| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- An, Feng-Wei, et al.
(författare)
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Establishment of a Large Animal Model for Eustachian Tube Functional Study in Miniature Pigs
- 2019
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Ingår i: Anatomical Record Part A-discoveries in Molecular Cellular and Evolutionary Biology. - : WILEY. - 1552-4884 .- 1932-8494. ; 302:6, s. 1024-1038
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Tidskriftsartikel (refereegranskat)abstract
- This study was performed to investigate whether miniature pigs are a suitable animal model for studies of the Eustachian tube (ET). Sixteen Chinese experimental miniature pigs were used in this investigation. Ten animals were used for anatomical and morphometric analyses to obtain qualitative and quantitative information regarding the ET. Three animals were used for histological analysis to determine the fine structure of ET cross-sections. Three animals were used to investigate the feasibility of balloon dilation of the Eustachian tube (BDET). The anatomical study indicated that the pharyngeal orifice and tympanic orifice of the miniature pig ET are located at the posterior end of the nasal lateral wall and anterior wall of the middle ear cavity, respectively. The cartilaginous tube was seen to pass through the whole length of the ET, the length of the cartilaginous part of the ET and the diameter of the isthmus were similar between humans and miniature pigs. The inclination of the ET in miniature pigs was larger than that in humans. The gross histology seemed to be slightly different between miniature pig and human, but the fine structures were essentially the same in both species. BDET experiments verified that the miniature pig model is suitable as a model for clinical operations. The miniature pig ET corresponds very well to that of humans. In addition, the miniature pig ET is suitable as a model for clinical operations. Therefore, the miniature pig is a valid animal model for ET study.
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| 4. |
- An, Junghwa, et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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| 5. |
- Guo, Hui-Hui, et al.
(författare)
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Alleviation of allergic asthma by rosmarinic acid via gut-lung axis
- 2024
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Ingår i: Phytomedicine. - : Elsevier. - 0944-7113 .- 1618-095X. ; 126
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. Purpose: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. Methods: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. Results: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NF kappa B mediated pulmonary inflammation and oxidative stress. Conclusions: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiotaderived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.
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| 6. |
- Hu, Hai-Xi, et al.
(författare)
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Structural insights into HetR-PatS interaction involved in cyanobacterial pattern formation
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The one-dimensional pattern of heterocyst in the model cyanobacterium Anabaena sp. PCC 7120 is coordinated by the transcription factor HetR and PatS peptide. Here we report the complex structures of HetR binding to DNA, and its hood domain (HetR(Hood)) binding to a PatS-derived hexapeptide (PatS6) at 2.80 and 2.10 angstrom, respectively. The intertwined HetR dimer possesses a couple of novel HTH motifs, each of which consists of two canonical alpha-helices in the DNA-binding domain and an auxiliary alpha-helix from the flap domain of the neighboring subunit. Two PatS6 peptides bind to the lateral clefts of HetR(Hood), and trigger significant conformational changes of the flap domain, resulting in dissociation of the auxiliary alpha-helix and eventually release of HetR from the DNA major grove. These findings provide the structural insights into a prokaryotic example of Turing model.
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| 7. |
- Jin, Ying-Hui, et al.
(författare)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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| 8. |
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| 9. |
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| 10. |
- Proletov, Ian, et al.
(författare)
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Primary and secondary glomerulonephritides 1.
- 2014
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
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Tidskriftsartikel (refereegranskat)
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| 11. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 12. |
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| 13. |
- An, De-Wei, et al.
(författare)
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Carotid-Femoral Pulse Transit Time Variability Predicted Mortality and Improved Risk Stratification in the Elderly
- 2021
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Ingår i: Hypertension. - 1524-4563. ; 78:5, s. 1287-1295
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Tidskriftsartikel (refereegranskat)abstract
- The carotid-to-femoral pulse wave velocity, determined by pulse transit time (PTT) and distance, is a well-established measure of arterial stiffness and predicts adverse outcomes. However, its predictive value decreases with aging. To explore new risk indicator in the elderly, we investigated if the variation of carotid-to-femoral pulse wave velocity, registered as beat-to-beat variability of carotid-to-femoral PTT (cf-PTT), could predict outcome. Totally 3015 (median age, 72.4 years; 39.6% men) and 1181 (75.6 years; 42.2% men) subjects from communities of Malmö, Sweden, and Shanghai, China, were analyzed, respectively. Continuous pulse waves for 10 seconds were recorded sequentially at carotid and femoral arterial sites with applanation tonometry (SphygmoCor, Atcor, Australia). During a median of 6.6 and 10.2 years, 389 and 427 deaths occurred in the Malmö and Shanghai cohorts, respectively. Each one-SD increase in the log-transformed coefficient of variation of cf-PTT was associated with 24% (95% CI, 13%–37%) and 21% (10%–33%) increased risk for all-cause mortality in the Malmö and Shanghai subjects, and 60% (33%–91%) for cardiovascular mortality in the Malmö subjects. Adding the coefficient of variation of cf-PTT to the models including conventional risk factors and carotid-to-femoral pulse wave velocity significantly (P<0.05) improved prediction for all-cause mortality in both cohorts (integrated discrimination improvement, 0.005–0.008) and cardiovascular mortality in the Malmö cohort (net reclassification improvement, 0.206). In both cohorts, a coefficient of variation of cf-PTT <6% was not associated with increased mortality risk. In conclusion, the beat-to-beat variability of cf-PTT predicted mortality and improved risk stratification, which might be a novel risk indicator for elderly people.
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| 14. |
- Cai, Chuner, et al.
(författare)
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Screening and verification of extranuclear genetic markers in green tide algae from the Yellow Sea : Extranuclear markers in green tide algae
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Over the past decade, Ulva compressa, a cosmopolitan green algal species, has been identified as a component of green tides in the Yellow Sea, China. In the present study, we sequenced and annotated the complete chloroplast genome of U. compressa (alpha-numeric code: RD9023) and focused on the assessment of genome length, homology, gene order and direction, intron size, selection strength, and substitution rate. We compared the chloroplast genome with the mitogenome. The generated phylogenetic tree was analyzed based on single and aligned genes in the chloroplast genome of Ulva compared to mitogenome genes to detect evolutionary trends. U. compressa and U. mutabilis chloroplast genomes had similar gene queues, with individual genes exhibiting high homology levels. Chloroplast genomes were clustered together in the entire phylogenetic tree and shared several forward/palindromic/tandem repetitions, similar to those in U. prolifera and U. linza. However, U. fasciata and U. ohnoi were more divergent, especially in sharing complementary/palindromic repetitions. In addition, phylogenetic analyses of the aligned genes from their chloroplast genomes and mitogenomes confirmed the evolutionary trends of the extranuclear genomes. From phylogenetic analysis, we identified the petA chloroplast genes as potential genetic markers that are similar to the tufA marker. Complementary/forward/palindromic interval repetitions were more abundant in chloroplast genomes than in mitogenomes. Interestingly, a few tandem repetitions were significant for some Ulva subspecies and relatively more evident in mitochondria than in chloroplasts. Finally, the tandem repetition [GAAATATATAATAATA × 3, abbreviated as TRg)] was identified in the mitogenome of U. compressa and the conspecific strain U. mutabilis but not in other algal species of the Yellow Sea. Owing to the high morphological plasticity of U. compressa, the findings of this study have implications for the rapid non-sequencing detection of this species during the occurrence of green tides in the region.
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| 15. |
- Cai, Yumeng, et al.
(författare)
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Characterization of Gate-Oxide Degradation Location for SiC MOSFETs Based on the Split C-V Method Under Bias Temperature Instability Conditions
- 2023
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Ingår i: IEEE transactions on power electronics. - : Institute of Electrical and Electronics Engineers (IEEE). - 0885-8993 .- 1941-0107. ; 38:5, s. 6081-6093
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Tidskriftsartikel (refereegranskat)abstract
- Gate-oxide degradation has been one of the major reliability challenges of SiC mosfets. Comprehensive and accurate localization of gate-oxide degradation under bias temperature instability (BTI) conditions is important to improve the device reliability. The split C-V [gate-source capacitance C-GS (v(G)) and gate-drain capacitance C-GD (v(G))] method is proposed in this article to locate gate-oxide degradation. Moreover, a BTI automated characterization system integrated I-V and split C-V test is presented. The effect of gate-oxide degradation on threshold voltage and split C-V under dc and ac BTI conditions is investigated and the degradation location is analyzed. Furthermore, the degradation simulation is conducted with technology computer aided design (TCAD) to reveal the mechanism. The results show that the different parts of split C-V can characterize degradation location, the type, and energy level of traps. The acceptor traps near valence band and donor traps near conduction band cause gate-oxide degradation above the channel and junction field effect transistor (JFET) region in positive bias temperature instability (PBTI) and Negative Bias Temperature Instability (NBTI), respectively. In ac BTI, the gate-oxide degradation at the channel region is independent of v(G) polarity, while the opposite is true above JFET region. These findings help to improve the long-term operation reliability of gate oxide from the perspective of chip design and application.
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| 16. |
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| 17. |
- Cong, Rihua, et al.
(författare)
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Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene
- 2020
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Ingår i: European Journal of Nutrition. - : Springer. - 1436-6207 .- 1436-6215. ; 59:6, s. 2497-2506
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe aim of this study was to investigate the effects of maternal high dietary protein intake on the hepatic growth axis in offspring.MethodsFourteen primiparous purebred Meishan sows were fed either a standard-protein (SP, n = 7) diet or a high-protein (HP, 150% of SP, n = 7) diet during pregnancy. Offspring (one male and one female per group, n = 14) on day 70 of the embryonic stage and on days 1, 35 and 180 after birth were selected, weighed and killed. Serum samples were analyzed for Tch, insulin and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Liver samples were analyzed for IGFBP-3 and IGF-I mRNA expression by qRT-PCR and for IGFBP-3, IGF1R and growth hormone receptor (GHR) protein expression by Western blotting. The underlying mechanism of IGFBP-3 regulation was determined by methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP).ResultsHigh-protein exposure resulted in significantly higher body and liver weights of piglets, and it increased their serum T3 and T4 levels at birth and/or at weaning. Furthermore, the IGFBP-3 protein content in the liver and serum was significantly reduced in the HP-exposed weaning piglets, whereas at the transcriptional level IGFBP-3 mRNA expression was downregulated in the livers of HP group piglets. Finally, DNA hypermethylation and higher enrichment of the histone repressive marks H3K27me3 and H3K9me3 were observed.ConclusionsTaken together, these results suggest that a maternal high-protein diet during gestation epigenetically reprograms IGFBP-3 gene expression to modulate the hepatic growth axis in weaning piglets.
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| 18. |
- Esteban, Pablo G., et al.
(författare)
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How to Build a Supervised Autonomous System for Robot-Enhanced Therapy for Children with Autism Spectrum Disorder
- 2017
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Ingår i: Paladyn - Journal of Behavioral Robotics. - : De Gruyter Open. - 2080-9778 .- 2081-4836. ; 8:1, s. 18-38
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Tidskriftsartikel (refereegranskat)abstract
- Robot-Assisted Therapy (RAT) has successfully been used to improve social skills in children with autism spectrum disorders (ASD) through remote control of the robot in so-called Wizard of Oz (WoZ) paradigms.However, there is a need to increase the autonomy of the robot both to lighten the burden on human therapists (who have to remain in control and, importantly, supervise the robot) and to provide a consistent therapeutic experience. This paper seeks to provide insight into increasing the autonomy level of social robots in therapy to move beyond WoZ. With the final aim of improved human-human social interaction for the children, this multidisciplinary research seeks to facilitate the use of social robots as tools in clinical situations by addressing the challenge of increasing robot autonomy.We introduce the clinical framework in which the developments are tested, alongside initial data obtained from patients in a first phase of the project using a WoZ set-up mimicking the targeted supervised-autonomy behaviour. We further describe the implemented system architecture capable of providing the robot with supervised autonomy.
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| 19. |
- Feng, Lei, et al.
(författare)
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Tea Consumption and Depressive Symptoms in Older People in Rural China
- 2013
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 61:11, s. 1943-1947
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo examine the association between tea consumption and depressive symptoms in Chinese older people and to explore the mediating role of cerebrovascular disease in the association. DesignPopulation-based cross-sectional study. SettingA rural community near Qufu in Shandong, China. ParticipantsCommunity-dwelling individuals aged 60 and older (mean 68.6; 59.3% female) from the Confucius Hometown Aging Project (N=1,368). MeasurmentsData were collected through interviews, clinical examinations, and psychological testing, following a standard procedure. Presence of high depressive symptoms was defined as a score of 5 or greater on the 15-item Geriatric Depression Scale. ResultsOf the 1,368 participants, 165 (12.1%) were weekly and 489 (35.7%) were daily tea consumers. Compared with no or irregular tea consumption, controlling for age, sex, education, leisure activities, number of comorbidities, and Mini-Mental State Examination score, the odds ratios of having high depressive symptoms were 0.86 (95% confidence interval (CI)=0.56-1.32) for weekly and 0.59 (95% CI=0.43-0.81) for daily tea consumption (P for linear trend=.001); the linear trend of the association remained statistically significant when further controlling for history of stroke, transient ischemic attacks, and presence of carotid plaques. ConclusionsDaily tea consumption is associated with a lower likelihood of depressive symptoms in Chinese older people living in a rural community. The association appears to be independent of cerebrovascular disease and atherosclerosis.
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| 20. |
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| 21. |
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| 22. |
- Haas, Brian J., et al.
(författare)
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Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
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Tidskriftsartikel (refereegranskat)abstract
- Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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| 23. |
- Jarvis, Erich D., et al.
(författare)
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Whole-genome analyses resolve early branches in the tree of life of modern birds
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
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Tidskriftsartikel (refereegranskat)abstract
- To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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| 24. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 25. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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