| 1. |
- Baird, Emily, et al.
(författare)
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X-ray micro computed-tomography
- 2017
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822. ; 27:8, s. 289-291
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Tidskriftsartikel (refereegranskat)abstract
- Emily Baird and Gavin Taylor describe how you can make three-dimensional models of biological samples using x-ray micro-computed tomography
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| 2. |
- Campbell, Brittany B., et al.
(författare)
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Comprehensive Analysis of Hypermutation in Human Cancer
- 2017
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 171:5
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Elsevier Inc. We present an extensive assessment of mutation burden through sequencing analysis of > 81,000 tumors from pediatric and adult patients, including tumors with hypermutation caused by chemotherapy, carcinogens, or germline alterations. Hypermutation was detected in tumor types not previously associated with high mutation burden. Replication repair deficiency was a major contributing factor. We uncovered new driver mutations in the replication-repair-associated DNA polymerases and a distinct impact of microsatellite instability and replication repair deficiency on the scale of mutation load. Unbiased clustering, based on mutational context, revealed clinically relevant subgroups regardless of the tumors' tissue of origin, highlighting similarities in evolutionary dynamics leading to hypermutation. Mutagens, such as UV light, were implicated in unexpected cancers, including sarcomas and lung tumors. The order of mutational signatures identified previous treatment and germline replication repair deficiency, which improved management of patients and families. These data will inform tumor classification, genetic testing, and clinical trial design. A large-scale analysis of hypermutation in human cancers provides insights into tumor evolution dynamics and identifies clinically actionable mutation signatures.
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| 3. |
- Gren, Johan, et al.
(författare)
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Molecular and microstructural inventory of an isolated fossil bird feather from the Eocene Fur Formation of Denmark
- 2017
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Ingår i: Palaeontology. - : Blackwell Publishing. - 0031-0239 .- 1475-4983. ; 60:1, s. 73-90
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Tidskriftsartikel (refereegranskat)abstract
- An isolated, yet virtually intact contour feather (FUM-1980) from the lower Eocene Fur Formation of Denmark was analysed using multiple imaging and molecular techniques, including field emission gun scanning electron microscopy (FEG-SEM), X-ray absorption spectroscopy and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Additionally, synchrotron radiation X-ray tomographic microscopy (SRXTM) was employed in order to produce a digital reconstruction of the fossil. Under FEG-SEM, the proximal, plumulaceous part of the feather revealed masses of ovoid microstructures, about 1.7 μm long and 0.5 μm wide. Microbodies in the distal, pennaceous portion were substantially smaller (averaging 0.9 × 0.2 μm), highly elongate, and more densely packed. Generally, the microbodies in both the plumulaceous and pennaceous segments were aligned along the barbs and located within shallow depressions on the exposed surfaces. Biomarkers consistent with animal eumelanins were co-localized with the microstructures, to suggest that they represent remnant eumelanosomes (i.e. eumelanin-housing cellular organelles). Additionally, ToF-SIMS analysis revealed the presence of sulfur-containing organics – potentially indicative of pheomelanins – associated with eumelanin-like compounds. However, since there was no correlation between melanosome morphology and sulfur content, we conclude these molecular structures derive from diagenetically incorporated sulfur rather than pheomelanin. Melanosomes corresponding roughly in both size and morphology with those in the proximal part of FUM-1980 are known from contour feathers of extant parrots (Psittaciformes), an avian clade that has previously been reported from the Fur Formation.
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| 4. |
- Palmer, Benjamin A., et al.
(författare)
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The image-forming mirror in the eye of the scallop
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 358:6367, s. 1172-1175
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Tidskriftsartikel (refereegranskat)abstract
- Scallops possess a visual system comprising up to 200 eyes, each containing a concave mirror rather than a lens to focus light. The hierarchical organization of the multilayered mirror is controlled for image formation, from the component guanine crystals at the nanoscale to the complex three-dimensional morphology at the millimeter level. The layered structure of the mirror is tuned to reflect the wavelengths of light penetrating the scallop’s habitat and is tiled with a mosaic of square guanine crystals, which reduces optical aberrations. The mirror forms images on a double-layered retina used for separately imaging the peripheral and central fields of view. The tiled, off-axis mirror of the scallop eye bears a striking resemblance to the segmented mirrors of reflecting telescopes.
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| 5. |
- Taylor, Gavin, et al.
(författare)
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Insects modify their behaviour depending on the feedback sensor used when walking on a trackball in virtual-reality
- 2015
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 218, s. 3118-3127
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Tidskriftsartikel (refereegranskat)abstract
- When using virtual-reality paradigms to study animal behaviour, careful attention must be paid to how the animal's actions are detected. This is particularly relevant in closed-loop experiments where the animal interacts with a stimulus. Many different sensor types have been used to measure aspects of behaviour, and although some sensors may be more accurate than others, few studies have examined whether, and how, such differences affect an animal's behaviour in a closed-loop experiment. To investigate this issue, we conducted experiments with tethered honeybees walking on an air-supported trackball and fixating a visual object in closed-loop. Bees walked faster and along straighter paths when the motion of the trackball was measured in the classical fashion - using optical motion sensors repurposed from computer mice - than when measured more accurately using a computer vision algorithm called 'FicTrac'. When computer mouse sensors were used to measure bees' behaviour, the bees modified their behaviour and achieved improved control of the stimulus. This behavioural change appears to be a response to a systematic error in the computer mouse sensor that reduces the sensitivity of this sensor system under certain conditions. Although the large perceived inertia and mass of the trackball relative to the honeybee is a limitation of tethered walking paradigms, observing differences depending on the sensor system used to measure bee behaviour was not expected. This study suggests that bees are capable of fine-tuning their motor control to improve the outcome of the task they are performing. Further, our findings show that caution is required when designing virtual-reality experiments, as animals can potentially respond to the artificial scenario in unexpected and unintended ways.
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| 6. |
- Taylor, Gavin J., et al.
(författare)
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Bumblebee visual allometry results in locally improved resolution and globally improved sensitivity
- 2019
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Ingår i: eLife. - 2050-084X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The quality of visual information that is available to an animal is limited by the size of its eyes. Differences in eye size can be observed even between closely related individuals, yet we understand little about how this affects vision. Insects are good models for exploring the effects of size on visual systems because many insect species exhibit size polymorphism. Previous work has been limited by difficulties in determining the 3D structure of eyes. We have developed a novel method based on x-ray microtomography to measure the 3D structure of insect eyes and to calculate predictions of their visual capabilities. We used our method to investigate visual allometry in the bumblebee Bombus terrestris and found that size affects specific aspects of vision, including binocular overlap, optical sensitivity, and dorsofrontal visual resolution. This reveals that differential scaling between eye areas provides flexibility that improves the visual capabilities of larger bumblebees.
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| 7. |
- Taylor, Gavin, et al.
(författare)
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The Dual Function of Orchid Bee Ocelli as Revealed by X-Ray Microtomography
- 2016
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Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; :26, s. 1319-1324
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Tidskriftsartikel (refereegranskat)abstract
- Visually guided flight control in the rainforest is arguablyone of the most complex insect behaviors: illuminationvaries dramatically depending on location[1], and the densely cluttered environment blocksout most of the sky [2]. What visual information doinsects sample for flight control in this habitat? Tobegin answering this question, we determined the visualfields of the ocelli—thought to play a role in attitudestabilization of some flying insects [3–5]—ofan orchid bee, Euglossa imperialis. High-resolution3D models of the ocellar system from X-ray microtomographywere used for optical ray tracing simulations.Surprisingly, these showed that each ocelluspossesses two distinct visual fields—a focusedmonocular visual field suitable for detecting featureselevated above the horizon and therefore assistingwith flight stabilization [3–5] and, unlike other ocelliinvestigated to date [4, 6, 7], a large trinocularfronto-dorsal visual field shared by all ocelli. Histologicalanalyses show that photoreceptors havesimilar orientations within each ocellus and are likelyto be sensitive to polarized light, as in some other hymenopterans[7, 8]. We also found that the averagereceptor orientation is offset between the ocelli,each having different axes of polarization sensitivityrelative to the head. Unlike the eyes of any otherinsect described to date, this ocellar system meetsthe requirements of a true polarization analyzer[9, 10]. The ocelli of E. imperialis could providesensitive compass information for navigation in therainforest and, additionally, provide cues for visualdiscrimination or flight control.
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| 8. |
- Van De Poll, Matthew N, et al.
(författare)
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Using an abstract geometry in virtual reality to explore choice behaviour: visual flicker preferences in honeybees
- 2015
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 218:21, s. 3448-3460
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Tidskriftsartikel (refereegranskat)abstract
- Closed-loop paradigms provide an effective approach to studying visual choice behaviour and attention in small animals. Different flying and walking paradigms have been developed to investigate behavioural and neuronal responses to competing stimuli in insects such as bees and flies. However, the variety of stimulus choices that can be presented over one experiment is often limited. Current choice paradigms are mostly constrained as single binary choice scenarios that are influenced by the linear structure of classical conditioning paradigms. Here, we present a novel behavioural choice paradigm that allows animals to explore a closed geometry of interconnected binary choices by repeatedly selecting among competing objects, thereby revealing stimulus preferences in an historical context. We employed our novel paradigm to investigate visual flicker preferences in honeybees (Apis mellifera), and found significant preferences for 20-25Hz flicker and avoidance of higher (50-100Hz) and lower (2-4Hz) flicker frequencies. Similar results were found when bees were presented with three simultaneous choices instead of two, and when they were given the chance to select previously rejected choices. Our results show that honeybees can discriminate among different flicker frequencies, and that their visual preferences are persistent even under different experimental conditions. Interestingly, avoided stimuli were more attractive if they were novel, suggesting that novelty salience can override innate preferences. Our recursive virtual reality environment provides a new approach to studying visual discrimination and choice behaviour in behaving animals.
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| 9. |
- Wang, Haidong, et al.
(författare)
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Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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| 10. |
- Whaley, Paul, et al.
(författare)
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Implementing systematic review techniques in chemical risk assessment : Challenges, opportunities and recommendations
- 2016
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 92-93, s. 556-564
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Forskningsöversikt (refereegranskat)abstract
- Systematic review (SR) is a rigorous, protocol-driven approach designed to minimise error and bias when summarising the body of research evidence relevant to a specific scientific question. Taking as a comparator the use of SR in synthesising research in healthcare, we argue that SR methods could also pave the way for a step change in the transparency, objectivity and communication of chemical risk assessments (CRA) in Europe and elsewhere. We suggest that current controversies around the safety of certain chemicals are partly due to limitations in current CRA procedures which have contributed to ambiguity about the health risks posed by these substances. We present an overview of how SR methods can be applied to the assessment of risks from chemicals, and indicate how challenges in adapting SR methods from healthcare research to the CRA context might be overcome. Regarding the latter, we report the outcomes from a workshop exploring how to increase uptake of SR methods, attended by experts representing a wide range of fields related to chemical toxicology, risk analysis and SR Priorities which were identified include: the conduct of CRA-focused prototype SRs; the development of a recognised standard of reporting and conduct for SRs in toxicology and CRA; and establishing a network to facilitate research, communication and training in SR methods. We see this paper as a milestone in the creation of a research climate that fosters communication between experts in CRA and SR and facilitates wider uptake of SR methods into CRA.
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