| 1. |
|
|
| 2. |
- Ge, Changrong P, et al.
(författare)
-
Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage
- 2017
-
Ingår i: JCI INSIGHT. - : AMER SOC CLINICAL INVESTIGATION INC. - 2379-3708. ; 2:13
-
Tidskriftsartikel (refereegranskat)abstract
- Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis.
|
|
| 3. |
- Hampel, Harald, et al.
(författare)
-
Advances in the therapy of Alzheimer's disease : targeting amyloid beta and tau and perspectives for the future
- 2015
-
Ingår i: Expert Review of Neurotherapeutics. - : Informa UK Limited. - 1473-7175 .- 1744-8360. ; 15:1, s. 83-105
-
Forskningsöversikt (refereegranskat)abstract
- Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD.
|
|
| 4. |
- Kalman, Janos L, et al.
(författare)
-
Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
-
Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
-
Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
|
|
| 5. |
|
|
| 6. |
- Schomerus, Georg, et al.
(författare)
-
Das Stigma von Suchterkrankungen verstehen und überwinden
- 2017
-
Ingår i: SUCHT. - : Hogrefe Publishing Group. - 0939-5911 .- 1664-2856. ; 63:5, s. 253-259
-
Tidskriftsartikel (refereegranskat)abstract
- Stigmatisierung schadet den Betroffenen und verstärkt Suchtprobleme. Sie ist ein Hindernis auf dem Weg zur Hilfe, führt zu schlechterer Behandlung und vergrößert die sozialen und gesundheitlichen Folgen einer Suchtkrankheit. Das gilt sowohl für die individuellen Folgen als auch für die gesellschaftlichen einschließlich der öffentlichen Gesundheitskosten. Zudem ist Stigmatisierung ein ethisches Problem, weil sie eine bestimmte Gruppe benachteiligt und die Menschenwürde der Betroffenen angreift. Ein stigmafreier Umgang mit Suchtkrankheiten ist möglich. Entstigmatisierung bedeutet, bessere Lösungen für Suchtprobleme zu finden und verfügbar zu machen. Nicht Abwertung, Ausgrenzung und Disziplinierung, sondern Wertschätzung und Befähigung (Empowerment) müssen im Zentrum von Prävention, Behandlung sowie dem alltäglichen Umgang mit Suchtkrankheiten stehen.
|
|
| 7. |
- Schuettpelz, Eric, et al.
(författare)
-
A community-derived classification for extant lycophytes and ferns
- 2016
-
Ingår i: Journal of Systematics and Evolution. - : Wiley. - 1674-4918 .- 1759-6831. ; 54:6, s. 563-603
-
Tidskriftsartikel (refereegranskat)abstract
- Phylogeny has long informed pteridophyte classification. As our ability to infer evolutionary trees has improved, classifications aimed at recognizing natural groups have become increasingly predictive and stable. Here, we provide a modern, comprehensive classification for lycophytes and ferns, down to the genus level, utilizing a community-based approach. We use monophyly as the primary criterion for the recognition of taxa, but also aim to preserve existing taxa and circumscriptions that are both widely accepted and consistent with our understanding of pteridophyte phylogeny. In total, this classification treats an estimated 11 916 species in 337 genera, 51 families, 14 orders, and two classes. This classification is not intended as the final word on lycophyte and fern taxonomy, but rather a summary statement of current hypotheses, derived from the best available data and shaped by those most familiar with the plants in question. We hope that it will serve as a resource for those wanting references to the recent literature on pteridophyte phylogeny and classification, a framework for guiding future investigations, and a stimulus to further discourse.
|
|
| 8. |
- Sharma, Sapna, et al.
(författare)
-
A global database of lake surface temperatures collected by in situ and satellite methods from 1985–2009
- 2015
-
Ingår i: Scientific Data. - : Macmillan Publishers Limited. - 2052-4463. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- Global environmental change has influenced lake surface temperatures, a key driver of ecosystem structure and function. Recent studies have suggested significant warming of water temperatures in individual lakes across many different regions around the world. However, the spatial and temporal coherence associated with the magnitude of these trends remains unclear. Thus, a global data set of water temperature is required to understand and synthesize global, long-term trends in surface water temperatures of inland bodies of water. We assembled a database of summer lake surface temperatures for 291 lakes collected in situ and/or by satellites for the period 1985–2009. In addition, corresponding climatic drivers (air temperatures, solar radiation, and cloud cover) and geomorphometric characteristics (latitude, longitude, elevation, lake surface area, maximum depth, mean depth, and volume) that influence lake surface temperatures were compiled for each lake. This unique dataset offers an invaluable baseline perspective on global-scale lake thermal conditions as environmental change continues.
|
|
| 9. |
- Veiga, Lene H. S., et al.
(författare)
-
Thyroid Cancer after Childhood Exposure to External Radiation : An Updated Pooled Analysis of 12 Studies
- 2016
-
Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 185:5, s. 473-484
-
Tidskriftsartikel (refereegranskat)abstract
- Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.
|
|
| 10. |
|
|
