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| 2. |
- 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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| 3. |
- Roberts, Jason D., et al.
(författare)
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Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy
- 2019
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Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 129:8, s. 3171-3184
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Tidskriftsartikel (refereegranskat)abstract
- Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death. Desmosomal structure and function appeared preserved in diseased human and murine specimens in the presence of markedly abnormal beta-catenin expression and patterning, leading to identification of a previously unknown interaction between ankyrin-B and beta-catenin. A pharmacological activator of the WNT/beta-catenin pathway, SB-216763, successfully prevented and partially reversed the murine ACM phenotypes. Our findings introduce what we believe to be a new pathway for ACM, a role of ankyrin-B in cardiac structure and signaling, a molecular link between ankyrin-B and beta-catenin, and evidence for targeted activation of the WNT/beta-catenin pathway as a potential treatment for this disease.
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| 4. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 5. |
- Furness, James, et al.
(författare)
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Acute Injuries in Recreational and Competitive Surfers : Incidence, Severity, Location, Type, and Mechanism
- 2015
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Ingår i: American Journal of Sports Medicine. - : Sage Publications. - 0363-5465 .- 1552-3365. ; 43:5, s. 1246-1254
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:There are an estimated 37 million surfers worldwide, with 2.5 million recreational surfers in Australia. The recreational activity and sport of surfing has grown dramatically since the 1960s, but scientific research has been poorly mirrored in comparison with most other mainstream sports.PURPOSE:To identify the incidence, severity, location, type, and mechanism of acute injuries in recreational and competitive surfers over a 12-month period.STUDY DESIGN:Descriptive epidemiology study.METHODS:An online survey using an open-source survey application was utilized. The survey consisted of 2 primary sections: Section 1 included demographic information and participation levels (age, height, weight, hours surfed, competitive level); section 2 incorporated injury type, mechanism, severity, and injury management.RESULTS:A total of 1348 participants (91.3% males; 43.1% competitive surfers) were included in data analysis. A total of 512 acute injuries were classified as major, providing an incidence proportion of 0.38 (CI, 0.35-0.41) acute injuries per year. The incidence rate was calculated to be 1.79 (CI, 1.67-1.92) major injuries per 1000 hours of surfing. The shoulder, ankle, and head/face regions had the highest frequencies of acute injury, representing 16.4%, 14.6%, and 13.3%, respectively. Injuries were predominantly of muscular, joint, and skin origin, representing 30.3%, 27.7%, and 18.9%, respectively. Skin injuries were primarily a result of direct trauma, while joint and muscular injuries were mainly a result of maneuvers performed and repetitive actions. Key risk factors that increased the incidence of sustaining an acute injury included competitive status, hours surfed (>6.5 hours/week), and the ability to perform aerial maneuvers. The incidence proportion for surfers completing aerial maneuvers was calculated to be 0.48 (CI, 0.39-0.58) major injuries per year, this being the highest incidence proportion irrespective of competitive status.CONCLUSION:This is the largest surfing-specific survey that included both recreational and competitive surfers conducted in Australia to date. The shoulder, ankle, head, and face were identified as the key regions where acute injuries occur in surfers. This research may aid in reducing the occurrence of injury through musculoskeletal screening in these key injury-prone regions and through the use of sport-specific strength training and conditioning.
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| 6. |
- Furness, James, et al.
(författare)
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Clinical methods to quantify trunk mobility in an elite male surfing population
- 2016
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Ingår i: Physical Therapy in Sport. - : Elsevier. - 1466-853X .- 1873-1600. ; 19, s. 28-35
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHigh numbers of acute shoulder and chronic lumbar injuries have been identified in a surfing population. A simple screening tool could be used to determine whether thoracic spine dysfunction is a possible contributor to shoulder or lumbar injuries. Importantly, thoracic mobility in the sagittal and horizontal planes are key requirements in the sport of surfing; however to date the normal values of these movements have not yet been quantified in a surfing population.ObjectivesTo develop a reliable method to quantify thoracic mobility in the sagittal plane; to assess the reliability of a thoracic rotation method, and quantify thoracic mobility in an elite male surfing population.DesignClinical Measurement, reliability (repeated measures) and comparative study. Methods: 27 subjects were used to determine the reliability of a new method to assess thoracic mobility in the sagittal plane and 30 subjects were used to confirm the reliability of an existing thoracic rotation method. A total of 15 elite surfers were used as part of a comparative analysis with age and gender matched controls. Results: Intra-rater reliability (within and between session) intraclass correlation coefficient (ICC) values ranged between 0.95 - 0.99 for both thoracic methods in the sagittal plane and between 0.95 – 0.98 for the rotation method. There was no significant difference in the amount of thoracic mobility in the sagittal plane between groups; however the elite surfing group had significantly (p ≤ 0.05) greater rotation than the comparative group (mean rotation 63.57° versus 40.80° respectively). Symmetry was also confirmed between left and right thoracic rotation in the elite surfing group (63.06 versus 64.01). Conclusion: This study has illustrated reliable methods to assess the thoracic spine in the sagittal and horizontal planes. It has also quantified ROM in a surfing cohort; identifying thoracic rotation as a key movement. This information may provide clinicians, coaches and athletic trainers with imperative information regarding the importance of maintaining adequate thoracic rotation and symmetry. From a screening perspective thoracic rotation should be assessed for performance purposes and to limit the potential for injury in the thoracic spine or in surrounding regions.
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| 7. |
- Furness, James, et al.
(författare)
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Retrospective analysis of chronic injuries in recreational and competitive surfers : injury, location, type and mechanism
- 2014
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Ingår i: International Journal of Aquatic Research and Education. - : Human Kinetics. - 1932-9997 .- 1932-9253. ; 8:3, s. 277-287
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Tidskriftsartikel (refereegranskat)abstract
- Only two studies have reported on chronic musculoskeletal surfing injuries. They found over half of the injuries were non-musculoskeletal, but did not consider mechanisms of injury. This study identified the location, type, and mechanisms of chronic injury in Australian recreational and competitive surfers using a cross-sectional retrospective observational design. A total of 1,348 participants (91.3% males, 43.1% competitive surfers) reported 1,068 chronic injuries, 883 of which were classified as major. Lower back (23.2%), shoulder (22.4%), and knee (12.1%) regions had the most chronic injuries. Competitive surfers had significantly (p < .05) more lower back, ankle/foot, and head/face injuries than recreational surfers. Injuries were mostly musculoskeletal with only 7.8% being of non-musculoskeletal origin. Prolonged paddling was the highest frequency (21.1%) for mechanism of injury followed by turning maneuvers (14.8%). The study results contribute to the limited research on chronic surfing injuries.
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