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- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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- Almstedt, Karin, 1980-, et al.
(författare)
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Unfolding a folding disease: folding, misfolding and aggregation of the marble brain syndrome-associated mutant H107Y of human carbonic anhydrase II
- 2004
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Ingår i: Journal of Molecular Biology. - Oxford : Elsevier. - 0022-2836 .- 1089-8638. ; 342:2, s. 619-633
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Tidskriftsartikel (refereegranskat)abstract
- Most loss-of-function diseases are caused by aberrant folding of important proteins. These proteins often misfold due to mutations. The disease marble brain syndrome (MBS), known also as carbonic anhydrase II deficiency syndrome (CADS), can manifest in carriers of point mutations in the human carbonic anhydrase II (HCA II) gene. One mutation associated with MBS entails the His107Tyr substitution. Here, we demonstrate that this mutation is a remarkably destabilizing folding mutation. The loss-of-function is clearly a folding defect, since the mutant shows 64% of CO2 hydration activity compared to that of the wild-type at low temperature where the mutant is folded. On the contrary, its stability towards thermal and guanidine hydrochloride (GuHCl) denaturation is highly compromised. Using activity assays, CD, fluorescence, NMR, cross-linking, aggregation measurements and molecular modeling, we have mapped the properties of this remarkable mutant. Loss of enzymatic activity had a midpoint temperature of denaturation (Tm) of 16 °C for the mutant compared to 55 °C for the wild-type protein. GuHCl-denaturation (at 4 °C) showed that the native state of the mutant was destabilized by 9.2 kcal/mol. The mutant unfolds through at least two equilibrium intermediates; one novel intermediate that we have termed the molten globule light state and, after further denaturation, the classical molten globule state is populated. Under physiological conditions (neutral pH; 37 °C), the His107Tyr mutant will populate the molten globule light state, likely due to novel interactions between Tyr107 and the surroundings of the critical residue Ser29 that destabilize the native conformation. This intermediate binds the hydrophobic dye 8-anilino-1-naphthalene sulfonic acid (ANS) but not as strong as the molten globule state, and near-UV CD reveals the presence of significant tertiary structure. Notably, this intermediate is not as prone to aggregation as the classical molten globule. As a proof of concept for an intervention strategy with small molecules, we showed that binding of the CA inhibitor acetazolamide increases the stability of the native state of the mutant by 2.9 kcal/mol in accordance with its strong affinity. Acetazolamide shifts the Tm to 34 °C that protects from misfolding and will enable a substantial fraction of the enzyme pool to survive physiological conditions.
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- Andersson, C, et al.
(författare)
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The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes
- 2011
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Ingår i: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 44:5, s. 394-405
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative.Methods: A total of 686 patients diagnosed in 1996–2005 in Skåne were analyzed for all the seven autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] in addition to HLA-DQ genotypes.Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%—a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1*X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA.Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1*X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
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- Andrén, Eva, et al.
(författare)
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Öppna prioriteringar inom nya områden : logopedi, nutritionsbedömning, habilitering och arbetsterapi
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det finns fortfarande ett behov av att öka kunskapen om och stödja den praktiska tillämpningen av riksdagens riktlinjer för öppna prioriteringar inom svensk hälso- och sjukvård. Flera förslag på hur ett sådant stöd kan se ut har tagits fram de senaste åren. Spridning av goda exempel är ett sådant förslag, metodstöd ett annat (PrioriteringsCentrum 2007). En mer påtaglig form av metodstöd är den nationella modell som vuxit fram för att konkretisera innebörden i riktlinjerna (Carlsson m fl 2007). Den får idag anses som välbeprövad inom ett flertal områden och har bidragit till att samsynen och kommunicerbarheten kring prioriteringar har ökat i landet. Erfarenheter visar dock att det behövs pedagogisk vägledning i hur modellen kan tillämpas. För att möta upp efterfrågan på sådant metodstöd erbjuder Prioriteringscentrum handledning i grupp. Den första handledningsgruppen är nu avslutad och det är deltagarnas prioriteringsarbeten som presenteras i denna rapport i syfte att sprida konkreta exempel på försök att tillämpa prioriteringsriktlinjerna.I rapporten presenteras fyra prioriteringsarbeten med fokus på: Regionsamverkan inom arbetsterapi Logopedi Yrkesspecifika prioriteringar på väg till teamet Från projekt till integrerat redskapExemplet med prioriteringar i regionsamverkan utgörs av det prioriteringsarbete som genomförts i det s k femklövernätverket bestående av en samverkansgrupp för arbetsterapeuter i ledningsposition på sjukhusen i Uppland, Västmanland, Södermanland, Gävleborg och Dalarna. Arbetet var ett försök att skapa gemensamma prioriteringar i regionen för ett sjukdomsområde som kändes relevant. Valet kom att falla på arbetsterapi inom reumatologi. Arbetet har sedan huvudsakligen bedrivits i en projektgrupp, bestående av en representant från varje sjukhus där arbetet växlat mellan arbete på hemmaplan och avstämningsträffar i projektgruppen.Försöket har visat att det finns en samsyn inom regionen kring prioriteringar inom arbetsterapi och reumatologi. Säkerheten i prioriteringarna har ökat i och med att fem arbetsterapiorganisationer tillsammans bidragit med ett stort underlagsmaterial bl a genom att delge varandra sina kliniska erfarenheter. Förutsättningarna för en mer likartad vård i regionen har ökat. Arbetet har också gett upphov till frågor om i vilka situationer det är att föredra att prioriteringsarbete bedrivs lokalt, regionvis och/eller nationellt.
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- Ax, Anna-Karin, 1980-, et al.
(författare)
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Exercise : A positive feature on functioning in daily life during cancer treatment — Experiences from the Phys-Can study
- 2020
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Ingår i: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 44
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Impaired functioning due to cancer treatment is a challenge for daily life. Exercise during treatment can improve functioning. However, research describing experiences of how exercise affects activities of daily life is limited. We aimed to explore how individuals with cancer receiving curative treatment and participating in an exercise intervention experienced their functioning in daily life.METHODS: Twenty-one participants were recruited from Phys-Can, an exercise intervention study. Semi-structured interviews were conducted after the intervention had finished, and data was analysed using thematic analysis.RESULTS: Two main themes evolved: "Striving to maintain a normal life in a new context" and "Struggling with impairments from side effects of cancer treatment". The supervised group exercise proved popular, and participants reported positive effects on physical and psychological functioning, as well as social and informative support from other participants. Participants struggled with impaired cognitive and physical functioning and exhaustion. They strove to maintain a normal life by adjusting their activities.CONCLUSIONS: Perceived physical and psychological benefits from exercise during cancer treatment suggest that exercise should be a part of cancer rehabilitation to facilitate activities and participation in daily life. Striving to maintain a normal life during cancer treatment is vital, and adjustments are needed to maintain activities and participation in daily life. Cancer nurses should motivate patients to engage in physical activity and encourage the introduction of exercise as part of their rehabilitation. They could also support patients in making adjustments to maintain functioning in daily life.
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