| 1. |
|
|
| 2. |
- Mahajan, Anubha, et al.
(författare)
-
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
|
|
| 3. |
- Turcot, Valerie, et al.
(författare)
-
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
|
|
| 4. |
- Justice, Anne E., et al.
(författare)
-
Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
|
|
| 5. |
- Marouli, Eirini, et al.
(författare)
-
Rare and low-frequency coding variants alter human adult height
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
|
|
| 6. |
- Kattge, Jens, et al.
(författare)
-
TRY plant trait database - enhanced coverage and open access
- 2020
-
Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
-
Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
|
|
| 7. |
- Mahajan, Anubha, et al.
(författare)
-
Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
-
Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
|
|
| 8. |
- Kumar, M., et al.
(författare)
-
Frontier review on the propensity and repercussion of SARS-CoV-2 migration to aquatic environment
- 2020
-
Ingår i: Journal of Hazardous Materials Letters. - : Elsevier BV. - 2666-9110. ; 1
-
Tidskriftsartikel (refereegranskat)abstract
- Increased concern has recently emerged pertaining to the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in aquatic environment during the current coronavirus disease 2019 (COVID-19) pandemic. While infectious SARS-CoV-2 has yet to be identified in the aquatic environment, the virus potentially enters the wastewater stream from patient excretions and a precautionary approach dictates evaluating transmission pathways to ensure public health and safety. Although enveloped viruses have presumed low persistence in water and are generally susceptible to inactivation by environmental stressors, previously identified enveloped viruses persist in the aqueous environment from days to several weeks. Our analysis suggests that not only the surface water, but also groundwater, represent SARS-CoV-2 control points through possible leaching and infiltrations of effluents from health care facilities, sewage, and drainage water. Most fecally transmitted viruses are highly persistent in the aquatic environment, and therefore, the persistence of SARS-CoV-2 in water is essential to inform its fate in water, wastewater and groundwater and subsequent human exposure.
|
|
| 9. |
- Luo, Y. -W, et al.
(författare)
-
Database of diazotrophs in global ocean : abundance, biomass and nitrogen fixation rates
- 2012
-
Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 4:1, s. 47-73
-
Tidskriftsartikel (refereegranskat)abstract
- Marine N-2 fixing microorganisms, termed di-azotrophs, are a key functional group in marine pelagic ecosystems. The biological fixation of dinitrogen ( N-2) to bioavailable nitrogen provides an important new source of nitrogen for pelagic marine ecosystems and influences primary productivity and organic matter export to the deep ocean. As one of a series of efforts to collect biomass and rates specific to different phytoplankton functional groups, we have constructed a database on diazotrophic organisms in the global pelagic upper ocean by compiling about 12 000 direct field measurements of cyanobacterial diazotroph abundances (based on microscopic cell counts or qPCR assays targeting the nifH genes) and N-2 fixation rates. Biomass conversion factors are estimated based on cell sizes to convert abundance data to diazotrophic biomass. The database is limited spatially, lacking large regions of the ocean especially in the Indian Ocean. The data are approximately log-normal distributed, and large variances exist in most sub-databases with non-zero values differing 5 to 8 orders of magnitude. Reporting the geometric mean and the range of one geometric standard error below and above the geometric mean, the pelagic N-2 fixation rate in the global ocean is estimated to be 62 (52-73) Tg Nyr(-1) and the pelagic diazotrophic biomass in the global ocean is estimated to be 2.1 (1.4-3.1) Tg C from cell counts and to 89 (43-150) Tg C from nifH- based abundances. Reporting the arithmetic mean and one standard error instead, these three global estimates are 140 +/- 9.2 Tg Nyr(-1), 18 +/- 1.8 Tg C and 590 +/- 70 Tg C, respectively. Uncertainties related to biomass conversion factors can change the estimate of geometric mean pelagic diazotrophic biomass in the global ocean by about +/- 70 %. It was recently established that the most commonly applied method used to measure N-2 fixation has underestimated the true rates. As a result, one can expect that future rate measurements will shift the mean N-2 fixation rate upward and may result in significantly higher estimates for the global N-2 fixation. The evolving database can nevertheless be used to study spatial and temporal distributions and variations of marine N-2 fixation, to validate geochemical estimates and to parameterize and validate biogeochemical models, keeping in mind that future rate measurements may rise in the future.
|
|
| 10. |
- R. Feifel, K. Ueda, A. De Fanis, K. Okada, S. Tanimoto, T. Furuta, H. Shindo, M. Kitajima, H. Tanaka, O. Björneholm, L. Karlsson, S. Svensson and S. L. Sorensen
(författare)
-
Probing doubly excited ionic states of N2+ via a triple excitation above the N1s threshold in the N2 moecule
- 2003
-
Ingår i: Phys. Rev.. ; A:67, s. 32504-
-
Tidskriftsartikel (refereegranskat)
|
|
| 11. |
- Feifel, R, et al.
(författare)
-
Probing doubly excited ionic states of N-2(+) via a triple excitation above the N 1s threshold in the N-2 molecule
- 2003
-
Ingår i: Physical Review A (Atomic, Molecular and Optical Physics). - 1050-2947. ; 67:3: 032504
-
Tidskriftsartikel (refereegranskat)abstract
- Angle-resolved resonant Auger-electron spectroscopy has been carried out on the nitrogen molecule at selected photon energies around 419 eV, where a 1s core electron and two valence electrons are promoted into the lowest unoccupied molecular orbital 1pi(g). Significant enhancement of a specific band, which cannot be disentangled in direct photoionization, is observed at a binding energy of 37.6 eV, with a value of the anisotropy parameter beta much smaller than 2. We assign this new band to the transition to a doubly excited cationic state of N-2, in which two of the excited valence electrons remain in the 1pi(g) orbital, proposing a "double spectator" type decay mechanism. This observation shows how to preferentially probe multiply excited configurations of cations using multiple resonant excitation.
|
|
| 12. |
|
|
| 13. |
- Kitajima, S, et al.
(författare)
-
A KDM6 inhibitor potently induces ATF4 and its target gene expression through HRI activation and by UTX inhibition
- 2021
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 4538-
-
Tidskriftsartikel (refereegranskat)abstract
- UTX/KDM6A encodes a major histone H3 lysine 27 (H3K27) demethylase, and is frequently mutated in various types of human cancers. Although UTX appears to play a crucial role in oncogenesis, the mechanisms involved are still largely unknown. Here we show that a specific pharmacological inhibitor of H3K27 demethylases, GSK-J4, induces the expression of transcription activating factor 4 (ATF4) protein as well as the ATF4 target genes (e.g. PCK2, CHOP, REDD1, CHAC1 and TRIB3). ATF4 induction by GSK-J4 was due to neither transcriptional nor post-translational regulation. In support of this view, the ATF4 induction was almost exclusively dependent on the heme-regulated eIF2α kinase (HRI) in mouse embryonic fibroblasts (MEFs). Gene expression profiles with UTX disruption by CRISPR-Cas9 editing and the following stable re-expression of UTX showed that UTX specifically suppresses the expression of the ATF4 target genes, suggesting that UTX inhibition is at least partially responsible for the ATF4 induction. Apoptosis induction by GSK-J4 was partially and cell-type specifically correlated with the activation of ATF4-CHOP. These findings highlight that the anti-cancer drug candidate GSK-J4 strongly induces ATF4 and its target genes via HRI activation and raise a possibility that UTX might modulate cancer formation by regulating the HRI-ATF4 axis.
|
|
| 14. |
|
|
| 15. |
- Kumar, M., et al.
(författare)
-
A chronicle of SARS-CoV-2 : Seasonality, environmental fate, transport, inactivation, and antiviral drug resistance
- 2021
-
Ingår i: Journal of Hazardous Materials. - : Elsevier B.V.. - 0304-3894 .- 1873-3336. ; 405
-
Tidskriftsartikel (refereegranskat)abstract
- In this review, we present the environmental perspectives of the viruses and antiviral drugs related to SARS-CoV-2. The present review paper discusses occurrence, fate, transport, susceptibility, and inactivation mechanisms of viruses in the environment as well as environmental occurrence and fate of antiviral drugs, and prospects (prevalence and occurrence) of antiviral drug resistance (both antiviral drug resistant viruses and antiviral resistance in the human). During winter, the number of viral disease cases and environmental occurrence of antiviral drug surge due to various biotic and abiotic factors such as transmission pathways, human behaviour, susceptibility, and immunity as well as cold climatic conditions. Adsorption and persistence critically determine the fate and transport of viruses in the environment. Inactivation and disinfection of virus include UV, alcohol, and other chemical-base methods but the susceptibility of virus against these methods varies. Wastewater treatment plants (WWTPs) are major reserviors of antiviral drugs and their metabolites and transformation products. Ecotoxicity of antiviral drug residues against aquatic organisms have been reported, however more threatening is the development of antiviral resistance, both in humans and in wild animal reservoirs. In particular, emergence of antiviral drug-resistant viruses via exposure of wild animals to high loads of antiviral residues during the current pandemic needs further evaluation.
|
|
| 16. |
- Ahltorp, Magnus, et al.
(författare)
-
Medical vocabulary mining using distributional semantics on Japanese patient blogs
- 2014
-
Ingår i: SMBM 2014 - Proceedings of the 6th International Symposium on Semantic Mining in Biomedicine. - : University of Aveiro. ; , s. 57-62
-
Konferensbidrag (refereegranskat)abstract
- Random indexing has previously been successfully used for medical vocabulary expansion for Germanic languages. In this study, we used this approach to extract medical terms from a Japanese patient blog corpus. The corpus was segmented into semantic units by a semantic role labeller, and different pre-processing and parameter settings were then evaluated. The evaluation showed that similar settings are suitable for Japanese as for previously explored Germanic languages, and that distributional semantics is equally useful for semi-automatic expansion of Japanese medical vocabularies as for medical vocabularies in Germanic languages.
|
|
| 17. |
- Feifel, R., et al.
(författare)
-
X-ray absorption and resonant Auger spectroscopy of O(2) in the vicinity of the O 1s ->sigma* resonance : Experiment and theory
- 2008
-
Ingår i: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 128:6
-
Tidskriftsartikel (refereegranskat)abstract
- We report on an experimental and theoretical investigation of x-ray absorption and resonant Auger electron spectra of gas phase O(2) recorded in the vicinity of the O 1s ->sigma* excitation region. Our investigation shows that core excitation takes place in a region with multiple crossings of potential energy curves of the excited states. We find a complete breakdown of the diabatic picture for this part of the x-ray absorption spectrum, which allows us to assign an hitherto unexplained fine structure in this spectral region. The experimental Auger data reveal an extended vibrational progression, for the outermost singly ionized X (2)Pi(g) final state, which exhibits strong changes in spectral shape within a short range of photon energy detuning (0 eV>Omega>-0.7 eV). To explain the experimental resonant Auger electron spectra, we use a mixed adiabatic/diabatic picture selecting crossing points according to the strength of the electronic coupling. Reasonable agreement is found between experiment and theory even though the nonadiabatic couplings are neglected. The resonant Auger electron scattering, which is essentially due to decay from dissociative core-excited states, is accompanied by strong lifetime-vibrational and intermediate electronic state interferences as well as an interference with the direct photoionization channel. The overall agreement between the experimental Auger spectra and the calculated spectra supports the mixed diabatic/adiabatic picture.
|
|
| 18. |
|
|
| 19. |
- Kitajima, M., et al.
(författare)
-
Angle-resolved photoion yield and resonant Auger spectroscopy for the doubly excited Rydberg states above the C 1s threshold of CO
- 2008
-
Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 78:3, s. 033422-
-
Tidskriftsartikel (refereegranskat)abstract
- Doubly excited core-hole states of carbon monoxide in the photon energy region of 300-305 eV, i.e., directly above the C 1s ionization threshold, have been studied using both angle-resolved ion-yield and high-resolution resonant Auger spectroscopies. The leading configurations of the most prominent doubly excited Rydberg states are assigned by careful analysis of the ion-yield spectra and the final-state spectra to C 1s(-1) (5 sigma(-1)2 pi S-1=1) 3s sigma (v'=0,1,2), C 1s(-1) (5 sigma(-1)2 pi S-1=0) 3s sigma (v'=0,1,2), and C 1s(-1) (5 sigma(-1)2 pi S-1=1) 4s sigma (v'=0,1), which can only be populated via a conjugate shake-up process. Analysis of the resonant Auger spectra provides an assignment of several two-hole-one-electron (2h-1e) final states.
|
|
| 20. |
- Kitajima, M., et al.
(författare)
-
Doppler effect in resonant photoemission from SF6 : Correlation between doppler profile and auger emission anisotropy
- 2003
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 91:21
-
Tidskriftsartikel (refereegranskat)abstract
- Fragmentation of the SF6 molecule upon F 1s excitation has been studied by resonant photoemission. The F atomiclike Auger line exhibits the characteristic Doppler profile that depends on the direction of the photoelectron momentum relative to the polarization vector of the radiation as well as on the photon energy. The measured Doppler profiles are analyzed by the model simulation that takes account of the anisotropy of the Auger emission in the molecular frame. The Auger anisotropy extracted from the data decreases with an increase in the F-SF5 internuclear distance.
|
|
| 21. |
- Kitajima, Toshihiro, et al.
(författare)
-
Improved Survival With Higher-risk Donor Grafts in Liver Transplant With Acute-on-chronic Liver Failure
- 2022
-
Ingår i: Transplantation direct. - : Lippincott Williams & Wilkins. - 2373-8731. ; 8:2
-
Tidskriftsartikel (refereegranskat)abstract
- Background Use of higher-risk grafts in liver transplantation for patients with acute-on-chronic liver failure (ACLF) has been associated with poor outcomes. This study analyzes trends in liver transplantation outcomes for ACLF over time based on the donor risk index (DRI).Methods Using the Organ Procurement and Transplantation Network and the United Network for Organ Sharing registry, 17 300 ACLF patients who underwent liver transplantation between 2002 and 2019 were evaluated. Based on DRI, adjusted hazard ratios for 1-y patient death were analyzed in 3 eras: Era 1 (2002–2007, n = 4032), Era 2 (2008–2013, n = 6130), and Era 3 (2014–2019, n = 7138). DRI groups were defined by DRI <1.2, 1.2–1.6, 1.6–2.0, and >2.0.Results ACLF patients had significantly lower risks of patient death within 1 y in Era 2 (adjusted hazard ratio, 0.69; 95% confidence interval, 0.61-0.78; P < 0.001) and Era 3 (adjusted hazard ratio, 0.48; 95% confidence interval, 0.42-0.55; P < 0.001) than in Era 1. All DRI groups showed lower hazards in Era 3 than in Era 1. Improvement of posttransplant outcomes were found both in ACLF-1/2 and ACLF-3 patients. In ACLF-1/2, DRI 1.2 to 1.6 and >2.0 had lower adjusted risk in Era 3 than in Era 1. In ACLF-3, DRI 1.2 to 2.0 had lower risk in Era 3. In the overall ACLF cohort, the 2 categories with DRI >1.6 had significantly higher adjusted risks of 1-y patient death than DRI <1.2. When analyzing hazards in each era, DRI > 2.0 carried significantly higher adjusted risks in Eras 1 and 3‚ whereas DRI 1.2 to 2.0 had similar adjusted risks throughout eras. Similar tendency was found in ACLF-1/2. In the non-ACLF cohort, steady improvement of posttransplant outcomes was obtained in all DRI categories. Similar results were obtained when only hepatitis C virus-uninfected ACLF patients were evaluated.Conclusions In ACLF patients, posttransplant outcomes have significantly improved, and outcomes with higher-risk organs have improved in all ACLF grades. These results might encourage the use of higher-risk donors in ACLF patients and provide improved access to transplant.
|
|
| 22. |
|
|
| 23. |
- Kitajima, Toshihiro, et al.
(författare)
-
Lymphopenia at the time of transplant is associated with short-term mortality after deceased donor liver transplantation
- 2023
-
Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 23:2, s. 248-256
-
Tidskriftsartikel (refereegranskat)abstract
- Absolute lymphocyte count (ALC) is considered a surrogate marker for nutritional status and immunocompetence. We investigated the association between ALC and post-liver transplant outcomes in patients who received a deceased donor liver transplant (DDLT). Patients were categorized by ALC at liver transplant: low (<500/mu L), mid (500-1000/mu L), and high ALC (>1000/mu L). Our main analysis used retrospective data (2013-2018) for DDLT recipients from Henry Ford Hospital (United States); the results were further validated using data from the Toronto General Hospital (Canada). Among 449 DDLT recipients, the low ALC group demonstrated higher 180-day mortality than mid and high ALC groups (83.1% vs 95.8% and 97.4%, respectively; low vs mid: P =.001; low vs high: P <.001). A larger proportion of patients with low ALC died of sepsis compared with the combined mid/high groups (9.1% vs 0.8%; P <.001). In multivariable analysis, pretransplant ALC was associated with 180-day mortality (hazard ratio, 0.20; P =.004). Patients with low ALC had higher rates of bacteremia (22.7% vs 8.1%; P <.001) and cytomegaloviremia (15.2% vs 6.8%; P =.03) than patients with mid/high ALC. Low ALC pretransplant through postoperative day 30 was associated with 180-day mortality among patients who received rabbit antithymocyte globulin induction (P =.001). Pretransplant lymphopenia is associated with short-term mortality and a higher incidence of posttransplant infections in DDLT patients.
|
|
| 24. |
- Kouznetsova, Anna, et al.
(författare)
-
Post-metaphase correction of aberrant kinetochore-microtubule attachments in mammalian eggs
- 2019
-
Ingår i: EMBO Reports. - : Wiley. - 1469-221X .- 1469-3178. ; 20:8
-
Tidskriftsartikel (refereegranskat)abstract
- The accuracy of the two sequential meiotic divisions in oocytes is essential for creating a haploid gamete with a normal chromosomal content. Here, we have analysed the 3D dynamics of chromosomes during the second meiotic division in live mouse oocytes. We find that chromosomes form stable kinetochore-microtubule attachments at the end of prometaphase II stage that are retained until anaphase II onset. Remarkably, we observe that more than 20% of the kinetochore-microtubule attachments at the metaphase II stage are merotelic or lateral. However, II are found to lag at the spindle equator and < 10% of the laggards missegregate and give rise to aneuploid gametes. Our results demonstrate that aberrant kinetochore-microtubule attachments are not corrected at the metaphase stage of the second meiotic division. Thus, the accuracy of the chromosome segregation process in mouse oocytes during meiosis II is ensured by an efficient correction process acting at the anaphase stage.
|
|
| 25. |
|
|
