| 1. |
- 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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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Heywood, I., et al.
(författare)
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Inflation of 430-parsec bipolar radio bubbles in the Galactic Centre by an energetic event
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 573:7773, s. 235-237
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Tidskriftsartikel (refereegranskat)abstract
- The Galactic Centre contains a supermassive black hole with a mass of four million Suns1 within an environment that differs markedly from that of the Galactic disk. Although the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings2. Also, although the levels of star formation in the Galactic Centre have been approximately constant over the past few hundred million years, there is evidence of increased short-duration bursts3, strongly influenced by the interaction of the black hole with the enhanced gas density present within the ring-like central molecular zone4 at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200-parsec region is characterized by large amounts of warm molecular gas5, a high cosmic-ray ionization rate6, unusual gas chemistry, enhanced synchrotron emission7,8, and a multitude of radio-emitting magnetized filaments9, the origin of which has not been established. Here we report radio imaging that reveals a bipolar bubble structure, with an overall span of 1 degree by 3 degrees (140 parsecs × 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 × 1052 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities.
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| 4. |
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| 5. |
- Davis-Merry, T. R., et al.
(författare)
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Collective excitations in the transitional nuclei Re-163 and Re-165
- 2015
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 91:3
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the neutron-deficient nuclei (163)(75) Re-88 and (165)(75) Re-90 were populated in the Cd-106(Ni-60, p2n gamma) and Mo-92(Kr-78, 3p2n gamma) fusion-evaporation reactions at bombarding energies of 270 and 380 MeV, respectively.. rays were detected at the target position using the JUROGAM spectrometer while recoiling ions were separated in-flight by the RITU gas-filled recoil separator and implanted in the GREAT spectrometer. The energy level schemes for Re-163 and Re-165 were identified using recoil-decay correlation techniques. At low spin, the yrast bands of these isotopes consist of signature partner bands based on a single pi h(11/2) quasiproton configuration. The bands display large energy splitting consistent with the soft triaxial shape typical of transitional nuclei above N = 82. The configurations of the excited states are proposed within the framework of the cranked shell model.
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| 6. |
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| 7. |
- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 8. |
- Byakika-Kibwika, Pauline, et al.
(författare)
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Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults.
- 2012
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 67:5, s. 1217-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisinin-based combination therapy has potential for drug interactions. We investigated the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir.METHODS: A two-arm parallel study of 13 HIV-infected ART-naive adults and 16 HIV-infected adults stable on 400/100 mg of lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (ClinicalTrials.gov, NCT 00619944). Each participant received a single dose of 80/480 mg of artemether/lumefantrine under continuous cardiac function monitoring. Plasma concentrations of artemether, dihydroartemisinin and lumefantrine were measured.RESULTS: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly reduced artemether maximum concentration (C(max)) and area under the concentration-time curve (AUC) [median (range): 112 (20-362) versus 56 (17-236) ng/mL, P = 0.03; and 264 (92-1129) versus 151 (38-606) ng · h/mL, P < 0.01]. Dihydroartemisinin C(max) and AUC were not affected [66 (10-111) versus 73 (31-224) ng/mL, P = 0.55; and 213 (68-343) versus 175 (118-262) ng · h/mL P = 0.27]. Lumefantrine C(max) and AUC increased during co-administration [2532 (1071-5957) versus 7097 (2396-9462) ng/mL, P < 0.01; and 41,119 (12,850-125,200) versus 199,678 (71,205-251,015) ng · h/mL, P < 0.01].CONCLUSIONS: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly increases lumefantrine exposure, but decreases artemether exposure. Population pharmacokinetic and pharmacodynamic trials will be highly valuable in evaluating the clinical significance of this interaction and determining whether dosage modifications are indicated.
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| 9. |
- De Brandt, Jana, 1991-, et al.
(författare)
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Update on the etiology, assessment, and management of copd cachexia : considerations for the clinician
- 2022
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - : Taylor & Francis. - 1176-9106 .- 1178-2005. ; 17, s. 2957-2976
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Tidskriftsartikel (refereegranskat)abstract
- Cachexia is a commonly observed but frequently neglected extra-pulmonary manifestation in patients with chronic obstructive pulmonary disease (COPD). Cachexia is a multifactorial syndrome characterized by severe loss of body weight, muscle, and fat, as well as increased protein catabolism. COPD cachexia places a high burden on patients (eg, increased mortality risk and disease burden, reduced exercise capacity and quality of life) and the healthcare system (eg, increased number, length, and cost of hospitalizations). The etiology of COPD cachexia involves a complex interplay of non-modifiable and modifiable factors (eg, smoking, hypoxemia, hypercapnia, physical inactivity, energy imbalance, and exacerbations). Addressing these modifiable factors is needed to prevent and treat COPD cachexia. Oral nutritional supplementation combined with exercise training should be the primary multimodal treatment approach. Adding a pharmacological agent might be considered in some, but not all, patients with COPD cachexia. Clinicians and researchers should use longitudinal measures (eg, weight loss, muscle mass loss) instead of cross-sectional measures (eg, low body mass index or fat-free mass index) where possible to evaluate patients with COPD cachexia. Lastly, in future research, more detailed phenotyping of cachectic patients to enable a better comparison of included patients between studies, prospective longitudinal studies, and more focus on the impact of exacerbations and the role of biomarkers in COPD cachexia, are highly recommended.
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| 10. |
- Dittrich, Christian, et al.
(författare)
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ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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