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| 2. |
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| 3. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Bjelic, Sinisa, et al.
(författare)
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Exploration of Alternate Catalytic Mechanisms and Optimization Strategies for Retroaldolase Design
- 2014
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 426:1, s. 256-271
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Tidskriftsartikel (refereegranskat)abstract
- Designed retroaldolases have utilized a nucleophilic lysine to promote carbon-carbon bond cleavage of β-hydroxy-ketones via a covalent Schiff base intermediate. Previous computational designs have incorporated a water molecule to facilitate formation and breakdown of the carbinolamine intermediate to give the Schiff base and to function as a general acid/base. Here we investigate an alternative active-site design in which the catalytic water molecule was replaced by the side chain of a glutamic acid. Five out of seven designs expressed solubly and exhibited catalytic efficiencies similar to previously designed retroaldolases for the conversion of 4-hydroxy-4-(6-methoxy-2-naphthyl)-2-butanone to 6-methoxy-2-naphthaldehyde and acetone. After one round of site-directed saturation mutagenesis, improved variants of the two best designs, RA114 and RA117, exhibited among the highest kcat (>10(-3)s(-1)) and kcat/KM (11-25M(-1)s(-1)) values observed for retroaldolase designs prior to comprehensive directed evolution. In both cases, the >10(5)-fold rate accelerations that were achieved are within 1-3 orders of magnitude of the rate enhancements reported for the best catalysts for related reactions, including catalytic antibodies (kcat/kuncat=10(6) to 10(8)) and an extensively evolved computational design (kcat/kuncat>10(7)). The catalytic sites, revealed by X-ray structures of optimized versions of the two active designs, are in close agreement with the design models except for the catalytic lysine in RA114. We further improved the variants by computational remodeling of the loops and yeast display selection for reactivity of the catalytic lysine with a diketone probe, obtaining an additional order of magnitude enhancement in activity with both approaches.
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| 10. |
- Chan, WT, et al.
(författare)
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Realist evaluation of a transdisciplinary mealtime management service for autistic children
- 2023
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Ingår i: Autism : the international journal of research and practice. - : SAGE Publications. - 1461-7005. ; 27:6, s. 1547-1559
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Tidskriftsartikel (refereegranskat)abstract
- Autistic children commonly experience mealtime difficulties; however, it is unknown what makes an effective transdisciplinary mealtime service for autistic children. This study used a realist evaluation framework to explore caregivers’ and therapists’ perceptions of the contexts, mechanisms and associated outcomes of a transdisciplinary mealtime management service for autistic children. Semi-structured interviews were conducted with six caregivers of autistic children engaged in a transdisciplinary mealtime service and 10 therapists providing the service, with interview data analysed using a realist evaluation approach. Four-context (child factors, family factors, therapist factors and institutional parameters), three-mechanism (transdisciplinary collaboration, child-centred approach and managing caregiver expectations) and two-outcome (impact on the child and impact on the caregiver) themes were identified. Findings highlighted that transdisciplinary collaboration, a child- and family-centred approach and managing caregiver expectations are key mechanisms providing a foundation for the development of evidence-based mealtime services for autistic children. Mealtimes and eating can be difficult for autistic children. A service where different professions work together is required to address the varied and complex mealtime difficulties of autistic children. Little is known about what is needed for such services to be effective. We interviewed six caregivers of autistic children who were engaged in a mealtime service and 10 therapists who are involved in delivering the service to understand their perspectives on the factors that were driving the effectiveness of the mealtime service. We found that different health professionals from different disciplines working together, focusing on adapting intervention to the child and family and managing expectations of the caregiver were important in contributing to outcomes of the mealtime service. The findings of this study can be used to inform the development of more effective interventions and services to support the well-being and development of autistic children.
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| 11. |
- Dans, Madeline G., et al.
(författare)
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Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
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| 12. |
- 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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| 13. |
- Kerrebrouck, Joris Van, et al.
(författare)
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High-speed PAM4-based Optical SDM Interconnects with Directly Modulated Long-wavelength VCSEL
- 2019
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Ingår i: Journal of Lightwave Technology. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0733-8724 .- 1558-2213. ; 37:2, s. 356-362
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports the demonstration of high-speed PAM-4 transmission using a 1.5-μm single-mode vertical cavity surface emitting laser (SM-VCSEL) over multicore fiber with 7 cores over different distances. We have successfully generated up to 70 Gbaud 4-level pulse amplitude modulation (PAM-4) signals with a VCSEL in optical back-to-back, and transmitted 50 Gbaud PAM-4 signals over both 1-km dispersion-uncompensated and 10-km dispersion-compensated in each core, enabling a total data throughput of 700 Gbps over the 7-core fiber. Moreover, 56 Gbaud PAM-4 over 1-km has also been shown, whereby unfortunately not all cores provide the required 3.8 × 10$^-3$bit error rate (BER) for the 7% overhead-hard decision forward error correction (7% OH HDFEC). The limited bandwidth of the VCSEL and the adverse chromatic dispersion of the fiber are suppressed with pre-equalization based on accurate end-to-end channel characterizations. With a digital post-equalization, BER performance below the 7% OH-HDFEC limit is achieved over all cores. The demonstrated results show a great potential to realize high-capacity and compact short-reach optical interconnects for data centers.
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| 14. |
- Lin, De-Chen, et al.
(författare)
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Adaptor protein Lnk binds to and inhibits normal and leukemic FLT3
- 2012
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 120:16, s. 3310-3317
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Tidskriftsartikel (refereegranskat)abstract
- Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase with important roles in hematopoietic progenitor cell survival and proliferation. It is mutated in approximately one-third of AML patients, mostly by internal tandem duplications (ITDs). Adaptor protein Lnk is a negative regulator of hematopoietic cytokine signaling. In the present study, we show that Lnk interacts physically with both wildtype FLT3 (FLT3-WT) and FLT3-ITD through the SH2 domains. We have identified the tyrosine residues 572, 591, and 919 of FLT3 as phosphorylation sites involved in direct binding to Lnk. Lnk itself was tyrosine phosphorylated by both FLT3 ligand (FL)-activated FLT3-WT and constitutively activated FLT3-ITD. Both shRNA-mediated depletion and forced overexpression of Lnk demonstrated that activation signals emanating from both forms of FLT3 are under negative regulation by Lnk. Moreover, Lnk inhibited 32D cell proliferation driven by different FLT3 variants. Analysis of primary BM cells from Lnk-knockout mice showed that Lnk suppresses the expansion of FL-stimulated hematopoietic progenitors, including lymphoid-primed multipotent progenitors. The results of the present study show that through direct binding to FLT3, Lnk suppresses FLT3-WT/ITD-dependent signaling pathways involved in the proliferation of hematopoietic cells. Therefore, modulation of Lnk expression levels may provide a unique therapeutic approach for FLT3-ITD-associated hematopoietic disease. (Blood. 2012;120(16):3310-3317)
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| 15. |
- Liu, Yi, et al.
(författare)
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Porous, robust, thermally stable, and flame retardant nanocellulose/polyimide separators for safe lithium-ion batteries
- 2023
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 11:43, s. 23360-23369
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Tidskriftsartikel (refereegranskat)abstract
- The safety of lithium-ion batteries (LIBs) is paramount for all users. One effective way to improve safety is incorporating heat-resistant polyimide (PI) separators, which can increase the thermal stability of batteries and minimize the risk of thermal runaway. However, preparing PI separators with both an ideal pore structure and adequate mechanical properties remains as a challenge. Here, we introduced decabromodiphenyl ethane (DBDPE) and cellulose nanofibers (CNFs) into PI and produced a hybrid separator with an outstanding pore structure and excellent mechanical properties. Aided with DBDPE, the separators attain a well-defined and uniform pore size (20 nm), while demonstrating high porosities (78%) through phase inversion processes. Owing to the addition of CNFs, the mechanical properties of the separators were significantly improved, with a tensile strength of 25.4 MPa and an elastic modulus of 550.1 MPa. Moreover, the separators demonstrate high ion conductivity (0.45 mS cm-1), excellent thermal-dimensional stability (up to 200 degrees C), remarkable flame retardancy, and outstanding electrolyte wettability. At room temperature, the batteries with the separators demonstrate comparable performance with those of polypropylene (PP) separators. However, when subjected to thermal shock treatments, the batteries with the separators outperform those with PP, showcasing their superior performance. The work introduces a novel strategy for designing high-performance separators, thereby paving the way for advancements in the fabrication of LIBs with enhanced safety features. A porous, robust, and thermally stable hybrid separator was developed to solve the dilemma between desired pore structures and mechanical properties in polyimide separators by introducing decabromodiphenyl ethane and cellulose nanofibers.
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| 16. |
- Ren, Xiaotong, et al.
(författare)
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Associations between home renovation and asthma, allergic rhinitis, and eczema among preschool children in Wuhan, China
- 2022
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Ingår i: International Journal of Environmental Health Research. - : Taylor & Francis Group. - 0960-3123 .- 1369-1619. ; 32:10, s. 2298-2308
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the potential associations between household renovation and allergic diseases among preschool children in Wuhan, we conducted a large cross-sectional questionnaire survey among 9455 preschool children aged 3-6 years in Wuhan during November to December 2019. Data on demographics, health status, and home decoration conditions were analysed based on a questionnaire. Compared with tiles/stone/cement floor covering, the use of composite floor significantly increased the risk of diagnosed rhinitis and eczema among children (rhinitis: AOR, 95% CI: 1.36, 1.06-1.73; eczema: AOR, 95% CI: 1.47, 1.17-1.85). Household renovation had significant associations with diagnosed eczema (within 1 year before pregnancy: AOR, 95% CI: 1.34, 1.20-1.50; during pregnancy: AOR, 95% CI: 1.25, 1.08-1.44). This study suggests that use of artificial synthetic materials in home renovation during early childhood and pregnancy may be potential risk factors for childhood asthma, allergic rhinitis, and eczema.
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| 17. |
- Vergaro, Giuseppe, et al.
(författare)
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NT-proBNP for Risk Prediction in Heart Failure : Identification of Optimal Cutoffs Across Body Mass Index Categories
- 2021
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Ingår i: JACC. Heart failure. - : American College of Cardiology. - 2213-1779 .- 2213-1787. ; 9:9, s. 653-663
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe goal of this study was to assess the predictive power of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and the decision cutoffs in heart failure (HF) across body mass index (BMI) categories.BackgroundConcentrations of NT-proBNP predict outcome in HF. Although the influence of BMI to reduce levels of NT-proBNP is known, the impact of obesity on prognostic value remains uncertain.MethodsIndividual data from the BIOS (Biomarkers In Heart Failure Outpatient Study) consortium were analyzed. Patients with stable HF were classified as underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), and mildly (BMI 30-34.9 kg/m2), moderately (BMI 35-39.9 kg/m2), or severely (BMI ≥40 kg/m2) obese. The prognostic role of NT-proBNP was tested for the endpoints of all-cause and cardiac death.ResultsThe study population included 12,763 patients (mean age 66 ± 12 years; 25% women; mean left ventricular ejection fraction 33% ± 13%). Most patients were overweight (n = 5,176), followed by normal weight (n = 4,299), mildly obese (n = 2,157), moderately obese (n = 612), severely obese (n = 314), and underweight (n = 205). NT-proBNP inversely correlated with BMI (β = –0.174 for 1 kg/m2; P < 0.001). Adding NT-proBNP to clinical models improved risk prediction across BMI categories, with the exception of severely obese patients. The best cutoffs of NT-proBNP for 5-year all-cause death prediction were lower as BMI increased (3,785 ng/L, 2,193 ng/L, 1,554 ng/L, 1,045 ng/L, 755 ng/L, and 879 ng/L, for underweight, normal weight, overweight, and mildly, moderately, and severely obese patients, respectively) and were higher in women than in men.ConclusionsNT-proBNP maintains its independent prognostic value up to 40 kg/m2 BMI, and lower optimal risk-prediction cutoffs are observed in overweight and obese patients.
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| 18. |
- Zhang, Ya Hong, et al.
(författare)
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AβPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease
- 2024
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Ingår i: Matrix Biology. - 0945-053X. ; 129, s. 29-43
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Tidskriftsartikel (refereegranskat)abstract
- As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AβPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AβPP/PS1 mice. Phosphorylated tau (p-tau) mediates AβPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AβPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems.
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| 19. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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