| 1. |
- Liu, Z. G., et al.
(författare)
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Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features
- 2023
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Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 32:20, s. 2981-2995
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Tidskriftsartikel (refereegranskat)abstract
- Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.
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| 2. |
- Adamo, Angela, et al.
(författare)
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Star Clusters Near and Far Tracing Star Formation Across Cosmic Time
- 2020
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 216:4
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Forskningsöversikt (refereegranskat)abstract
- Star clusters are fundamental units of stellar feedback and unique tracers of their host galactic properties. In this review, we will first focus on their constituents, i.e. detailed insight into their stellar populations and their surrounding ionised, warm, neutral, and molecular gas. We, then, move beyond the Local Group to review star cluster populations at various evolutionary stages, and in diverse galactic environmental conditions accessible in the local Universe. At high redshift, where conditions for cluster formation and evolution are more extreme, we are only able to observe the integrated light of a handful of objects that we believe will become globular clusters. We therefore discuss how numerical and analytical methods, informed by the observed properties of cluster populations in the local Universe, are used to develop sophisticated simulations potentially capable of disentangling the genetic map of galaxy formation and assembly that is carried by globular cluster populations.
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| 5. |
- Kogan, PS, et al.
(författare)
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Uncovering the molecular identity of cardiosphere-derived cells (CDCs) by single-cell RNA sequencing
- 2022
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Ingår i: Basic research in cardiology. - : Springer Science and Business Media LLC. - 1435-1803 .- 0300-8428. ; 117:1, s. 11-
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Tidskriftsartikel (refereegranskat)abstract
- Cardiosphere-derived cells (CDCs) generated from human cardiac biopsies have been shown to have disease-modifying bioactivity in clinical trials. Paradoxically, CDCs’ cellular origin in the heart remains elusive. We studied the molecular identity of CDCs using single-cell RNA sequencing (sc-RNAseq) in comparison to cardiac non-myocyte and non-hematopoietic cells (cardiac fibroblasts/CFs, smooth muscle cells/SMCs and endothelial cells/ECs). We identified CDCs as a distinct and mitochondria-rich cell type that shared biological similarities with non-myocyte cells but not with cardiac progenitor cells derived from human-induced pluripotent stem cells. CXCL6 emerged as a new specific marker for CDCs. By analysis of sc-RNAseq data from human right atrial biopsies in comparison with CDCs we uncovered transcriptomic similarities between CDCs and CFs. By direct comparison of infant and adult CDC sc-RNAseq data, infant CDCs revealed GO-terms associated with cardiac development. To analyze the beneficial effects of CDCs (pro-angiogenic, anti-fibrotic, anti-apoptotic), we performed functional in vitro assays with CDC-derived extracellular vesicles (EVs). CDC EVs augmented in vitro angiogenesis and did not stimulate scarring. They also reduced the expression of pro-apoptotic Bax in NRCMs. In conclusion, CDCs were disclosed as mitochondria-rich cells with unique properties but also with similarities to right atrial CFs. CDCs displayed highly proliferative, secretory and immunomodulatory properties, characteristics that can also be found in activated or inflammatory cell types. By special culture conditions, CDCs earn some bioactivities, including angiogenic potential, which might modify disease in certain disorders.
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| 6. |
- Manrique, H. M., et al.
(författare)
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Behavioural mimicry as an indicator of affiliation
- 2021
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 16:5
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has shown that behavioural mimicry fosters affiliation, and can be used to infer whether people belong to the same social unit. However, we still know very little about the generalizability of these findings and the individual factors involved. The present study intends to disentangle two important variables and assess their importance for affiliation: the matching in time of the behaviours versus their matching in form. In order to address this issue, we presented participants with short videos in which two actors displayed a set of small movements (e.g. crossing their legs, folding their arms, tapping their fingers) arranged to be either contingent in time or in form. A dark filter was used to eliminate ostensive group marks, such us phenotype or clothing. Participants attributed the highest degree of affiliation to the actors when their subsequent movements matched in form, but were delayed by 4-5 seconds, and the lowest degree when the timing of their movements matched, but they differed in form. To assess the generalizability of our findings, we took our study outside the usual Western context and tested a matching sample of participants from a traditional small-scale society in Kenya. In all, our results suggest that movements are used to judge the degree of affiliation between two individuals in both large- and small-scale societies. While moving in different ways at the same time seems to increase the perceived distance between two individuals, movements which match in form seem to invoke closeness.
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| 7. |
- Ständer, S., et al.
(författare)
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EADV Task Force Pruritus White Paper on chronic pruritus and chronic prurigo : Current challenges and future solutions
- 2024
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - 0926-9959. ; 38:9, s. 1687-1693
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Tidskriftsartikel (refereegranskat)abstract
- Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prurigo (CPG) is the most severe disease in the chronic pruritus spectrum, being associated with long-standing scratch-induced skin lesions and a therapy refractory itch-scratch-cycle. It is thus important to raise disease awareness for CP and CPG in the general public and among decision-makers in the health system. Further, there is a need to support a rational clinical framework to optimize both diagnostics and therapeutics. Currently, there is still a shortcoming regarding approved therapies and understanding CP/CPG as severe medical conditions. Therefore, the EADV Task Force Pruritus decided to publish this white paper based on several consensus meetings. The group consented on the following goals: (a) ensure that CP is recognized as a serious condition, (b) increase public awareness and understanding of CP and CPG as chronic and burdensome diseases that can greatly affect a person's quality of life, (c) clarify that in most cases CP and CPG are non-communicable and not caused by a psychiatric disease, (d) improve the support and treatment given to patients with CP to help them manage their disease and (e) publicize existing therapies including current guidelines. We aim to point to necessary improvements in access and quality of care directed to decision-makers in health policy, among payers and administrations as well as in practical care.
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| 8. |
- Ständer, Sonja, et al.
(författare)
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IFSI-Guideline on Chronic Prurigo including Prurigo nodularis.
- 2020
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Ingår i: ITCH. - : Ovid Technologies (Wolters Kluwer Health). - 2380-5048. ; 5:4, s. 1-13
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Forskningsöversikt (refereegranskat)abstract
- Chronic prurigo (CPG) is a highly burdensome pruritic disease characterized by chronic itch, a prolonged scratching behavior and the development of localized or generalized hyperkeratotic pruriginous lesions. Neuronal sensitization and the development of an itch-scratch cycle contribute to the augmentation of pruritus and the chronicity of the disease. We provide here the first international guideline for a rational diagnostic and therapeutic approach for CPG. Recommendations are based on available evidence and expert opinion. The diagnosis of CPG is made clinically. A detailed medical history together with laboratory and radiological examinations are advised in order to determine the severity of CPG, identify the underlying origin of the itch and assist in the elaboration of a treatment plan. Therapeutically, it is advised to adopt a multimodal approach, including general strategies to control itch, treatment of the underlying pruritic conditions, and of the pruriginous lesions. Topical (corticosteroids, calcineurin inhibitors, capsaicin) and systemic antipruritic agents (eg, gabapentinoids, immunosuppressants, and opioid modulators) as well as physical treatment modalities (phototherapy, cryotherapy) should be employed in a step-wise approach. Psychosomatic or psychological interventions may be recommended in CPG patients with signs of psychiatric/psychological comorbidities.
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