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- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Heil, Katharina F., 1987-
(författare)
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A Systems Biological Approach to Parkinson's Disease
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson’s Disease (PD) is the second most common neurodegenerative disease in the Western world. Itshows a high degree of genetic and phenotypic complexity with many implicated factors, various diseasemanifestations but few clear causal links. Ongoing research has identified a growing number of molecularalterations linked to the disease.Dopaminergic neurons in the substantia nigra, specifically their synapses, are the key-affected region in PD.Therefore, this work focuses on understanding the disease effects on the synapse, aiming to identify potentialgenetic triggers and synaptic PD associated mechanisms. Currently, one of the main challenges in this area isdata quality and accessibility.In order to study PD, publicly available data were systematically retrieved and analysed. 418 PD associatedgenes could be identified, based on mutations and curated annotations. I curated an up-to-date and completesynaptic proteome map containing a total of 6,706 proteins. Region specific datasets describing thepresynapse, postsynapse and synaptosome were also delimited. These datasets were analysed, investigatingsimilarities and differences, including reproducibility and functional interpretations.The use of Protein-Protein-Interaction Network (PPIN) analysis was chosen to gain deeper knowledgeregarding specific effects of PD on the synapse. Thus I generated a customised, filtered, human specificProtein-Protein Interaction (PPI) dataset, containing 211,824 direct interactions, from four public databases.Proteomics data and PPI information allowed the construction of PPINs. These were analysed and a set oflow level statistics, including modularity, clustering coefficient and node degree, explaining the network’stopology from a mathematical point of view were obtained.Apart from low-level network statistics, high-level topology of the PPINs was studied. To identify functionalnetwork subgroups, different clustering algorithms were investigated. In the context of biological networks, theunderlying hypothesis is that proteins in a structural community are more likely to share common functions.Therefore I attempted to identify PD enriched communities of synaptic proteins. Once identified, they werecompared amongst each other. Three community clusters could be identified as containing largely overlappinggene sets. These contain 24 PD associated genes. Apart from the known disease associated genes in thesecommunities, a total of 322 genes was identified. Each of the three clusters is specifically enriched for specificbiological processes and cellular components, which include neurotransmitter secretion, positive regulation ofsynapse assembly, pre- and post-synaptic membrane, scaffolding proteins, neuromuscular junctiondevelopment and complement activation (classical pathway) amongst others.The presented approach combined a curated set of PD associated genes, filtered PPI information andsynaptic proteomes. Various small- and large-scale analytical approaches, including PPIN topology analysis,clustering algorithms and enrichment studies identified highly PD affected synaptic proteins and subregions.Specific disease associated functions confirmed known research insights and allowed me to propose a newlist of so far unknown potential disease associated genes. Due to the open design, this approach can be usedto answer similar research questions regarding other complex diseases amongst others.
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- Itzhaki, Ruth F., et al.
(författare)
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Microbes and Alzheimer's Disease
- 2016
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 51:4, s. 979-984
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We are researchers and clinicians working on Alzheimer’s disease (AD) or related topics, and we write to express our concern that one particular aspect of the disease has been neglected, even though treatment based on it might slow or arrest AD progression. We refer to the many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochaete, in the etiology of AD [1–4]. Fungal infection of AD brain [5, 6] has also been described, as well as abnormal microbiota in AD patient blood [7]. The first observations of HSV1 in AD brain were reported almost three decades ago [8]. The ever-increasing number of these studies (now about 100 on HSV1 alone) warrants re-evaluation of the infection and AD concept.AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide, a cleavage product of the amyloid-β protein precursor (AβPP), and abnormal forms of tau protein, markers that have been used as diagnostic criteria for the disease [9, 10]. These constitute the hallmarks of AD, but whether they are causes of AD or consequences is unknown. We suggest that these are indicators of an infectious etiology. In the case of AD, it is often not realized that microbes can cause chronic as well as acute diseases; that some microbes can remain latent in the body with the potential for reactivation, the effects of which might occur years after initial infection; and that people can be infected but not necessarily affected, such that ‘controls’, even if infected, are asymptomatic
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