Moreover, exclusively CBT-I+CRS enhanced responsiveness of the left insula, which occurred in proportion to the reduction in depressive symptom severity (r = -0.37, p = .042).
    Conclusions: This functional magnetic resonance imaging study on insomnia treatment, the largest to date, shows that a combined cognitive, behavioral, and circadian intervention enhances emotional brain responsiveness and might improve resilience in patients with insomnia who are at high risk of developing depression.
    MeSH term(s) Humans ; Sleep Initiation and Maintenance Disorders/therapy ; Treatment Outcome ; Brain ; Emotions ; Circadian Rhythm ; Cognition
    Language English
    Publishing date 2023-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2879089-3
    ISSN 2451-9030 ; 2451-9022
    ISSN (online) 2451-9030
    ISSN 2451-9022
    DOI 10.1016/j.bpsc.2023.03.007
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  9. Article ; Online: Transcriptome Profiling of Osteoblasts in a Medaka (Oryzias latipes) Osteoporosis Model Identifies Mmp13b as Crucial for Osteoclast Activation

    Ranran Liu / Nurgul Imangali / Lalith Prabha Ethiraj / Tom James Carney / Christoph Winkler

    Frontiers in Cell and Developmental Biology, Vol

    2022  Volume 10

    Abstract: Matrix metalloproteases (MMPs) play crucial roles in extracellular matrix (ECM) modulation during osteoclast-driven bone remodeling. In the present study, we used transcriptome profiling of bone cells in a medaka model for osteoporosis and bone ... ...

    Abstract Matrix metalloproteases (MMPs) play crucial roles in extracellular matrix (ECM) modulation during osteoclast-driven bone remodeling. In the present study, we used transcriptome profiling of bone cells in a medaka model for osteoporosis and bone regeneration to identify factors critical for bone remodeling and homeostasis. This identified mmp13b, which was strongly expressed in osteoblast progenitors and upregulated under osteoporotic conditions and during regeneration of bony fin rays. To characterize the role of mmp13b in bone remodeling, we generated medaka mmp13b mutants by CRISPR/Cas9. We found that mmp13b mutants form normal numbers of osteoblasts and osteoclasts. However, osteoclast activity was severely impaired under osteoporotic conditions. In mmp13b mutants and embryos treated with the MMP13 inhibitor CL-82198, unmineralized collagens and mineralized bone matrix failed to be degraded. In addition, the dynamic migratory behavior of activated osteoclasts was severely affected in mmp13b mutants. Expression analysis showed that maturation genes were downregulated in mmp13b deficient osteoclasts suggesting that they remain in an immature and non-activated state. We also found that fin regeneration was delayed in mmp13b mutants with a concomitant alteration of the ECM and reduced numbers of osteoblast progenitors in regenerating joint regions. Together, our findings suggest that osteoblast-derived Mmp13b alters the bone ECM to allow the maturation and activation of osteoclasts during bone remodeling in a paracrine manner. Mmp13b-induced ECM alterations are also required to facilitate osteoblast progenitor recruitment and full regeneration of bony fin rays.
    Keywords osteoblasts ; osteoclasts ; matrix metalloprotease ; medaka (Oryzias lapites) ; osteoporosis ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
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  10. Article ; Online: Approaches to understanding COVID-19 and its neurological associations.

    Beghi, Ettore / Michael, Benedict D / Solomon, Tom / Westenberg, Erica / Winkler, Andrea S

    Annals of neurology

    2021  

    Abstract: There is an accumulating volume of research into neurological manifestations of COVID-19. However, inconsistent study designs, inadequate controls, poorly-validated tests, and differing settings, interventions, and cultural norms weaken study quality, ... ...

    Abstract There is an accumulating volume of research into neurological manifestations of COVID-19. However, inconsistent study designs, inadequate controls, poorly-validated tests, and differing settings, interventions, and cultural norms weaken study quality, comparability, and thus the understanding of the spectrum, burden and pathophysiology of these complications. Therefore, a global COVID-19 Neuro Research Coalition, together with the WHO, has reviewed reports of COVID-19 neurological complications and harmonised clinical measures for future research. This will facilitate well-designed studies using precise, consistent case definitions of SARS-CoV2 infection and neurological complications, with standardised forms for pooled data analyses that non-specialists can use, including in low-income settings. This article is protected by copyright. All rights reserved.
    Language English
    Publishing date 2021-04-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80362-5
    ISSN 1531-8249 ; 0364-5134
    ISSN (online) 1531-8249
    ISSN 0364-5134
    DOI 10.1002/ana.26076
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    Zs.A 1370: Show issues Location:
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