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| 2. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 5. |
- Christensen, Lise Lotte, et al.
(författare)
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The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population
- 2008
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 9, s. 52-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mutations in the mismatch repair genes hMLH1 and hMSH2 predispose to hereditary non-polyposis colorectal cancer (HNPCC). Genetic screening of more than 350 Danish patients with colorectal cancer (CRC) has led to the identification of several new genetic variants (e.g. missense, silent and non-coding) in hMLH1 and hMSH2. The aim of the present study was to investigate the frequency of these variants in hMLH1 and hMSH2 in Danish patients with sporadic colorectal cancer and in the healthy background population. The purpose was to reveal if any of the common variants lead to increased susceptibility to colorectal cancer. METHODS: Associations between genetic variants in hMLH1 and hMSH2 and sporadic colorectal cancer were evaluated using a case-cohort design. The genotyping was performed on DNA isolated from blood from the 380 cases with sporadic colorectal cancer and a sub-cohort of 770 individuals. The DNA samples were analyzed using Single Base Extension (SBE) Tag-arrays. A Bonferroni corrected Fisher exact test was used to test for association between the genotypes of each variant and colorectal cancer. Linkage disequilibrium (LD) was investigated using HaploView (v3.31). RESULTS: Heterozygous and homozygous changes were detected in 13 of 35 analyzed variants. Two variants showed a borderline association with colorectal cancer, whereas the remaining variants demonstrated no association. Furthermore, the genomic regions covering hMLH1 and hMSH2 displayed high linkage disequilibrium in the Danish population. Twenty-two variants were neither detected in the cases with sporadic colorectal cancer nor in the sub-cohort. Some of these rare variants have been classified either as pathogenic mutations or as neutral variants in other populations and some are unclassified Danish variants. CONCLUSION: None of the variants in hMLH1 and hMSH2 analyzed in the present study were highly associated with colorectal cancer in the Danish population. High linkage disequilibrium in the genomic regions covering hMLH1 and hMSH2, indicate that common genetic variants in the two genes in general are not involved in the development of sporadic colorectal cancer. Nevertheless, some of the rare unclassified variants in hMLH1 and hMSH2 might be involved in the development of colorectal cancer in the families where they were originally identified.
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| 6. |
- Ebbesson, LE, et al.
(författare)
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Nitric oxide synthase in the gill of Atlantic salmon: colocalization with and inhibition of Na+,K+-ATPase
- 2005
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 208:6, s. 1011-1017
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the relationship between nitric oxide (NO) and Na+,K+-ATPase (NKA) in the gill of anadromous Atlantic salmon. Cells containing NO-producing enzymes were revealed by means of nitric oxide synthase (NOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochernistry, which can be used as an indicator of NOS activity, i.e. NO production. Antibodies against the two constitutive NOS isoforms, neuronal and endothelial NOS, both produced immunoreactivity restricted to large cells at the base and along the secondary lamellae. NADPHd-positive cells showed a corresponding distribution. Antibodies against the inducible NOS isoform only labeled small cells located deep in the filament. Using in situ hybridization and NKA immunoreactivity, cells expressing Na+,K+-ATPase alpha-subunit mRNA were found to have a similar distribution to the NOS cells. Double labeling for NOS immunoreactivity and NKA cc-subunit mRNA revealed cellular colocalization of NKA alpha-subunit mRNA and nNOS protein in putative chloride cells at the base of the lamellae and interlamellar space. Along the lamellae, some NOS- or NKA-immunoreactive cells possessed a relatively lower expression of NKA a-subunit mRNA in smolts. A clear increase in NADPHd staining in the gill was demonstrated from parr to smolt. The regulatory role of NO on gill NKA activity was studied in vitro using sodium nitroprusside (SNP; 1 mmol l(-1)) and PAPA-NONOate (NOC-15; 0.5 mmol l(-1)) as NO donors. Both SNP and NOC-15 inhibited gill NKA activity by 30% when compared to controls. The study shows that NO systems are abundant in the gill of Atlantic salmon, that NO may be produced preferentially by a constitutive NOS isoform, and suggests that NO influence on gill functions is mediated via intracellular, possibly both auto/paracrine, inhibition of Na+,K+-ATPase activity in chloride cells. Furthermore, the increase in NADPHd in the gill during smoltification suggests a regulatory role of NO in the attenuation of the smoltification-related increase in Na+,K+-ATPase activity prior to entering seawater.
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| 7. |
- Edwards, N.V., et al.
(författare)
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Optical characterization of wide bandgap semiconductors
- 2000
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Ingår i: Thin Solid Films. - 0040-6090 .- 1879-2731. ; 364:1, s. 98-106
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Tidskriftsartikel (refereegranskat)abstract
- Our work primarily concerns the characterization of wide-gap III-V nitride semiconductors, nondestructively and at variable temperature, with spectroscopic ellipsometry (SE) and reflectometry in the spectral range from 1.5 to 6 eV. In the case of GaN, there are three main concerns associated with such data: (a) the quantification of the dispersion of the index of refraction with energy, (b) the removal of surface overlayers in real-time, and (c) the determination of the variation of valence bands with biaxial stress and the quantification of residual stress in thin films. The SE and reflectance capabilities provide (1) broadband spectra from 1.5 to 6 eV, which yield information about (a) below the bandgap and (b) above it, and (2) high resolution spectra (less than 1 meV at 3.4 eV) in the vicinity of the gap (3.3-3.6 eV), which enables (c). Here we will discuss issues concerning the relation of (c) to GaN material and growth parameters, though similar data for other wide bandgap materials will be discussed where relevant. Specifically, optimal heterostructure design for potential valence band engineering applications will be discussed in the context of trends in residual stress as a function of film thickness, growth temperature and substrate orientation for GaN/AlN/6H-SiC heterostructures. Standard heterostructures are mostly compressive for samples less than about 0.7 µm thick, are tensile up to about 2 µm and then abruptly become less tensile with stress values near 1 kbar thereafter. Additionally, these trends can be circumvented for moderately thick (approximately 2 µm) GaN layers (normally>2 kbar, tensile) by the introduction of a `buried interface' approach, namely, a strain mediating layer (SML) above the standard high-temperature AlN buffer layer designed to yield a range of compressive stresses from 0 to 2 kbar. The strain characteristics but also the growth rates of subsequently deposited nitride layers can be modulated by changing the growth parameters of the SML. This is achieved by in situ techniques during crystal growth without degrading the optical and structural properties of the deposited layer, as confirmed by XRD, SEM, PL, and AFM data taken on the overlying GaN layers. These results are interpreted in terms of coefficient of thermal expansion data for the layers and data concerning the planarization of GaN layers and growth behavior in non-(0001) directions.
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| 8. |
- Flannick, Jason, et al.
(författare)
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Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:4, s. 357-357
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Tidskriftsartikel (refereegranskat)abstract
- Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
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| 9. |
- Grigoryan, Ani, et al.
(författare)
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Engineering human mini-bones for the standardized modeling of healthy hematopoiesis, leukemia, and solid tumor metastasis
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 14:666, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- The bone marrow microenvironment provides indispensable factors to sustain blood production throughout life. It is also a hotspot for the progression of hematologic disorders and the most frequent site of solid tumor metastasis. Preclinical research relies on xenograft mouse models, but these models preclude the human-specific functional interactions of stem cells with their bone marrow microenvironment. Instead, human mesenchymal cells can be exploited for the in vivo engineering of humanized niches, which confer robust engraftment of human healthy and malignant blood samples. However, mesenchymal cells are associated with major reproducibility issues in tissue formation. Here, we report the fast and standardized generation of human mini-bones by a custom-designed human mesenchymal cell line. These resulting humanized ossicles (hOss) consist of fully mature bone and bone marrow structures hosting a human mesenchymal niche with retained stem cell properties. As compared to mouse bones, we demonstrate superior engraftment of human cord blood hematopoietic cells and primary acute myeloid leukemia samples and also validate hOss as a metastatic site for breast cancer cells. We further report the engraftment of neuroblastoma patient-derived xenograft cells in a humanized model, recapitulating clinically described osteolytic lesions. Collectively, our human mini-bones constitute a powerful preclinical platform to model bone-developing tumors using patient-derived materials.
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| 10. |
- Grøn, Ole, et al.
(författare)
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Acoustic mapping of submerged stone age sites—A HALD approach
- 2021
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Ingår i: Remote Sensing. - : MDPI AG. - 2072-4292. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Acoustic response from lithics knapped by humans has been demonstrated to facilitate effective detection of submerged Stone Age sites exposed on the seafloor or embedded within its sediments. This phenomenon has recently enabled the non-invasive detection of several hitherto unknown submerged Stone Age sites, as well as the registration of acoustic responses from already known localities. Investigation of the acoustic-response characteristics of knapped lithics, which appear not to be replicated in naturally cracked lithic pieces (geofacts), is presently on-going through laboratory experiments and finite element (FE) modelling of high-resolution 3D-scanned pieces. Experimental work is also being undertaken, employing chirp sub-bottom systems (reflection seismic) on known sites in marine areas and inland water bodies. Fieldwork has already yielded positive results in this initial stage of development of an optimised Human-Altered Lithic Detection (HALD) method for mapping submerged Stone Age sites. This paper reviews the maritime archaeological perspectives of this promising approach, which potentially facilitates new and improved practice, summarizes existing data, and reports on the present state of development. Its focus is not reflection seismics as such, but a useful resonance phenomenon induced by the use of high-resolution reflection seismic systems.
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