| 1. |
- Allentoft, Morten E., et al.
(author)
-
100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
-
In: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
-
Journal article (peer-reviewed)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
|
|
| 2. |
- Allentoft, Morten E., et al.
(author)
-
Population genomics of post-glacial western Eurasia
- 2024
-
In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
-
Journal article (peer-reviewed)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
|
|
| 3. |
- Gron, Kurt J., et al.
(author)
-
Archaeological cereals as an isotope record of long-term soil health and anthropogenic amendment in southern Scandinavia
- 2021
-
In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 253
-
Journal article (peer-reviewed)abstract
- Maintaining soil health is integral to agricultural production, and the archaeological record contains multiple lines of palaeoclimatic and palaeoenvironmental proxy evidence that can contribute to the understanding and analysis of long-term trajectories of change that are key for contextualizing 21st century global environmental challenges. Soil is a capital resource and its nutrient balance is modified by agricultural activities, making it necessary to ensure soil productivity is maintained and managed through human choices and actions. Since prehistory this has always been the case; soil is a non-renewable resource within a human lifetime. Here, we present and interpret carbon and nitrogen isotope analysis of charred cereals from southern Scandinavia. Anthropogenic effects on soils are evident from the initiation of farming 6000 years ago, as is amendment to counteract its effects. The earliest cereals were planted on pristine soils, and by the late Neolithic, agriculture extensified. By the Iron Age it was necessary to significantly amend depleted soils to maintain crop yields. We propose that these data provide a record of soil water retention, net precipitation and amendment. From the start of the Neolithic there is a concurrent decrease in both Δ13C and δ15N, mitigated only by the replacement of soil organic content in the form of manure in the Iron Age. The cereal isotopes provide a record of trajectories of agricultural sustainability and anthropogenic adaptation for nearly the entire history of farming in the region.
|
|
| 4. |
- Mohanty, Tirthankar, et al.
(author)
-
A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa.
- 2015
-
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 126:18, s. 2128-2137
-
Journal article (peer-reviewed)abstract
- Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had undergone NETosis in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl lewis(X) present on salival mucins to L-selectin on neutrophils. This led to rapid loss of nuclear membrane and intracellular release of granule proteins with subsequent NET release independent of elastase and NADPH-oxidase activation. The saliva-induced NETs were more DNase-resistant and had higher capacity to bind and kill bacteria than NETs induced by bacteria or by PMA. Furthermore, saliva/sialyl lewis(X) mediated signaling enhanced intracellular killing of bacteria by neutrophils. Saliva from patients with aphthous ulcers and Behçet's disease prone to oral ulcers, failed to induce NETosis, but for different reasons, demonstrating that disordered homeostasis in the oral cavity may result in deficient saliva-mediated NETosis.
|
|
| 5. |
- Sørensen, Ole E, et al.
(author)
-
Papillon-Lefevre syndrome patient reveals species-dependent requirements for neutrophil defenses
- 2014
-
In: Journal of Clinical Investigation. - 0021-9738. ; 124:10, s. 4539-4548
-
Journal article (peer-reviewed)abstract
- Papillon-Lefevre syndrome (PLS) results from mutations that inactivate cysteine protease cathepsin C (CTSC), which processes a variety of serine proteases considered essential for antimicrobial defense. Despite serine protease-deficient immune cell populations, PLS patients do not exhibit marked immunodeficiency. Here, we characterized a 24-year-old woman who had suffered from severe juvenile periodontal disease, but was otherwise healthy, and identified a homozygous missense mutation in CTSC indicative of PLS. Proteome analysis of patient neutrophil granules revealed that several proteins that normally localize to azurophil granules, including the major serine proteases, elastase, cathepsin G, and proteinase 3, were absent. Accordingly, neutrophils from this patient were incapable of producing neutrophil extracellular traps (NETs) in response to ROS and were unable to process endogenous cathelicidin hCAP-18. into the antibacterial peptide LL-37 in response to ionomycin. In immature myeloid cells from patient bone marrow, biosynthesis of CTSC and neutrophil serine proteases appeared normal along with initial processing and sorting to cellular storage. In contrast, these proteins were completely absent in mature neutrophils, indicating that CTSC mutation promotes protease degradation in more mature hematopoietic subsets, but does not affect protease production in progenitor cells. Together, these data indicate CTSC protects serine proteases from degradation in mature immune cells and suggest that neutrophil serine proteases are dispensable for human immunoprotection.
|
|
| 6. |
- Alzuhairi, Karam Sadoon, et al.
(author)
-
Sub-acute cardiac magnetic resonance to predict irreversible reduction in left ventricular ejection fraction after ST-segment elevation myocardial infarction : A DANAMI-3 sub-study
- 2020
-
In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 301, s. 215-219
-
Journal article (peer-reviewed)abstract
- Aims: To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD). Methods and results: A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF>35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class >1 (OR 7.39; CI:1.47–36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07–50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27–47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83–328.29, P < 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value. Conclusion: Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization.
|
|
| 7. |
- Beck, Astrid L, et al.
(author)
-
Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring : A prospective nested case-control study
- 2024
-
In: International Journal of Cancer. - 0020-7136. ; 154:1, s. 71-80
-
Journal article (peer-reviewed)abstract
- Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.
|
|
| 8. |
- Bentham, James, et al.
(author)
-
A century of trends in adult human height
- 2016
-
In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 9. |
|
|
| 10. |
- Borregaard, Niels, et al.
(author)
-
Neutrophil granules: a library of innate immunity proteins
- 2007
-
In: Trends in Immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; 28:8, s. 340-345
-
Research review (peer-reviewed)abstract
- Gene expression profiling has revealed that circulating neutrophils rest between two major bursts of transcriptional and protein synthetic activities. The first occurs in the bone marrow. This equips the neutrophil with stocks of innate defense armory that are packaged into different granule subsets. The second burst occurs when the neutrophil exits circulation and migrates into tissues to find, capture and phagocytose microorganisms. This burst results in the synthesis and secretion of cytokines and chemokines that support resolution of inflammation and healing of damaged tissue. Gene expression profiling has revealed that neutrophils express a variety of innate immunity proteins, known previously only to be expressed in other cells. Likewise, it has become clear that some proteins previously thought to be specific to the neutrophil are expressed in epithelial cells during inflammation.
|
|
