| 1. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 2. |
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| 3. |
- Breitburg, D. L., et al.
(författare)
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And on top of all that…: Coping with ocean acidification in the midst of many stressors by denise
- 2015
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Ingår i: Oceanography. - : The Oceanography Society. - 1042-8275. ; 28:2, s. 48-61
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Tidskriftsartikel (refereegranskat)abstract
- Oceanic and coastal waters are acidifying due to processes dominated in the open ocean by increasing atmospheric CO2 and dominated in estuaries and some coastal waters by nutrient-fueled respiration. The patterns and severity of acidification, as well as its effects, are modified by the host of stressors related to human activities that also influence these habitats. Temperature, deoxygenation, and changes in food webs are particularly important co-stressors because they are pervasive, and both their causes and effects are often mechanistically linked to acidification. Development of a theoretical underpinning to multiple stressor research that considers physiological, ecological, and evolutionary perspectives is needed because testing all combinations of stressors and stressor intensities experimentally is impossible. Nevertheless, use of a wide variety of research approaches is a logical and promising strategy for improving understanding of acidification and its effects. Future research that focuses on spatial and temporal patterns of stressor interactions and on identifying mechanisms by which multiple stressors affect individuals, populations, and ecosystems is critical. It is also necessary to incorporate consideration of multiple stressors into management, mitigation, and adaptation to acidification and to increase public and policy recognition of the importance of addressing acidification in the context of the suite of other stressors with which it potentially interacts. © 2015 by The Oceanography Society. All rights reserved.
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| 4. |
- Cooper, Ian R., et al.
(författare)
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Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors
- 2016
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 26:17, s. 4179-4183
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.
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| 5. |
- Frieman, Catherine J., et al.
(författare)
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Aging well: Treherne’s ‘warrior’s beauty’ two decades later
- 2017
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Ingår i: European Journal of Archaeology. - : Cambridge University Press (CUP). - 1461-9571 .- 1741-2722. ; 20:1, s. 36-73
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Tidskriftsartikel (refereegranskat)abstract
- Over the (slightly more than) two decades that the European Journal of Archaeology (formerly the Journal of European Archaeology) has been in print, we have published a number of excellent and high profile articles. Among these, Paul Treherne's seminal meditation on Bronze Age male identity and warriorhood stands out as both the highest cited and the most regularly downloaded paper in our archive. Speaking informally with friends and colleagues who work on Bronze Age topics as diverse as ceramics, metalwork, landscape phenomenology, and settlement structure, I found that this paper holds a special place in their hearts. Certainly, it is a staple of seminar reading lists and, in my experience at least, is prone to provoke heated discussions among students on topics as far ranging as gender identity in the past and present, theoretically informed methods for material culture studies, and the validity of using Classical texts for understanding prehistoric worlds. Moreover, in its themes of violence, embodiment, materiality, and the fluidity or ephemeral nature of gendered identities, it remains a crucial foundational text for major debates raging in European prehistoric archaeology in the present day.
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| 7. |
- Sotiropoulou, Georgia, et al.
(författare)
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Atmospheric conditions during the Arctic Clouds in Summer Experiment (ACSE) : Contrasting open-water and sea-ice surfaces during melt and freeze-up seasons
- 2016
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Ingår i: Journal of Climate. - 0894-8755 .- 1520-0442. ; 29:24, s. 8721-8744
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Tidskriftsartikel (refereegranskat)abstract
- The Arctic Clouds in Summer Experiment (ACSE) was conducted during summer and early autumn 2014, providing a detailed view of the seasonal transition from ice melt into freeze-up. Measurements were taken over both ice-free and ice-covered surfaces, near the ice edge, offering insight to the role of the surface state in shaping the atmospheric conditions. The initiation of the autumn freeze-up was related to a change in air mass, rather than to changes in solar radiation alone; the lower atmosphere cooled abruptly leading to a surface heat loss. During melt season, strong surface inversions persisted over the ice, while elevated inversions were more frequent over open water. These differences disappeared during autumn freeze-up, when elevated inversions persisted over both ice-free and ice-covered conditions. These results are in contrast to previous studies that found a well-mixed boundary layer persisting in summer and an increased frequency of surface-based inversions in autumn, suggesting that our knowledge derived from measurements taken within the pan-Arctic area and on the central ice-pack does not necessarily apply closer to the ice-edge. This study offers an insight to the atmospheric processes that occur during a crucial period of the year; understanding and accurately modeling these processes is essential for the improvement of ice-extent predictions and future Arctic climate projections.
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| 8. |
- Tjernström, Michael, et al.
(författare)
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Warm-air advection, air mass transformation and fog causes rapid ice melt
- 2015
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:13, s. 5594-5602
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Tidskriftsartikel (refereegranskat)abstract
- Direct observations during intense warm-air advection over the East Siberian Sea reveal a period of rapid sea-ice melt. A semistationary, high-pressure system north of the Bering Strait forced northward advection of warm, moist air from the continent. Air-mass transformation over melting sea ice formed a strong, surface-based temperature inversion in which dense fog formed. This induced a positive net longwave radiation at the surface while reducing net solar radiation only marginally; the inversion also resulted in downward turbulent heat flux. The sum of these processes enhanced the surface energy flux by an average of similar to 15Wm(-2) for a week. Satellite images before and after the episode show sea-ice concentrations decreasing from > 90% to similar to 50% over a large area affected by the air-mass transformation. We argue that this rapid melt was triggered by the increased heat flux from the atmosphere due to the warm-air advection.
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| 11. |
- Howell, Matthew, et al.
(författare)
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Absence of the Polar Organizing Protein PopZ Results in Reduced and Asymmetric Cell Division in Agrobacterium tumefaciens
- 2017
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Ingår i: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 199:17
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Tidskriftsartikel (refereegranskat)abstract
- Agrobacterium tumefaciens is a rod-shaped bacterium that grows by polar insertion of new peptidoglycan during cell elongation. As the cell cycle progresses, peptidoglycan synthesis at the pole ceases prior to insertion of new peptidoglycan at midcell to enable cell division. The A. tumefaciens homolog of the Caulobacter crescentus polar organelle development protein PopZ has been identified as a growth pole marker and a candidate polar growth-promoting factor. Here, we characterize the function of PopZ in cell growth and division of A. tumefaciens. Consistent with previous observations, we observe that PopZ localizes specifically to the growth pole in wild-type cells. Despite the striking localization pattern of PopZ, we find the absence of the protein does not impair polar elongation or cause major changes in the peptidoglycan composition. Instead, we observe an atypical cell length distribution, including minicells, elongated cells, and cells with ectopic poles. Most minicells lack DNA, suggesting a defect in chromosome segregation. Furthermore, the canonical cell division proteins FtsZ and FtsA are misplaced, leading to asymmetric sites of cell constriction. Together, these data suggest that PopZ plays an important role in the regulation of chromosome segregation and cell division.IMPORTANCE A. tumefaciens is a bacterial plant pathogen and a natural genetic engineer. However, very little is known about the spatial and temporal regulation of cell wall biogenesis that leads to polar growth in this bacterium. Understanding the molecular basis of A. tumefaciens growth may allow for the development of innovations to prevent disease or to promote growth during biotechnology applications. Finally, since many closely related plant and animal pathogens exhibit polar growth, discoveries in A. tumefaciens may be broadly applicable for devising antimicrobial strategies.
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| 12. |
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| 13. |
- Prytherch, John, et al.
(författare)
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Direct determination of the air-sea CO2 gas transfer velocity in Arctic sea ice regions
- 2017
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 44:8, s. 3770-3778
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Tidskriftsartikel (refereegranskat)abstract
- The Arctic Ocean is an important sink for atmospheric CO2. The impact of decreasing sea ice extent and expanding marginal ice zones on Arctic air-sea CO2 exchange depends on the rate of gas transfer in the presence of sea ice. Sea ice acts to limit air-sea gas exchange by reducing contact between air and water but is also hypothesized to enhance gas transfer rates across surrounding open-water surfaces through physical processes such as increased surface-ocean turbulence from ice-water shear and ice-edge form drag. Here we present the first direct determination of the CO2 air-sea gas transfer velocity in a wide range of Arctic sea ice conditions. We show that the gas transfer velocity increases near linearly with decreasing sea ice concentration. We also show that previous modeling approaches overestimate gas transfer rates in sea ice regions.
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| 14. |
- Shcherbina, Anna, et al.
(författare)
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Accuracy in wrist-worn, sensor-based measurements of heart rate and energy expenditure in a diverse cohort
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The ability to measure activity and physiology through wrist-worn devices provides an opportunity for cardiovascular medicine. However, the accuracy of commercial devices is largely unknown. Objective: To assess the accuracy of seven commercially available wrist-worn devices in estimating heart rate (HR) and energy expenditure (EE) and to propose a wearable sensor evaluation framework. Methods: We evaluated the Apple Watch, Basis Peak, Fitbit Surge, Microsoft Band, Mio Alpha 2, PulseOn, and Samsung Gear S2. Participants wore devices while being simultaneously assessed with continuous telemetry and indirect calorimetry while sitting, walking, running, and cycling. Sixty volunteers (29 male, 31 female, age 38 +/- 11 years) of diverse age, height, weight, skin tone, and fitness level were selected. Error in HR and EE was computed for each subject/device/activity combination. Results: Devices reported the lowest error for cycling and the highest for walking. Device error was higher for males, greater body mass index, darker skin tone, and walking. Six of the devices achieved a median error for HR below 5% during cycling. No device achieved an error in EE below 20 percent. The Apple Watch achieved the lowest overall error in both HR and EE, while the Samsung Gear S2 reported the highest. Conclusions: Most wrist-worn devices adequately measure HR in laboratory-based activities, but poorly estimate EE, suggesting caution in the use of EE measurements as part of health improvement programs. We propose reference standards for the validation of consumer health devices (http://precision.stanford.edu/).
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