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| 2. |
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| 3. |
- Mangano, M. C., et al.
(författare)
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The aquaculture supply chain in the time of covid-19 pandemic : Vulnerability, resilience, solutions and priorities at the global scale
- 2022
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Ingår i: Environmental Science and Policy. - : Elsevier. - 1462-9011 .- 1873-6416. ; 127, s. 98-110
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 global pandemic has had severe, unpredictable and synchronous impacts on all levels of perishable food supply chains (PFSC), across multiple sectors and spatial scales. Aquaculture plays a vital and rapidly expanding role in food security, in some cases overtaking wild caught fisheries in the production of high quality animal protein in this PFSC. We performed a rapid global assessment to evaluate the effects of the COVID19 pandemic and related emerging control measures on the aquaculture supply chain. Socio-economic effects of the pandemic were analysed by surveying the perceptions of stakeholders, who were asked to describe potential supply-side disruption, vulnerabilities and resilience patterns along the production pipeline with four main supply chain components: a) hatchery, b) production/processing, c) distribution/logistics and d) market. We also assessed different farming strategies, comparing land-vs. sea-based systems; extensive vs. intensive methods; and with and without integrated multi-trophic aquaculture, IMTA. In addition to evaluating levels and sources of economic distress, interviewees were asked to identify mitigation solutions adopted at local / internal (i.e., farm site) scales, and to express their preference on national / external scale mitigation measures among a set of a priori options. Survey responses identified the potential causes of disruption, ripple effects, sources of food insecurity, and socio-economic conflicts. They also pointed to various levels of mitigation strategies. The collated evidence represents a first baseline useful to address future disaster-driven responses, to reinforce the resilience of the sector and to facilitate the design reconstruction plans and mitigation measures, such as financial aid strategies.
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| 4. |
- Meinander, K., et al.
(författare)
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Pseudopeptides with a centrally positioned alkene-based disulphide bridge mimetic stimulate kallikrein-related peptidase 3 activity
- 2013
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Ingår i: Medchemcomm. - : Royal Society of Chemistry (RSC). - 2040-2503 .- 2040-2511. ; 4:3, s. 549-553
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Tidskriftsartikel (refereegranskat)abstract
- Pseudopeptides based on the kallikrein-related peptidase 3 (KLK3) activating bicyclic peptide “C-4” comprising hydrocarbon-based disulphide bridge mimetics have been synthesized. After investigating different synthetic approaches, the pseudopeptides were successfully cyclized from two L-allylglycine side chains via an alkene ring-closing metathesis reaction during the peptide synthesis. The alkene-linker was formed in a 1 : 1 E/Z isomer ratio. The resulting pseudopeptides were almost as potent as the parent peptide, increasing the activity of KLK3 over four-fold at 200 μg ml−1 (130–140 μM) concentrations.
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| 10. |
- Sarà, G., et al.
(författare)
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The Synergistic Impacts of Anthropogenic Stressors and COVID-19 on Aquaculture : A Current Global Perspective
- 2022
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Ingår i: Reviews in Fisheries Science & Aquaculture. - : Informa UK Limited. - 2330-8249 .- 2330-8257. ; 30:1, s. 123-135
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Tidskriftsartikel (refereegranskat)abstract
- The rapid, global spread of COVID-19, and the measures intended to limit or slow its propagation, are having major impacts on diverse sectors of society. Notably, these impacts are occurring in the context of other anthropogenic-driven threats including global climate change. Both anthropogenic stressors and the COVID-19 pandemic represent significant economic challenges to aquaculture systems across the globe, threatening the supply chain of one of the most important sources of animal protein, with potential disproportionate impacts on vulnerable communities. A web survey was conducted in 47 countries in the midst of the COVID-19 pandemic to assess how aquaculture activities have been affected by the pandemic, and to explore how these impacts compare to those from climate change. A positive correlation between the effects of the two categories of drivers was detected, but analysis suggests that the pandemic and the anthropogenic stressors affect different parts of the supply chain. The immediate measurable reported losses varied with aquaculture typology (land vs. marine, and intensive vs. extensive). A comparably lower impact on farmers reporting the use of integrated multitrophic aquaculture (IMTA) methods suggests that IMTA might enhance resilience to multiple stressors by providing different market options under the COVID-19 pandemic. Results emphasize the importance of assessing detrimental effects of COVID-19 under a multiple stressor lens, focusing on areas that have already locally experienced economic loss due to anthropogenic stressors in the last decade. Holistic policies that simultaneously address other ongoing anthropogenic stressors, rather than focusing solely on the acute impacts of COVID-19, are needed to maximize the long-term resilience of the aquaculture sector.
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| 13. |
- Arnerić, S. P., et al.
(författare)
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Cerebrospinal fluid biomarkers for Alzheimer's disease: A view of the regulatory science qualification landscape from the coalition against major diseases CSF biomarker team
- 2017
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 55:1, s. 19-35
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) drug development is burdened with the current requirement to conduct large, lengthy, and costly trials to overcome uncertainty in patient progression and effect size on treatment outcome measures. There is an urgent need for the discovery, development, and implementation of novel, objectively measured biomarkers for AD that would aid selection of the appropriate subpopulation of patients in clinical trials, and presumably, improve the likelihood of successfully evaluating innovative treatment options. Amyloid deposition and tau in the brain, which are most commonly assessed either in cerebrospinal fluid (CSF) or by molecular imaging, are consistently and widely accepted. Nonetheless, a clear gap still exists in the accurate identification of subjects that truly have the hallmarks of AD. The Coalition Against Major Diseases (CAMD), one of 12 consortia of the Critical Path Institute (C-Path), aims to streamline drug development for AD and related dementias by advancing regulatory approved drug development tools for clinical trials through precompetitive data sharing and adoption of consensus clinical data standards. This report focuses on the regulatory process for biomarker qualification, briefly comments on how it contrasts with approval or clearance of companion diagnostics, details the qualifications currently available to the field of AD, and highlights the current challenges facing the landscape of CSF biomarkers qualified as hallmarks of AD. Finally, it recommends actions to accelerate regulatory qualification of CSF biomarkers that would, in turn, improve the efficiency of AD therapeutic development. © 2017 - IOS Press and the authors.
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| 14. |
- Becanovic, K, et al.
(författare)
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New loci regulating rat myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis
- 2003
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 170:2, s. 1062-1069
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Tidskriftsartikel (refereegranskat)abstract
- Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in rats that closely mimics many clinical and histopathological aspects of multiple sclerosis. Non-MHC quantitative trait loci regulating myelin oligodendrocyte glycoprotein-induced EAE have previously been identified in the EAE-permissive strain, DA, on rat chromosomes 4,10,15, and 18. To find any additional gene loci in another well-known EAE-permissive strain and thereby to assess any genetic heterogeneity in the regulation of the disease, we have performed a genome-wide linkage analysis in a reciprocal (LEW.1AV1 x PVG.1AV1) male/female F-2 population (n = 185). We examined reciprocal crosses, but no parent-of-origin effect was detected. The parental rat strains share the RT1(av1) MHC haplotype; thus, non-MHC genes control differences in EAE susceptibility. We identified Eae(16) on chromosome 8 and Eae17 on chromosome 13, significantly linked to EAE phenotypes. Two loci, on chromosomes 1 and 17, respectively showed suggestive linkage to clinical and histopathological EAE phenotypes. Eae16 and Eae17 differ from those found in previously studied strain combinations, thus demonstrating genetic heterogeneity of EAE. Furthermore, we detected a locus-specific parent-of-origin effect with suggestive linkage in Eae17. Further genetic and functional dissection of these loci may disclose critical disease-regulating molecular mechanisms.
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| 15. |
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| 16. |
- Bergström, Christel A S, et al.
(författare)
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Absorption classification of oral drugs based on molecular surface properties
- 2003
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 46:4, s. 558-570
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate whether easily calculated and comprehended molecular surface properties can predict drug solubility and permeability with sufficient accuracy to allow theoretical absorption classification of drug molecules. For this purpose, structurally diverse, orally administered model drugs were selected from the World Health Organization (WHO)'s list of essential drugs. The solubility and permeability of the drugs were determined using well-established in vitro methods in highly accurate experimental settings. Descriptors for molecular surface area were generated from low-energy conformations obtained by conformational analysis using molecular mechanics calculations. Correlations between the calculated molecular surface area descriptors, on one hand, and solubility and permeability, on the other, were established with multivariate data analysis (partial least squares projection to latent structures (PLS)) using training and test sets. The obtained models were challenged with external test sets. Both solubility and permeability of the druglike molecules could be predicted with high accuracy from the calculated molecular surface properties alone. The established correlations were used to perform a theoretical biopharmaceutical classification of the WHO-listed drugs into six classes, resulting in a correct prediction for 87% of the essential drugs. An external test set consisting of Food and Drug Administration (FDA) standard compounds for biopharmaceutical classification was predicted with 77% accuracy. We conclude that PLS models of easily comprehended molecular surface properties can be used to rapidly provide absorption profiles of druglike molecules early on in drug discovery.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Enberg, B, et al.
(författare)
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Characterisation of novel missense mutations in the GH receptor gene causing severe growth retardation
- 2000
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Ingår i: European journal of endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 143:1, s. 71-76
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Tidskriftsartikel (refereegranskat)abstract
- Two Swedish brothers, 2.5 and 4 years of age, were found to fulfil all the clinical and laboratory characteristics of Laron's syndrome. They were shown to have unique missense mutations in the GH receptor gene. Both of their parents were of normal height, but they both separately carried one of the identified gene alterations. A molecular model of the first receptor alteration suggests that a collapse in three-dimensional receptor structure most likely contributed to the GH insensitivity in these patients.
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| 22. |
- EstenneBouhtou, G, et al.
(författare)
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Design, synthesis, tandem mass spectrometric sequencing and biological activity of NGF mimetics
- 1996
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Ingår i: International journal of peptide & protein research. - 0367-8377. ; 48:4, s. 337-346
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Tidskriftsartikel (refereegranskat)abstract
- Nine low molecular weight nerve growth factor (NGF)-like peptides have been designed to mimic the putative receptor-binding epitope of NGF defined by two beta-hairpin loops. Eight different spacers were used as variable links between the beta-loop amino acid residues, which from mutagenesis experiments were found to play an important role in the biological activity of NGF. These spacers were amino acids, natural or non-natural, differing in length (5-13 A) and polarity. The peptides were synthesized via the Fmoc solid-phase peptide synthesis and purified by reversed-phase HPLC. Their primary sequences were analyzed by a combination of automated Edman degradation and mass spectrometry. The peptides were tested using two different biological assays, the fibre outgrowth from chick embryonic sympathetic ganglia and the PC12 cell differentiation assay. Weak antagonistic effects could be observed for some peptides.
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| 23. |
- Fridén-Saxin, Maria, 1979, et al.
(författare)
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Proline-mediated formation of novel chroman-4-one tetrahydropyrimidines
- 2012
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020. ; 68:35, s. 7035-7040
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Tidskriftsartikel (refereegranskat)abstract
- Novel tricyclic N-benzylated chroman-4-one tetrahydropyrimidine derivatives have been prepared through a multi-component reaction between various 2-substituted chroman-4-one derivatives, N-methylenebenzylamine and a catalytic amount of proline under mild reaction conditions. The tricyclic structure of 1a was determined by NMR spectroscopy and confirmed by X-ray crystallography. An additional product, 2a, was isolated from the reaction mixture and its structure and conformation were determined by a combination of theoretical (Monte Carlo conformational search) and NMR-based (NOE and (3)J(HH) couplings) conformational analysis. The NMR analysis revealed one preferred geometry for 1a and 2a in CHCl3 solution. (C) 2012 Elsevier Ltd. All rights reserved.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Lehmann, Fredrik, 1976, et al.
(författare)
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Novel and potent small-molecule urotensin II receptor agonists
- 2009
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 17:13, s. 4657-4665
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Tidskriftsartikel (refereegranskat)abstract
- A series of analogs of the non-peptidic urotensin II receptor agonist N-[1-(4-chlorophenyl)-3-(dimethylamino)propyl]-4-phenylbenzamide (FL104) has been synthesized and evaluated pharmacologically. The enantiomers of the two most potent racemic analogues were obtained from the corresponding diastereomeric mandelic amides. In agreement with previously observed SAR, most of the agonist potency resided in the (S) enantiomers. The most potent UII receptor agonist in the new series was (S)-N-[3-dimethylamino-1-(2-naphthyl)propyl]-4-(4-chlorophenyl)benzamide (EC50 = 23 nM at the urotensin II receptor).
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| 34. |
- Luthman, K, et al.
(författare)
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Synthesis and use of pseudopeptides derived from 1,2,4-oxadiazole-, 1,3,4-oxadiazole-, and 1,2,4-triazole-based dipeptidomimetics.
- 1999
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Ingår i: Methods Mol. Med.. ; 23, s. 1-
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Tidskriftsartikel (refereegranskat)
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Nystedt, Björn, et al.
(författare)
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The Norway spruce genome sequence and conifer genome evolution
- 2013
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 497:7451, s. 579-584
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Tidskriftsartikel (refereegranskat)abstract
- Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
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| 39. |
- Pettersson, Mariell, 1984, et al.
(författare)
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Design, Synthesis and Evaluation of 2,5-Diketopiperazines as Inhibitors of the MDM2-p53 Interaction
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor p53 is the main tumour suppressor in cells and many cancer types have p53 mutations resulting in a loss of its function. In tumours that retain wild-type p53 function, p53 activity is down-regulated by MDM2 (human murine double minute 2) via a direct protein-protein interaction. We have designed and synthesised two series of 2,5-diketopiperazines as inhibitors of the MDM2-p53 interaction. The first set was designed to directly mimic the alpha-helical region of the p53 peptide, containing key residues in the i, i+4 and i+7 positions of a natural alpha-helix. Conformational analysis indicated that 1,3,6-trisubstituted 2,5-diketopiperazines were able to place substituents in the same spatial orientation as an alpha-helix template. The key step of the synthesis involved the cyclisation of substituted dipeptides. The other set of tetrasubstituted 2,5-diketopiperazines were designed based on structure-based docking studies and the Ugi multicomponent reaction was used for the synthesis. This latter set comprised the most potent inhibitors which displayed micromolar IC50 values in a biochemical fluorescence polarisation assay.
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| 40. |
- Seifert, Tina, 1985, et al.
(författare)
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A scaffold replacement approach towards new sirtuin 2 inhibitors
- 2020
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 28:2
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Tidskriftsartikel (refereegranskat)abstract
- Sirtuins (SIRT1-SIRT7) are an evolutionary conserved family of NAD(+)-dependent protein deacylases regulating the acylation state of epsilon-N-lysine residues of proteins thereby controlling key biological processes. Numerous studies have found association of the aberrant enzymatic activity of SIRTs with various diseases like diabetes, cancer and neurodegenerative disorders. Previously, we have shown that substituted 2-alkyl-chroman-4-one/chromone derivatives can serve as selective inhibitors of SIRT2 possessing an antiproliferative effect in two human cancer cell lines. In this study, we have explored the bioisosteric replacement of the chroman-4-one/chromone core structure with different less lipophilic bicyclic scaffolds to overcome problems associated to poor physiochemical properties due to a highly lipophilic substitution pattern required for achieve a good inhibitory effect. Various new derivatives based on the quinolin-4(1H)-one scaffold, bicyclic secondary sulfonamides or saccharins were synthesized and evaluated for their SIRT inhibitory effect. Among the evaluated scaffolds, the benzothiadiazine-1,1-dioxide-based compounds showed the highest SIRT2 inhibitory activity. Molecular modeling studies gave insight into the binding mode of the new scaffold-replacement analogues.
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| 41. |
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| 46. |
- Tadd, AC, et al.
(författare)
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Synthesis of Orthogonally Protected Disulfide Bridge Mimetics
- 2011
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Ingår i: Journal of organic chemistry. - 0022-3263. ; 76:2, s. 673-675
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Tidskriftsartikel (refereegranskat)abstract
- Concise routes to four orthogonally protected, enantiopure disulfide bridge mimetics are reported. These four dicarba analogues possess an alkyne, an (E)-alkene, a (Z)-alkene, and an alkane as substitutes for the disulfide bridge. Selective deprotection of one of these mimetics is also illustrated.
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| 47. |
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| 48. |
- Våbenø, Jon, et al.
(författare)
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Benzyl-5-[N-(tert-butoxycarbonyl)amino]-4-oxo-6-phenylhexanoate
- 2005
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Ingår i: Acta Crystallographica Section E-Structure Reports Online. ; 61
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Tidskriftsartikel (refereegranskat)abstract
- The title compound, C24H29NO5, the benzyl ester of the Phe-Gly dipeptidomimetic containing a ketomethylene motif, was synthesized from the readily available α,β-unsaturated γ-ketoester. The methylene group in the benzyl part of the molecule is disordered. There is an intermolecular N-H••• O hydrogen bond linking the molecules in the crystal structure.
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| 49. |
- Wiktelius, Daniel, 1976, et al.
(författare)
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Chemoenzymatic synthesis of enantiomerically enriched alpha-chiral 3-oxy-propionaldehydes by lipase-catalyzed kinetic resolution and desymmetrization
- 2006
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Ingår i: Tetrahedron-Asymmetry. - : Elsevier BV. - 0957-4166. ; 17:14, s. 2088-2100
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Tidskriftsartikel (refereegranskat)abstract
- Enantiomerically enriched phenylalanine- and leucine aldehyde analogues have been prepared by lipase catalyzed desymmetrization or kinetic resolution of 1,3-propanediol derivatives as key steps. Observations of unusual enantioselectivity were made, and most notably, Candida antarctica lipase B showed an opposite enantiopreference from other lipases, which was exploited in the synthesis. A thorough evaluation of chemoenzymatic routes to both enantiorners of the target alpha-chiral 3-oxy-propionaldehydes resulted in simple, inexpensive, and efficient procedures that provide the products in up to 92% enantiomeric excess and 55% total yield in five steps from easily accessible starting materials. (c) 2006 Elsevier Ltd. All rights reserved.
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