| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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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. |
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| 5. |
- Hu, Bei, et al.
(författare)
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Timing of allogeneic hematopoietic cell transplantation (alloHCT) for chronic myeloid leukemia (CML) patients
- 2020
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:12, s. 2811-2820
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Tidskriftsartikel (refereegranskat)abstract
- While TKI are the preferred first-line treatment for chronic phase (CP) CML, alloHCT remains an important consideration. The aim is to estimate residual life expectancy (RLE) for patients initially diagnosed with CP CML based on timing of alloHCT or continuation of TKI in various settings: CP1 CML, CP2 + [after transformation to accelerated phase (AP) or blast phase (BP)], AP, or BP. Non-transplant cohort included single-institution patients initiating TKI and switched TKI due to failure. CIBMTR transplant cohort included CML patients who underwent HLA sibling matched (MRD) or unrelated donor (MUD) alloHCT. AlloHCT appeared to shorten survival in CP1 CML with overall mortality hazard ratio (HR) for alloHCT of 2.4 (95% CI 1.2-4.9;p = .02). In BP CML, there was a trend toward higher survival with alloHCT; HR = 0.7 (0.5-1.1;p = .099). AlloHCT in CP2 + [HR = 2.0 (0.8-4.9),p = .13] and AP [HR = 1.1 (0.6-2.1);p = .80] is less clear and should be determined on a case-by-case basis.
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| 6. |
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| 7. |
- Froese, L, et al.
(författare)
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Practical Considerations for Continuous Time-Domain Cerebrovascular Reactivity Indices in Traumatic Brain Injury: Do Scaling Errors in Parent Signals Matter?
- 2022
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 13, s. 857617-
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Tidskriftsartikel (refereegranskat)abstract
- Literature pertaining to traumatic brain injury care involves the mediation and control of secondary brain injury mechanisms, chief among these is cerebral autoregulation. Cerebral autoregulation is frequently assessed through surrogate measures of cerebrovascular reactivity. An important aspect to acknowledge when calculating cerebrovascular reactivity indices is the linearity within two-parent bio-signals or variables. We highlighted the concept of linearity in raw parent bio-signals used for the calculation of the cerebrovascular reactivity index and what potential implications linearity carries for index derivation. Key of which is that the initial differencing or location of the pressure probes does not influence linear methods of cerebral reactivity calculations so long as the slow-wave vasogenic changes are being recorded.
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| 8. |
- Gomez, A, et al.
(författare)
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The Quantitative Associations Between Near Infrared Spectroscopic Cerebrovascular Metrics and Cerebral Blood Flow: A Scoping Review of the Human and Animal Literature
- 2022
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Ingår i: Frontiers in physiology. - : Frontiers Media SA. - 1664-042X. ; 13, s. 934731-
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- Cerebral blood flow (CBF) is an important physiologic parameter that is vital for proper cerebral function and recovery. Current widely accepted methods of measuring CBF are cumbersome, invasive, or have poor spatial or temporal resolution. Near infrared spectroscopy (NIRS) based measures of cerebrovascular physiology may provide a means of non-invasively, topographically, and continuously measuring CBF. We performed a systematically conducted scoping review of the available literature examining the quantitative relationship between NIRS-based cerebrovascular metrics and CBF. We found that continuous-wave NIRS (CW-NIRS) was the most examined modality with dynamic contrast enhanced NIRS (DCE-NIRS) being the next most common. Fewer studies assessed diffuse correlation spectroscopy (DCS) and frequency resolved NIRS (FR-NIRS). We did not find studies examining the relationship between time-resolved NIRS (TR-NIRS) based metrics and CBF. Studies were most frequently conducted in humans and animal studies mostly utilized large animal models. The identified studies almost exclusively used a Pearson correlation analysis. Much of the literature supported a positive linear relationship between changes in CW-NIRS based metrics, particularly regional cerebral oxygen saturation (rSO2), and changes in CBF. Linear relationships were also identified between other NIRS based modalities and CBF, however, further validation is needed.
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| 9. |
- Hausmann, Annika, et al.
(författare)
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Intestinal epithelial NAIP/NLRC4 restricts systemic dissemination of the adapted pathogen Salmonella Typhimurium due to site-specific bacterial PAMP expression
- 2020
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219 .- 1935-3456. ; 13:3, s. 530-544
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Tidskriftsartikel (refereegranskat)abstract
- Inflammasomes can prevent systemic dissemination of enteropathogenic bacteria. As adapted pathogens including Salmonella Typhimurium (S. Tm) have evolved evasion strategies, it has remained unclear when and where inflammasomes restrict their dissemination. Bacterial population dynamics establish that the NAIP/NLRC4 inflammasome specifically restricts S. Tm migration from the gut to draining lymph nodes. This is solely attributable to NAIP/NLRC4 within intestinal epithelial cells (IECs), while S. Tm evades restriction by phagocyte NAIP/NLRC4. NLRP3 and Caspase-11 also fail to restrict S. Tm mucosa traversal, migration to lymph nodes, and systemic pathogen growth. The ability of IECs (not phagocytes) to mount a NAIP/NLRC4 defense in vivo is explained by particularly high NAIP/NLRC4 expression in IECs and the necessity for epithelium-invading S. Tm to express the NAIP1-6 ligands—flagella and type-III-secretion-system-1. Imaging reveals both ligands to be promptly downregulated following IEC-traversal. These results highlight the importance of intestinal epithelial NAIP/NLRC4 in blocking bacterial dissemination in vivo, and explain why this constitutes a uniquely evasion-proof defense against the adapted enteropathogen S. Tm.
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| 10. |
- Hirani, Nikhil, et al.
(författare)
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Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis
- 2021
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 57:5
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Tidskriftsartikel (refereegranskat)abstract
- Galectin (Gal)-3 is a profibrotic β-galactoside-binding lectin that plays a key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and IPF exacerbations. TD139 is a novel and potent small-molecule inhibitor of Gal-3. A randomised, double-blind, multicentre, placebo-controlled, phase 1/2a study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled TD139 in 36 healthy subjects and 24 patients with IPF. Six dose cohorts of six healthy subjects were evaluated (4:2 TD139:placebo ratio) with single doses of TD139 (0.15–50 mg) and three dose cohorts of eight patients with IPF (5:3 TD139: placebo ratio) with once-daily doses of TD139 (0.3–10 mg) for 14 days. Inhaled TD139 was well tolerated with no significant treatment-related side-effects. TD139 was rapidly absorbed, with mean time taken to reach maximum plasma concentration (Cmax) values ranging from 0.6 to 3 h and a plasma half-life (T1/2) of 8 h. The concentration of TD139 in the lung was >567-fold higher than in the blood, with systemic exposure predicting exposure in the target compartment. Gal-3 expression on alveolar macrophages was reduced in the 3 and 10 mg dose groups compared with placebo, with a concentration-dependent inhibition demonstrated. Inhibition of Gal-3 expression in the lung was associated with reductions in plasma biomarkers centrally relevant to IPF pathobiology (platelet-derived growth factor-BB, plasminogen activator inhibitor-1, Gal-3, CCL18 and YKL-40). TD139 is safe and well tolerated in healthy subjects and IPF patients. It was shown to suppress Gal-3 expression on bronchoalveolar lavage macrophages and, in a concerted fashion, decrease plasma biomarkers associated with IPF progression.
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| 11. |
- Maurer, Matthew J., et al.
(författare)
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International Assessment of Event-Free Survival at 24 Months and Subsequent Survival in Peripheral T-Cell Lymphoma
- 2017
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 35:36, s. 4019-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Peripheral T-cell lymphomas (PTCLs) have aggressive clinical behavior. We have previously shown that event-free survival (EFS) at 24 months (EFS24) is a clinically useful end point in diffuse large B-cell lymphoma. Here, we assess EFS24 and subsequent overall survival (OS) in large, multinational PTCL cohorts. Patients and Methods Patients with systemic PTCL newly diagnosed from 2000 to 2012 and treated with curative intent were included from the United States and Sweden (initial cohorts) and from Canada (replication cohort). EFS was defined as time from date of diagnosis to progression after primary treatment, retreatment, or death. Subsequent OS was measured after achieving EFS24 or from the time of progression if it occurred within 24 months. OS rates were compared with the age-, sex-, and country-matched general population. Results Seven hundred seventy-five patients were included in the study (the median age at diagnosis was 64 years; 63% were men). Results were similar in the initial and replication cohorts, and a combined analysis was undertaken. Sixty-four percent of patients progressed within the first 24 months and had a median OS of only 4.9 months (5-year OS, 11%). In contrast, median OS after achieving EFS24 was not reached (5-year OS, 78%), although relapses within 5 years of achieving EFS24 occurred in 23% of patients. Superior outcomes after achieving EFS24 were observed in younger patients (≤ 60 years of age: 5-year OS, 91%). Conclusion EFS24 stratifies subsequent outcome in PTCL. Patients with PTCL with primary refractory disease or early relapse have extremely poor survival. However, more than one third of patients with PTCL remain in remission 2 years after diagnosis with encouraging subsequent OS, especially in younger patients. These marked differences in outcome suggest that EFS24 has utility for patient counseling, study design, and risk stratification in PTCL.
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| 12. |
- Sainbhi, AS, et al.
(författare)
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Non-Invasive and Minimally-Invasive Cerebral Autoregulation Assessment: A Narrative Review of Techniques and Implications for Clinical Research
- 2022
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 13, s. 872731-
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Tidskriftsartikel (refereegranskat)abstract
- The process of cerebral vessels regulating constant cerebral blood flow over a wide range of systemic arterial pressures is termed cerebral autoregulation (CA). Static and dynamic autoregulation are two types of CA measurement techniques, with the main difference between these measures relating to the time scale used. Static autoregulation looks at the long-term change in blood pressures, while dynamic autoregulation looks at the immediate change. Techniques that provide regularly updating measures are referred to as continuous, whereas intermittent techniques take a single at point in time. However, a technique being continuous or intermittent is not implied by if the technique measures autoregulation statically or dynamically. This narrative review outlines technical aspects of non-invasive and minimally-invasive modalities along with providing details on the non-invasive and minimally-invasive measurement techniques used for CA assessment. These non-invasive techniques include neuroimaging methods, transcranial Doppler, and near-infrared spectroscopy while the minimally-invasive techniques include positron emission tomography along with magnetic resonance imaging and radiography methods. Further, the advantages and limitations are discussed along with how these methods are used to assess CA. At the end, the clinical considerations regarding these various techniques are highlighted.
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| 13. |
- von, Rottkay K, et al.
(författare)
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Influence of stoichiometry on electrochromic cerium-titanium oxide compounds
- 1998
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Ingår i: SOLID STATE IONICS. - : ELSEVIER SCIENCE BV. - 0167-2738. ; 115, s. 425-430
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- CeO2-TiO2 finds use as passive counter-electrode in electrochromic devices. Thin films were produced by de-sputtering in a wide range of compositions. Influence of total pressure and oxygen partial pressure on the optical constants of TiO2 was investigate
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