| 1. |
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| 2. |
- Librado, P., et al.
(författare)
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The origins and spread of domestic horses from the Western Eurasian steppes
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region. Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).
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| 3. |
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| 4. |
- Bastard, P, et al.
(författare)
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Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1
- 2021
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 218:7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti–IFN-β and another anti–IFN-ε, but none had anti–IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
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| 5. |
- Sikora, M., et al.
(författare)
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The population history of northeastern Siberia since the Pleistocene
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 570:7760
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Tidskriftsartikel (refereegranskat)abstract
- Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.
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| 6. |
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| 7. |
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| 8. |
- Maltseva, A. L., et al.
(författare)
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Orphan gene in Littorina: An unexpected role of symbionts in the host evolution
- 2022
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Ingår i: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 824
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Tidskriftsartikel (refereegranskat)abstract
- Mechanisms of reproductive isolation between closely related sympatric species are of high evolutionary significance as they may function as initial drivers of speciation and protect species integrity afterwards. Proteins involved in the establishment of reproductive barriers often evolve fast and may be key players in cessation of gene flow between the incipient species. The five Atlantic Littorina (Neritrema) species represent a notable example of recent radiation. The geographic ranges of these young species largely overlap and the mechanisms of reproductive isolation are poorly understood. In this study, we performed a detailed analysis of the reproductive protein LOSP, previously identified in Littorina. We showed that this protein is evolutionary young and taxonomically restricted to the genus Littorina. It has high sequence variation both within and between Littorina species, which is compatible with its presumable role in the reproductive isolation. The strongest differences in the LOSP structure were detected between Littorina subgenera with distinctive repetitive motifs present exclusively in the Neritrema species, but not in L. littorea. Moreover, the sequence of these repetitive structural elements demonstrates a high homology with genetic elements of bacteria, identified as components of Littorina associated microbiomes. We suggest that these elements were acquired from a symbiotic bacterial donor via horizontal genetic transfer (HGT), which is indirectly confirmed by the presence of multiple transposable elements in the LOSP flanking and intronic regions. Furthermore, we hypothesize that this HGT-driven evolutionary innovation promoted LOSP function in reproductive isolation, which might be one of the factors determining the intensive cladogenesis in the Littorina (Neritrema) lineage in contrast to the anagenesis in the L. littorea clade.
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| 9. |
- Dmitriev, Alexey A, et al.
(författare)
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Genetic and epigenetic analysis of non-small cell lung cancer with NotI-microarrays
- 2012
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Ingår i: Epigenetics. - : Landes Bioscience. - 1559-2294 .- 1559-2308. ; 7:5, s. 502-513
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to clarify genetic and epigenetic alterations that occur during lung carcinogenesis and to design perspective sets of newly identified biomarkers. The original method includes chromosome 3 specific NotI-microarrays containing 180 NotI clones associated with genes for hybridization with 40 paired normal/tumor DNA samples of primary lung tumors: 28 squamous cell carcinomas (SCC) and 12 adenocarcinomas (ADC). The NotI-microarray data were confirmed by qPCR and bisulfite sequencing analyses. Forty-four genes showed methylation and/or deletions in more than 15% of non-small cell lung cancer (NSCLC) samples. In general, SCC samples were more frequently methylated/deleted than ADC. Moreover, the SCC alterations were observed already at stage I of tumor development, whereas in ADC many genes showed tumor progression specific methylation/deletions. Among genes frequently methylated/deleted in NSCLC, only a few were already known tumor suppressor genes: RBSP3 (CTDSPL), VHL and THRB. The RPL32, LOC285205, FGD5 and other genes were previously not shown to be involved in lung carcinogenesis. Ten methylated genes, i.e., IQSEC1, RBSP3, ITGA9, FOXP1, LRRN1, GNAI2, VHL, FGD5, ALDH1L1 and BCL6 were tested for expression by qPCR and were found downregulated in the majority of cases. Three genes (RBSP3, FBLN2 and ITGA9) demonstrated strong cell growth inhibition activity. A comprehensive statistical analysis suggested the set of 19 gene markers, ANKRD28, BHLHE40, CGGBP1, RBSP3, EPHB1, FGD5, FOXP1, GORASP1/TTC21, IQSEC1, ITGA9, LOC285375, LRRC3B, LRRN1, MITF, NKIRAS1/RPL15, TRH, UBE2E2, VHL, WNT7A, to allow early detection, tumor progression, metastases and to discriminate between SCC and ADC with sensitivity and specificity of 80-100%.
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| 10. |
- Maltseva, Arina L., et al.
(författare)
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Phylogeography of the closely related Littorina (Neritrema) species in the North-East Atlantic
- 2022
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Ingår i: Invertebrate Zoology. - : KMK Scientific Press. - 1812-9250 .- 1814-0815. ; 19:4, s. 404-424
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Tidskriftsartikel (refereegranskat)abstract
- Phylogeographic studies of evolutionary young species co-existing over a vast geographic area can provide insights in the process of evolutionary divergence and its cohesiveness in different parts of the species ranges. The Littorina snails of the ‘saxatilis’ cryptic group diverged in near-glacial time, and tend to live in sympatry. L. saxatilis is widely distributed on both sides of the North Atlantic, while L. arcana and L. compressa are patchy distributed on the shores of Europe and Atlantic islands. The biogeographic history of the Littorina ‘saxatilis’ cryptic group is still obscure, with L. saxatilis studied much better than the other two species. We evaluated the population structure of the three ‘saxatilis’ species on the coasts of Wales, the Norwegian and the Barents seas using several genetic markers: the mitochondrial cytochrome b gene (cytb, partial, 26 haplotypes for 268 sequences), nuclear (5 microsatellite loci in 458 individuals) and whole-genome (2bRAD, 63 417 loci in 114 individuals) markers. Analyses based on the cytb and microsatellite markers showed a deep divergence between the British and the North European populations of all three species with a high genetic similarity between their sympatric populations from Wales. L. compressa had the highest differentiation from both L. arcana and L. saxatilis and demonstrated the clear population structure due to allele frequency. The degree of the genetic differentiation between sympatric L. arcana and L. saxatilis in some regions was lower than between the regions within a species. Moreover, analyses of all three types of used markers indicate that the continental populations of L. arcana include individuals with contrasting genomic profiles. Our results suggest that L. arcana and L. compressa separated from their common ancestor L. islandica after L. saxatilis. The three sibling species survived glaciation in a refugium (or refugia) on the British coasts, separated from the mainland refugium (or refugia). After the glaciation, L. compressa colonised the mainland, most likely from a single European refugium. Post-glacial continental repopulation by L. arcana could have occurred from at least two sources, with two differentiated lineages still recognisable. Further inclusion of Littorina populations from South Norway and France is needed to complete the reconstruction of biogeographic history in these three evolutionary young species of Littorina snails.
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| 11. |
- Marques, André R A, et al.
(författare)
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Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular β-glucosidases.
- 2016
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Ingår i: Journal of Lipid Research. - 1539-7262. ; 57, s. 451-463
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Tidskriftsartikel (refereegranskat)abstract
- The membrane lipid glucosylceramide (GlcCer) is continuously formed and degraded. Cells express two GlcCer-degrading β-glucosidases, GBA and GBA2, located in and outside the lysosome, respectively. Here we demonstrate that through transglucosylation both GBA and GBA2 are able to catalyze in vitro the transfer of glucosyl-moieties from GlcCer to cholesterol, and vice versa. Furthermore, the natural occurrence of 1-O-cholesteryl-β-D-glucopyranoside (GlcChol) in mouse tissues and human plasma is demonstrated using LC-MS/MS and 13C6-labelled GlcChol as internal standard. In cells the inhibition of GBA increases GlcChol, whereas inhibition of GBA2 decreases glucosylated sterol. Similarly, in GBA2-deficient mice GlcChol is reduced. Depletion of GlcCer by inhibition of GlcCer synthase decreases GlcChol in cells and likewise in plasma of inhibitor-treated Gaucher disease patients. In tissues of mice with Niemann-Pick type C, a condition characterized by intralysosomal accumulation of cholesterol, marked elevations in GlcChol occur as well. When lysosomal accumulation of cholesterol is induced in cultured cells, GlcChol is formed via lysosomal GBA. This illustrates that reversible transglucosylation reactions are highly dependent on local availability of suitable acceptors. In conclusion, mammalian tissues contain GlcChol formed by transglucosylation through β-glucosidases using GlcCer as donor. Our findings reveal a novel metabolic function for GlcCer.
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| 12. |
- Schwarz, J., et al.
(författare)
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F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort
- 2013
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 19:1, s. 113-118
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Tidskriftsartikel (refereegranskat)abstract
- Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in haemophilia A. It has been suggested that differences in the distribution of FVIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Data from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and inhibitor risk among individuals of genetically determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and human leucocyte antigen (HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified (N = 49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N = 223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Haplotype 3 was not an independent predictor of inhibitor risk. Furthermore, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual.
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| 13. |
- Sinding, Mikkel-Holger S., et al.
(författare)
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Arctic-adapted dogs emerged at the Pleistocene-Holocene transition
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 368:6498
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Tidskriftsartikel (refereegranskat)abstract
- Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an similar to 9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an similar to 33,000-year-old Siberian wolf. We found noteworthy genetic similarity between the ancient dog and modern sled dogs. We detected gene flow from Pleistocene Siberian wolves, but not modern American wolves, to present-day sled dogs. The results indicate that the major ancestry of modern sled dogs traces back to Siberia, where sled dog-specific haplotypes of genes that potentially relate to Arctic adaptation were established by 9500 years ago.
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| 14. |
- Bannikova, Anna A., et al.
(författare)
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Who are you, Griselda? A replacement name for a new genus of the Asiatic short-tailed shrews (Mammalia, Eulipotyphla, Soricidae) : molecular and morphological analyses with the discussion of tribal affinities
- 2019
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Ingår i: ZooKeys. - : Pensoft Publishers. - 1313-2989 .- 1313-2970. ; :888, s. 133-158
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Tidskriftsartikel (refereegranskat)abstract
- The first genetic study of the holotype of the Gansu short-tailed shrew, Blarinella griselda Thomas, 1912, is presented. The mitochondrial analysis demonstrated that the type specimen of B. griselda is close to several recently collected specimens from southern Gansu, northern Sichuan and Shaanxi, which are highly distinct from the two species of Asiatic short-tailed shrews of southern Sichuan, Yunnan, and Vietnam, B. quadraticauda and B. wardi. Our analysis of four nuclear genes supported the placement of B. griselda as sister to B. quadraticauda / B. wardi, with the level of divergence between these two clades corresponding to that among genera of Soricinae. A new generic name, Parablarinella, is proposed for the Gansu short-tailed shrew. Karyotypes of Parablarinella griselda (2n = 49, NFa = 50) and B. quadraticauda (2n = 49, NFa = 62) from southern Gansu are described. The tribal affinities of Blarinellini and Blarinini are discussed.
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| 15. |
- Bergström, Anders, et al.
(författare)
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Grey wolf genomic history reveals a dual ancestry of dogs
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 607:7918, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.
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| 16. |
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| 17. |
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| 18. |
- El Kharraz, S., et al.
(författare)
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The androgen receptor depends on ligand-binding domain dimerization for transcriptional activation
- 2021
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Ingår i: Embo Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 22:12
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Tidskriftsartikel (refereegranskat)abstract
- Whereas dimerization of the DNA-binding domain of the androgen receptor (AR) plays an evident role in recognizing bipartite response elements, the contribution of the dimerization of the ligand-binding domain (LBD) to the correct functioning of the AR remains unclear. Here, we describe a mouse model with disrupted dimerization of the AR LBD (AR(Lmon/Y)). The disruptive effect of the mutation is demonstrated by the feminized phenotype, absence of male accessory sex glands, and strongly affected spermatogenesis, despite high circulating levels of testosterone. Testosterone replacement studies in orchidectomized mice demonstrate that androgen-regulated transcriptomes in AR(Lmon/Y) mice are completely lost. The mutated AR still translocates to the nucleus and binds chromatin, but does not bind to specific AR binding sites. In vitro studies reveal that the mutation in the LBD dimer interface also affects other AR functions such as DNA binding, ligand binding, and co-regulator binding. In conclusion, LBD dimerization is crucial for the development of AR-dependent tissues through its role in transcriptional regulation in vivo. Our findings identify AR LBD dimerization as a possible target for AR inhibition.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Haraldson, Klas, et al.
(författare)
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LRRC3B gene is frequently epigenetically inactivated in several epithelial malignancies and inhibits cell growth and replication
- 2012
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Ingår i: Biochimie. - : Elsevier. - 0300-9084 .- 1638-6183. ; 94:5, s. 1151-1157
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome 3 specific NotI microarrays containing 180 NotI linking clones associated with 188 genes were hybridized to NotI representation probes prepared using matched tumor/normal samples from major epithelial cancers: breast (47 pairs), lung (40 pairs) cervical (43 pairs), kidney (34 pairs of clear cell renal cell carcinoma), colon (24 pairs), ovarian (25 pairs) and prostate (18 pairs). In all tested primary tumors (compared to normal controls) methylation and/or deletions was found. For the first time we showed that the gene LRRC3B was frequently methylated and/or deleted in breast carcinoma - 32% of samples, cervical - 35%, lung - 40%, renal - 35%, ovarian - 28%, colon - 33% and prostate cancer - 44%. To check these results bisulfite sequencing using cloned PCR products with representative two breast, one cervical, two renal, two ovarian and two colon cancer samples was performed. In all cases methylation was confirmed. Expression analysis using RT-qPCR showed that LRRC3B is strongly down-regulated at the latest stages of RCC and ovarian cancers. In addition we showed that LRRC3B exhibit strong cell growth inhibiting activity (more than 95%) in colony formation experiments in vitro in KRC/Y renal cell carcinoma line. All these data suggest that LRRC3B gene could be involved in the process of carcinogenesis as a tumor suppressor gene.
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| 24. |
- Kashuba, Vladimir, et al.
(författare)
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NotI Microarrays: Novel Epigenetic Markers for Early Detection and Prognosis of High Grade Serous Ovarian Cancer
- 2012
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 13:10, s. 13352-13377
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Tidskriftsartikel (refereegranskat)abstract
- Chromosome 3-specific NotI microarray (NMA) containing 180 clones with 188 genes was used in the study to analyze 18 high grade serous ovarian cancer (HGSOC) samples and 7 benign ovarian tumors. We aimed to find novel methylation-dependent biomarkers for early detection and prognosis of HGSOC. Thirty five NotI markers showed frequency of methylation/deletion more or equal to 17%. To check the results of NMA hybridizations several samples for four genes (LRRC3B, THRB, ITGA9 and RBSP3 (CTDSPL)) were bisulfite sequenced and confirmed the results of NMA hybridization. A set of eight biomarkers: NKIRAS1/RPL15, THRB, RBPS3 (CTDSPL), IQSEC1, NBEAL2, ZIC4, LOC285205 and FOXP1, was identified as the most prominent set capable to detect both early and late stages of ovarian cancer. Sensitivity of this set is equal to (72 +/- 11)% and specificity (94 +/- 5)%. Early stages represented the most complicated cases for detection. To distinguish between Stages I + II and Stages III + IV of ovarian cancer the most perspective set of biomarkers would include LOC285205, CGGBP1, EPHB1 and NKIRAS1/RPL15. The sensitivity of the set is equal to (80 +/- 13)% and the specificity is (88 +/- 12)%. Using this technique we plan to validate this panel with new epithelial ovarian cancer samples and add markers from other chromosomes.
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| 25. |
- Krzeminska, U., et al.
(författare)
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Population mitogenomics provides insights into evolutionary history, source of invasions and diversifying selection in the House Crow (Corvus splendens)
- 2018
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Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 120:4, s. 296-309
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Tidskriftsartikel (refereegranskat)abstract
- The House Crow (Corvus splendens) is a useful study system for investigating the genetic basis of adaptations underpinning successful range expansion. The species originates from the Indian subcontinent, but has successfully spread through a variety of thermal environments across Asia, Africa and Europe. Here, population mitogenomics was used to investigate the colonisation history and to test for signals of molecular selection on the mitochondrial genome. We sequenced the mitogenomes of 89 House Crows spanning four native and five invasive populations. A Bayesian dated phylogeny, based on the 13 mitochondrial protein-coding genes, supports a mid-Pleistocene (similar to 630,000 years ago) divergence between the most distant genetic lineages. Phylogeographic patterns suggest that northern South Asia is the likely centre of origin for the species. Codon-based analyses of selection and assessments of changes in amino acid properties provide evidence of positive selection on the ND2 and ND5 genes against a background of purifying selection across the mitogenome. Protein homology modelling suggests that four amino acid substitutions inferred to be under positive selection may modulate coupling efficiency and proton translocation mediated by OXPHOS complex I. The identified substitutions are found within native House Crow lineages and ecological niche modelling predicts suitable climatic areas for the establishment of crow populations within the invasive range. Mitogenomic patterns in the invasive range of the species are more strongly associated with introduction history than climate. We speculate that invasions of the House Crow have been facilitated by standing genetic variation that accumulated due to diversifying selection within the native range.
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| 26. |
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| 27. |
- Morales, Hernán E., 1985, et al.
(författare)
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Concordant divergence of mitogenomes and a mitonuclear gene cluster in bird lineages inhabiting different climates
- 2018
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:8, s. 1258-1267
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic processes in eukaryotic cells depend on interactions between mitochondrial and nuclear gene products (mitonuclear interactions). These interactions could have a direct role in population divergence. Here, we study mitonuclear co-evolution in a widespread bird that experienced population divergence followed by bidirectional mitochondrial introgression into different nuclear backgrounds. Using >60,000 single nucleotide polymorphisms, we quantify patterns of nuclear genetic differentiation between populations that occupy areas with different climates and harbour deeply divergent mitochondrial lineages despite ongoing nuclear gene flow. We find that strong genetic differentiation and sequence divergence in a region of similar to 15.4 mega-bases on chromosome 1A mirror the geographic pattern of mitochondrial DNA divergence. This result is seen in two different transects representing populations with different nuclear backgrounds. The chromosome 1A region is enriched for genes performing mitochondrial functions (N-mt genes). Molecular signatures of selective sweeps in this region alongside those in the mitochondrial genome suggest a history of adaptive mitonuclear co-introgression. Moreover, evidence for large linkage disequilibrium blocks in this genomic region suggests that low recombination could facilitate functional interactions between co-evolved nuclear alleles. Our results are consistent with mitonuclear co-evolution as an important mechanism for population divergence and local adaptation.
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| 28. |
- van Hullebusch, E. D., et al.
(författare)
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Nature-based units as building blocks for resource recovery systems in cities
- 2021
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Ingår i: Water. - : MDPI AG. - 2073-4441. ; 13:22
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Tidskriftsartikel (refereegranskat)abstract
- Cities are producers of high quantities of secondary liquid and solid streams that are still poorly utilized within urban systems. In order to tackle this issue, there has been an ever-growing push for more efficient resource management and waste prevention in urban areas, following the concept of a circular economy. This review paper provides a characterization of urban solid and liquid resource flows (including water, nutrients, metals, potential energy, and organics), which pass through selected nature-based solutions (NBS) and supporting units (SU), expanding on that characterization through the study of existing cases. In particular, this paper presents the currently implemented NBS units for resource recovery, the applicable solid and liquid urban waste streams and the SU dedicated to increasing the quality and minimizing hazards of specific streams at the source level (e.g., concentrated fertilizers, disinfected recovered products). The recovery efficiency of systems, where NBS and SU are combined, operated at a micro-or meso-scale and applied at technology readiness levels higher than 5, is reviewed. The importance of collection and transport infrastructure, treatment and recovery technology, and (urban) agricultural or urban green reuse on the quantity and quality of input and output materials are discussed, also regarding the current main circularity and application challenges.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Astermark, Jan, et al.
(författare)
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The polygenic nature of inhibitors in hemophilia A: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort.
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 121:8, s. 1446-1454
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Tidskriftsartikel (refereegranskat)abstract
- Studies of determinants of development of inhibitory antibodies to factor VIII in people with hemophilia A indicate a complex process involving multiple factors. The Hemophilia Inhibitor Genetics Study Combined Cohort was formed to extend understanding of the genetic background of risk. The study group contains 833 subjects from three independent cohorts: brother pairs and singletons with and without a history of inhibitors, as well as 104 brother pairs discordant for inhibitor status. Using an Illumina iSelect platform, 13,331 SNPs from 1,081 genes, primarily immune response and immune modifier genes, were typed. Each cohort was analyzed separately with results combined using a meta-analytic technique. After adjustment for potential confounders, 53 SNPs were significant predictors of inhibitor status using the criteria of odds ratios (OR) in the same direction in all cohorts, or allowing for a 20% interval around an OR of 1 in one of the three, and significant in at least two. Of the 53, 13 markers had meta p-values of <0.001. Eight of the 53 were significant predictors among the discordant pairs. Results support the complexity of the immune response, and encourage further research with the goal of understanding the pathways involved.
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| 33. |
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| 34. |
- Dmitriev, AA, et al.
(författare)
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Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis
- 2015
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Ingår i: Disease markers. - : Hindawi Limited. - 1875-8630 .- 0278-0240. ; 2015, s. 241301-
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Tidskriftsartikel (refereegranskat)abstract
- A significant need for reliable and accurate cancer diagnostics and prognosis compels the search for novel biomarkers that would be able to discriminate between indolent and aggressive tumors at the early stages of disease. The aim of this work was identification of potential diagnostic biomarkers for characterization of different types of prostate tumors. NotI-microarrays with 180 clones associated with chromosome 3 genes/loci were applied to determine genetic and epigenetic alterations in 33 prostate tumors. For 88 clones, aberrations were detected in more than 10% of tumors. The major types of alterations were DNA methylation and/or deletions. Frequent methylation of the discovered loci was confirmed by bisulfite sequencing on selective sampling of genes:FGF12,GATA2, andLMCD1. Three genes (BHLHE40,BCL6, andITGA9) were tested for expression level alterations using qPCR, and downregulation associated with hypermethylation was shown in the majority of tumors. Based on these data, we proposed the set of potential biomarkers for detection of prostate cancer and discrimination between prostate tumors with different malignancy and aggressiveness:BHLHE40,FOXP1,LOC285205,ITGA9,CTDSPL,FGF12,LOC440944/SETD5,VHL,CLCN2,OSBPL10/ZNF860,LMCD1,FAM19A4,CAND2,MAP4,KY, andLRRC58. Moreover, we probabilistically estimated putative functional relations between the genes within each set using the network enrichment analysis.
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| 35. |
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| 36. |
- Estrada, S, et al.
(författare)
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The contribution of N-terminal region residues of cystatin A (stefin A) to the affinity and kinetics of inhibition of papain, cathepsin B, and cathepsin L.
- 1999
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 38:22, s. 7339-45
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Tidskriftsartikel (refereegranskat)abstract
- The affinity and kinetics of binding of three N-terminally truncated variants of the cysteine proteinase inhibitor cystatin A to cysteine proteinases were characterized. Deletion of Met-1 only minimally altered the inhibitory properties of the protein. However, deletion also of Ile-2 resulted in reduced affinities of 900-, >/=3-, and 200-fold for papain and cathepsins L and B, respectively. Further truncation of Pro-3 substantially increased the inhibition constants to approximately 0.5 microM for papain and cathepsin L and to 60 microM for cathepsin B, reflecting additionally 2 x 10(3)-, 2 x 10(4)-, and 400-fold decreased affinities, respectively. The reductions in affinity shown by the latter mutant indicate that the N-terminal region contributes about 40% of the total free energy of binding of cystatin A to cysteine proteinases. Moreover, Pro-3 and to a lesser extent Ile-2 are the residues responsible for this binding energy. The reduced affinities for papain and cathepsin L were due only to higher dissociation rate constants, whereas both lower association and higher dissociation rate constants contributed to the decreased affinity for cathepsin B. These differential effects indicate that the N-terminal portion of cystatin A primarily functions by stabilizing the complexes with enzymes having easily accessible active-site clefts, e.g., papain and cathepsin L. In contrast, the N-terminal region is required also for an initial binding of cystatin A to cathepsin B, presumably by promoting the displacement of the occluding loop and allowing facile interaction of the rest of the inhibiting wedge with the active-site cleft of the enzyme.
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| 37. |
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| 38. |
- Gan, H. M., et al.
(författare)
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Genomic evidence of neo-sex chromosomes in the eastern yellow robin
- 2019
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Ingår i: Gigascience. - : Oxford University Press (OUP). - 2047-217X. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Understanding sex-biased natural selection can be enhanced by access to well-annotated chromosomes including ones inherited in sex-specific fashion. The eastern yellow robin (EYR) is an endemic Australian songbird inferred to have experienced climate-driven sex-biased selection and is a prominent model for studying mitochondrial-nuclear interactions in the wild. However, the lack of an EYR reference genome containing both sex chromosomes (in birds, a female bearing Z and W chromosomes) limits efforts to understand the mechanisms of these processes. Here, we assemble the genome for a female EYR and use low-depth (10x) genome resequencing data from 19 individuals of known sex to identify chromosome fragments with sex-specific inheritance. Findings: MaSuRCA hybrid assembly using Nanopore and Illumina reads generated a 1.22-Gb EYR genome in 20,702 scaffolds (94.2% BUSCO completeness). Scaffolds were tested for W-linked (female-only) inheritance using a k-mer approach, and for Z-linked inheritance using median read-depth test in male and female reads (read-depths must indicate haploid female and diploid male representation). This resulted in 2,372 W-linked scaffolds (total length: 97,872,282 bp, N50: 81,931 bp) and 586 Z-linked scaffolds (total length: 121,817,358 bp, N50: 551,641 bp). Anchoring of the sex-linked EYR scaffolds to the reference genome of a female zebra finch revealed 2 categories of sex-linked genomic regions. First, 653 W-linked scaffolds (25.7 Mb) were anchored to the W sex chromosome and 215 Z-linked scaffolds (74.4 Mb) to the Z. Second, 1,138 W-linked scaffolds (70.9 Mb) and 179 Z-linked scaffolds (51.0 Mb) were anchored to a large section (coordinates similar to 5 to similar to 60 Mb) of zebra finch chromosome 1A. The first similar to 5 Mb and last similar to 14 Mb of the reference chromosome 1A had only autosomally behaving EYR scaffolds mapping to them. Conclusions: We report a female (W chromosome-containing) EYR genome and provide genomic evidence for a neo-sex (neo-W and neo-Z) chromosome system in the EYR, involving most of a large chromosome (1A) previously only reported to be autosomal in passerines.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Malinkin, Sergey O., et al.
(författare)
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Zinc(II) Complexes with Asymmetric 3,5-Substituted 1H-Pyrazoles
- 2012
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Ingår i: European Journal of Inorganic Chemistry. - : Wiley. - 1099-0682 .- 1434-1948. ; :10, s. 1639-1649
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Tidskriftsartikel (refereegranskat)abstract
- Two new pyrazolate-based ligands, N'-[1-(3-acetyl-4-methyl-1H-pyrazol-5-yl)ethylidene]-2-(hydroxyimino)propanehydrazide (L1) and 5-[(E)-1-(2-{(E)-2-(hydroxyimino}propanoyl}hydrazono)ethyl]-4-methyl-1H-pyrazole-3-carboxylic acid (L2), were synthesized and studied for zinc(II) complexation. A set of pH-dependent UV/Vis measurements has been performed to determine the complex formation properties of L2. According to the calculations, in solution, L2 forms variously protonated mononuclear (ZnII/L2 = 1:1) and dinuclear (ZnII/L2 = 2:1) complexes. The reaction of the deprotonated ligands with hydrated ZnII salts and slow diffusion of ammonia into the reaction mixtures gave mononuclear [Zn(L1-2H)(NH3)2]center dot DMF (1) and trinuclear mu-pyrazolato-bridged [Zn3(L2-3H)2(NH3)5]center dot 4H2O (3). In both complexes, the zinc ions are in the same distorted trigonal-bipyramidal environment, coordinated to two nitrogen atoms of the ammonia and one oxygen and two nitrogen atoms of the pyrazolate and hydrazide groups. The molecular structures of all of the ligands and complexes have been elucidated by X-ray crystallography.
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| 45. |
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| 46. |
- Morales, Hernan E., et al.
(författare)
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Neutral and selective drivers of colour evolution in a widespread Australian passerine
- 2017
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Ingår i: Journal of Biogeography. - : WILEY-BLACKWELL. - 0305-0270 .- 1365-2699. ; 44:3, s. 522-536
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Tidskriftsartikel (refereegranskat)abstract
- AimRump plumage coloration of the Eastern Yellow Robin (Eopsaltria australis), a widespread Australian songbird, varies from bright yellow in the tropical north to olive-green in the temperate south. Here, we test whether colour variation: (1) correlates most strongly with neutral genetic variation and so is best explained by historical processes, (2) reflects selection associated with different visual environments (dense versus open habitats) and/or (3) reflects selection associated with climatic variation. LocationEastern Australia. MethodsWe quantified colour variation using reflectance spectrometry and visual models. We performed geographical cline analysis of colour and neutral genetic variation (genome-wide single nucleotide polymorphisms). We tested for correlations of colour variation with climate, vegetation density, geographical location and genetic variation. We accounted for covariation and spatial autocorrelation, and conducted analyses at continental and regional spatial scales. ResultsClinal variation of colour traits and neutral genetic markers were largely concordant. At the continental scale, colour variation was strongly associated with neutral genetic structure and geography, and to a lesser extent with environment. At the regional scale, environmental variation was a better predictor of colour variation than it was at the larger scale. Main conclusionAt the continental scale, colour variation is strongly associated with large-scale population history. In contrast, at the regional scale, where the influence of history and geography is weaker, environmental variation has a role in facilitating the maintenance of colour variation. Our results highlight the need to assess selective and neutral alternatives at multiple spatial scales when studying geographical variation.
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| 47. |
- Mostovich, Luydmila A, et al.
(författare)
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Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors
- 2011
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Ingår i: CELL ADHESION and MIGRATION. - : Landes Bioscience. - 1933-6918 .- 1933-6926. ; 5:5, s. 395-401
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Tidskriftsartikel (refereegranskat)abstract
- Integrin alpha9 (ITGA9) is one of the less studied integrin subunits that facilitates accelerated cell migration and regulates diverse biological functions such as angiogenesis, lymphangiogenesis, cancer cell proliferation and migration. In this work, integrin alpha9 expression and its epigenetic regulation in normal human breast tissue, primary breast tumors and breast cancer cell line MCF7 were studied. It was shown that integrin alpha9 is expressed in normal human breast tissue. In breast cancer, ITGA9 expression was downregulated or lost in 44% of tumors while another 45% of tumors showed normal or increased ITGA9 expression level (possible aberrations in the ITGA9 mRNA structure were supposed in 11% of tumors). Methylation of ITGA9 CpG-island located in the first intron of the gene was shown in 90% of the breast tumors with the decreased ITGA9 expression while no methylation at 5-untranslated region of ITGA9 was observed. 5-aza-dC treatment restored integrin alpha9 expression in ITGA9-negative MCF7 breast carcinoma cells, Trichostatin A treatment did not influenced it but a combined treatment of the cells with 5-aza-dC/Trichostatin A doubled the ITGA9 activation. The obtained results suggest CpG methylation as a major mechanism of integrin alpha9 inactivation in breast cancer with a possible involvement of other yet unidentified molecular pathways.
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| 48. |
- Pavlova, A, et al.
(författare)
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Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration by release of loop anchoring through mutation of His110
- 2000
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Ingår i: FEBS Letters. - 1873-3468. ; 487:2, s. 156-156
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Tidskriftsartikel (refereegranskat)abstract
- Cystatins A and C were both shown to inhibit cathepsin B by a two-step mechanism, involving an initial weak interaction followed by a conformational change. Disruption of the major salt bridge anchoring the occluding loop of cathepsin B to the main body of the enzyme by mutation of His110 to Ala converted the binding to an apparent one-step reaction. The second step of cystatin binding to cathepsin B must therefore be due to the inhibitor having to alter the conformation of the enzyme by displacing the occluding loop to allow a tight complex to be formed. Cystatin A was appreciably less effective in displacing the loop than cystatin C, resulting in a considerably lower overall inhibition rate constant.
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| 49. |
- Pavlova, A., et al.
(författare)
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Impact of polymorphisms of the major histocompatibility complex class II, interleukin-10, tumor necrosis factor-alpha and cytotoxic T-lymphocyte antigen-4 genes on inhibitor development in severe hemophilia A
- 2009
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 7:12, s. 2006-2015
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Tidskriftsartikel (refereegranskat)abstract
- Background: Approximately 25% of severe hemophilia A (HA) patients develop antibodies to factor VIII protein. Patients: In the present case-controlled cohort study, 260 severely affected, mutation-type-matched HA patients were studied for association of human leukocyte antigen (HLA) class II molecules and polymorphisms in the genes encoding interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) and development of inhibitors. Results: Our results demonstrate a higher frequency of DRB1*15 and DQB1*0602 alleles as well as of the haplotype DRB1*15/DQB1*0602 in inhibitor patients [odds ratio (OR) 1.9; P < 0.05]. In TNF-alpha, the A allele of the -308G > A polymorphism was found with higher frequency in the inhibitor cohort (0.22 vs. 0.13, OR 1.80). This finding was more pronounced for the homozygous A/A genotype (OR 4.7). For IL-10, the -1082G allele was observed more frequently in patients with inhibitors (0.55 vs. 0.43; P = 0.008). The functional cytokine phenotype was determined for the first time, on the basis of the genetic background, and this showed that 12% of patients with inhibitors were high-TNF-alpha/high-IL-10 producers, as compared with 3% of non-inhibitor patients (OR 4.4). A trend for a lower frequency of the A allele of the CT60 polymorphism in CTLA-4 was found in inhibitor patients (0.42 vs. 0.50). Conclusions: In conclusion, the reported data clearly highlighted the participation of HLA molecules in inhibitor formation in a large cohort of patients. The higher frequencies of the -308G > A polymorphism in TNF-alpha and -1082A > G in IL-10 in inhibitor patients confirmed the earlier published data. The CT60 single-nucleotide polymorphism in CTLA-4 is of apparently less importance.
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| 50. |
- Pavlova, A., et al.
(författare)
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Inhibition of mammalian cathepsins by Plesiomonas shigelloides
- 2006
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Ingår i: Folia microbiologica (Prague). - 0015-5632 .- 1874-9356. ; 51:5, s. 393-400
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Tidskriftsartikel (refereegranskat)abstract
- To study molecular mechanisms underlying self-defense of the bacterial pathogen Plesiomonas shigelloides against host inflammatory and immune responses, we evaluated its interactions with mammalian papain-like cathepsins that are essential for host immunity. When grown under anaerobic, but not aerobic, conditions, P. shigelloides was shown to bind and inhibit papain, a model representative of the papain family of cysteine proteinases. This points to mammalian cathepsins as likely physiological targets of a novel cysteine-proteinase inhibitor expressed on bacterial cell surface. Both papain and mammalian cathepsins L and B were inhibited by periplasmic extracts of aerobically and anaerobically grown bacteria, the inhibitory activity being higher in the latter. Inhibition by both intact cells and periplasmic samples was rapid and efficient. The results suggest a possible defensive role of bacterial inhibitors of cathepsins during invasion of a mammalian host. The bacteria thus may modulate host protective responses through inhibiting cathepsins involved in antigen processing and presentation.
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