| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 6. |
- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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| 12. |
- Peters, S., et al.
(författare)
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Reconditioning the Neurogenic Niche of Adult Non-human Primates by Antisense Oligonucleotide-Mediated Attenuation of TGFβ Signaling
- 2021
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Ingår i: Neurotherapeutics. - : Springer Nature. - 1933-7213 .- 1878-7479. ; 18:3, s. 1963-1979
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Tidskriftsartikel (refereegranskat)abstract
- Adult neurogenesis is a target for brain rejuvenation as well as regeneration in aging and disease. Numerous approaches showed efficacy to elevate neurogenesis in rodents, yet translation into therapies has not been achieved. Here, we introduce a novel human TGFβ-RII (Transforming Growth Factor—Receptor Type II) specific LNA-antisense oligonucleotide (“locked nucleotide acid”—“NVP-13”), which reduces TGFβ-RII expression and downstream receptor signaling in human neuronal precursor cells (ReNcell CX® cells) in vitro. After we injected cynomolgus non-human primates repeatedly i.th. with NVP-13 in a preclinical regulatory 13-week GLP-toxicity program, we could specifically downregulate TGFβ-RII mRNA and protein in vivo. Subsequently, we observed a dose-dependent upregulation of the neurogenic niche activity within the hippocampus and subventricular zone: human neural progenitor cells showed significantly (up to threefold over control) enhanced differentiation and cell numbers. NVP-13 treatment modulated canonical and non-canonical TGFβ pathways, such as MAPK and PI3K, as well as key transcription factors and epigenetic factors involved in stem cell maintenance, such as MEF2A and pFoxO3. The latter are also dysregulated in clinical neurodegeneration, such as amyotrophic lateral sclerosis. Here, we provide for the first time in vitro and in vivo evidence for a novel translatable approach to treat neurodegenerative disorders by modulating neurogenesis.
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| 16. |
- Ambros, Inge M, et al.
(författare)
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A multilocus technique for risk evaluation of patients with neuroblastoma.
- 2011
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 17:4, s. 792-804
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Tidskriftsartikel (refereegranskat)abstract
- Precise and comprehensive analysis of neuroblastoma genetics is essential for accurate risk evaluation and only pangenomic/multilocus approaches fulfill the present-day requirements. We present the establishment and validation of the PCR-based multiplex ligation-dependent probe amplification (MLPA) technique for neuroblastoma.
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| 17. |
- Haghikia, A., et al.
(författare)
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Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism
- 2022
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 43:6, s. 518-533
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Tidskriftsartikel (refereegranskat)abstract
- Aims Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism. Methods and results Using both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels. In apolipoprotein E-/- (Apoe(-/-)) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe(-/-) mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [-15.9 mg/dL (-8.1%) vs. -1.6 mg/dL (-0.5%), P = 0.016], total [-19.6 mg/dL (-7.3%) vs. -5.3 mg/dL (-1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: -18.9 mg/dL (-9.1%) vs. -0.6 mg/dL (-0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels. Conclusion Our findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs.
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| 18. |
- Himmerich, Hubertus, et al.
(författare)
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World Federation of Societies of Biological Psychiatry (WFSBP) guidelines update 2023 on the pharmacological treatment of eating disorders
- 2023
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Ingår i: World Journal of Biological Psychiatry. - : Taylor & Francis. - 1562-2975 .- 1814-1412. ; 24:8, s. 643-706
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Forskningsöversikt (refereegranskat)abstract
- Objectives: This 2023 update of the WFSBP guidelines for the pharmacological treatment of eating disorders (EDs) reflects the latest diagnostic and psychopharmacological progress and the improved WFSBP recommendations for the assessment of the level of evidence (LoE) and the grade of recommendation (GoR).Methods: The WFSBP Task Force EDs reviewed the relevant literature and provided a timely grading of the LoE and the GoR.Results: In anorexia nervosa (AN), only a limited recommendation (LoE: A; GoR: 2) for olanzapine can be given, because the available evidence is restricted to weight gain, and its effect on psychopathology is less clear. In bulimia nervosa (BN), the current literature prompts a recommendation for fluoxetine (LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1). In binge-eating disorder (BED), lisdexamfetamine (LDX; LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1) can be recommended. There is only sparse evidence for the drug treatment of avoidant restrictive food intake disorder (ARFID), pica, and rumination disorder (RD).Conclusion: In BN, fluoxetine, and topiramate, and in BED, LDX and topiramate can be recommended. Despite the published evidence, olanzapine and topiramate have not received marketing authorisation for use in EDs from any medicine regulatory agency.
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| 19. |
- Kempermann, G., et al.
(författare)
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Human Adult Neurogenesis: Evidence and Remaining Questions
- 2018
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Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 23:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan.
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| 20. |
- Klaubauf, Sylvia, 1981, et al.
(författare)
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Similar is not the same: Differences in the function of the (hemi-)cellulolytic regulator XlnR (Xlr1/Xyr1) in filamentous fungi
- 2014
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Ingår i: Fungal Genetics and Biology. - 1096-0937 .- 1087-1845. ; 72, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- The transcriptional activator XlnR (Xlr1/Xyr1) is a major regulator in fungal xylan and cellulose degradation as well as in the utilization of d-xylose via the pentose catabolic pathway. XlnR homologs are commonly found in filamentous ascomycetes and often assumed to have the same function in different fungi. However, a comparison of the saprobe Aspergillus niger and the plant pathogen Magnaporthe oryzae showed different phenotypes for deletion strains of XlnR. In this study wild type and xlnR/xlr1/xyr1 mutants of five fungi were compared: Fusarium graminearum, M. oryzae, Trichoderma reesei, A. niger and Aspergillus nidulans. Growth profiling on relevant substrates and a detailed analysis of the secretome as well as extracellular enzyme activities demonstrated a common role of this regulator in activating genes encoding the main xylanolytic enzymes. However, large differences were found in the set of genes that is controlled by XlnR in the different species, resulting in the production of different extracellular enzyme spectra by these fungi. This comparison emphasizes the functional diversity of a fine-tuned (hemi-)cellulolytic regulatory system in filamentous fungi, which might be related to the adaptation of fungi to their specific biotopes. Data are available via ProteomeXchange with identifier PXD001190.
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| 21. |
- Krueger, P., et al.
(författare)
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Potential roughness near lithographically fabricated atom chips
- 2007
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 76:6
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Tidskriftsartikel (refereegranskat)abstract
- Potential roughness has been reported to severely impair experiments in magnetic microtraps. We show that these obstacles can be overcome as we measure disorder potentials that are reduced by two orders of magnitude near lithographically patterned high-quality gold layers on semiconductor atom chip substrates. The spectrum of the remaining field variations exhibits a favorable scaling. A detailed analysis of the magnetic field roughness of a 100-mu m-wide wire shows that these potentials stem from minute variations of the current flow caused by local properties of the wire rather than merely from rough edges. A technique for further reduction of potential roughness by several orders of magnitude based on time-orbiting magnetic fields is outlined.
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| 22. |
- Kruger, P., et al.
(författare)
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Ultracold atoms on atom chips : Manipulation at the mu m distance scale
- 2005
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Ingår i: ATOMIC PHYSICS 19. - : AIP. ; , s. 144-153
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Konferensbidrag (refereegranskat)abstract
- Miniaturized potentials near the surface of atom chips can be used as flexible and versatile tools for the manipulation of ultracold atoms on a microscale. The full scope of possibilities is only accessible if atom‐surface distances can be reduced to microns. We discuss experiments in this regime and potential obstacles and solutions. We show that appropriate fabrication techniques lead to a reduction of disorder potentials so that one‐dimensional condensates can be prepared. We demonstrate how electrostatic potentials can be used to modify magnetic trapping potentials and how they can be used to study condensate formation in situations of different dimensionality. © 2005 American Institute of Physics
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| 23. |
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| 24. |
- Perez-Alcazar, Marta, et al.
(författare)
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Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro
- 2016
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling.
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