| 1. |
- Lundberg, Mathias, et al.
(author)
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Challenges and opportunities in the diagnosis and treatment of early-onset psychosis : a case series from the youth affective disorders clinic in Stockholm, Sweden
- 2024
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In: Schizophrenia. - : Springer Nature. - 2754-6993. ; 10:1
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Journal article (peer-reviewed)abstract
- Early-onset psychosis is linked to adverse long-term outcomes, recurrent disease course, and prolonged periods of untreated illness; thus highlighting the urgency of improving early identification and intervention. This paper discusses three cases where initial emphasis on psychosocial treatments led to diagnostic and therapeutic delays: (1) a 15-year-old misdiagnosed with emotionally unstable personality disorder and autism, who improved on bipolar medication and antipsychotics; (2) another 15-year-old misdiagnosed with autism, who stabilized on lithium and antipsychotics, subsequently allowing for gender dysphoria evaluation; (3) a 9-year-old autistic boy incorrectly treated for ADHD, who recovered with appropriate antipsychotic treatment. These cases illuminate the vital importance of adhering to a diagnostic hierarchy, prioritizing diagnostic utility, and conducting longitudinal evaluations to facilitate early targeted treatment of psychotic symptoms in early-onset psychosis. Adherence to such strategies can minimize delays in managing early-onset psychosis and improve long-term prognoses.
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| 2. |
- Owe-Larsson, Björn, et al.
(author)
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Increased plasma levels of thioredoxin-1 in patients with first episode psychosis and long-term schizophrenia.
- 2011
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In: Progress in neuro-psychopharmacology & biological psychiatry. - : Elsevier BV. - 1878-4216 .- 0278-5846. ; 35:4, s. 1117-21
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Journal article (peer-reviewed)abstract
- Excessive level of radicals and/or dysfunctional antioxidant response, oxidative stress, is implicated in the pathogenesis of schizophrenia. A condition of oxidative stress has been detected in the brain, peripheral tissues and fluids including plasma. Plasma thioredoxin-1 (Trx1) is well characterized and a putative marker for oxidative stress and recently shown to be increased in plasma at the onset of schizophrenia. The present study aimed to explore whether Trx1 can be used as a marker to identify schizophrenic patients at the time-point when patients have their first episode of psychosis as compared to patients with long-term schizophrenia and mentally healthy patients, respectively. Plasma samples obtained from 18 patients at first episode of psychosis, from 49 long-term schizophrenic patients and from 20 mentally healthy controls (admitted with minor physical injury to the general ward) where analyzed by ELISA for Trx1. The patients with first episode of psychosis were diagnosed at least 6months later and shown to constitute various psychotic syndromes, including schizophrenia, or affective disorder. The concentration of Trx1 in the patients with first episode of psychosis was 1.5±1.0ng/ml and 0.8±0.6ng/ml in controls. In the long-term schizophrenic patients the plasma concentration was 1.5±0.7. The differences between the groups of acute psychotic or long-term schizophrenia patients to controls were significant (p<0.016 and p<0.001, respectively). Our data indicate that Trx1 may not be used as an early marker to identify schizophrenic patients in a mixed population of first episode psychotic patients. Further, Trx1 did not discriminate with reliable accuracy patients with psychotic disorder from mentally healthy controls on an individual basis due to overlap in levels of Trx1. However, our observations show that psychotic patients in general are in a significant long-term condition of oxidative stress, with possible implications for the profound morbidity and mortality found in this patient population.
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| 3. |
- Sköldberg, Håkan, et al.
(author)
-
BIO-CCS I FJÄRRVÄRMESEKTORN – SYNTES
- 2022
-
Reports (other academic/artistic)abstract
- Den svenska fjärrvärmesektorn har stor potential att bidra med negativa koldioxidutsläpp genom bio-CCS, minst 10 Mton per år. Den största osäkerheten beträffande möjligheterna för bio-CCS gäller marknads förutsättningarna. Uppvärmningsbranschen har en vision om att år 2045 utgöra en kolsänka. Ett sätt att åstadkomma detta är genom att avskilja och lagra koldioxidutsläpp med biogent ursprung. Ett antal fjärrvärmeföretag har redan olika långt gångna planer på att satsa på bio-CCS. De har sett ett värde i att samarbeta kring hur detta kan åstadkommas. Ett led i detta är projektet Bio-CCS i fjärrvärmesektorn som består av ett gediget underlag baserat på forskning kring olika aspekter av frågan samt en strategi baserad på det underlaget. I denna rapport redovisas en syntes av detta forskningsarbete. Projektet visar att fjärrvärmesektorn har stor teoretisk potential att bidra med negativa koldioxidutsläpp, minst 10 Mton per år. I huvudsak är avskiljning, transport och lagring av koldioxid beprövad teknik även om tillämpningen i detta fall är ny. Även om bio-CCS är förknippad med energianvändning så bidrar tekniken sett ur ett systemperspektiv med stor nytta för att minska koldioxid[1]utsläppen. Bio-CCS är en relativt dyr teknik och det är angeläget att utnyttja samverkan och kluster för att exempelvis skapa ökad kostnadseffektivitet i transport och mellanlagring. Tillgång till lagringsplatser är en förutsättning för framgång och flera alternativ bedöms bli tillgängliga. Det kan dock uppstå konkurrens om tillgången till lagringsplatserna. De regelmässiga förutsättningarna för bio-CCS i Sverige har förbättrats avsevärt de senaste dryga decenniet. Flera regelmässiga hinder kvarstår dock. En del utgör mindre barriärer, andra är av mer betydande karaktär. Den största osäkerheten beträffande möjligheterna för bio-CCS gäller ekonomin. Flera potentiella finansieringsmetoder har studerats, både stöd, regleringar och frivilligmarknader. Det finns fortfarande oklarheter kring syftet med planerade stöd och det framtida ägandet av de negativa utsläppen. Det genomförda projektet har skapat ett forum för kunskapsuppbyggnad, erfarenhetsutbyte och nätverkande, vilket de deltagande företagen bedömt vara mycket värdefullt.
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| 4. |
- Adhikari, Subash, et al.
(author)
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A high-stringency blueprint of the human proteome
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Research review (peer-reviewed)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 5. |
- Aebersold, Ruedi, et al.
(author)
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How many human proteoforms are there?
- 2018
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In: Nature Chemical Biology. - : NATURE PUBLISHING GROUP. - 1552-4450 .- 1552-4469. ; 14:3, s. 206-214
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Journal article (peer-reviewed)abstract
- Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA-and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.
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| 6. |
- Ahmad, Yasmeen, et al.
(author)
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Systematic Analysis of Protein Pools, Isoforms, and Modifications Affecting Turnover and Subcellular Localization
- 2012
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 11:3
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Journal article (peer-reviewed)abstract
- In higher eukaryotes many genes encode protein isoforms whose properties and biological roles are often poorly characterized. Here we describe systematic approaches for detection of either distinct isoforms, or separate pools of the same isoform, with differential biological properties. Using information from ion intensities we have estimated protein abundance levels and using rates of change in stable isotope labeling with amino acids in cell culture isotope ratios we measured turnover rates and subcellular distribution for the HeLa cell proteome. Protein isoforms were detected using three data analysis strategies that evaluate differences between stable isotope labeling with amino acids in cell culture isotope ratios for specific groups of peptides within the total set of peptides assigned to a protein. The candidate approach compares stable isotope labeling with amino acids in cell culture isotope ratios for predicted isoform- specific peptides, with ratio values for peptides shared by all the isoforms. The rule of thirds approach compares the mean isotope ratio values for all peptides in each of three equal segments along the linear length of the protein, assessing differences between segment values. The three in a row approach compares mean isotope ratio values for each sequential group of three adjacent peptides, assessing differences with the mean value for all peptides assigned to the protein. Protein isoforms were also detected and their properties evaluated by fractionating cell extracts on one- dimensional SDS- PAGE prior to trypsin digestion and MS analysis and independently evaluating isotope ratio values for the same peptides isolated from different gel slices. The effect of protein phosphorylation on turnover rates was analyzed by comparing mean turnover values calculated for all peptides assigned to a protein, either including, or excluding, values for cognate phosphopeptides. Collectively, these experimental and analytical approaches provide a framework for expanding the func- tional annotation of the genome.
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| 7. |
- Akan, Pelin, et al.
(author)
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Comprehensive analysis of the genome transcriptome and proteome landscapes of three tumor cell lines
- 2012
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In: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X .- 1756-994X. ; 4, s. 86-
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Journal article (peer-reviewed)abstract
- We here present a comparative genome, transcriptome and functional network analysis of three human cancer cell lines (A431, U251MG and U2OS), and investigate their relation to protein expression. Gene copy numbers significantly influenced corresponding transcript levels; their effect on protein levels was less pronounced. We focused on genes with altered mRNA and/or protein levels to identify those active in tumor maintenance. We provide comprehensive information for the three genomes and demonstrate the advantage of integrative analysis for identifying tumor-related genes amidst numerous background mutations by relating genomic variation to expression/protein abundance data and use gene networks to reveal implicated pathways.
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| 8. |
- Al-Saadi, Jonathan, et al.
(author)
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Endovascular transplantation of mRNA-enhanced mesenchymal stromal cells results in superior therapeutic protein expression in swine heart
- 2024
-
In: Molecular therapy. Methods & clinical development. - : Elsevier BV. - 2399-6951 .- 2329-0501. ; 32:2
-
Journal article (peer-reviewed)abstract
- Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- and cell-based therapies to improve cardiac function. The safe and efficient delivery of these therapies to solid organs is challenging. Herein, we demonstrate the feasibility of using an endovascular intramyocardial delivery approach to safely administer mRNA drug products and perform cell transplantation procedures in swine. Using a trans-vessel wall (TW) device, we delivered chemically modified mRNAs (modRNA) and mRNA-enhanced mesenchymal stromal cells expressing vascular endothelial growth factor A (VEGF-A) directly to the heart. We monitored and mapped the cellular distribution, protein expression, and safety tolerability of such an approach. The delivery of modRNA-enhanced cells via the TW device with different flow rates and cell concentrations marginally affect cell viability and protein expression in situ. Implanted cells were found within the myocardium for at least 3 days following administration, without the use of immunomodulation and minimal impact on tissue integrity. Finally, we could increase the protein expression of VEGF-A over 500-fold in the heart using a cell-mediated modRNA delivery system compared with modRNA delivered in saline solution. Ultimately, this method paves the way for future research to pioneer new treatments for cardiac disease.
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| 9. |
- Alm, Tove, et al.
(author)
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A Chromosome-Centric Analysis of Antibodies Directed toward the Human Proteome Using Antibodypedia
- 2014
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:3, s. 1669-1676
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Journal article (peer-reviewed)abstract
- Antibodies are crucial for the study of human proteins and have been defined as one of the three pillars in the human chromosome-centric Human Proteome Project (CHPP). In this article the chromosome-centric structure has been used to analyze the availability of antibodies as judged by the presence within the portal Antibodypedia, a database designed to allow comparisons and scoring of publicly available antibodies toward human protein targets. This public database displays antibody data from more than one million antibodies toward human protein targets. A summary of the content in this knowledge resource reveals that there exist more than 10 antibodies to over 70% of all the putative human genes, evenly distributed over the 24 human chromosomes. The analysis also shows that at present, less than 10% of the putative human protein-coding genes (n = 1882) predicted from the genome sequence lack antibodies, suggesting that focused efforts from the antibody-based and mass spectrometry-based proteomic communities should be encouraged to pursue the analysis of these missing proteins. We show that Antibodypedia may be used to track the development of available and validated antibodies to the individual chromosomes, and thus the database is an attractive tool to identify proteins with no or few antibodies yet generated.
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| 10. |
- Alm, Tove, et al.
(author)
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Introducing the Affinity Binder Knockdown Initiative-A public-private partnership for validation of affinity reagents
- 2016
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In: EuPA Open Proteomics. - : Elsevier. - 2212-9685. ; 10, s. 56-58
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Journal article (peer-reviewed)abstract
- The newly launched Affinity Binder Knockdown Initiative encourages antibody suppliers and users to join this public-private partnership, which uses crowdsourcing to collect characterization data on antibodies. Researchers are asked to share validation data from experiments where gene-editing techniques (such as siRNA or CRISPR) have been used to verify antibody binding. The initiative is launched under the aegis of Antibodypedia, a database designed to allow comparisons and scoring of publicly available antibodies towards human protein targets. What is known about an antibody is the foundation of the scoring and ranking system in Antibodypedia.
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