| 1. |
- Clemente, Florian J, et al.
(författare)
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A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 95:5
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Tidskriftsartikel (refereegranskat)abstract
- Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype data from native Siberians have previously highlighted a 3 Mb chromosome 11 region containing 79 protein-coding genes as the strongest candidates for positive selection in Northeast Siberians. However, it was not possible to determine which of the genes might be driving the selection signal. Here, using whole-genome high-coverage sequence data, we identified the most likely causative variant as a nonsynonymous G>A transition (rs80356779; c.1436C>T [p.Pro479Leu] on the reverse strand) in CPT1A, a key regulator of mitochondrial long-chain fatty-acid oxidation. Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample. We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6-23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment.
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| 2. |
- Goldsmith, Paul F., et al.
(författare)
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Herschel Measurements of Molecular Oxygen in Orion
- 2011
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 737:2, s. 96 (1-17)
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Tidskriftsartikel (refereegranskat)abstract
- We report observations of three rotational transitions of molecular oxygen (O2) in emission from the H2 Peak 1 position of vibrationally excited molecular hydrogen in Orion. We observed the 487 GHz, 774 GHz, and 1121 GHz lines using the Heterodyne Instrument for the Far Infrared on the Herschel Space Observatory, having velocities of 11 km s–1 to 12 km s–1 and widths of 3 km s–1. The beam-averaged column density is N(O2) = 6.5 × 1016 cm–2, and assuming that the source has an equal beam-filling factor for all transitions (beam widths 44, 28, and 19''), the relative line intensities imply a kinetic temperature between 65 K and 120 K. The fractional abundance of O2 relative to H2 is (0.3-7.3) × 10–6. The unusual velocity suggests an association with a ~5'' diameter source, denoted Peak A, the Western Clump, or MF4. The mass of this source is ~10 Msun and the dust temperature is ≥150 K. Our preferred explanation of the enhanced O2 abundance is that dust grains in this region are sufficiently warm (T ≥ 100 K) to desorb water ice and thus keep a significant fraction of elemental oxygen in the gas phase, with a significant fraction as O2. For this small source, the line ratios require a temperature ≥180 K. The inferred O2 column density sime5 × 1018 cm–2 can be produced in Peak A, having N(H2) sime 4 × 1024 cm–2. An alternative mechanism is a low-velocity (10-15 km s–1) C-shock, which can produce N(O2) up to 1017 cm–2.
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| 3. |
- Guichard, Etienne, et al.
(författare)
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Impact of non-LTR retrotransposons in the differentiation and evolution of anatomically modern humans
- 2018
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Ingår i: Mobile DNA. - : BMC. - 1759-8753. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transposable elements are biologically important components of eukaryote genomes. In particular, non-LTR retrotransposons (N-LTRrs) played a key role in shaping the human genome throughout evolution. In this study, we compared retrotransposon insertions differentially present in the genomes of Anatomically Modern Humans, Neanderthals, Denisovans and Chimpanzees, in order to assess the possible impact of retrotransposition in the differentiation of the human lineage. Results: We first identified species-specific N-LTRrs and established their distribution in present day human populations. These analyses shortlisted a group of N-LTRr insertions that were found exclusively in Anatomically Modern Humans. These insertions are associated with an increase in the number of transcriptional/splicing variants of those genes they inserted in. The analysis of the functionality of genes containing human-specific N-LTRr insertions reflects changes that occurred during human evolution. In particular, the expression of genes containing the most recent N-LTRr insertions is enriched in the brain, especially in undifferentiated neurons, and these genes associate in networks related to neuron maturation and migration. Additionally, we identified candidate N-LTRr insertions that have likely produced new functional variants exclusive to modern humans, whose genomic loci show traces of positive selection. Conclusions: Our results strongly suggest that N-LTRr impacted our differentiation as a species, most likely inducing an increase in neural complexity, and have been a constant source of genomic variability all throughout the evolution of the human lineage.
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| 4. |
- Hammarén, Rickard, 1989-
(författare)
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From the migrations of herders and farmers to the colonial era and the modern-day : Genetic inferences on African demographic history
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Africa is the birthplace of the human species and home to great linguistic, cultural, and genetic diversity. Despite this, the genetics of the peoples of the continent remains understudied. In this thesis, I apply population genetic approaches, to contribute to the knowledge of human demographic history in Africa. Specifically, I investigated three events that have had major impacts on human population genetics in Africa. Paper I, investigated Eurasian back migrations into Northeast Africa and what genetic patterns this has left in the current-day populations of the area. I identified complex demography and linguistic stratification of Eurasian admixture in the region. These genetic patterns coincide in time with historical events such as the spread of Islam, the fall of the Kingdom of Aksum, and trade routes across the Red Sea. Paper II focused on the Bantu expansion, the different migratory routes of Bantu-speakers out of West Africa, and how they shaped the genetic makeup of the peoples of sub-equatorial Africa. We compiled the most comprehensive geographically distributed genetic dataset of Bantu-speaking individuals to date. I investigated the spatial patterns of migrations and the decline of genetic diversity from their homeland. I find evidence for serial founder events and migrations across Zambia and the Congo basin to the rest of sub-equatorial Africa. Paper III and IV involved South Africa and the effects that European colonialism and 20:th century policies have had on the country's genetic landscape. Paper III focuses on the Afrikaner population of South Africa, descendants of the first European settlers of the Cape colony, I describe the extent of African and Asian admixture in this population and investigate evidence of selection and adaptive admixture. Paper IV focuses on the Coloured population of South Africa, an emergent cultural identity. The Coloured population traces their origin primarily to Khoe-San women, manumitted slaves, and European men from the Cape colony. The term Coloured was also used for admixed individuals under the Apartheid racial classification system. The Coloured has one of the most complex admixture histories in the world, with genetic ancestry from Europe, East and South Asia, West and East Africa, as well as southern African Khoe-San. In our paper, we describe these complex patterns, the differences in sex-biased admixture, and determine the admixture dates across an extensive collection of Coloured, across South Africa. My work thus highlights complex genetic patterns within African human demographic history and shows how profoundly it has been shaped by the movement of people in the last 5 000 years.
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| 5. |
- Ilumae, Anne-Mai, et al.
(författare)
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Phylogenetic history of patrilineages rare in northern and eastern Europe from large-scale re-sequencing of human Y-chromosomes
- 2021
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Ingår i: European Journal of Human Genetics. - : Springer Nature. - 1018-4813 .- 1476-5438. ; 29:10, s. 1510-1519
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Tidskriftsartikel (refereegranskat)abstract
- The most frequent Y-chromosomal (chrY) haplogroups in northern and eastern Europe (NEE) are well-known and thoroughly characterised. Yet a considerable number of men in every population carry rare paternal lineages with estimated frequencies around 5%. So far, limited sample-sizes and insufficient resolution of genotyping have obstructed a truly comprehensive look into the variety of rare paternal lineages segregating within populations and potential signals of population history that such lineages might convey. Here we harness the power of massive re-sequencing of human Y chromosomes to identify previously unknown population-specific clusters among rare paternal lineages in NEE. We construct dated phylogenies for haplogroups E2-M215, J2-M172, G-M201 and Q-M242 on the basis of 421 (of them 282 novel) high-coverage chrY sequences collected from large-scale databases focusing on populations of NEE. Within these otherwise rare haplogroups we disclose lineages that began to radiate similar to 1-3 thousand years ago in Estonia and Sweden and reveal male phylogenetic patterns testifying of comparatively recent local demographic expansions. Conversely, haplogroup Q lineages bear evidence of ancient Siberian influence lingering in the modern paternal gene pool of northern Europe. We assess the possible direction of influx of ancestral carriers for some of these male lineages. In addition, we demonstrate the congruency of paternal haplogroup composition of our dataset with two independent population-based cohorts from Estonia and Sweden.
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| 6. |
- Karmin, Monika, et al.
(författare)
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A recent bottleneck of Y chromosome diversity coincides with a global change in culture.
- 2015
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 25:4
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Tidskriftsartikel (refereegranskat)abstract
- It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
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| 7. |
- Liseau, René, 1949, et al.
(författare)
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Multi-line detection of O2 toward rho Ophiuchi A
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541
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Tidskriftsartikel (refereegranskat)abstract
- Context. Models of pure gas-phase chemistry in well-shielded regions of molecular clouds predict relatively high levels of molecular oxygen, O-2, and water, H2O. These high abundances imply high cooling rates, leading to relatively short timescales for the evolution of gravitationally unstable dense cores, forming stars and planets. Contrary to expectations, the dedicated space missions SWAS and Odin typically found only very small amounts of water vapour and essentially no O-2 in the dense star-forming interstellar medium. Aims. Only toward rho OphA did Odin detect a very weak line of O-2 at 119 GHz in a beam of size 10 arcmin. The line emission of related molecules changes on angular scales of the order of some tens of arcseconds, requiring a larger telescope aperture such as that of the Herschel Space Observatory to resolve the O-2 emission and pinpoint its origin. Methods. We use the Heterodyne Instrument for the Far Infrared (HIFI) aboard Herschel to obtain high resolution O-2 spectra toward selected positions in the rho Oph A core. These data are analysed using standard techniques for O2 excitation and compared to recent PDR-like chemical cloud models. Results. The N-J = 3(3)-1(2) line at 487.2 GHz is clearly detected toward all three observed positions in the rho Oph A core. In addition, an oversampled map of the 5(4)-3(4) transition at 773.8 GHz reveals the detection of the line in only half of the observed area. On the basis of their ratios, the temperature of the O-2 emitting gas appears to vary quite substantially, with warm gas (greater than or similar to 50 K) being adjacent to a much colder region, of temperatures lower than 30 K. Conclusions. The exploited models predict that the O-2 column densities are sensitive to the prevailing dust temperatures, but rather insensitive to the temperatures of the gas. In agreement with these models, the observationally determined O-2 column densities do not seem to depend strongly on the derived gas temperatures, but fall into the range N(O-2) = 3 to greater than or similar to 6 x 10(15) cm(-2). Beam-averaged O-2 abundances are about 5 x 10(-8) relative to H-2. Combining the HIFI data with earlier Odin observations yields a source size at 119 GHz in the range of 4 to 5 arcmin, encompassing the entire rho Oph A core. We speculate that one of the reasons for the generally very low detection rate of O-2 is the short period of time during which O-2 molecules are reasonably abundant in molecular clouds.
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| 8. |
- Sartelli, Massimo, et al.
(författare)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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