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Sökning: WFRF:(Stephan Katharina)

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1.
  • Biechele, Gloria, et al. (författare)
  • Associations between sex, body mass index and the individual microglial response in Alzheimer's disease
  • 2024
  • Ingår i: JOURNAL OF NEUROINFLAMMATION. - 1742-2094. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and objectives18-kDa translocator protein position-emission-tomography (TSPO-PET) imaging emerged for in vivo assessment of neuroinflammation in Alzheimer's disease (AD) research. Sex and obesity effects on TSPO-PET binding have been reported for cognitively normal humans (CN), but such effects have not yet been systematically evaluated in patients with AD. Thus, we aimed to investigate the impact of sex and obesity on the relationship between beta-amyloid-accumulation and microglial activation in AD.Methods49 patients with AD (29 females, all A beta-positive) and 15 A beta-negative CN (8 female) underwent TSPO-PET ([18F]GE-180) and beta-amyloid-PET ([18F]flutemetamol) imaging. In 24 patients with AD (14 females), tau-PET ([18F]PI-2620) was additionally available. The brain was parcellated into 218 cortical regions and standardized-uptake-value-ratios (SUVr, cerebellar reference) were calculated. Per region and tracer, the regional increase of PET SUVr (z-score) was calculated for AD against CN. The regression derived linear effect of regional A beta-PET on TSPO-PET was used to determine the A beta-plaque-dependent microglial response (slope) and the A beta-plaque-independent microglial response (intercept) at the individual patient level. All read-outs were compared between sexes and tested for a moderation effect of sex on associations with body mass index (BMI).ResultsIn AD, females showed higher mean cortical TSPO-PET z-scores (0.91 +/- 0.49; males 0.30 +/- 0.75; p = 0.002), while A beta-PET z-scores were similar. The A beta-plaque-independent microglial response was stronger in females with AD (+ 0.37 +/- 0.38; males with AD - 0.33 +/- 0.87; p = 0.006), pronounced at the prodromal stage. On the contrary, the A beta-plaque-dependent microglial response was not different between sexes. The A beta-plaque-independent microglial response was significantly associated with tau-PET in females (Braak-II regions: r = 0.757, p = 0.003), but not in males. BMI and the A beta-plaque-independent microglial response were significantly associated in females (r = 0.44, p = 0.018) but not in males (BMI*sex interaction: F(3,52) = 3.077, p = 0.005).ConclusionWhile microglia response to fibrillar A beta is similar between sexes, women with AD show a stronger A beta-plaque-independent microglia response. This sex difference in A beta-independent microglial activation may be associated with tau accumulation. BMI is positively associated with the A beta-plaque-independent microglia response in females with AD but not in males, indicating that sex and obesity need to be considered when studying neuroinflammation in AD.
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2.
  • Finze, Anika, et al. (författare)
  • Individual regional associations between Aβ-, tau- and neurodegeneration (ATN) with microglial activation in patients with primary and secondary tauopathies
  • 2023
  • Ingår i: MOLECULAR PSYCHIATRY. - 1359-4184 .- 1476-5578. ; 28:10, s. 4438-4450
  • Tidskriftsartikel (refereegranskat)abstract
    • & beta;-amyloid (A & beta;) and tau aggregation as well as neuronal injury and atrophy (ATN) are the major hallmarks of Alzheimer's disease (AD), and biomarkers for these hallmarks have been linked to neuroinflammation. However, the detailed regional associations of these biomarkers with microglial activation in individual patients remain to be elucidated. We investigated a cohort of 55 patients with AD and primary tauopathies and 10 healthy controls that underwent TSPO-, A & beta;-, tau-, and perfusion-surrogate-PET, as well as structural MRI. Z-score deviations for 246 brain regions were calculated and biomarker contributions of A & beta; (A), tau (T), perfusion (N1), and gray matter atrophy (N2) to microglial activation (TSPO, I) were calculated for each individual subject. Individual ATN-related microglial activation was correlated with clinical performance and CSF soluble TREM2 (sTREM2) concentrations. In typical and atypical AD, regional tau was stronger and more frequently associated with microglial activation when compared to regional A & beta; (AD: & beta;(T) = 0.412 & PLUSMN; 0.196 vs. & beta;(A) = 0.142 & PLUSMN; 0.123, p < 0.001; AD-CBS: & beta;(T) = 0.385 & PLUSMN; 0.176 vs. & beta;(A) = 0.131 & PLUSMN; 0.186, p = 0.031). The strong association between regional tau and microglia reproduced well in primary tauopathies (& beta;(T) = 0.418 & PLUSMN; 0.154). Stronger individual associations between tau and microglial activation were associated with poorer clinical performance. In patients with 4RT, sTREM2 levels showed a positive association with tau-related microglial activation. Tau pathology has strong regional associations with microglial activation in primary and secondary tauopathies. Tau and A & beta; related microglial response indices may serve as a two-dimensional in vivo assessment of neuroinflammation in neurodegenerative diseases.
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3.
  • Hippe, Andreas, et al. (författare)
  • EGFR/Ras-induced CCL20 production modulates the tumour microenvironment.
  • 2020
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 123:6, s. 942-954
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.METHODS: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.RESULTS: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system.CONCLUSION: We propose that the chemokine axis CCL20-CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.
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4.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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5.
  • Mörwald, Katharina, et al. (författare)
  • Serum Ferritin Correlates With Liver Fat in Male Adolescents With Obesity.
  • 2020
  • Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-alcoholic fatty liver disease (NAFLD) contributes essentially to the burden of obesity and can start in childhood. NAFLD can progress to cirrhosis and hepatocellular carcinoma. The early phase of NAFLD is crucial because during this time the disease is fully reversible. Pediatric NAFLD shows unique features of histology and pathophysiology compared to adults. Changes in serum iron parameters are common in adult NAFLD and have been termed dysmetabolic iron overload syndrome characterized by increased serum ferritin levels and normal transferrin saturation; however, the associations of serum ferritin, inflammation, and liver fat content have been incompletely investigated in children. As magnetic resonance imaging (MRI) is an excellent measure for the degree of liver steatosis, we applied this method herein to clarify the interaction between ferritin and fatty liver in male adolescents. For this study, one hundred fifty male pediatric patients with obesity and who are overweight were included. We studied a subgroup of male patients with (n = 44) and without (n = 18) NAFLD in whom we determined liver fat content, visceral adipose tissue, and subcutaneous adipose tissue extent with a 1.5T MRI (Philips NL). All patients underwent a standardized oral glucose tolerance test. We measured uric acid, triglycerides, HDL-, LDL-, total cholesterol, liver transaminases, high sensitive CRP (hsCRP), interleukin-6, HbA1c, and insulin. In univariate analysis, ferritin was associated with MRI liver fat, visceral adipose tissue content, hsCRP, AST, ALT, and GGT, while transferrin and soluble transferrin receptor were not associated with ferritin. Multivariate analysis identified hsCRP and liver fat content as independent predictors of serum ferritin in the pediatric male patients. Our data indicate that serum ferritin in male adolescents with obesity is mainly determined by liver fat content and inflammation but not by body iron status.
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6.
  • Richter, Katharina N., et al. (författare)
  • Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy
  • 2018
  • Ingår i: EMBO Journal. - : WILEY. - 0261-4189 .- 1460-2075. ; 37:1, s. 139-159
  • Tidskriftsartikel (refereegranskat)abstract
    • Paraformaldehyde (PFA) is the most commonly used fixative for immunostaining of cells, but has been associated with various problems, ranging from loss of antigenicity to changes in morphology during fixation. We show here that the small dialdehyde glyoxal can successfully replace PFA. Despite being less toxic than PFA, and, as most aldehydes, likely usable as a fixative, glyoxal has not yet been systematically tried in modern fluorescence microscopy. Here, we tested and optimized glyoxal fixation and surprisingly found it to be more efficient than PFA-based protocols. Glyoxal acted faster than PFA, cross-linked proteins more effectively, and improved the preservation of cellular morphology. We validated glyoxal fixation in multiple laboratories against different PFA-based protocols and confirmed that it enabled better immunostainings for a majority of the targets. Our data therefore support that glyoxal can be a valuable alternative to PFA for immunostaining.
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7.
  • Watson, Hunna J., et al. (författare)
  • Common Genetic Variation and Age of Onset of Anorexia Nervosa
  • 2022
  • Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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8.
  • Baraldi, Stephan, et al. (författare)
  • The Importance of Commitment to Change in Public Reform : an Example from Pakistan
  • 2010
  • Ingår i: Journal of Change Management. - : Informa UK Limited. - 1469-7017 .- 1479-1811. ; 10:4, s. 347-368
  • Tidskriftsartikel (refereegranskat)abstract
    • The public sectors in many developing countries have undergone major restructuring over the past decades. Earlier research suggests that such restructuring is inherently linked to feelings of ambiguity and insecurity among employees, undermining behavioral support for change, and thus, chances of change success. Using survey data from a restructured public sector organization in Pakistan, this study investigated the mediating role of commitment to change on the relationship between role ambiguity/job insecurity and behavioral support for change. The results show that role ambiguity and job insecurity were negatively related to both commitment to change and behavioral support for change. More importantly, however, the results support the notion that the negative effects of role ambiguity and job insecurity on behavioral support for change are fully mediated by individuals’ commitment to change. The study emphasizes the importance of mobilizing commitment to change in restructuring processes.
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9.
  • Baumeister, Hannah, et al. (författare)
  • A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings
  • Ingår i: Brain : a journal of neurology. - 1460-2156. ; 147:7, s. 2400-2413
  • Tidskriftsartikel (refereegranskat)abstract
    • Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± SD age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (CU; n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (SCD; n = 342), mild cognitive impairment (MCI; n = 118), or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid AD biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5), as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test if baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and MCI conversion rates of CU and SCD participants. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy first affected the medial temporal lobes, followed by further temporal and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological AD biomarker levels, APOE ε4 carriership, and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive AD biomarkers and was associated with more generalised cognitive impairment. Limbic-predominant atrophy, in all and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of MCI conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, both on the subject and group level, were excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for AD in applied settings. The implementation of atrophy subtype- and stage-specific end-points may increase the statistical power of pharmacological trials targeting early AD.
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10.
  • Beyerlein, Kenneth R., et al. (författare)
  • Mix-and-diffuse serial synchrotron crystallography
  • 2017
  • Ingår i: IUCrJ. - : INT UNION CRYSTALLOGRAPHY. - 2052-2525. ; 4:6, s. 769-777
  • Tidskriftsartikel (refereegranskat)abstract
    • Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzyme at a high level of detail. The success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.
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11.
  • Fazey, Ioan, et al. (författare)
  • Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
  • 2020
  • Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
  • Tidskriftsartikel (refereegranskat)abstract
    • Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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12.
  • Gyger, Samuel, et al. (författare)
  • Metropolitan single-photon distribution at 1550 nm for random number generation
  • 2022
  • Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 121:19, s. 194003-
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantum communication networks will connect future generations of quantum processors, enable metrological applications, and provide security through quantum key distribution. We present a testbed that is part of the municipal fiber network in the greater Stockholm metropolitan area for quantum resource distribution through a 20 km long fiber based on semiconductor quantum dots emitting in the telecom C-band. We utilize the service to generate random numbers passing the NIST test suite SP800-22 at a subscriber 8 km outside of the city with a bit rate of 23.4 kbit/s.
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13.
  • Gyger, Samuel, et al. (författare)
  • Metropolitan Single-Photon Distribution at 1550 nm for Random Number Generation
  • 2023
  • Ingår i: 2023 Conference on Lasers and Electro-Optics, CLEO 2023. - : Institute of Electrical and Electronics Engineers Inc..
  • Konferensbidrag (refereegranskat)abstract
    • Quantum communication networks are used for QKD and metrological applications. We present research connecting two nodes ≈ 20 kilometers apart over the municipal fiber network using semiconductor quantum dots emitting at 1550 nm.
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14.
  • Hess, Timo, et al. (författare)
  • Dissecting the genetic heterogeneity of gastric cancer
  • 2023
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. 
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15.
  • Hildenbeutel, Markus, et al. (författare)
  • Assembly factors monitor sequential hemylation of cytochrome b to regulate mitochondria! translation
  • 2014
  • Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 205:4, s. 511-524
  • Tidskriftsartikel (refereegranskat)abstract
    • Mitochondrial respiratory chain complexes convert chemical energy into a membrane potential by connecting electron transport with charge separation. Electron transport relies on redox cofactors that occupy strategic positions in the complexes. How these redox cofactors are assembled into the complexes is not known. Cytochrome b, a central catalytic subunit of complex III, contains two henne bs. Here, we unravel the sequence of events in the mitochondrial inner membrane by which cytochrome b is hemylated. Heme incorporation occurs in a strict sequential process that involves interactions of the newly synthesized cytochrome b with assembly factors and structural complex III subunits. These interactions are functionally connected to cofactor acquisition that triggers the progression of cytochrome b through successive assembly intermediates. Failure to hemylate cytochrome b sequesters the Cbp3-Cbp6 complex in early assembly intermediates, thereby causing a reduction in cytochrome b synthesis via a feedback loop that senses hemylation of cytochrome b.
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16.
  • Huber, Maria, et al. (författare)
  • Metabolic correlates of dopaminergic loss in dementia with lewy bodies
  • 2020
  • Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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17.
  • Hugentobler, Katharina Gloria, et al. (författare)
  • Lipid Composition Affects the Efficiency in the Functional Reconstitution of the Cytochrome c Oxidase
  • 2020
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:19
  • Tidskriftsartikel (refereegranskat)abstract
    • The transmembrane protein cytochrome c oxidase (CcO) is the terminal oxidase in the respiratory chain of many aerobic organisms and catalyzes the reduction of dioxygen to water. This process maintains an electrochemical proton gradient across the membrane hosting the oxidase. CcO is a well-established model enzyme in bioenergetics to study the proton-coupled electron transfer reactions and protonation dynamics involved in these processes. Its catalytic mechanism is subject to ongoing intense research. Previous research, however, was mainly focused on the turnover of oxygen and electrons in CcO, while studies reporting proton turnover rates of CcO, that is the rate of proton uptake by the enzyme, are scarce. Here, we reconstitute CcO from R. sphaeroides into liposomes containing a pH sensitive dye and probe changes of the pH value inside single proteoliposomes using fluorescence microscopy. CcO proton turnover rates are quantified at the single-enzyme level. In addition, we recorded the distribution of the number of functionally reconstituted CcOs across the proteoliposome population. Studies are performed using proteoliposomes made of native lipid sources, such as a crude extract of soybean lipids and the polar lipid extract of E. coli, as well as purified lipid fractions, such as phosphatidylcholine extracted from soybean lipids. It is shown that these lipid compositions have only minor effects on the CcO proton turnover rate, but can have a strong impact on the reconstitution efficiency of functionally active CcOs. In particular, our experiments indicate that efficient functional reconstitution of CcO is strongly promoted by the addition of anionic lipids like phosphatidylglycerol and cardiolipin. 
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18.
  • Kalyal, Hina Jawaid, et al. (författare)
  • The moderating role of employability on the relationship between job insecurity and commitment to change
  • 2010
  • Ingår i: Economic and Industrial Democracy. - : Sage. - 0143-831X .- 1461-7099. ; 31:3, s. 327-344
  • Tidskriftsartikel (refereegranskat)abstract
    • The development of commitment to change is an underresearched area especially in non-western settings. The aim of the present study was to determine whether employability can moderate the negative effects of job insecurity on individuals’ commitment to change. A survey method approach was used to collect 149 responses from managers of a large public sector organization in Pakistan undergoing restructuring. Hierarchical multiple regression results suggest that employability is an important coping resource during organizational change as it helps mitigate the negative effects of job insecurity on the most desirable form of commitment to change, namely affective commitment to change. Theoretical and practical implications of the study are discussed.
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19.
  • Kessler, Henrik, et al. (författare)
  • Visuospatial computer game play after memory reminder delivered three days after a traumatic film reduces the number of intrusive memories of the experimental trauma
  • 2020
  • Ingår i: Journal of Behavior Therapy and Experimental Psychiatry. - : Elsevier. - 0005-7916 .- 1873-7943. ; 67
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The experience of intrusive memories is a core clinical symptom of posttraumatic stress disorder (PTSD), and can be distressing in its own right. Notions of dual task interference and reconsolidation-update mechanisms suggest novel approaches to target intrusive memories. This study tested the hypothesis that a single-session cognitive intervention (memory reminder task plus Tetris gameplay) would reduce the occurrence of experimental trauma memories even when delivered 3 days post-trauma. Critically, this study tested effects against two control groups: Reminder-only, and reminder plus another computer game (a form of Quiz).METHODS: 86 healthy volunteers (59% female, age M = 24.35, SD = 4.59 years) watched a trauma film and then recorded their intrusive memories in a diary for 3 days (pre-intervention). They then returned to the lab. After presentation of visual reminder cues for the film plus a 10 min wait period (memory reminder task), participants were randomized into one of three task conditions (Tetris game play, Quiz game play, vs. reminder-only). They then kept the diary for a further 3 days (post-intervention).RESULTS: As predicted, after the experimental manipulation, the reminder + Tetris group experienced significantly fewer intrusions than the reminder-only group (d = 1.37). Further, the reminder + Tetris group also experienced significantly fewer intrusions than the reminder + Quiz (d = 0.65) group. Contrary to predictions, the reminder + Quiz group experienced significantly fewer intrusions than the reminder-only group (d = 0.69). Prior to the experimental manipulation, there was no significant difference between groups in number of intrusions. Recognition memory test scores for facts of the trauma film after 6 days were comparable between groups.CONCLUSIONS: We demonstrated that 3 days after experimental trauma (i.e. after memory consolidation) an intervention comprising a reminder task prior to a 15 min cognitive interference task (one of two computer games) led to a reduction in intrusion occurrence compared to reminder only. We interpret and discuss our findings within the framework of supposed reconsolidation-update mechanisms and competition for limited (visuospatial) working memory resources. Should these effects hold true in clinical populations, this type of simple intervention approach could help contribute to reducing intrusive memories of trauma.
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20.
  • Kleineidam, Luca, et al. (författare)
  • Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve
  • 2022
  • Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Several lifestyle factors promote protection against Alzheimer's disease (AD) throughout a person's lifespan. Although such protective effects have been described for occupational cognitive requirements (OCR) in midlife, it is currently unknown whether they are conveyed by brain maintenance (BM), brain reserve (BR), or cognitive reserve (CR) or a combination of them. Methods: We systematically derived hypotheses for these resilience concepts and tested them in the population-based AgeCoDe cohort and memory clinic-based AD high-risk DELCODE study. The OCR score (OCRS) was measured using job activities based on the O*NET occupational classification system. Four sets of analyses were conducted: (1) the interaction of OCR and APOE-ε4 with regard to cognitive decline (N = 2,369, AgeCoDe), (2) association with differentially shaped retrospective trajectories before the onset of dementia of the Alzheimer's type (DAT; N = 474, AgeCoDe), (3) cross-sectional interaction of the OCR and cerebrospinal fluid (CSF) AD biomarkers and brain structural measures regarding memory function (N = 873, DELCODE), and (4) cross-sectional and longitudinal association of OCR with CSF AD biomarkers and brain structural measures (N = 873, DELCODE). Results: Regarding (1), higher OCRS was associated with a reduced association of APOE-ε4 with cognitive decline (mean follow-up = 6.03 years), consistent with CR and BR. Regarding (2), high OCRS was associated with a later onset but subsequently stronger cognitive decline in individuals converting to DAT, consistent with CR. Regarding (3), higher OCRS was associated with a weaker association of the CSF Aβ42/40 ratio and hippocampal volume with memory function, consistent with CR. Regarding (4), OCR was not associated with the levels or changes in CSF AD biomarkers (mean follow-up = 2.61 years). We found a cross-sectional, age-independent association of OCRS with some MRI markers, but no association with 1-year-change. OCR was not associated with the intracranial volume. These results are not completely consistent with those of BR or BM. Discussion: Our results support the link between OCR and CR. Promoting and seeking complex and stimulating work conditions in midlife could therefore contribute to increased resistance to pathologies in old age and might complement prevention measures aimed at reducing pathology.
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21.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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22.
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23.
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24.
  • Lettner, Thomas, et al. (författare)
  • Strain-controlled quantum dot fine-structure for entangled-photon generation at 1550 nm
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Entangled-photon generation at 1550nm in the telecom C-band is of critical importance, since it enables the realization of quantum communication protocols over long distance using deployed telecommunication infrastructure. InAs epitaxial quantum dots have recently enabled on-demand generation of entangled pairs of photons in this wavelength range. However, time-dependent state evolution, caused by the fine-structure splitting, currently limits the fidelity to a specific entangled state. Here, we show suppression of the fine-structure for InAs quantum dots using micromachined piezoelectric actuators and demonstrate generation of highly entangled photons in the telecom C-band. At the lowest fine-structure setting, we obtain a maximum fidelity of (90.0 ± 2.7)% (concurrence of (87.5 ± 3.1)%). The concurrence remains high also for moderate (weak) temporal-filtering, with values close to 80% (50%), corresponding to 30% (80%) of collected photons, respectively. The presented fine-structure control opens the way for the exploitation of entangled photons from quantum dots in fiber-based quantum communication protocols.
  •  
25.
  • Lettner, Thomas, et al. (författare)
  • Strain-Controlled Quantum Dot Fine Structure for Entangled Photon Generation at 1550 nm
  • 2021
  • Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 21:24, s. 10501-10506
  • Tidskriftsartikel (refereegranskat)abstract
    • Entangled photon generation at 1550 nm in the telecom C-band is of critical importance as it enables the realization of quantum communication protocols over long distance using deployed telecommunication infrastructure. InAs epitaxial quantum dots have recently enabled on-demand generation of entangled photons in this wavelength range. However, time-dependent state evolution, caused by the fine-structure splitting, currently limits the fidelity to a specific entangled state. Here, we show fine-structure suppression for InAs quantum dots using micromachined piezoelectric actuators and demonstrate generation of highly entangled photons at 1550 nm. At the lowest fine-structure setting, we obtain a maximum fidelity of 90.0 +/- 2.7% (concurrence of 87.5 +/- 3.1%). The concurrence remains high also for moderate (weak) temporal filtering, with values close to 80% (50%), corresponding to 30% (80%) of collected photons, respectively. The presented fine-structure control opens the way for exploiting entangled photons from quantum dots in fiber-based quantum communication protocols.
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26.
  • Ludwig, Sebastian, et al. (författare)
  • Transcatheter Mitral Valve Replacement versus Medical Therapy for Secondary Mitral Regurgitation: A Propensity Score-Matched Comparison.
  • 2023
  • Ingår i: Circulation. Cardiovascular interventions. - 1941-7632. ; 16:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone. Methods: The CHOICE-MI registry included patients with MR undergoing TMVR using dedicated devices. Patients with MR etiologies other than secondary MR were excluded. Patients treated with GDMT alone were derived from the control arm of the COAPT trial. We compared outcomes between the TMVR and GDMT groups, using propensity score (PS)-matching to adjust for baseline differences. Results: After PS-matching, 97 patient pairs undergoing TMVR (72.9±8.7 years, 60.8% male, transapical access 91.8%) versus GDMT (73.1±11.0 years, 59.8% male) were compared. At 1 and 2 years, residual MR was ≤1+ in all patients of the TMVR group compared to 6.9% and 7.7%, respectively, in those receiving GDMT alone (both p<0.001). The 2-year rate of HF hospitalization was significantly lower in the TMVR group (32.8% vs. 54.4%, HR 0.59, 95% CI 0.35-0.99; p=0.04). Among survivors, a higher proportion of patients were in NYHA functional class I or II in the TMVR group at 1 year (78.2% vs. 59.7%, p=0.03) and at 2 years (77.8% vs. 53.2%, p=0.09). Two-year mortality was similar in the two groups (TMVR vs. GDMT, 36.8% vs. 40.8%, HR 1.01, 95% CI 0.62-1.64; p=0.98). Conclusions: In this observational comparison, over 2-year follow-up, TMVR using mostly transapical devices in patients with secondary MR was associated with significant reduction of MR, symptomatic improvement, less frequent hospitalizations for HF and similar mortality compared with GDMT.
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27.
  • Miller, Rachael, et al. (författare)
  • Socio-ecological correlates of neophobia in corvids
  • 2022
  • Ingår i: Current Biology. - : Elsevier BV. - 0960-9822. ; 32:1, s. 4-85
  • Tidskriftsartikel (refereegranskat)abstract
    • Behavioral responses to novelty, including fear and subsequent avoidance of novel stimuli, i.e., neophobia, determine how animals interact with their environment. Neophobia aids in navigating risk and impacts on adaptability and survival. There is variation within and between individuals and species; however, lack of large-scale, comparative studies critically limits investigation of the socio-ecological drivers of neophobia. In this study, we tested responses to novel objects and food (alongside familiar food) versus a baseline (familiar food alone) in 10 corvid species (241 subjects) across 10 labs worldwide. There were species differences in the latency to touch familiar food in the novel object and novel food conditions relative to the baseline. Four of seven socio-ecological factors influenced object neophobia: (1) use of urban habitat (versus not), (2) territorial pair versus family group sociality, (3) large versus small maximum flock size, and (4) moderate versus specialized caching (whereas range, hunting live animals, and genus did not), while only maximum flock size influenced food neophobia. We found that, overall, individuals were temporally and contextually repeatable (i.e., consistent) in their novelty responses in all conditions, indicating neophobia is a stable behavioral trait. With this study, we have established a network of corvid researchers, demonstrating potential for further collaboration to explore the evolution of cognition in corvids and other bird species. These novel findings enable us, for the first time in corvids, to identify the socio-ecological correlates of neophobia and grant insight into specific elements that drive higher neophobic responses in this avian family group. Video abstract: [Figure presented]
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28.
  • Ntalla, Ioanna, et al. (författare)
  • Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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29.
  • Näswall, Katharina, et al. (författare)
  • The salaried employee in the modern working life: Threats and challenges. : Technical report on the sample, data collection, and measurement properties of the instruments.
  • 2006
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The present report presents data collected within a project focusing on salaried employees, among whom we have witnessed profound changes both in the conditions under which work is carried out and in the reported frequencies of psychological health complaints. The aim has been to capture traditional and new demands that have previously not been the focus of empirical studies, as well as to investigate what factors related to attitudes, behavior, and well-being among salaried workers. The project has consisted in a longitudinal data collection among white-collar workers in four Swedish organizations. Documentation on the procedure, samples, and questionnaire items is presented in the present technical report, along with measurement properties and descriptive statistics at both time points for the scales used. The results indicate that the measures are for the most part satisfactory, and the report provides a solid basis for future research on the data collected in this project.
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30.
  • Otto, Katharina, et al. (författare)
  • MASCOT’s in situ analysis of asteroid Ryugu in the context of regolith samples and remote sensing data returned by Hayabusa2
  • 2023
  • Ingår i: Earth Planets and Space. - : Springer. - 1343-8832 .- 1880-5981. ; 75:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Hayabusa2 mission provided a unique data set of asteroid Ryugu that covers a wide range of spatial scale from the orbiter remote sensing instruments to the returned samples. The MASCOT lander that was delivered onto the surface of Ryugu aimed to provide context for these data sets by producing in situ data collected by a camera (MasCam), a radiometer (MARA), a magnetometer (MasMag) and a spectrometer (MicrOmega). In this work, we evaluate the success of MASCOT as an integrated lander to bridge the gap between orbiter and returned sample analysis. We find that MASCOT’s measurements and derivatives thereof, including the rock morphology, colour in the visible wavelengths, possible meteorite analogue, density, and porosity of the rock at the landing site are in good agreement with those of the orbiter and the returned samples. However, it also provides information on the spatial scale (sub-millimetres to centimetres) at which some physical properties such as the thermal inertia and reflectance undergo scale-dependent changes. Some of the in situ observations such as the presence of clast/inclusions in rocks and the absence of fine particles at the landing site was uniquely identified by MASCOT. Thus, we conclude that the delivery of an in situ instrument like MASCOT provides a valuable data set that complements and provides context for remote sensing and returned sample analyses.
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31.
  • Palm, Jenny, et al. (författare)
  • New Clean Energy Communities in a Changing European Energy System (NEWCOMERS) : Deliverable D3.1 Description of polycentric settings in the partner countries
  • 2020
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This deliverable maps the prevailing polycentric settings of six studied countries. The studied countries are the partner countries for the NEWCOMERS project, i.e. Germany, Italy, the Netherlands, Slovenia, Sweden and the United Kingdom. In this report, the countries' polycentric settings will be described in relation to the polycentric framework developed in WP 2, with specific focus on the technical system and actors. The factors in focus for the country descriptions are socio-economic conditions, technical system (electricity and heat), institutional arrangements as well as actors. Additionally, a description of energy communities in each country is presented, showing different developments in this area.The research was conducted through a desktop research. Existing literature, reports as well as statistical information were gathered and then organised according to the factors chosen.The aim in this delivery is to describe and understand the national polycentric settings as a first step to understand the emergence of new forms of energy communities. This deliverable is the basis for delivery 3.2, which will compare different polycentric national settings and delivery 3.3, which will evaluate what forms of energy communities work best in different polycentric setting and what are the potentials for learning between different polycentric settings.
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32.
  • Petrie, Ruth, et al. (författare)
  • Coordinating an operational data distribution network for CMIP6 data
  • 2021
  • Ingår i: Geoscientific Model Development. - Goettingen, Germany : Copernicus Gesellschaft MBH. - 1991-959X .- 1991-9603. ; 14:1, s. 629-644
  • Tidskriftsartikel (refereegranskat)abstract
    • The distribution of data contributed to the Coupled Model Intercomparison Project Phase 6 (CMIP6) is via the Earth System Grid Federation (ESGF). The ESGF is a network of internationally distributed sites that together work as a federated data archive. Data records from climate modelling institutes are published to the ESGF and then shared around the world. It is anticipated that CMIP6 will produce approximately 20 PB of data to be published and distributed via the ESGF. In addition to this large volume of data a number of value-added CMIP6 services are required to interact with the ESGF; for example the citation and errata services both interact with the ESGF but are not a core part of its infrastructure. With a number of interacting services and a large volume of data anticipated for CMIP6, the CMIP Data Node Operations Team (CDNOT) was formed. The CDNOT coordinated and implemented a series of CMIP6 preparation data challenges to test all the interacting components in the ESGF CMIP6 software ecosystem. This ensured that when CMIP6 data were released they could be reliably distributed. No. DE-ACO2-05CH11231 and authors at Lawrence Livermore National Laboratory (LLNL) under contract DE-AC52-07NA27344 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan).
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33.
  • Prencipe, Alessandro, et al. (författare)
  • Wavelength meter on thin film lithium niobate based on superconducting single photon detectors
  • 2023
  • Ingår i: 2023 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference, CLEO/Europe-EQEC 2023. - : Institute of Electrical and Electronics Engineers (IEEE).
  • Konferensbidrag (refereegranskat)abstract
    • Photonic integrated circuits (PICs) present significant benefits with respect to table-top optical systems regarding footprint, stability, and power consumption. Among the materials used to fabricate PICs, thin film lithium niobate (TFLN) is one of the most attractive ones, as its χ(2) nonlinearity and electro-optic properties allow to implement on-chip light generation and routing [1]. On-chip detection of light has also been demonstrated on TFLN, based on the waveguide integration of superconducting nanowire single photon detectors (SNSPDs) [1]. Combining efficient detectors with TFLN nanophotonic waveguides holds promises for the realization of quantum photonics experiments fully on-chip. On the other hand, the sensitivity of SNSPDs changes with the wavelength of the detected photons [2], setting a boundary to the longest detectable wavelength and limiting the use of the wide transparency window of TFLN. However, this wavelength dependency in the response of SNSPDs can be leveraged to achieve new on-chip functionalities. In this work, by performing a straightforward analysis of the light signal measured at different bias currents [2], we operate hairpin SNSPDs on TFLN as waveguide-integrated wavelength-meters in the telecom bandwidth.
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34.
  • Prencipe, Alessandro, et al. (författare)
  • Wavelength-Sensitive Superconducting Single-Photon Detectors on Thin Film Lithium Niobate Waveguides
  • 2023
  • Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 23:21, s. 9748-9752
  • Tidskriftsartikel (refereegranskat)abstract
    • Lithium niobate, because of its nonlinear and electro-optical properties, is one of the materials of choice for photonic applications. The development of nanostructuring capabilities of thin film lithium niobate (TFLN) permits fabrication of small footprint, low-loss optical circuits. With the recent implementation of on-chip single-photon detectors, this architecture is among the most promising for realizing on-chip quantum optics experiments. In this Letter, we report on the implementation of superconducting nanowire single-photon detectors (SNSPDs) based on NbTiN on 300 nm thick TFLN ridge nano-waveguides. We demonstrate a waveguide-integrated wavelength meter based on the photon energy dependence of the superconducting detectors. The device operates at the telecom C- and L-bands and has a footprint smaller than 300 × 180 μm2 and critical currents between ∼12 and ∼14 μA, which ensures operation with minimum heat dissipation. Our results hold promise for future densely packed on-chip wavelength-multiplexed quantum communication systems.
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35.
  • Rohm, Maria, et al. (författare)
  • An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice
  • 2016
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 22:10, s. 1120-1130
  • Tidskriftsartikel (refereegranskat)abstract
    • Cachexia represents a fatal energy-wasting syndrome in a large number of patients with cancer that mostly results in a pathological loss of skeletal muscle and adipose tissue. Here we show that tumor cell exposure and tumor growth in mice triggered a futile energy-wasting cycle in cultured white adipocytes and white adipose tissue (WAT), respectively. Although uncoupling protein 1 (Ucp1)-dependent thermogenesis was dispensable for tumor-induced body wasting, WAT from cachectic mice and tumor-cell-supernatant-treated adipocytes were consistently characterized by the simultaneous induction of both lipolytic and lipogenic pathways. Paradoxically, this was accompanied by an inactivated AMP-activated protein kinase (Ampk), which is normally activated in peripheral tissues during states of low cellular energy. Ampk inactivation correlated with its degradation and with upregulation of the Ampk-interacting protein Cidea. Therefore, we developed an Ampk-stabilizing peptide, ACIP, which was able to ameliorate WAT wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on Ampk. Thus, our data establish the Ucp1-independent remodeling of adipocyte lipid homeostasis as a key event in tumor-induced WAT wasting, and we propose the ACIP-dependent preservation of Ampk integrity in the WAT as a concept in future therapies for cachexia.
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36.
  • Roselli, Carolina, et al. (författare)
  • Multi-ethnic genome-wide association study for atrial fibrillation
  • 2018
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
  • Tidskriftsartikel (refereegranskat)abstract
    • Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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37.
  • Schaufler, Katharina, et al. (författare)
  • Genomic and Functional Analysis of Emerging Virulent and Multidrug-Resistant Escherichia coli Lineage Sequence Type 648
  • 2019
  • Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 63:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The pathogenic extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli lineage ST648 is increasingly reported from multiple origins. Our study of a large and global ST648 collection from various hosts (87 whole-genome sequences) combining core and accessory genomics with functional analyses and in vivo experiments suggests that ST648 is a nascent and generalist lineage, lacking clear phylogeographic and host association signals. By including large numbers of ST131 (n = 107) and ST10 (n = 96) strains for comparative genomics and phenotypic analysis, we demonstrate that the combination of multidrug resistance and high-level virulence are the hallmarks of ST648, similar to international high-risk clonal lineage ST131. Specifically, our in silico, in vitro, and in vivo results demonstrate that ST648 is well equipped with biofilm-associated features, while ST131 shows sophisticated signatures indicative of adaption to urinary tract infection, potentially conveying individual ecological niche adaptation. In addition, we used a recently developed NFDS (negative frequency-dependent selection) population model suggesting that ST648 will increase significantly in frequency as a cause of bacteremia within the next few years. Also, ESBL plasmids impacting biofilm formation aided in shaping and maintaining ST648 strains to successfully emerge worldwide across different ecologies. Our study contributes to understanding what factors drive the evolution and spread of emerging international high-risk clonal lineages.
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38.
  • Stephan, Katharina, 1986- (författare)
  • Biogenesis of the bc1 complex in mitochondria
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Mitochondria perform a variety of tasks, but the function they are most prominent for is the energy conversion to form ATP, the universal energy equivalent of the cell. The majority of this ATP is created by the oxidative phosphorylation system, consisting of the respiratory chain and the ATP synthase. These elaborate machineries channel electrons through the respiratory complexes and thereby generate an electrochemical gradient across the inner mitochondrial membrane. This, so called proton motive force, is in turn utilized by the ATP Synthase to produce ATP.A particularity of the oxidative phosphorylation complexes is that their subunits are derived from two genetic sources. As a result, and the fact that the respiratory chain complexes contain redox cofactors, the biogenesis of these enzymes is challenging and involves multiple, highly coordinated and regulated assembly steps. For the obligate homodimeric bc1 complex, a handful of assembly factors are known and its assembly can be divided into distinct assembly intermediates. In this work we provided insights into the maturation of the catalytic subunit cytochrome b. We revealed that the insertion of the redox active heme b groups is sequential and that it depends on the interaction with the early assembly factor Cbp4. With successful insertion of both heme bs, the binding of the structural subunit Qcr7 is necessary for stabilization and further assembly.Furthermore, we were able to delineate the dimerization event in detail. We could establish that the interaction of the two matrix subunits, Cor1 and Cor2, with the bc1 complex assembly intermediate II, as well as the dissociation of Cbp4, are the triggering point for dimerization.In our subsequent work we investigated the roles of the fairly uncharacterized assembly factor Bca1 and its interplay with the structural subunit Qcr7. We could demonstrate that Bca1 interacts early and transiently during assembly and is an important factor for efficient assembly. Additionally, we could show that Qcr7 is not only a structural subunit but also serves as an assembly checkpoint for the maturation of the bc1 complex.With our work we could illustrate the necessity for basic biochemical research within the model organism yeast, as the fundamental molecular mechanisms are well conserved. This is exemplified by our work on UQCC3, the human orthologue of the bc1 complex assembly factor Cbp4.
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39.
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40.
  • Stephan, Katharina, 1986-, et al. (författare)
  • Timing of dimerization of the bc1 complex during mitochondrial respiratory chain assembly
  • 2020
  • Ingår i: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728 .- 1879-2650. ; 1861:5-6
  • Tidskriftsartikel (refereegranskat)abstract
    • The mitochondrial bc1 complex plays an important role in mitochondrial respiration. It transfers electrons from ubiquinol to the soluble electron shuttle cytochrome c and thereby contributes to the proton motive force across the inner mitochondrial membrane. In the yeast Saccharomyces cerevisiae, each monomer consists of three catalytic and seven accessory subunits. The bc1 complex is an obligate homo-dimer in all systems. It is currently not known when exactly during the assembly dimerization occurs. In this study, we determined that the dimer formation is an early event. Specifically, dimerization is mediated by the interaction of a stable tetramer formed by the two Cor subunits, Cor1 and Cor2, that joins assembly intermediate II, containing the fully hemylated cytochrome b and the two small accessory proteins, Qcr7 and Qcr8. Addition of cytochrome c1 and Qcr6 can either occur concomitantly or independently of dimerization. These results reveal a strict order in assembly, where dimerization occurs after stabilization of co-factor acquisition by cytochrome b. Finally, assembly is completed by addition of the remaining subunits.
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41.
  • Stockbauer, Anna, et al. (författare)
  • Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission
  • 2024
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 51:4, s. 1023-1034
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA).Methods FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level.Results Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912).Conclusion Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.
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42.
  • van de Vegte, Yordi, et al. (författare)
  • Genetic insights into resting heart rate and its role in cardiovascular disease
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
  •  
43.
  • Vargas Möller-Hergt, Braulio, et al. (författare)
  • The ribosome receptors Mrx15 and Mba1 jointly organize cotranslational insertion and protein biogenesis in mitochondria
  • 2018
  • Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 29:20, s. 2359-2507
  • Tidskriftsartikel (refereegranskat)abstract
    • Mitochondrial gene expression in Saccharomyces cerevisiae is responsible for the production of highly hydrophobic subunits of the oxidative phosphorylation system. Membrane insertion occurs cotranslationally on membrane-bound mitochondrial ribosomes. Here, by employing a systematic mass spectrometry-based approach, we discovered the previously uncharacterized membrane protein Mrx15 that interacts via a soluble C-terminal domain with the large ribosomal subunit. Mrx15 contacts mitochondrial translation products during their synthesis and plays, together with the ribosome receptor Mba1, an overlapping role in cotranslational protein insertion. Taken together, our data reveal how these ribosome receptors organize membrane protein biogenesis in mitochondria.
  •  
44.
  • Volf, Carlo, et al. (författare)
  • Why daylight should be a priority for urban planning
  • 2024
  • Ingår i: Journal of Urban Management. - : Elsevier. - 2226-5856 .- 2589-0360.
  • Tidskriftsartikel (refereegranskat)abstract
    • Daylight is essential for ecosystems and for the physical and mental well-being of people. In densely populated cities, only a small proportion of total daylight is available to support urban greenery and most people have little daily exposure to natural daylight. Despite this, many cities have followed a strategy of densification as a way of preventing urban sprawl and reducing energy consumption. In this article, we review the biological importance of daylight and show that urban densification leads to a reduction in the daylight available for both people and nature. We conclude that daylight in cities should be treated as a limiting resource that needs to be planned and managed carefully, much like water or energy. We suggest elements for a policy framework aimed at optimizing urban daylight, including how to determine daylight needs, how to determine the maximum viable urban density, and policy options for built and unbuilt areas.
  •  
45.
  • Wanschers, Bas F. J., et al. (författare)
  • A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:23, s. 6356-6365
  • Tidskriftsartikel (refereegranskat)abstract
    • Complex III (cytochrome bc(1)) is a protein complex of the mitochondrial inner membrane that transfers electrons from ubiquinol to cytochrome c. Its assembly requires the coordinated expression of mitochondrial-encoded cytochrome b and nuclear-encoded subunits and assembly factors. Complex III deficiency is a severe multisystem disorder caused by mutations in subunit genes or assembly factors. Sequence-profile-based orthology predicts C11orf83, hereafter named UQCC3, to be the ortholog of the fungal complex III assembly factor CBP4. We describe a homozygous c.59T > A missense mutation in UQCC3 from a consanguineous patient diagnosed with isolated complex III deficiency, displaying lactic acidosis, hypoglycemia, hypotonia and delayed development without dysmorphic features. Patient fibroblasts have reduced complex III activity and lower levels of the holocomplex and its subunits than controls. They have no detectable UQCC3 protein and have lower levels of cytochrome b protein. Furthermore, in patient cells, cytochrome b is absent from a high-molecular-weight complex III. UQCC3 is reduced in cells depleted for the complex III assembly factors UQCC1 and UQCC2. Conversely, absence of UQCC3 in patient cells does not affect UQCC1 and UQCC2. This suggests that UQCC3 functions in the complex III assembly pathway downstream of UQCC1 and UQCC2 and is consistent with what is known about the function of Cbp4 and of the fungal orthologs of UQCC1 and UQCC2, Cbp3 and Cbp6. We conclude that UQCC3 functions in complex III assembly and that the c.59T > A mutation has a causal role in complex III deficiency.
  •  
46.
  • Weinbruch, Stephan, et al. (författare)
  • Chemical composition and sources of aerosol particles at Zeppelin Mountain (Ny Alesund, Svalbard) : An electron microscopy study
  • 2012
  • Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 49, s. 142-150
  • Tidskriftsartikel (refereegranskat)abstract
    • Aerosol particles were collected at the Zeppelin Mountain Atmospheric Research Station (474 m asl) near Ny Alesund (Svalbard, Norway) on 27 different days between July 2007 and December 2008. The size, morphology and chemical composition of 57,617 individual particles were studied by high-resolution scanning electron microscopy and energy-dispersive X-ray microanalysis. Based on chemical composition, morphology, mixing state and stability under electron bombardment, the particles were assigned to one of the following groups: sea salt, aged sea salt, Ca sulphates, Na sulphates, carbonates, soot, silicates, fly ashes, secondary aerosol, secondary aerosol plus sodium, secondary aerosol plus soot, mixed particles and others. Sea salt, aged sea salt, silicates and mixed particles (mixtures of sea salt, silicates and Ca sulphates) are the most abundant groups for particles with aerodynamic diameters > 0.5 mu m, secondary aerosol, mixed particles and secondary aerosol with soot inclusions below 0.5 mu m. Silicate fly ashes (major source coal burning) and metal fly ashes (from metallurgical high temperature processes) occur only at very low number concentrations. In contrast to previous work, the fly ash abundance is not correlated with air masses that crossed industrialized regions in Central and Eastern Europe, Scandinavia or Russia. These observations indicate a significant reduction of long-range transport of heavy metals to Svalbard. Soot (external and internally mixed with secondary aerosol) shows a pronounced seasonal pattern with a much lower abundance during summer compared to spring, autumn and winter. The soot abundance is not correlated with the air mass back-trajectories. During summer (July and August), soot was only observed when cruise ships were present in the area around Ny Alesund (Kongsfjorden). Pronounced seasonal patterns were observed for the abundance of the mineral dust component which is generally lower in summer compared to the other seasons. The observed seasonal dependence of anthropogenic primary particles (soot, fly ashes) is in good agreement with the Arctic circulation pattern.
  •  
47.
  • Zeuner, Katharina D., et al. (författare)
  • A stable wavelength-tunable triggered source of single photons and cascaded photon pairs at the telecom C-band
  • 2018
  • Ingår i: Applied Physics Letters. - : AMER INST PHYSICS. - 0003-6951 .- 1077-3118. ; 112:17
  • Tidskriftsartikel (refereegranskat)abstract
    • The implementation of fiber-based long-range quantum communication requires tunable sources of single photons at the telecom C-band. Stable and easy-to-implement wavelength-tunability of individual sources is crucial to (i) bring remote sources into resonance, (ii) define a wavelength standard, and (iii) ensure scalability to operate a quantum repeater. So far, the most promising sources for true, telecom single photons are semiconductor quantum dots, due to their ability to deterministically and reliably emit single and entangled photons. However, the required wavelength-tunability is hard to attain. Here, we show a stable wavelength-tunable quantum light source by integrating strain-released InAs quantum dots on piezoelectric substrates. We present triggered single-photon emission at 1.55 mu m with a multi-photon emission probability as low as 0.097, as well as photon pair emission from the radiative biexciton-exciton cascade. We achieve a tuning range of 0.25 nm which will allow us to spectrally overlap remote quantum dots or tuning distant quantum dots into resonance with quantum memories. This opens up realistic avenues for the implementation of photonic quantum information processing applications at telecom wavelengths. 
  •  
48.
  • Zeuner, Katharina, 1991-, et al. (författare)
  • On-demand generation of entangled photon pairs in the telecom C-band for fiber-based quantum networks
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • On–demand sources of entangled photons for the transmission of quantum information in the telecom C–band are required to realize fiber–based quantum networks. So far, non–deterministic sources of quantum states of light were used for long distance entanglement distribution in this lowest loss wavelength range. However, they are fundamentally limited in either efficiency or security due to their Poissonian emission statistics. Here, we show on–demand generation of entangled photon pairs in the telecom C-band by an InAs/GaAs semiconductor quantum dot. Using a robust phonon–assisted excitation scheme we measurea concurrence of 91.4% and a fidelity of 95.2% to Φ+ . On–demand generation of polarization entangled photons will enable secure quantum communication in fiber–based networks.Furthermore, applying this excitation scheme to several remote quantum dots tuned into resonance will enable first on–demand entanglement distribution over large distances for scalable real–life quantum applications.
  •  
49.
  • Zeuner, Katharina, et al. (författare)
  • On-Demand Generation of Entangled Photon Pairs in the Telecom C-Band with InAs Quantum Dots
  • 2021
  • Ingår i: ACS Photonics. - : AMER CHEMICAL SOC. - 2330-4022. ; 8:8, s. 2337-2344
  • Tidskriftsartikel (refereegranskat)abstract
    • Entangled photons are an integral part in quantum optics experiments and a key resource in quantum imaging, quantum communication, and photonic quantum information processing. Making this resource available on-demand has been an ongoing scientific challenge with enormous progress in recent years. Of particular interest is the potential to transmit quantum information over long distances, making photons the only reliable flying qubit. Entangled photons at the telecom C-band could be directly launched into single-mode optical fibers, enabling worldwide quantum communication via existing telecommunication infrastructure. However, the on-demand generation of entangled photons at this desired wavelength window has been elusive. Here, we show a photon pair generation efficiency of 69.9 +/- 3.6% in the telecom C-band by an InAs/GaAs semiconductor quantum dot on a metamorphic buffer layer. Using a robust phonon-assisted two-photon excitation scheme we measure a maximum concurrence of 91.4 +/- 3.8% and a peak fidelity to the Phi(+) state of 95.2 +/- 1.1%, verifying on-demand generation of strongly entangled photon pairs and marking an important milestone for interfacing quantum light sources with our classical fiber networks.
  •  
50.
  • Zeuner, Katharina (författare)
  • Semiconductor Quantum Optics at Telecom Wavelengths
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Quantum technologies are an expanding field in physics and engineering concerning the development of protocols and devices that enable augmented or novel applications based on quantum mechanics. This includes amongst others quantum computation and quantum communication. Quantum computers promise a computational speed–up based on superposition relevant for optimization and simulation problems, as well as for factorizing of large numbers, which poses a threat to our classical encryption schemes. Quantum communication offers a solution to this issue by providing an unconditionally secure communication channel based on the laws of quantum mechanics. Moreover, quantum communication would allow the exchange of quantum information between remote quantum computers, enabling distributed quantum computing. An infrastructure that links quantum computers or processors is referred to as a quantum network. Stationary quantum bits at the network nodes are used for performing information processing or storing operations, while flying quantum bits connect the nodes and enable the transfer of quantum information. Photons are excellent flying quantum bits, as they travel at the speed of light and have a small interaction cross–section. Consequently, quantum networks require sources of quantum states of light to provide flying quantum bits. These quantum states of light need to be entangled, indistinguishable and wavelength–matched such that they either experience low transmission losses in networks or can be interfaced with other quantum technologies like atom–based quantum memories. In this thesis the emission of single, indistinguishable or entangled photons from single self–assembled optically active semiconductor quantum dots, our quantum emitter of choice, has been studied. The investigated quantum dots emit either in the telecom range or close to the D1–transition in Rubidium. The main aspects of the experiments performed in this thesis were to research the integrability of the emitters into future quantum networks by making them wavelength–tunable, integrating them into photonic structures and employing resonant excitation schemes in order to generate photons with unprecedented purity, indistinguishability or entanglement concurrence. In the telecom range, we study InAsP nanowire quantum dots whose emission is shifted from the near–infrared range up to the telecom O–band and C–band. Single photon emission is demonstrated with decay times of the quantum dots similar to their near–infrared counterparts. Furthermore, InAs/GaAs quantum dots emitting in the telecom C–band are integrated onto piezo–electric substrates, and their emission is modulated into sidebands by using commercial telecommunication equipment. We generate on–demand single photons using a two–photon resonant excitation scheme and on–demand entangled photons via a phonon–assisted resonant scheme. Droplet–etched GaAs quantum dots with emission in the vicinity of the D1–Rubidium transition have been excited via two–photon resonant excitation to generate single photons with unparalleled purity and highly entangled photon pairs to perform entanglement swapping. Under resonance fluorescence, single and highly indistinguishable photons are extracted. Both resonant excitation schemes are theoretically compared to reveal the limitations of the two techniques. Moreover, these quantum dots are integrated into piezo–tunable broad–band micro parabolic cavities for an enhanced extraction efficiency.  
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