| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- Burstein, R., et al.
(author)
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Mapping 123 million neonatal, infant and child deaths between 2000 and 2017
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7778, s. 353-358
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Journal article (peer-reviewed)abstract
- Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations. © 2019, The Author(s).
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| 3. |
- Sbarra, AN, et al.
(author)
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Mapping routine measles vaccination in low- and middle-income countries
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
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Journal article (peer-reviewed)abstract
- The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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| 4. |
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| 5. |
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| 6. |
- Kinyoki, DK, et al.
(author)
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Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
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In: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
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Journal article (peer-reviewed)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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| 7. |
- Escala-Garcia, Maria, et al.
(author)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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| 8. |
- Graetz, N, et al.
(author)
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Mapping disparities in education across low- and middle-income countries
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 577:77907789, s. 235-238
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Journal article (peer-reviewed)abstract
- Educational attainment is an important social determinant of maternal, newborn, and child health1–3. As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting4–6. The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness7,8; however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health9–11. Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but—to our knowledge—no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries12–14. By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations.
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| 9. |
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| 10. |
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| 11. |
- Kinyoki, DK, et al.
(author)
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Mapping child growth failure across low- and middle-income countries
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 577:7789, s. 231-
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Journal article (peer-reviewed)abstract
- Childhood malnutrition is associated with high morbidity and mortality globally1. Undernourished children are more likely to experience cognitive, physical, and metabolic developmental impairments that can lead to later cardiovascular disease, reduced intellectual ability and school attainment, and reduced economic productivity in adulthood2. Child growth failure (CGF), expressed as stunting, wasting, and underweight in children under five years of age (0–59 months), is a specific subset of undernutrition characterized by insufficient height or weight against age-specific growth reference standards3–5. The prevalence of stunting, wasting, or underweight in children under five is the proportion of children with a height-for-age, weight-for-height, or weight-for-age z-score, respectively, that is more than two standard deviations below the World Health Organization’s median growth reference standards for a healthy population6. Subnational estimates of CGF report substantial heterogeneity within countries, but are available primarily at the first administrative level (for example, states or provinces)7; the uneven geographical distribution of CGF has motivated further calls for assessments that can match the local scale of many public health programmes8. Building from our previous work mapping CGF in Africa9, here we provide the first, to our knowledge, mapped high-spatial-resolution estimates of CGF indicators from 2000 to 2017 across 105 low- and middle-income countries (LMICs), where 99% of affected children live1, aggregated to policy-relevant first and second (for example, districts or counties) administrative-level units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the ambitious World Health Organization Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and progress exist across and within countries; our maps identify high-prevalence areas even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where the highest-need populations reside, these geospatial estimates can support policy-makers in planning interventions that are adapted locally and in efficiently directing resources towards reducing CGF and its health implications.
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| 12. |
- Namjou, Bahram, et al.
(author)
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High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups
- 2009
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1085-1095
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT-1 and STAT-4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility. METHODS: Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population-based case-control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. RESULTS: We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 x 10(-25)). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4. CONCLUSION: Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets.
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| 13. |
- Langefeld, Carl D., et al.
(author)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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| 14. |
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| 15. |
- Scott, Robert A., et al.
(author)
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A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
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Journal article (peer-reviewed)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
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| 16. |
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| 17. |
- Kennedy, K. M., et al.
(author)
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Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 613:7945, s. 639-649
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Journal article (peer-reviewed)abstract
- Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.
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| 18. |
- Kraemer, MUG, et al.
(author)
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Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus
- 2019
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In: Nature microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:5, s. 854-863
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Journal article (peer-reviewed)abstract
- The global population at risk from mosquito-borne diseases—including dengue, yellow fever, chikungunya and Zika—is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus. The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally.
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| 19. |
- Kraemer, MUG, et al.
(author)
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Publisher Correction: Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus
- 2019
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In: Nature microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:5, s. 900-900
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Journal article (other academic/artistic)abstract
- In the version of this Article originally published, the affiliation for author Catherine Linard was incorrectly stated as ‘6Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK’. The correct affiliation is ‘9Spatial Epidemiology Lab (SpELL), Universite Libre de Bruxelles, Brussels, Belgium’. The affiliation for author Hongjie Yu was also incorrectly stated as ‘11Department of Statistics, Harvard University, Cambridge, MA, USA’. The correct affiliation is ‘15School of Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China’. This has now been amended in all versions of the Article.
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| 20. |
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| 21. |
- Blösch, Günter, et al.
(author)
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Twenty-three unsolved problems in hydrology (UPH) - a community perspective
- 2019
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In: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
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Journal article (peer-reviewed)abstract
- This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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| 30. |
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| 31. |
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| 32. |
- Brincat, Scott L., et al.
(author)
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Interhemispheric transfer of working memories
- 2021
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In: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 109:6, s. 1055-1066
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Journal article (peer-reviewed)abstract
- Visual working memory (WM) storage is largely independent between the left and right visual hemifields/cerebral hemispheres, yet somehow WM feels seamless. We studied how WM is integrated across hemifields by recording neural activity bilaterally from lateral prefrontal cortex. An instructed saccade during the WM delay shifted the remembered location from one hemifield to the other. Before the shift, spike rates and oscillatory power showed clear signatures of memory laterality. After the shift, the lateralization inverted, consistent with transfer of the memory trace from one hemisphere to the other. Transferred traces initially used different neural ensembles from feedforward-induced ones, but they converged at the end of the delay. Around the time of transfer, synchrony between the two prefrontal hemispheres peaked in theta and beta frequencies, with a directionality consistent with memory trace transfer. This illustrates how dynamics between the two cortical hemispheres can stitch together WM traces across visual hemifields.
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| 33. |
- Cowan, Georgia, et al.
(author)
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Fixation patterns of individuals with and without Autism Spectrum disorder : Do they differ in shared zones and in zebra crossings?
- 2018
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In: Journal of Transport & Health. - : Elsevier. - 2214-1405 .- 2214-1413. ; 8, s. 112-122
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Journal article (peer-reviewed)abstract
- Shared zones are a contemporary traffic zone that promotes equality between multiple road users and efficiently utilizes available space, while simultaneously maintaining safety and function. As this is a relatively new traffic zone, it is important to understand how pedestrians navigate a shared zone and any potential challenges this may pose to individuals with impairments. The aim of this study was to utilize eye-tracking technology to determine fixations and fixation duration on traffic relevant objects, non-traffic relevant objects, and eye contact, in 40 individuals with and without Autism Spectrum Disorder (ASD) in a shared zone and a zebra crossing. It was assumed that individuals with ASD would make less eye contact in the shared zone compared to the group of typically developing adults. A total of 3287 fixations across the shared zone and zebra crossing were analysed for areas of interest that were traffic relevant, non-traffic relevant, and eye contact, and for fixation duration. Individuals with ASD did not display any difference in terms of eye contact in the shared zone and the zebra crossing when compared to the controls. All pedestrians were more likely to look at traffic relevant objects at the zebra crossing compared to the shared zone. Individuals with ASD had an overall shorter fixation duration compared to the control group, indicating people with ASD either process information quickly, or they do not process it for long enough, although these findings require further investigation. While shared zones have many benefits for traffic movement and environmental quality, it appeared that pedestrians displayed safer road crossing behaviours at a zebra crossing than in a shared zone, indicating that more education and environmental adaptations are required to make shared zones safe for all pedestrians.
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| 34. |
- Earl, Robyn, et al.
(author)
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Viewpoints of pedestrians with and without cognitive impairment on shared zones and zebra crossings
- 2018
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:9
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Journal article (peer-reviewed)abstract
- BackgroundShared zones are characterised by an absence of traditional markers that segregate the road and footpath. Negotiation of a shared zone relies on an individual’s ability to perceive, assess and respond to environmental cues. This ability may be impacted by impairments in cognitive processing, which may lead to individuals experiencing increased anxiety when negotiating a shared zone.MethodQ method was used in order to identify and explore the viewpoints of pedestrians, with and without cognitive impairments as they pertain to shared zones.ResultsTwo viewpoints were revealed. Viewpoint one was defined by “confident users” while viewpoint two was defined by users who “know what [they] are doing but drivers might not”.DiscussionOverall, participants in the study would not avoid shared zones. Pedestrians with intellectual disability were, however, not well represented by either viewpoint, suggesting that shared zones may pose a potential barrier to participation for this group.
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| 35. |
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| 36. |
- Green, Richard E., et al.
(author)
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Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1335-
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Journal article (peer-reviewed)abstract
- To provide context for the diversification of archosaurs-the group that includes crocodilians, dinosaurs, and birds-we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.
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| 37. |
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| 38. |
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| 39. |
- Klasson, Lisa, et al.
(author)
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Genome evolution of Wolbachia strain wPip from the Culex pipiens group.
- 2008
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 25:9, s. 1877-87
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Journal article (peer-reviewed)abstract
- The obligate intracellular bacterium Wolbachia pipientis strain wPip induces cytoplasmic incompatibility (CI), patterns of crossing sterility, in the Culex pipiens group of mosquitoes. The complete sequence is presented of the 1.48-Mbp genome of wPip which encodes 1386 coding sequences (CDSs), representing the first genome sequence of a B-supergroup Wolbachia. Comparisons were made with the smaller genomes of Wolbachia strains wMel of Drosophila melanogaster, an A-supergroup Wolbachia that is also a CI inducer, and wBm, a mutualist of Brugia malayi nematodes that belongs to the D-supergroup of Wolbachia. Despite extensive gene order rearrangement, a core set of Wolbachia genes shared between the 3 genomes can be identified and contrasts with a flexible gene pool where rapid evolution has taken place. There are much more extensive prophage and ankyrin repeat encoding (ANK) gene components of the wPip genome compared with wMel and wBm, and both are likely to be of considerable importance in wPip biology. Five WO-B-like prophage regions are present and contain some genes that are identical or highly similar in multiple prophage copies, whereas other genes are unique, and it is likely that extensive recombination, duplication, and insertion have occurred between copies. A much larger number of genes encode ankyrin repeat (ANK) proteins in wPip, with 60 present compared with 23 in wMel, many of which are within or close to the prophage regions. It is likely that this pattern is partly a result of expansions in the wPip lineage, due for example to gene duplication, but their presence is in some cases more ancient. The wPip genome underlines the considerable evolutionary flexibility of Wolbachia, providing clear evidence for the rapid evolution of ANK-encoding genes and of prophage regions. This host-Wolbachia system, with its complex patterns of sterility induced between populations, now provides an excellent model for unraveling the molecular systems underlying host reproductive manipulation.
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| 40. |
- Lai, En Yin, et al.
(author)
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Effects of the antioxidant drug tempol on renal oxygenation in mice with reduced renal mass
- 2012
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In: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 303:1, s. F64-74
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Journal article (peer-reviewed)abstract
- We tested the hypothesis that reactive oxygen species (ROS) contributed to renal hypoxia in C57BL/6 mice with ⅚ surgical reduction of renal mass (RRM). ROS can activate the mitochondrial uncoupling protein 2 (UCP-2) and increase O(2) usage. However, UCP-2 can be inactivated by glutathionylation. Mice were fed normal (NS)- or high-salt (HS) diets, and HS mice received the antioxidant drug tempol or vehicle for 3 mo. Since salt intake did not affect the tubular Na(+) transport per O(2) consumed (T(Na/)Q(O2)), further studies were confined to HS mice. RRM mice had increased excretion of 8-isoprostane F(2α) and H(2)O(2), renal expression of UCP-2 and renal O(2) extraction, and reduced T(Na/)Q(O2) (sham: 20 ± 2 vs. RRM: 10 ± 1 μmol/μmol; P < 0.05) and cortical Po(2) (sham: 43 ± 2, RRM: 29 ± 2 mmHg; P < 0.02). Tempol normalized all these parameters while further increasing compensatory renal growth and glomerular volume. RRM mice had preserved blood pressure, glomeruli, and patchy tubulointerstitial fibrosis. The patterns of protein expression in the renal cortex suggested that RRM kidneys had increased ROS from upregulated p22(phox), NOX-2, and -4 and that ROS-dependent increases in UCP-2 led to hypoxia that activated transforming growth factor-β whereas erythroid-related factor 2 (Nrf-2), glutathione peroxidase-1, and glutathione-S-transferase mu-1 were upregulated independently of ROS. We conclude that RRM activated distinct processes: a ROS-dependent activation of UCP-2 leading to inefficient renal O(2) usage and cortical hypoxia that was offset by Nrf-2-dependent glutathionylation. Thus hypoxia in RRM may be the outcome of NADPH oxidase-initiated ROS generation, leading to mitochondrial uncoupling counteracted by defense pathways coordinated by Nrf-2.
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| 41. |
- Lundqvist, Mikael, et al.
(author)
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Gamma and beta bursts during working memory readout suggest roles in its volitional control
- 2018
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Journal article (peer-reviewed)abstract
- Working memory (WM) activity is not as stationary or sustained as previously thought. There are brief bursts of gamma (similar to 50-120 Hz) and beta (similar to 20-35 Hz) oscillations, the former linked to stimulus information in spiking. We examined these dynamics in relation to readout and control mechanisms of WM. Monkeys held sequences of two objects in WM to match to subsequent sequences. Changes in beta and gamma bursting suggested their distinct roles. In anticipation of having to use an object for the match decision, there was an increase in gamma and spiking information about that object and reduced beta bursting. This readout signal was only seen before relevant test objects, and was related to premotor activity. When the objects were no longer needed, beta increased and gamma decreased together with object spiking information. Deviations from these dynamics predicted behavioral errors. Thus, beta could regulate gamma and the information in WM.
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| 42. |
- Lundqvist, Mikael, et al.
(author)
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Gamma and Beta Bursts Underlie Working Memory
- 2016
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In: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 90:1, s. 152-164
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Journal article (peer-reviewed)abstract
- Working memory is thought to result from sustained neuron spiking. However, computational models suggest complex dynamics with discrete oscillatory bursts. We analyzed local field potential (LFP) and spiking from the prefrontal cortex (PFC) of monkeys performing a working memory task. There were brief bursts of narrow-band gamma oscillations (45-100 Hz), varied in time and frequency, accompanying encoding and re-activation of sensory information. They appeared at a minority of recording sites associated with spiking reflecting the to-be-remembered items. Beta oscillations (20-35 Hz) also occurred in brief, variable bursts but reflected a default state interrupted by encoding and decoding. Only activity of neurons reflecting encoding/decoding correlated with changes in gamma burst rate. Thus, gamma bursts could gate access to, and prevent sensory interference with, working memory. This supports the hypothesis that working memory is manifested by discrete oscillatory dynamics and spiking, not sustained activity.
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| 43. |
- Lundqvist, Mikael, et al.
(author)
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Reduced variability of bursting activity during working memory
- 2022
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In: Scientific Reports. - Stockholm : Karolinska Institutet, Dept of Clinical Neuroscience. - 2045-2322.
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Journal article (peer-reviewed)abstract
- Working memories have long been thought to be maintained by persistent spiking. However, mounting evidence from multiple-electrode recording (and single-trial analyses) shows that the underlying spiking is better characterized by intermittent bursts of activity. A counterargument suggested this intermittent activity is at odds with observations that spike-time variability reduces during task performance. However, this counterargument rests on assumptions, such as randomness in the timing of the bursts, which may not be correct. Thus, we analyzed spiking and LFPs from monkeys' prefrontal cortex (PFC) to determine if task-related reductions in variability can co-exist with intermittent spiking. We found that it does because both spiking and associated gamma bursts were task-modulated, not random. In fact, the task-related reduction in spike variability could largely be explained by a related reduction in gamma burst variability. Our results provide further support for the intermittent activity models of working memory as well as novel mechanistic insights into how spike variability is reduced during cognitive tasks.
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| 44. |
- Lundqvist, Mikael, et al.
(author)
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Working memory control dynamics follow principles of spatial computing
- 2023
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In: Nature communications. - Stockholm : Karolinska Institutet, Dept of Clinical Neuroscience. - 2041-1723.
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Journal article (peer-reviewed)abstract
- Working memory (WM) allows us to remember and selectively control a limited set of items. Neural evidence suggests it is achieved by interactions between bursts of beta and gamma oscillations. However, it is not clear how oscillations, reflecting coherent activity of millions of neurons, can selectively control individual WM items. Here we propose the novel concept of spatial computing where beta and gamma interactions cause item-specific activity to flow spatially across the network during a task. This way, control-related information such as item order is stored in the spatial activity independent of the detailed recurrent connectivity supporting the item-specific activity itself. The spatial flow is in turn reflected in low-dimensional activity shared by many neurons. We verify these predictions by analyzing local field potentials and neuronal spiking. We hypothesize that spatial computing can facilitate generalization and zero-shot learning by utilizing spatial component as an additional information encoding dimension.
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| 45. |
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| 46. |
- Mlynczak, Martin G., et al.
(author)
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Atomic oxygen in the mesosphere and lower thermosphere derived from SABER : Algorithm theoretical basis and measurement uncertainty
- 2013
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In: Journal of Geophysical Research - Atmospheres. - : American Geophysical Union (AGU). - 2169-897X .- 2169-8996. ; 118:11, s. 5724-5735
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Journal article (peer-reviewed)abstract
- Atomic oxygen (O) is a fundamental component in chemical aeronomy of Earth's mesosphere and lower thermosphere region extending from approximately 50 km to over 100 km in altitude. Atomic oxygen is notoriously difficult to measure, especially with remote sensing techniques from orbiting satellite sensors. It is typically inferred from measurements of the ozone concentration in the day or from measurements of the Meinel band emission of the hydroxyl radical (OH) at night. The Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the NASA Thermosphere-Ionosphere-Mesosphere Energetics and Dynamics (TIMED) satellite measures OH emission and ozone for the purpose of determining the O-atom concentration. In this paper, we present the algorithms used in the derivation of day and night atomic oxygen from these measurements. We find excellent consistency between the day and night O-atom concentrations from daily to annual time scales. We also examine in detail the collisional relaxation of the highly vibrationally excited OH molecule at night measured by SABER. Large rate coefficients for collisional removal of vibrationally excited OH molecules by atomic oxygen are consistent with the SABER observations if the deactivation of OH(9) proceeds solely by collisional quenching. An uncertainty analysis of the derived atomic oxygen is also given. Uncertainty in the rate coefficient for recombination of O and molecular oxygen is shown to be the largest source of uncertainty in the derivation of atomic oxygen day or night.
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| 47. |
- Mlynczak, Martin G., et al.
(author)
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Evidence for a solar cycle influence on the infrared energy budget and radiative cooling of the thermosphere
- 2007
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In: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 112:A12
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Journal article (peer-reviewed)abstract
- We present direct observational evidence for solar cycle influence on the infrared energy budget and radiative cooling of the thermosphere. By analyzing nearly five years of data from the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument, we show that the annual mean infrared power radiated by the nitric oxide (NO) molecule at 5.3 μm has decreased by a factor of 2.9. This decrease is correlated (r = 0.96) with the decrease in the annual mean F10.7 solar index. Despite the sharp decrease in radiated power (which is equivalent to a decrease in the vertical integrated radiative cooling rate), the variability of the power as given in the standard deviation of the annual means remains approximately constant. A simple relationship is shown to exist between the infrared power radiated by NO and the F10.7 index, thus providing a fundamental relationship between solar activity and the thermospheric cooling rate for use in thermospheric models. The change in NO radiated power is also consistent with changes in absorbed ultraviolet radiation over the same time period. Computations of radiated power using an empirical model show much less variability than observed by SABER.
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| 48. |
- Mlynczak, Martin G., et al.
(author)
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Observations of infrared radiative cooling in the thermosphere on daily to multiyear timescales from the TIMED/SABER instrument
- 2010
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In: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 115:A3
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Journal article (peer-reviewed)abstract
- We present observations of the infrared radiative cooling by carbon dioxide (CO2) and nitric oxide (NO) in Earth's thermosphere. These data have been taken over a period of 7 years by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the NASA Thermosphere-Ionosphere-Mesosphere Energetics and Dynamics (TIMED) satellite and are the dominant radiative cooling mechanisms for the thermosphere. From the SABER observations we derive vertical profiles of radiative cooling rates (W m−3), radiative fluxes (W m−2), and radiated power (W). In the period from January 2002 through January 2009, we observe a large decrease in the cooling rates, fluxes, and power consistent with the declining phase of solar cycle 23. The power radiated by NO during 2008 when the Sun exhibited few sunspots was nearly one order of magnitude smaller than the peak power observed shortly after the mission began. Substantial short-term variability in the infrared emissions is also observed throughout the entire mission duration. Radiative cooling rates and radiative fluxes from NO exhibit fundamentally different latitude dependence than do those from CO2, with the NO fluxes and cooling rates being largest at high latitudes and polar regions. The cooling rates are shown to be derived relatively independent of the collisional and radiative processes that drive the departure from local thermodynamic equilibrium (LTE) in the CO2 15 μm and the NO 5.3 μm vibration-rotation bands. The observed NO and CO2 cooling rates have been compiled into a separate data set and represent a climate data record that is available for use in assessments of radiative cooling in upper atmosphere general circulation models.
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| 49. |
- Mlynczak, Martin G., et al.
(author)
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Solar-terrestrial coupling evidenced by periodic behavior in geomagnetic indexes and the infrared energy budget of the thermosphere
- 2008
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 35:5
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Journal article (peer-reviewed)abstract
- We examine time series of the daily global power (W) radiated by carbon dioxide (at 15 μm) and by nitric oxide (at 5.3 μm) from the Earth's thermosphere between 100 km and 200 km altitude. Also examined is a time series of the daily absorbed solar ultraviolet power in the same altitude region in the wavelength span 0 to 175 run. The infrared data are derived from the SABER instrument and the solar data are derived from the SEE instrument, both on the NASA TIMED satellite. The time series cover nearly 5 years from 2002 through 2006. The infrared and solar time series exhibit a decrease in radiated and absorbed power consistent with the declining phase of the current 11-year solar cycle. The infrared time series also exhibits high frequency variations that are not evident in the solar power time series. Spectral analysis shows a statistically significant 9-day periodicity in the infrared data but not in the solar data. A very strong 9-day periodicity is also found to exist in the time series of daily Ap and Kp geomagnetic indexes. These 9-day periodicities are linked to the recurrence of coronal holes on the Sun. These results demonstrate a direct coupling between the upper atmosphere of the Sun and the infrared energy budget of the thermosphere. Copyright 2008 by the American Geophysical Union.
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| 50. |
- Mlynczak, Martin G., et al.
(author)
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Sounding of the Atmosphere using Broadband Emission Radiometry observations of daytime mesospheric O2(1Δ) 1.27 μm emission and derivation of ozone, atomic oxygen, and solar and chemical energy deposition rates
- 2007
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In: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 112:D15
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Journal article (peer-reviewed)abstract
- We report observations of the daytime O2(1Δ) airglow emission at 1.27 μm recorded by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the NASA Thermosphere-Ionosphere-Mesosphere Energetics and Dynamics (TIMED) satellite. The measured limb radiances are inverted to yield vertical profiles of the volume emission rate of energy from the O2 molecule. From these emission rates we subsequently derive the mesospheric ozone concentrations using a nonlocal thermodynamic equilibrium (non-LTE) radiative and kinetic model. Rates of energy deposition due to absorption of ultraviolet radiation in the Hartley band of ozone are also derived, independent of knowledge of the ozone abundance and solar irradiances. Atomic oxygen concentrations are obtained from the ozone abundance using photochemical steady state assumptions. Rates of energy deposition due to exothermic chemical reactions are also derived. The data products illustrated here are from a test day (4 July 2002) of SABER Version 1.07 data which are now becoming publicly available. This test day illustrates the high quality of the SABER O2(1Δ) airglow and ozone data and the variety of fundamental science questions to which they can be applied.
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