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- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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- Namkoong, H, et al.
(author)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Journal article (peer-reviewed)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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6. |
- Wang, QBS, et al.
(author)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Journal article (peer-reviewed)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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- Parra, M. A., et al.
(author)
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Biomarkers for dementia in Latin American countries: Gaps and opportunities
- 2023
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:2, s. 721-735
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Journal article (peer-reviewed)abstract
- Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.
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- De Jong, VMT, et al.
(author)
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Clinical prediction models for mortality in patients with covid-19: external validation and individual participant data meta-analysis
- 2022
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In: BMJ (Clinical research ed.). - : BMJ. - 1756-1833. ; 378, s. e069881-
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Journal article (peer-reviewed)abstract
- ObjectiveTo externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19.DesignTwo stage individual participant data meta-analysis.SettingSecondary and tertiary care.Participants46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021.Data sourcesMultiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published inThe BMJ, and through PROSPERO, reference checking, and expert knowledge.Model selection and eligibility criteriaPrognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor.MethodsEight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters.Main outcome measures30 day mortality or in-hospital mortality.ResultsDatasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al’s model (0.96, 0.59 to 1.55, 0.21 to 4.28).ConclusionThe prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.
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21. |
- Inagaki-Kawata, Y, et al.
(author)
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Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants
- 2020
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 578-
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Journal article (peer-reviewed)abstract
- The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.
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- Helfricht, A, et al.
(author)
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Loss of ZBTB24 impairs nonhomologous end-joining and class-switch recombination in patients with ICF syndrome
- 2020
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:11
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Journal article (peer-reviewed)abstract
- The autosomal recessive immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a genetically heterogeneous disorder. Despite the identification of the underlying gene defects, it is unclear how mutations in any of the four known ICF genes cause a primary immunodeficiency. Here we demonstrate that loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance. Mechanistically, we found that ZBTB24 associates with poly(ADP-ribose) polymerase 1 (PARP1) and stimulates its auto-poly(ADP-ribosyl)ation. The zinc-finger in ZBTB24 binds PARP1-associated poly(ADP-ribose) chains and mediates the PARP1-dependent recruitment of ZBTB24 to DNA breaks. Moreover, through its association with poly(ADP-ribose) chains, ZBTB24 protects them from degradation by poly(ADP-ribose) glycohydrolase (PARG). This facilitates the poly(ADP-ribose)-dependent assembly of the LIG4/XRCC4 complex at DNA breaks, thereby promoting error-free NHEJ. Thus, we uncover ZBTB24 as a regulator of PARP1-dependent NHEJ and class-switch recombination, providing a molecular basis for the immunodeficiency in ICF2 syndrome.
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35. |
- Swift, Imogen J, et al.
(author)
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A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.
- 2024
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In: Alzheimer's Research & Therapy. - 1758-9193. ; 16:1
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Journal article (peer-reviewed)abstract
- Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p=0.007) with a trend in non-carriers (p=0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
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- Thodeti, CK, et al.
(author)
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ADAM12/syndecan-4 signaling promotes beta(1) integrin-dependent cell spreading through protein kinase C alpha and RhoA
- 2003
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In: Journal of Biological Chemistry. - 1083-351X. ; 278:11, s. 9576-9584
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Journal article (peer-reviewed)abstract
- The ADAMs (a disintegrin and metalloprotease) comprise a large family of multidomain proteins with cell-binding and metalloprotease activities. The ADAM12 cysteine-rich domain (rADAM12-cys) supports cell attachment using syndecan-4 as a primary cell surface receptor that subsequently triggers beta(1) integrin-dependent cell spreading, stress fiber assembly, and focal adhesion formation. This process contrasts with cell adhesion on fibronectin, which is integrin-initiated but syndecan-4-dependent. In the present study, we investigated ADAM12/syndecan-4 signaling leading to cell spreading and stress fiber formation. We demonstrate that syndecan-4, when present in significant amounts, promotes beta(1) integrin-dependent cell spreading and stress fiber formation in response to rADAM12-cys. A mutant form of syndecan-4 deficient in protein kinase C (PKC)alpha activation or a different member of the syndecan family, syndecan-2, was unable to promote cell spreading. GF109203X and Go6976, inhibitors of PKC, completely inhibited ADAM12/syndecan-4-induced cell spreading. Expression of syndecan-4, but not syn4DeltaI, resulted in the accumulation of activated beta(1) integrins at the cell periphery in Chinese hamster ovary beta1 cells as revealed by 12G10 staining. Further, expression of myristoylated, constitutively active PKCalpha resulted in beta(1) integrin-dependent cell spreading, but additional activation of RhoA was required to induce stress fiber formation. In summary, these data provide novel insights into syndecan-4 signaling. Syndecan-4 can promote cell spreading in a beta(1) integrin-dependent fashion through PKCalpha and RhoA, and PKCalpha and RhoA likely function in separate pathways.
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39. |
- Altman, S, et al.
(author)
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Catalysis by the RNA subunit of RNase P
- 1989
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In: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 82:1, s. 63-64
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Research review (peer-reviewed)abstract
- RNase P, an enzyme that contains both RNA and protein components, cleaves tRNA precursors to generate mature 5' termini. The catalytic activity of RNase P resides in the RNA component, with the protein cofactor affecting the rate of the cleavage reaction. The reaction is also influenced by the nature of the tRNA substrate.
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40. |
- Endo, Satoshi, et al.
(author)
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Instability of C154Y variant of aldo-keto reductase 1C3
- 2017
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In: Chemico-Biological Interactions. - : Elsevier. - 0009-2797 .- 1872-7786. ; 276, s. 194-202
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Journal article (peer-reviewed)abstract
- Aldo-keto reductase (AKR) 1C3 is a cytosolic enzyme that metabolizes steroids, prostaglandins, toxic aldehydes and drugs. Recently, some nonsynonymous single nucleotide polymorphisms of AKR1C3 have been suggested to impact steroid and drug metabolism. In this study, we examined the effects of C154Y and L159V variants of AKR1C3 on stability and function of the enzyme. Both variants had been detected in patients with the neurodegenerative disease amyotrophic lateral sclerosis. Recombinant wild-type (WT), C154Y and L159V enzymes were similar in specific activity, but C154Y displayed much lower thermostability than WT and L159V. C154Y was inactivated by 10-min incubation at >25 °C, and about 90% of its activity was lost at 40 °C. Differential scanning fluorimetry revealed that Tm (thermal denaturation midpoint) of C154Y was lower than that of WT. In order to study the cause of thermosensitivity of C154Y, we prepared C154F and C154S mutant AKR1C3s. Like C154Y, C154F was highly sensitive to thermal inactivation, whereas C154S showed almost the same thermostability as WT. The C154F and C154Y variants induced secondary and tertiary structural changes in AKR1C3 at 40 °C as reflected by their altered circular dichroism and 8-anilinonaphthalene-1-sulfonate fluorescence characteristics. These results suggest that the replacement of C154 with a residue possessing a bulky aromatic side-chain impairs the folding of the α-helix containing C154 and its neighboring secondary structures, leading to low thermostability of AKR1C3. AKR1C3 metabolizes cytotoxic 4-oxo-2-nonenal into a less toxic metabolite, and overexpression of WT in HEK293 cells alleviated the 4-oxo-2-nonenal-induced cytotoxicity. In contrast, the overexpression of C154Y in the cells did not show such a significant protective effect, suggesting that C154Y is unstable in cells.
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41. |
- Keika, K., et al.
(author)
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Response of the inner magnetosphere and the plasma sheet to a sudden impulse
- 2008
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 113:A7, s. A07S35-
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Journal article (peer-reviewed)abstract
- [1] The passage of an interplanetary shock caused a sudden compression of the magnetosphere between 0900 UT and 0915 UT on 24 August 2005. An estimate of the shock normal from solar wind data obtained by Geotail upstream of the bow shock indicates symmetric compression with respect to the noon-midnight meridian. Compression-related disturbances of the magnetic and electric field and plasma motion were observed by Double Star Program (DSP) Tan Ce 1 (TC1) and Tan Ce 2 (TC2) in the inner magnetosphere and by the Cluster spacecraft in the dawnside plasma sheet. DSP/TC1 and TC2 observations suggest that the disturbances in the inner magnetosphere are propagating from the dayside magnetopause. Cluster S/C 4 observations indicate that the front normal of the disturbances in the dawnside plasma sheet is phi similar to 180 degrees at 0902: 50 UT and phi = 107 degrees at 0904: 34 UT, where phi is the longitude in GSM coordinates, if we assume that the measured electric field is on the front plane and the normal lies on the X-Y plane. The timing analysis applied to magnetic field data from the four Cluster spacecraft independently gives a front normal, which is calculated to be phi =131 degrees at about 0904: 20 UT. Shock-associated magnetic and electric field disturbances propagating from both the dayside and flank magnetopauses are detected in the plasma sheet; the latter makes the dominant contribution. Substorms are, however, not triggered at the passage of the disturbances.
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- Rajan, Anandi, 1988-, et al.
(author)
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Enteric species F human adenoviruses use laminin-binding integrins as co-receptors for infection of Ht-29 cells
- 2018
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 8:1
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Journal article (peer-reviewed)abstract
- The enteric species F human adenovirus types 40 and 41 (HAdV-40 and -41) are the third most common cause of infantile gastroenteritis in the world. Knowledge about HAdV-40 and -41 cellular infection is assumed to be fundamentally different from that of other HAdVs since HAdV-40 and -41 penton bases lack the αV-integrin-interacting RGD motif. This motif is used by other HAdVs mainly for internalization and endosomal escape. We hypothesised that the penton bases of HAdV-40 and -41 interact with integrins independently of the RGD motif. HAdV-41 transduction of a library of rodent cells expressing specific human integrin subunits pointed to the use of laminin-binding α2-, α3- and α6-containing integrins as well as other integrins as candidate co-receptors. Specific laminins prevented internalisation and infection, and recombinant, soluble HAdV-41 penton base proteins prevented infection of human intestinal HT-29 cells. Surface plasmon resonance analysis demonstrated that HAdV-40 and -41 penton base proteins bind to α6-containing integrins with an affinity similar to that of previously characterised penton base:integrin interactions. With these results, we propose that laminin-binding integrins are co-receptors for HAdV-40 and -41.
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44. |
- Sato, T., et al.
(author)
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Evaluation of dose rate reduction in a spacecraft compartment due to additional water shield
- 2011
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In: Cosmic Research (English translation of Kosimicheskie Issledovaniya). - 0010-9525 .- 1608-3075. ; 49:4, s. 319-324
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Journal article (peer-reviewed)abstract
- The dose reduction rates brought about by the installation of additional water shielding in a spacecraft are calculated in the paper using the particles and heavy ion transport code system PHITS, which can deal with transport of all kinds of hadrons and heavy ions with energies up to 100 GeV/n in three-dimensional phase spaces. In the PHITS simulation, an imaginary spacecraft was irradiated isotropically by cosmic rays with charges up to 28 and energies up to 100 GeV/n, and the dose reduction rates due to water shielding were evaluated for 5 types of doses: the dose equivalents obtained from the LET and linear energy spectra, the dose equivalents to skin and red bone marrow, and the effective dose equivalent. The results of the simulation indicate that the dose reduction rates differ according to the type of dose evaluated. For example, 5 g/cm(2) water shielding reduces the effective dose equivalent and the LET dose equivalent by approximately 14% and 32%, respectively. Such degrees of dose reduction can be regarded to make water shielding worth the efforts required to install it.
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45. |
- Sato, T., et al.
(author)
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PARMA: PHITS-based analytical radiation model in the atmosphere - Verification of its accuracy in estimating cosmic radiation doses
- 2008
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In: AIP Conference Proceedings. - : AIP. - 1551-7616 .- 0094-243X. - 9780735405592 ; 1034, s. 99-102
-
Conference paper (peer-reviewed)abstract
- Estimation of cosmic-ray spectra in the atmosphere has been an essential issue in the evaluation of the aircrew doses. We therefore developed an analytical model that can predict the terrestrial neutron, proton, He nucleus, muon, electron, positron and photon spectra at altitudes below 20 km, based on the Monte Carlo simulation results of cosmic-ray propagation in the atmosphere performed by the PHITS code. The model was designated PARMA. In order to examine the accuracy of PARMA in terms of the neutron dose estimation, we measured the neutron dose rates at the altitudes between 20 to 10400 m, using our developed dose monitor DARWIN mounted on an aircraft. Excellent agreement was observed between the measured dose rates and the corresponding data calculated by PARMA coupled with the fluence-to-dose conversion coefficients, indicating the applicability of the model to be utilized in the route-dose calculation.
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47. |
- Teuten, Emma L, et al.
(author)
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Transport and release of chemicals from plastics to the environment and to wildlife
- 2009
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In: PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 364:1526, s. 2027-2045
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Journal article (peer-reviewed)abstract
- Plastics debris in the marine environment, including resin pellets, fragments and microscopic plastic fragments, contain organic contaminants, including polychlorinated biphenyls ( PCBs), polycyclic aromatic hydrocarbons, petroleum hydrocarbons, organochlorine pesticides (2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane, hexachlorinated hexanes), polybrominated diphenylethers, alkylphenols and bisphenol A, at concentrations from sub ng g(-1) to mg g(-1). Some of these compounds are added during plastics manufacture, while others adsorb from the surrounding seawater. Concentrations of hydrophobic contaminants adsorbed on plastics showed distinct spatial variations reflecting global pollution patterns. Model calculations and experimental observations consistently show that polyethylene accumulates more organic contaminants than other plastics such as polypropylene and polyvinyl chloride. Both a mathematical model using equilibrium partitioning and experimental data have demonstrated the transfer of contaminants from plastic to organisms. A feeding experiment indicated that PCBs could transfer from contaminated plastics to streaked shearwater chicks. Plasticizers, other plastics additives and constitutional monomers also present potential threats in terrestrial environments because they can leach from waste disposal sites into groundwater and/or surface waters. Leaching and degradation of plasticizers and polymers are complex phenomena dependent on environmental conditions in the landfill and the chemical properties of each additive. Bisphenol A concentrations in leachates from municipal waste disposal sites in tropical Asia ranged from sub mu g l(-1) to mg l(-1) and were correlated with the level of economic development.
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48. |
- Ulugut, Hulya, et al.
(author)
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Clinical recognition of frontotemporal dementia with right anterior temporal predominance : A multicenter retrospective cohort study
- 2024
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In: Alzheimer's and Dementia. - 1552-5260.
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS: Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS: Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION: This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. Highlights: This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.
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49. |
- Yukimune, M., et al.
(author)
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GaAs/GaNAs core-multishell nanowires with nitrogen composition exceeding 2%
- 2018
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In: Applied Physics Letters. - : AMER INST PHYSICS. - 0003-6951 .- 1077-3118. ; 113:1
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Journal article (peer-reviewed)abstract
- We report the growth of GaAs/GaNAs/GaAs core-multishell nanowires having N compositions exceeding 2%. The structures were grown by plasma-assisted molecular beam epitaxy using constituent Ga-induced vapor-liquid-solid growth on Si(111) substrates. The GaNAs shell nominally contains 0%, 2%, and 3% nitrogen. The axial cross-sectional scanning transmission electron microscopy measurements confirm the existence of core-multishell structure. The room temperature micro-photoluminescence measurements reveal a red-shift of the detected emission with increasing N content in the nanowires, consistent with the expected changes in the GaNAs bandgap energy due to the bowing effect. Published by AIP Publishing.
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