| 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. |
- Lachat, Mario, et al.
(författare)
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Periscope Endograft Technique to Revascularize the Left Subclavian Artery During Thoracic Endovascular Aortic Repair
- 2013
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Ingår i: Journal of Endovascular Therapy. - 1526-6028 .- 1545-1550. ; 20:6, s. 728-734
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To present early and midterm results of the periscope endograft (PG) technique to maintain left subclavian artery (LSA) blood flow in thoracic endovascular aortic repairs (TEVAR) involving zone 3. Methods: From April 2010 to January 2013, 14 consecutive high-risk patients (11 men; mean age 70 8 years, range 56-87) underwent TEVAR with the PG technique for 10 thoracic aortic aneurysms (TAA), 2 traumatic aortic ruptures, and 2 aortic dissections without a suitable landing zone (>2 cm distal to the LSA). Five procedures were performed emergently for rupture (3 TAAs and the 2 trauma cases). Two patients had a periscope deployed in an aberrant right subclavian artery. The periscope endografts were sized 1 to 2 mm larger than the branch artery at the intended landing zone. The caudal end was extended distal to the intended distal landing site of the thoracic stent-graft, which was usually deployed after the PG. Both the PG and thoracic stent-grafts were generally molded using the kissing balloon technique. Outcomes analyzed were immediate technical success, perioperative mortality and morbidity, aneurysm diameter change, and periscope endograft patency. Results: Immediate technical success was 100%, with all procedures completed as planned. Perioperatively, one periscope occluded and one of the ruptured TAA patients died. One percutaneous access site hematoma required only conservative management. At a mean follow-up of 26 +/- 9 months (range 9-37), there was no additional PG occlusion. The Kaplan-Meier estimate of PG patency was 93% at 2 years. Conclusion: The periscope endograft is a simple technique to maintain perfusion to the LSA in cases where the aortic stent-graft crosses its ostium. The PG technique can be performed transfemorally and even percutaneously, and it can be applied to all supraaortic branches. Early and midterm results are encouraging, but more experience and long-term results are mandatory before this technique can be widely recommended.
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| 3. |
- Bentley, Michael J., et al.
(författare)
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A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum
- 2014
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse la. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community.
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| 4. |
- Chapman, Henry N, et al.
(författare)
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Femtosecond X-ray protein nanocrystallography.
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 470:7332, s. 73-7
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Tidskriftsartikel (refereegranskat)abstract
- X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200nm to 2μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.
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| 5. |
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| 6. |
- Hämmerle, Christoph H F, et al.
(författare)
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Biology of soft tissue wound healing and regeneration : consensus report of group 1 of the 10th European workshop on periodontology
- 2014
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Ingår i: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 41:s15, s. S1-S5
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND:The scope of this consensus was to review the biological processes of soft tissue wound healing in the oral cavity and to histologically evaluate soft tissue healing in clinical and pre-clinical models. AIMS:To review the current knowledge regarding the biological processes of soft tissue wound healing at teeth, implants and on the edentulous ridge. Furthermore, to review soft tissue wound healing at these sites, when using barrier membranes, growth and differentiation factors and soft tissue substitutes. COLLECTION OF DATA:Searches of the literature with respect to recessions at teeth and soft tissue deficiencies at implants, augmentation of the area of keratinized tissue and soft tissue volume were conducted. The available evidence was collected, categorized and summarized. FUNDAMENTAL PRINCIPLES OF ORAL SOFT TISSUE WOUND HEALING:Oral mucosal and skin wound healing follow a similar pattern of the four phases of haemostasis, inflammation, proliferation and maturation/matrix remodelling. The soft connective tissue determines the characteristics of the overlaying oral epithelium. Within 7-14 days, epithelial healing of surgical wounds at teeth is completed. Soft tissue healing following surgery at implants requires 6-8 weeks for maturation. The resulting tissue resembles scar tissue. Well-designed pre-clinical studies providing histological data have been reported describing soft tissue wound healing, when using barrier membranes, growth and differentiation factors and soft tissue substitutes. Few controlled clinical studies with low numbers of patients are available for some of the treatments reviewed at teeth. Whereas, histological new attachment has been demonstrated in pre-clinical studies resulting from some of the treatments reviewed, human histological data commonly report a lack of new attachment but rather long junctional epithelial attachment and connective tissue adhesion. Regarding soft tissue healing at implants human data are very scarce. CONCLUSIONS:Oral soft tissue healing at teeth, implants and the edentulous ridge follows the same phases as skin wound healing. Histological studies in humans have not reported new attachment formation at teeth for the indications studied. Human histological data of soft tissue wound healing at implants are limited. CLINICAL RECOMMENDATIONS:The use of barriers membranes, growth and differentiation factors and soft tissue substitutes for the treatment of localized gingival/mucosal recessions, insufficient amount of keratinized tissue and insufficient soft tissue volume is at a developing stage.
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| 7. |
- Larter, Robert D., et al.
(författare)
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Reconstruction of changes in the Amundsen Sea and BellingshausenSea sector of the West Antarctic Ice Sheet since the Last GlacialMaximum
- 2013
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 56-86
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Marine and terrestrial geological and marine geophysical data that constrain deglaciation since the LastGlacial Maximum (LGM) of the sector of theWest Antarctic Ice Sheet (WAIS) draining into the AmundsenSea and Bellingshausen Sea have been collated and used as the basis for a set of time-slice reconstructions.The drainage basins in these sectors constitute a little more than one-quarter of the area ofthe WAIS, but account for about one-third of its surface accumulation. Their mass balance is becomingincreasingly negative, and therefore they account for an even larger fraction of currentWAIS discharge. Ifall of the ice in these sectors of the WAIS were discharged to the ocean, global sea level would rise byca 2 m.There is compelling evidence that grounding lines of palaeo-ice streams were at, or close to, thecontinental shelf edge along the Amundsen Sea and Bellingshausen Sea margins during the last glacialperiod. However, the few cosmogenic surface exposure ages and ice core data available from the interiorofWest Antarctica indicate that ice surface elevations there have changed little since the LGM. In the fewareas from which cosmogenic surface exposure ages have been determined near the margin of the icesheet, they generally suggest that there has been a gradual decrease in ice surface elevation since pre-Holocene times. Radiocarbon dates from glacimarine and the earliest seasonally open marine sedimentsin continental shelf cores that have been interpreted as providing approximate ages for post-LGMgrounding-line retreat indicate different trajectories of palaeo-ice stream recession in the Amundsen Seaand Bellingshausen Sea embayments. The areas were probably subject to similar oceanic, atmosphericand eustatic forcing, in which case the differences are probably largely a consequence of how topographicand geological factors have affected ice flow, and of topographic influences on snow accumulation andwarm water inflow across the continental shelf.Pauses in ice retreat are recorded where there are “bottle necks” in cross-shelf troughs in both embayments.The highest retreat rates presently constrained by radiocarbon dates from sediment cores arefound where the grounding line retreated across deep basins on the inner shelf in the Amundsen Sea,which is consistent with the marine ice sheet instability hypothesis. Deglacial ages from the Amundsen Sea Embayment (ASE) and Eltanin Bay (southern Bellingshausen Sea) indicate that the ice sheet hadalready retreated close to its modern limits by early Holocene time, which suggests that the rapid icethinning, flow acceleration, and grounding line retreat observed in this sector over recent decades areunusual in the context of the past 10,000 years.
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| 8. |
- Middleton, Matthew J., et al.
(författare)
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Bright radio emission from an ultraluminous stellar-mass microquasar in M 31
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7431, s. 187-190
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Tidskriftsartikel (refereegranskat)abstract
- A subset of ultraluminous X-ray sources (those with luminosities of less than 10(40) erg s(-1); ref. 1) are thought to be powered by the accretion of gas onto black holes with masses of similar to 5-20M(circle dot), probably by means of an accretion disk(2,3). The X-ray and radio emission are coupled in such Galactic sources; the radio emission originates in a relativistic jet thought to be launched from the innermost regions near the black hole(4,5), with the most powerful emission occurring when the rate of infalling matter approaches a theoretical maximum (the Eddington limit). Only four such maximal sources are known in the Milky Way(6), and the absorption of soft X-rays in the interstellar medium hinders the determination of the causal sequence of events that leads to the ejection of the jet. Here we report radio and X-ray observations of a bright new X-ray source in the nearby galaxy M 31, whose peak luminosity exceeded 10(39) erg s(-1). The radio luminosity is extremely high and shows variability on a timescale of tens of minutes, arguing that the source is highly compact and powered by accretion close to the Eddington limit onto a black hole of stellar mass. Continued radio and X-ray monitoring of such sources should reveal the causal relationship between the accretion flow and the powerful jet emission.
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| 9. |
- Seibert, M. Marvin, et al.
(författare)
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Single mimivirus particles intercepted and imaged with an X-ray laser
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 470:7332, s. 78-81
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Tidskriftsartikel (refereegranskat)abstract
- X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions(1-4). Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma(1). The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval(2). Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a noncrystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source(5). Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000 K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.
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| 10. |
- Stoehlker, Thomas, et al.
(författare)
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SPARC collaboration : new strategy for storage ring physics at FAIR
- 2014
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Ingår i: Hyperfine interactions. - : Springer Science and Business Media LLC. - 0304-3843 .- 1572-9540. ; , s. 45-53
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Konferensbidrag (refereegranskat)abstract
- SPARC collaboration at FAIR pursues the worldwide unique research program by utilizing storage ring and trapping facilities for highly-charged heavy ions. The main focus is laid on the exploration of the physics at strong, ultra-short electromagnetic fields including the fundamental interactions between electrons and heavy nuclei as well as on the experiments at the border between nuclear and atomic physics. Very recently SPARC worked out a realization scheme for experiments with highly-charged heavy-ions at relativistic energies in the High-Energy Storage Ring HESR and at very low-energies at the CRYRING coupled to the present ESR. Both facilities provide unprecedented physics opportunities already at the very early stage of FAIR operation. The installation of CRYRING, dedicated Low-energy Storage Ring (LSR) for FLAIR, may even enable a much earlier realisation of the physics program of FLAIR with slow anti-protons.
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| 11. |
- Witjes, J. Alfred, et al.
(författare)
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Hexaminolevulinate-Guided Fluorescence Cystoscopy in the Diagnosis and Follow-Up of Patients with Non-Muscle-Invasive Bladder Cancer : Review of the Evidence and Recommendations
- 2010
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 57:4, s. 607-614
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Forskningsöversikt (refereegranskat)abstract
- Context: Compared with standard white-light cystoscopy, photodynamic diagnosis with blue light and the photosensitiser hexaminolevulinate has been shown to improve the visualisation of bladder tumours, reduce residual tumour rates by at least 20%, and improve recurrence-free survival. There is currently no overall European consensus outlining specifically where hexaminolevulinate is or is not indicated. Objective: Our aim was to define specific indications for hexaminolevulinate guided fluorescence cystoscopy in the diagnosis and management of non-muscle invasive bladder cancer (NMIBC). Evidence acquisition: A European expert panel was convened to review the evidence for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of NMIBC (identified through a PubMed MESH search) and available guidelines from across Europe. On the basis of this information and drawing on the extensive clinical experience of the panel, specific indications for the technique were then identified through discussion. Evidence synthesis: The panel recommends that hexaminolevulinate-guided fluorescence cystoscopy be used to aid diagnosis at initial transurethral resection following suspicion of bladder cancer and in patients with positive urine cytology but negative white-light cystoscopy for the assessment of tumour recurrences in patients not previously assessed with hexaminolevulinate, in the initial follow-up of patients with carcinoma in situ (CIS) or multifocal tumours, and as a teaching tool. The panel does not currently recommend the use of hexaminolevulinate-guided fluorescence cystoscopy in patients for whom cystectomy is indicated or for use in the outpatient setting with flexible cystoscopy. Conclusions: Evidence is available to support the use of hexaminolevulinate-guided fluorescence cystoscopy in a range of indications, as endorsed by an expert panel. (c) 2010 European Association of Urology.
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