| 1. |
- Boersema, P. J., et al.
(författare)
-
Biology/Disease-Driven Initiative on Protein-Aggregation Diseases of the Human Proteome Project: Goals and Progress to Date
- 2018
-
Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:12, s. 4072-4084
-
Tidskriftsartikel (refereegranskat)abstract
- The Biology/Disease-driven (B/D) working groups of the Human Proteome Project are alliances of research groups aimed at developing or improving proteomic tools to support specific biological or disease-related research areas. Here, we describe the activities and progress to date of the B/D working group focused on protein aggregation diseases (PADs). PADs are characterized by the intra- or extracellular accumulation of aggregated proteins and include devastating diseases such as Parkinson's and Alzheimer's disease and systemic amyloidosis. The PAD B/D working group aims for the development of proteomic assays for the quantification of aggregation-prone proteins involved in PADs to support basic and clinical research on PADs. Because the proteins in PADs undergo aberrant conformational changes, a goal is to quantitatively resolve altered protein structures and aggregation states in complex biological specimens. We have developed protein-extraction protocols and a set of mass spectrometric (MS) methods that enable the detection and quantification of proteins involved in the systemic and localized amyloidosis and the probing of aberrant protein conformational transitions in cell and tissue extracts. In several studies, we have demonstrated the potential of MS-based proteomics approaches for specific and sensitive clinical diagnoses and for the subtyping of PADs. The developed methods have been detailed in both protocol papers and manuscripts describing applications to facilitate implementation by nonspecialized laboratories, and assay coordinates are shared through public repositories and databases. Clinicians actively involved in the PAD working group support the transfer to clinical practice of the developed methods, such as assays to quantify specific disease related proteins and their fragments in biofluids and multiplexed MS-based methods for the diagnosis and typing of systemic amyloidosis. We believe that the increasing availability of tools to precisely measure proteins involved in PADs will positively impact research on the molecular bases of these diseases and support early disease diagnosis and a more-confident subtyping.
|
|
| 2. |
- Campanella, A., et al.
(författare)
-
Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments : A study by ERIC, the European Research Initiative on CLL
- 2024
-
Ingår i: American Journal of Hematology. - : John Wiley & Sons. - 0361-8609 .- 1096-8652. ; 99:4, s. 745-750
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.
|
|
| 3. |
- Brauer, C. C., et al.
(författare)
-
Anatomy of extraordinary rainfall and flash flood in a Dutch lowland catchment
- 2011
-
Ingår i: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 15, s. 1991-2005
-
Tidskriftsartikel (refereegranskat)abstract
- On 26 August 2010 the eastern part of The Netherlands and the bordering part of Germany were struck by a series of rainfall events lasting for more than a day. Over an area of 740 km(2) more than 120 mm of rainfall were observed in 24 h. This extreme event resulted in local flooding of city centres, highways and agricultural fields, and considerable financial loss. In this paper we report on the unprecedented flash flood triggered by this exceptionally heavy rainfall event in the 6.5 km(2) Hupsel Brook catchment, which has been the experimental watershed employed by Wageningen University since the 1960s. This study aims to improve our understanding of the dynamics of such lowland flash floods. We present a detailed hydrometeorological analysis of this extreme event, focusing on its synoptic meteorological characteristics, its space-time rainfall dynamics as observed with rain gauges, weather radar and a microwave link, as well as the measured soil moisture, groundwater and discharge response of the catchment. At the Hupsel Brook catchment 160 mm of rainfall was observed in 24 h, corresponding to an estimated return period of well over 1000 years. As a result, discharge at the catchment outlet increased from 4.4x10(-3) to nearly 5m(3) s(-1). Within 7 h discharge rose from 5x10(-2) to 4.5m(3) s(-1). The catchment response can be divided into four phases: (1) soil moisture reservoir filling, (2) groundwater response, (3) surface depression filling and surface runoff and (4) backwater feedback. The first 35mm of rainfall were stored in the soil without a significant increase in discharge. Relatively dry initial conditions (in comparison to those for past discharge extremes) prevented an even faster and more extreme hydrological response.
|
|
| 4. |
- Lyon, Steve, et al.
(författare)
-
Combining radar and rain gauges to capture the space-time variability of monsoon rainfall during an extreme flood event
- 2008
-
Ingår i: EGU General Assembly.
-
Konferensbidrag (refereegranskat)abstract
- Monsoon rainfall events are typified by high spatial and temporal variability in both rainfall amount and intensity. Monsoon rainfall events occurring in Tucson, AZ, USA over seven consecutive days in July, 2006 lead to the highest ever recorded stream flows in Sabino Canyon Creek and resulted in flash flooding that caused large-scale property damage. Concurrent to these monsoon events, a network of 40 tipping bucket rain gauges were in place throughout the Sabino Canyon Creek watershed. In addition to this rain gauge network, radar data (NEXRAD) was collected during this monsoon period and used to derive rainfall accumulation maps with at 15-minute temporal resolution and 1 km2 spatial resolution. An event based, kinematic-wave overland flow runoff model (KINEROS) was used to model stream flow in Sabino Canyon Creek for the largest of the flooding events using rainfall data from both rain gauge observations and radar estimation. While the modeling results based solely on rain gauge observations agreed well with observed flow, the results were highly reliant on the extent of the spatial coverage of the rain gauge network. To overcome the reliance, geostatistics (kriging with external drift) were used to combine the rain gauge data with the radar data. By combining these two datasets, we could compensate for restricted spatial coverage in the rain gauge network. This allowed for high quality modeling of the flood event even with a great reduction in the spatial extent of the observational rain gauge network. Techniques to combine data from rain gauge networks and radar estimates are quite valuable as the development of real-time rain gauge network with good spatial extent and high spatial density is difficult and costly.
|
|
| 5. |
- Maas, Coen, et al.
(författare)
-
Misfolded proteins activate Factor XII in humans, leading to kallikrein formation without initiating coagulation
- 2008
-
Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 118:9, s. 3208-3218
-
Tidskriftsartikel (refereegranskat)abstract
- When blood is exposed to negatively charged surface materials such as glass, an enzymatic cascade known as the contact system becomes activated. This cascade is initiated by autoactivation of Factor XII and leads to both coagulation (via Factor XI) and an inflammatory response (via the kallikrein-kinin system). However, while Factor XII is important for coagulation in vitro, it is not important for physiological hemostasis, so the physiological role of the contact system remains elusive. Using patient blood samples and isolated proteins, we identified a novel class of Factor XII activators. Factor XII was activated by misfolded protein aggregates that formed by denaturation or by surface adsorption, which specifically led to the activation of the kallikreinkinin system without inducing coagulation. Consistent with this, we found that Factor XII, but not Factor XI, was activated and kallikrein was formed in blood from patients with systemic amyloidosis, a disease marked by the accumulation and deposition of misfolded plasma proteins. These results show that the kallikrein-kinin system can be activated by Factor XII, in a process separate from the coagulation cascade, and point to a protective role for Factor XII following activation by misfolded protein aggregates.
|
|
| 6. |
- Adams, David, et al.
(författare)
-
First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy
- 2016
-
Ingår i: Current Opinion in Neurology. - : Lippincott Williams & Wilkins. - 1350-7540 .- 1473-6551. ; 29, s. S14-S26
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose of review Early and accurate diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP) represents one of the major challenges faced by physicians when caring for patients with idiopathic progressive neuropathy. There is little consensus in diagnostic and management approaches across Europe. Recent findings The low prevalence of TTR-FAP across Europe and the high variation in both genotype and phenotypic expression of the disease means that recognizing symptoms can be difficult outside of a specialized diagnostic environment. The resulting delay in diagnosis and the possibility of misdiagnosis can misguide clinical decision-making and negatively impact subsequent treatment approaches and outcomes. Summary This review summarizes the findings from two meetings of the European Network for TTR-FAP (ATTReuNET). This is an emerging group comprising representatives from 10 European countries with expertise in the diagnosis and management of TTR-FAP, including nine National Reference Centres. The current review presents management strategies and a consensus on the gold standard for diagnosis of TTR-FAP as well as a structured approach to ongoing multidisciplinary care for the patient. Greater communication, not just between members of an individual patient's treatment team, but also between regional and national centres of expertise, is the key to the effective management of TTR-FAP.
|
|
| 7. |
- Banerjee, Sambhasan, et al.
(författare)
-
Amyloid fibril structure from the vascular variant of systemic AA amyloidosis
- 2022
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic AA amyloidosis is a debilitating protein misfolding disease in humans and animals. In humans, it occurs in two variants that are called 'vascular' and 'glomerular', depending on the main amyloid deposition site in the kidneys. Using cryo electron microscopy, we here show the amyloid fibril structure underlying the vascular disease variant. Fibrils purified from the tissue of such patients are mainly left-hand twisted and contain two non-equal stacks of fibril proteins. They contrast in these properties to the fibrils from the glomerular disease variant which are right-hand twisted and consist of two structurally equal stacks of fibril proteins. Our data demonstrate that the different disease variants in systemic AA amyloidosis are associated with different fibril morphologies.
|
|
| 8. |
- Benson, Merrill D., et al.
(författare)
-
Tissue biopsy for the diagnosis of amyloidosis : experience from some centres
- 2022
-
Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 29:1, s. 8-13
-
Tidskriftsartikel (refereegranskat)abstract
- A reliable diagnosis of amyloidosis is usually based on a tissue biopsy. With increasing options for specific treatments of the different amyloid diseases, an exact and valid diagnosis including determination of the biochemical fibril nature is imperative. Biopsy sites as well as amyloid typing principles vary and this paper describes methods employed at some laboratories specialised in amyloidosis in Europe, Japan and USA.
|
|
| 9. |
- Liberta, Falk, et al.
(författare)
-
Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids
- 2019
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic AA amyloidosis is a worldwide occurring protein misfolding disease of humans and animals. It arises from the formation of amyloid fibrils from the acute phase protein serum amyloid A. Here, we report the purification and electron cryo-microscopy analysis of amyloid fibrils from a mouse and a human patient with systemic AA amyloidosis. The obtained resolutions are 3.0 angstrom and 2.7 angstrom for the murine and human fibril, respectively. The two fibrils differ in fundamental properties, such as presence of right-hand or left-hand twisted cross-beta sheets and overall fold of the fibril proteins. Yet, both proteins adopt highly similar beta-arch conformations within the N-terminal similar to 21 residues. Our data demonstrate the importance of the fibril protein N-terminus for the stability of the analyzed amyloid fibril morphologies and suggest strategies of combating this disease by interfering with specific fibril polymorphs.
|
|
| 10. |
|
|
| 11. |
- Sjölander, Daniel, et al.
(författare)
-
Sensitive and rapid assessment of amyloid by oligothiophene fluorescence in subcutaneous fat tissue
- 2015
-
Ingår i: Amyloid. - : Informa Healthcare. - 1350-6129 .- 1744-2818. ; 22:1, s. 19-25
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic amyloidosis (SA) is often diagnosed late. Combining clinical and biochemical biomarkers is necessary for raising suspicion of disease. Fine needle aspiration (FNA) of subcutaneous fat enables SA detection by Congo red staining. The luminescent conjugated probe heptameric formic thiophene acetic acid (h-FTAA) is a sensitive alternative to Congo red-staining of tissue samples. Our objective was to compare h-FTAA fluorescence with the Congo red stain for amyloid detection in FNA-obtained fat tissue. Herein, we studied samples from 57 patients with established SA (19 with AA, 20 with AL, and 18 with ATTR) and 17 age-matched controls (34–75 years). Positivity for h-FTAA was graded according to a Congo red-based grading scale ranging from 0 to 4+. Amyloid grading by both methods correlated strongly (r = 0.87). Here h-FTAA was positive in 53 of 54 Congo red-positive cases (sensitivity 98%) and h-FTAA was negative in 7 of 17 Congo red-negative controls (specificity 41%), but was also positive for 3 Congo red-negative SA cases. We conclude that h-FTAA fluorescence is more sensitive than Congo red staining in this small exploratory study of fat tissue samples, implicating potential sensitivity for prodromal amyloidosis, but is less specific for clinical amyloidosis defined by Congo red positivity. Given its simplicity h-FTAA staining may therefore be the most appropriate method for rapid screening of fat tissue samples but should presently treat grade 1+ as only suggestive, whereas 2+ or higher as positive for amyloidosis. Parallel assessment of h-FTAA and Congo red staining appears highly promising for clinical applications.
|
|
| 12. |
- van Lier, Y. F., et al.
(författare)
-
Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients
- 2020
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 12:556
-
Tidskriftsartikel (refereegranskat)abstract
- Disruption of the intestinal microbiota occurs frequently in allogeneic hematopoietic cell transplantation (allo-HCT) recipients and predisposes them to development of graft-versus-host disease (GvHD). In a prospective, single-center, single-arm study, we investigated the effect of donor fecal microbiota transplantation (FMT) on symptoms of steroid-refractory or steroid-dependent, acute or late-onset acute intestinal GvHD in 15 individuals who had undergone allo-HCT. Study participants received a fecal suspension from an unrelated healthy donor via nasoduodenal infusion. Donor FMT was well tolerated, and infection-related adverse events did not seem to be related to the FMT procedure. In 10 of 15 study participants, a complete clinical response was observed within 1 month after FMT, without additional interventions to alleviate GvHD symptoms. This response was accompanied by an increase in gut microbial a-diversity, a partial engraft-ment of donor bacterial species, and increased abundance of butyrate-producing bacteria, including Clostridiales and Blautia species. In 6 of the 10 responding donor FMT recipients, immunosuppressant drug therapy was successfully tapered. Durable remission of steroid-refractory or steroid-dependent GvHD after donor FMT was associated with improved survival at 24 weeks after donor FMT. This study highlights the potential of donor FMT as a treatment for steroid-refractory or steroid-dependent GvHD, but larger clinical trials are needed to confirm the safety and efficacy of this procedure.
|
|
