| 1. |
- Barnes, DR, et al.
(författare)
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Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
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| 2. |
- Merlone, A., et al.
(författare)
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The MeteoMet project - metrology for meteorology: challenges and results
- 2015
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Ingår i: Meteorological Applications. - : Wiley. - 1350-4827 .- 1469-8080. ; 22, s. 820-829
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Tidskriftsartikel (refereegranskat)abstract
- The study describes significant outcomes of the Metrology for Meteorology' project, MeteoMet, which is an attempt to bridge the meteorological and metrological communities. The concept of traceability, an idea used in both fields but with a subtle difference in meaning, is at the heart of the project. For meteorology, a traceable measurement is the one that can be traced back to a particular instrument, time and location. From a metrological perspective, traceability further implies that the measurement can be traced back to a primary realization of the quantity being measured in terms of the base units of the International System of Units, the SI. These two perspectives reflect long-standing differences in culture and practice and this project - and this study - represents only the first step towards better communication between the two communities. The 3 year MeteoMet project was funded by the European Metrology Research Program (EMRP) and involved 18 European National Metrological Institutes, 3 universities and 35 collaborating stakeholders including national meteorology organizations, research institutes, universities, associations and instrument companies. The project brought a metrological perspective to several long-standing measurement problems in meteorology and climatology, varying from conventional ground-based measurements to those made in the upper atmosphere. It included development and testing of novel instrumentation as well as improved calibration procedures and facilities, instrument intercomparison under realistic conditions and best practice dissemination. Additionally, the validation of historical temperature data series with respect to measurement uncertainties and a methodology for recalculation of the values were included.
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| 3. |
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| 4. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)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.
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| 5. |
- Petroni, M, et al.
(författare)
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SMO-M2 mutation does not support cell-autonomous Hedgehog activity in cerebellar granule cell precursors
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 19623-
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Tidskriftsartikel (refereegranskat)abstract
- Growth and patterning of the cerebellum is compromised if granule cell precursors do not properly expand and migrate. During embryonic and postnatal cerebellar development, the Hedgehog pathway tightly regulates granule cell progenitors to coordinate appropriate foliation and lobule formation. Indeed, granule cells impairment or defects in the Hedgehog signaling are associated with developmental, neurodegenerative and neoplastic disorders. So far, scant and inefficient cellular models have been available to study granule cell progenitors, in vitro. Here, we validated a new culture method to grow postnatal granule cell progenitors as hedgehog-dependent neurospheres with prolonged self-renewal and ability to differentiate into granule cells, under appropriate conditions. Taking advantage of this cellular model, we provide evidence that Ptch1-KO, but not the SMO-M2 mutation, supports constitutive and cell-autonomous activity of the hedgehog pathway.
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| 6. |
- Oláh, János, et al.
(författare)
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Lineage sorting by parameres in Limnephilinae subfamily (Trichoptera): with description of a new tribe, new genera and new species
- 2019
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Ingår i: Opuscula Zoologica Instituti Zoosystematici et Oecologici Universitatis Budapestinensis. - 0237-5419 .- 2063-1588. ; 50:S1, s. 3-98
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of the new Agaphylax genus with unique paramere organisation has initiated our lineage sorting oftribes by parameres in the Limnephilinae subfamily applying the principles and procedures of fine phenomics in order toestablish transformation series of the polarized plesiomorphy-apomorphy character states for each limnephiline genera.According to the extraordinary high diversity the paramere that is the stimulatory and titillating structure of the phallic organis a speciation supertrait. This adaptive trait is directly involved in the processes of reproductive isolation and diverging assubtle initial split of lineages producing the incipient sibling species in the recent past of contemporary speciation processes.Contrary, the drastic divergence of the Agaphylax plated paramere is much older, similarly to the many-spined parameres ofthe Hesperophylacini tribe. It has been initiated by drastic combined and synchronous external and internal stochastic effects,processed in ancestral sexual integrative adaptation as well as organised and fixed in older and deeper coalescence events andappears as a character with tribe ranking potential. To open a wider perspective, a systemic relational analysis is required inthe future including other adaptive or neutral character transformation series, due to the burden of taxonomic incongruencesgrounded by chimerism in stochastic genetic reticulation. Traits of species are mixed products coming from various sources.Only character combinations can and ought to be analysed in terms how to classify taxa. We have polarized eight genitaliccharacters additional to parameres for a future analysis of the potential of character combinations.Limnephilinae subfamily is composed of Limnephilini, Chilostigmatini, Chaetopterygini, Stenophylacini and Hesperophylacinitribes and here we established the new Agaphylacini tribe. Based on parameres we have delineated taxa in lineagesorting and described two new genera: Fogophylax gen. nov., Simaphylax gen. nov. and fourteen new species: Anaboliaalsoja, A. hepehupa, Asynarchus kimaros, Limnephilus kerekes, L. maghrebensis, L. oblos, Homophylax beges, H. coros,Chaetopteroides plackovicensis, C. rilaensis, Allogamus ketpar, Platyphylax beshkovi, Pycnopsyche letova and P. telea spp.nov. The by-product of this survey is a world atlas of paramere drawings for the entire Limnephilinae subfamily.
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| 7. |
- Oláh, János, et al.
(författare)
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Revision of European Wormaldia species (Trichoptera, Philopotamidae):Chimeric taxa of integrative organisation
- 2019
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Ingår i: Opuscula Zoologica Instituti Zoosystematici et Oecologici Universitatis Budapestinensis. - : Opuscula Zoologica. - 0237-5419 .- 2063-1588. ; 50:1, s. 31-85
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Tidskriftsartikel (refereegranskat)abstract
- We have recognised significant incongruences among the most commonly used taxonomic characters in theEuropean species of Wormaldia genus of the Philopotamidae caddisfly family. During taxonomical analysis and rankingprocedures we have recorded incongruent, discorcordant characters also in the taxa in Rhyacophilidae, Hydropsychidae andLimnephilidae caddisfly families. Based on theoretical background we concluded that taxa of examined caddisflies andprobably all living creatures are chimeric entities composed of components of different origin. Genomes and phenomes aretree-like on the surface but more reticulated in the deep. We understand chimerism with universal consequences, expandingwell beyond the evolutionary tree-thinking of reductionism and determinism. Taxa are chimeric or at least chimerical in astochastic universe under the permanent fluxes of the external and internal impacts created by intercourses between entropyand energy gradients. We have surveyed how to create and correct synonymies in the splitter/lumper perspectives along theprinciples of compositional and specification hierarchies understood as quantitative variability of non-adaptive neutral andqualitative stability of adaptive, non-neutral traits. We outlined how the apophantic (declaratory) hybris creates synonymiesand underestimates biodiversity. After redrawing the diverging genitalic structures, particularly the speciation traits we havereinstated species status of eight taxa: W. trifida Andersen, 1983 stat.restit, stat. nov., W. albanica Oláh, 2010 stat. restit., W.bulgarica Novak, 1971 stat. nov., W. daga Oláh, 2014 stat. restit., W. graeca Oláh, 2014 stat. restit., W. busa Oláh, 2014 stat.restit., W. homora Oláh, 2014 stat. restit. W. nielseni Moretti, 1981 stat. nov. Character selection and lineage sortingprocedures established the following species groups, species complexes and species clades in the European species ofWormaldia: W. occipitalis species group: W. occipitalis species complex; W. charalambi species group; W. copiosa speciesgroup; W. triangulifera species group: W. bulgarica species complex, W. khourmai species complex, W. subnigra speciescomplex: W. asterusia species clade, W. subnigra species clade, W. vercorsica species clade; W. triangulifera speciescomplex, W. variegate species complex. Unplaced species: W. ambigua, W. algirica, W. sarda. In this revision we havedescribed fourteen new species: W. longiseta, W. carpathica, W. kurta, W. parba, W. foslana, W. kumanskii, W. libohova, W.silva, W. gorba, W. kera, W. rona, W. sima, W. granada, W. telva.
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| 8. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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