| 1. |
- Borsato, M., et al.
(författare)
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Unleashing the full power of LHCb to probe stealth new physics
- 2022
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Ingår i: Reports on Progress in Physics. - : IOP Publishing. - 0034-4885 .- 1361-6633. ; 85:2
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.
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| 2. |
- Baumgartner, T., et al.
(författare)
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A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies
- 2021
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Ingår i: Epilepsia Open. - : Wiley. - 2470-9239. ; 6:1, s. 160-170
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. Methods: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease. Results: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. Significance: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers. © 2020 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy
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| 3. |
- Cassemiro, F. A. S., et al.
(författare)
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Landscape dynamics and diversification of the megadiverse South American freshwater fish fauna
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 120:2
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Tidskriftsartikel (refereegranskat)abstract
- Landscape dynamics are widely thought to govern the tempo and mode of continental radiations, yet the effects of river network rearrangements on dispersal and lineage diversification remain poorly understood. We integrated an unprecedented occurrence dataset of 4,967 species with a newly compiled, time-calibrated phylogeny of South American freshwater fishes-the most species-rich continental vertebrate fauna on Earth-to track the evolutionary processes associated with hydrogeographic events over 100 Ma. Net lineage diversification was heterogeneous through time, across space, and among clades. Five abrupt shifts in net diversification rates occurred during the Paleogene and Miocene (between 30 and 7 Ma) in association with major landscape evolution events. Net diversification accelerated from the Miocene to the Recent (c. 20 to 0 Ma), with Western Amazonia having the highest rates of insitu diversification, which led to it being an important source of species dispersing to other regions. All regional biotic interchanges were associated with documented hydrogeographic events and the formation of biogeographic corridors, including the Early Miocene (c. 23 to 16 Ma) uplift of the Serra do Mar and Serra da Mantiqueira and the Late Miocene (c. 10 Ma) uplift of the Northern Andes and associated formation of the modern transcontinental Amazon River. The combination of high diversification rates and extensive biotic interchange associated with Western Amazonia yielded its extraordinary contemporary richness and phylogenetic endemism. Our results support the hypothesis that landscape dynamics, which shaped the history of drainage basin connections, strongly affected the assembly and diversification of basin-wide fish faunas.
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| 4. |
- Cecchi, N. J., et al.
(författare)
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Identifying Factors Associated with Head Impact Kinematics and Brain Strain in High School American Football via Instrumented Mouthguards
- 2021
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Ingår i: Annals of Biomedical Engineering. - : Springer Nature. - 0090-6964 .- 1573-9686. ; 49:10, s. 2814-2826
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Tidskriftsartikel (refereegranskat)abstract
- Repeated head impact exposure and concussions are common in American football. Identifying the factors associated with high magnitude impacts aids in informing sport policy changes, improvements to protective equipment, and better understanding of the brain’s response to mechanical loading. Recently, the Stanford Instrumented Mouthguard (MiG2.0) has seen several improvements in its accuracy in measuring head kinematics and its ability to correctly differentiate between true head impact events and false positives. Using this device, the present study sought to identify factors (e.g., player position, helmet model, direction of head acceleration, etc.) that are associated with head impact kinematics and brain strain in high school American football athletes. 116 athletes were monitored over a total of 888 athlete exposures. 602 total impacts were captured and verified by the MiG2.0’s validated impact detection algorithm. Peak values of linear acceleration, angular velocity, and angular acceleration were obtained from the mouthguard kinematics. The kinematics were also entered into a previously developed finite element model of the human brain to compute the 95th percentile maximum principal strain. Overall, impacts were (mean ± SD) 34.0 ± 24.3 g for peak linear acceleration, 22.2 ± 15.4 rad/s for peak angular velocity, 2979.4 ± 3030.4 rad/s2 for peak angular acceleration, and 0.262 ± 0.241 for 95th percentile maximum principal strain. Statistical analyses revealed that impacts resulting in Forward head accelerations had higher magnitudes of peak kinematics and brain strain than Lateral or Rearward impacts and that athletes in skill positions sustained impacts of greater magnitude than athletes in line positions. 95th percentile maximum principal strain was significantly lower in the observed cohort of high school football athletes than previous reports of collegiate football athletes. No differences in impact magnitude were observed in athletes with or without previous concussion history, in athletes wearing different helmet models, or in junior varsity or varsity athletes. This study presents novel information on head acceleration events and their resulting brain strain in high school American football from our advanced, validated method of measuring head kinematics via instrumented mouthguard technology.
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| 5. |
- Rangel-Pozzo, A, et al.
(författare)
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p53 CRISPR Deletion Affects DNA Structure and Nuclear Architecture
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- The TP53 gene is a key tumor suppressor. Although the tumor suppressor p53 was one of the first to be characterized as a transcription factor, with its main function potentiated by its interaction with DNA, there are still many unresolved questions about its mechanism of action. Here, we demonstrate a novel role for p53 in the maintenance of nuclear architecture of cells. Using three-dimensional (3D) imaging and spectral karyotyping, as well as super resolution microscopy of DNA structure, we observe significant differences in 3D telomere signatures, DNA structure and DNA-poor spaces as well gains or losses of chromosomes, between normal and tumor cells with CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-deleted or wild-type TP53. Additionally, treatment with Nutlin-3 results in differences in nuclear architecture of telomeres in wild-type but not in p53 knockout MCF-7 (Michigan Cancer Foundation-7) cells. Nutlin-3 binds to the p53-binding pocket of mouse double minute 2 (MDM2) and blocks the p53-MDM2 interaction. Moreover, we demonstrate that another p53 stabilizing small molecule, RITA (reactivation of p53 and induction of tumor cell apoptosis), also induces changes in 3D DNA structure, apparently in a p53 independent manner. These results implicate p53 activity in regulating nuclear organization and, additionally, highlight the divergent effects of the p53 targeting compounds Nutlin-3 and RITA.
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| 6. |
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| 7. |
- Kurt, S., 1985-, et al.
(författare)
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Increased proportion of circulating neutrophils with impaired phagocytosis capacity in patients with peripheral arterial disease
- 2023
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 379:Suppl. 1, s. S22-S22
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and Aims: Peripheral arterial disease (PAD) is a clinical manifestation of atherosclerosis, affecting arteries in the leg. Based on their symptoms and severity, PAD patients are characterized into three sub-groups: asymptomatic, intermittent claudication (IC) and critical limb ischemia (CLI). Despite its high prevalence, PAD remains under diagnosed and the role of immune cells in PAD pathophysiology remains poorly understood. In this study, we characterized the innate immune responses in PAD patients compared to healthy controls.Methods: Blood samples were collected from 14 patients with PAD (IC) and 30 healthy controls, to assess the phenotype of monocytes and neutrophils by using 10-colour flow cytometry. Phagocytosis assay was performed with labelled E.coli particles. Mann-Whitney U non-parametrical test was used for statistical comparison between PAD patients and healthy controls.Results: A significant higher proportion of leukocytes (p<0.05) and neutrophils (p<0.01) was observed in PAD patients compared to healthy controls, whereas monocyte subsets showed no significant differences. Interestingly, neutrophils showed a significantly impaired phagocytosis capability (p<0.05) and reduced expression of myeloperoxidase (MPO) (p<0.05) in PAD patients compared to healthy controls.Conclusions: Taken together these results, suggest that PAD patients have an increased proportion of neutrophils in circulation, with impaired phagocytosis capability, compared to healthy controls.
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| 8. |
- Pirronello, F., 1983-, et al.
(författare)
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Phenotypic and functional characterization of T cell immune responses in peripheral arterial disease
- 2023
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 379:Suppl. 1, s. S25-S25
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and Aims: Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis, affecting the lower limbs. T cells are among the principal contributors to the development of atherosclerotic plaques. However, T cell immune responses in PAD pathophysiology are poorly understood and a detailed phenotypic and functional characterization of T cell immune responses in PAD is needed.Methods: Blood samples were collected from PAD patients with claudicatio intermittens (n=14) and healthy controls (HCs, n=30). We assessed the phenotype of active, effector and memory T cell subsets by evaluating the expression of specific surface and intracellular markers analysed by 10-colour flow cytometry. Functional responses were evaluated by performing T cell receptor (TCR) stimulation of PBMCs in a 3D cell culture system to assess cytokine production by ELISA. Statistical analyses were performed using the Mann-Whitney U test.Results: No differences were observed between PAD and HCs in terms of active, effector and memory T cell phenotypes and in the frequency of cells expressing CCR6 and CXCR3 (markers associated with T cells producing IL-17 and IFN-γ). However, lower frequencies of IFN-γ+ cells among CD8+ (P=0.04), and CD4+CD8+ cells (P=0.03) were observed in PAD compared to HCs. TNF-α production in PAD-derived PBMCs, via TCR stimulation was increased at both 48- (P=0.004) and 72-hour time points (P=0.003). No differences were observed in IL-1β, IFN-γ and IL-17 secretion.Conclusions: Taken together these results suggest that increased TNF-α secretion by PBMCs in response to TCR activation might contribute to the pro-inflammatory environment in PAD pathogenesis.
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