| 1. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 8. |
- Kinsella, Cormac M., et al.
(författare)
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Programmed DNA elimination of germline development genes in songbirds
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- In some eukaryotes, germline and somatic genomes differ dramatically in their composition. Here we characterise a major germline-soma dissimilarity caused by a germline-restricted chromosome (GRC) in songbirds. We show that the zebra finch GRC contains >115 genes paralogous to single-copy genes on 18 autosomes and the Z chromosome, and is enriched in genes involved in female gonad development. Many genes are likely functional, evidenced by expression in testes and ovaries at the RNA and protein level. Using comparative genomics, we show that genes have been added to the GRC over millions of years of evolution, with embryonic development genes bicc1 and trim71 dating to the ancestor of songbirds and dozens of other genes added very recently. The somatic elimination of this evolutionarily dynamic chromosome in songbirds implies a unique mechanism to minimise genetic conflict between germline and soma, relevant to antagonistic pleiotropy, an evolutionary process underlying ageing and sexual traits.
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| 11. |
- Flentie, Kelly, et al.
(författare)
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Chemical disarming of isoniazid resistance in Mycobacterium tuberculosis
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : The National Academy of Scionces of the United States of America. - 0027-8424 .- 1091-6490. ; 116:21, s. 10510-10517
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium tuberculosis (Mtb) killed more people in 2017 than any other single infectious agent. This dangerous pathogen is able to withstand stresses imposed by the immune system and tolerate exposure to antibiotics, resulting in persistent infection. The global tuberculosis (TB) epidemic has been exacerbated by the emergence of mutant strains of Mtb that are resistant to frontline antibiotics. Thus, both phenotypic drug tolerance and genetic drug resistance are major obstacles to successful TB therapy. Using a chemical approach to identify compounds that block stress and drug tolerance, as opposed to traditional screens for compounds that kill Mtb, we identified a small molecule, C10, that blocks tolerance to oxidative stress, acid stress, and the frontline antibiotic isoniazid (INH). In addition, we found that C10 prevents the selection for INH-resistant mutants and restores INH sensitivity in otherwise INH-resistant Mtb strains harboring mutations in the katG gene, which encodes the enzyme that converts the prodrug INH to its active form. Through mechanistic studies, we discovered that C10 inhibits Mtb respiration, revealing a link between respiration homeostasis and INH sensitivity. Therefore, by using C10 to dissect Mtb persistence, we discovered that INH resistance is not absolute and can be reversed.
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| 12. |
- Gonzalez-Acuna, Daniel A., et al.
(författare)
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Parasites of chinstrap penguins (Pygoscelis antarctica) from three localities in the Antarctic Peninsula and a review of their parasitic fauna
- 2021
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Ingår i: Polar Biology. - : Springer. - 0722-4060 .- 1432-2056. ; 44, s. 2099-2105
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Tidskriftsartikel (refereegranskat)abstract
- Studies of parasitism in chinstrap penguins (Pygoscelis antarctica) are infrequent and mainly refer to the identification and description of its parasites, with little ecological data. In an attempt to address that lack of knowledge, we collected endo- and ecto-parasites from 326 live and four dead of chinstrap penguins, in three different localities of Antarctica not studied before. Three species of endoparasites and two of ectoparasites were found parasitizing birds: two tapeworms, Tetrabothrius pauliani (Cestoda: Tetrabothriidae) and Parorchites zederi (Cestoda: Dilepididae); one roundworm, Stegophorus macronectes (Nematoda: Acuariidae), and one feather louse: Austrogoniodes gressitti (Insecta: Phthiraptera: Philopteridae). Ticks (Ixodes uriae-Acari: Ixodidae) were collected from the ground near the penguin nesting colonies at two localities, Shirreff Cape and Narebsky Point. New ecological data are given for the two species of ectoparasites. No parasites were found in the blood collected from 300 live penguins.
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| 13. |
- Gonzalez-Acuna, Daniel, et al.
(författare)
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Health evaluation of wild gentoo penguins (Pygoscelis papua) in the Antarctic Peninsula
- 2013
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Ingår i: Polar Biology. - : Springer Science and Business Media LLC. - 0722-4060 .- 1432-2056. ; 36:12, s. 1749-1760
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Tidskriftsartikel (refereegranskat)abstract
- Historically wildlife conservation was based on habitat protection and exploitation control. Only recently have diseases been considered an important issue. However, pathogens are usually described during or after disease outbreaks, but to determine which pathogens may be emerging, surveys of wildlife health are critical in a given time. This study deals with the health status of gentoo penguins Pygoscelis papua in two localities at the Antarctica Peninsula and one at Ardley Island off the South Shetland Islands. Cloacal swaps, fresh fecal samples, ectoparasites, and blood smears were collected. We examined and dissected 14 penguin corpses found dead. Fecal samples were positive for Campylobacter, Escherichia coli and in the carcasses four endoparasitic species were found: Diphyllobothrium sp. and Parorchites zederi, Corynosoma shackletoni and Stegophorus adeliae. The tick Ixodes uriae occurred in five of the examined penguins, and the louse Austrogoniodes gressitti on six birds. From the colony grounds, we collected 1,184 I. uriae. We recorded antibiotic-resistant bacteria, such as E. coli, in ecosystems where gentoo penguins breed. Cloacal samples (300) were negative for Chlamydia, as well as for Salmonella, Campylobacter, E. coli, Newcastle and Influenza viruses.
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| 14. |
- Kinsella, N., et al.
(författare)
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Active surveillance for prostate cancer: A systematic review of contemporary worldwide practices
- 2018
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Ingår i: Translational Andrology and Urology. - : AME Publishing Company. - 2223-4683 .- 2223-4691. ; 7:1, s. 83-97
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Tidskriftsartikel (refereegranskat)abstract
- In the last decade, active surveillance (AS) has emerged as an acceptable choice for low-risk prostate cancer (PC), however there is discordance amongst large AS cohort studies with respect to entry and monitoring protocols. We systematically reviewed worldwide AS practices in studies reporting =5 years follow-up. We searched PubMed and Medline 2000-now and identified 13 AS cohorts. Three key areas were identified: (I) patient selection; (II) monitoring protocols; (III) triggers for intervention-(I) all studies defined clinically localised PC diagnosis as T2b disease or less and most agreed on prostate-specific antigen (PSA) threshold ( < 10 μg/L) and Gleason score threshold (3+3). Inconsistency was most notable regarding pathologic factors (e.g., number of positive cores); (II) all agreed on PSA surveillance as crucial for monitoring, and most agreed that confirmatory biopsy was required within 12 months of initiation. No consensus was reached on optimal timing of digital rectal examination (DRE), general health assessment or re-biopsy strategies thereafter; (III) there was no universal agreement for intervention triggers, although Gleason score, number or percentage of positive cancer cores, maximum cancer length (MCL) and PSA doubling time were used by several studies. Some also used imaging or re-biopsy. Despite consistent high progression-free/cancer-free survival and conversion-to-treatment rates, heterogeneity exists amongst these large AS cohorts. Combining existing evidence and gathering more long-term evidence [e.g., the Movember's Global AS database or additional information on use of magnetic resonance imaging (MRI)] is needed to derive a broadly supported guideline to reduce variation in clinical practice. © Translational Andrology and Urology.
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| 15. |
- Lamb, Alastair D, et al.
(författare)
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Aiming for a holistic integrated service for men diagnosed with prostate cancer – Definitions of standards and skill sets for nurses and allied healthcare professionals
- 2017
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Ingår i: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889. ; 29, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To establish a comprehensive set of recommendations for the service structure and skill set of nurses and allied healthcare professionals in prostate cancer care. Methods Using components of formal consensus methodology, a 30-member multidisciplinary panel produced 53 items for discussion relating to the provision of care for prostate cancer patients by specialist nurses and allied healthcare professionals. Items were developed by two rounds of email correspondence in which, first, items were generated and, second, items refined to form the basis of a consensus meeting which constituted the third round of review. The fourth and final round was an email review of the consensus output. Results The panel agreed on 33 items that were appropriate for recommendations to be made. These items were grouped under categories of “Environment” and “Patient Pathway” and included comments on training, leadership, communication and quality assessment as well as specific items related to prostate diagnosis clinics, radical treatment clinics and follow-up survivor groups. Conclusions Specialist nurses and allied healthcare professionals play a vital role alongside urologists and oncologists to provide care to men with prostate cancer and their families. We present a set of standards and consensus recommendations for the roles and skill-set required for these practitioners to provide gold-standard prostate cancer care. These recommendations could form the basis for development of comprehensive integrated prostate cancer pathways in prostate cancer centres as well as providing guidance for any units treating men with prostate cancer.
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| 19. |
- von Sarnowski, Bettina, et al.
(författare)
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Prevalence of stenoses and occlusions of brain-supplying arteries in young stroke patients.
- 2013
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Ingår i: Neurology. - 1526-632X. ; 80:14, s. 1287-1294
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Atherosclerosis is believed to be a minor cause of TIA and stroke in younger and middle-aged patients. However, data from large cohorts are limited. This study investigates the prevalence of extracranial and intracranial atherosclerosis in stroke and TIA patients aged 18-55 years in the multinational sifap1 study. METHODS: From the sifap1 cohort (n = 5,023), we analyzed a subset of patients with complete data from carotid ultrasound studies. Patients with arterial dissections, vasculitis, and mobile thrombi were excluded. Among the remaining 2,187 patients (men: n = 1,319; 18-44 years: n = 744), intracranial arteries were additionally examined with ultrasonography in 1,612 patients (73.7%). Patients were stratified by sex and age groups (younger: 18-44 years; middle-aged: 45-55 years). RESULTS: In patients with ischemic stroke, the overall prevalence of carotid artery stenoses and occlusions was 8.9% (younger: 4.9%; middle-aged: 11.0%), of which 81% were symptomatic. Nonstenotic carotid plaques were more common in men than in women (15.8% vs 7.7%; p < 0.001), and in middle-aged than in younger patients (17.0% vs 4.9%; p < 0.001). Supratentorial intracranial artery stenoses and occlusions amounted to 11.8%. Supratentorial stenoses occurred more frequently in middle-aged patients (13.0% vs 7.8%; p < 0.001), whereas occlusions were equally common (both 3.2%; not significant). CONCLUSIONS: We observed a substantial proportion of atherosclerotic carotid artery stenoses and occlusions in younger stroke patients. Intracranial stenoses and occlusions were even more prevalent than extracranial carotid artery disease. Together with nonstenotic plaques, one-fifth of patients (21.2%) had symptomatic or asymptomatic large-artery atherosclerosis, which should encourage future stroke prevention campaigns to target risk factor modification in young people.
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