| 1. |
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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 4. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 5. |
- Chaste, Pauline, et al.
(författare)
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Mutation screening of the ARX gene in patients with autism.
- 2007
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Ingår i: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 144B:2, s. 228-230
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the Aristaless related homeobox (ARX) gene are associated with a broad spectrum of disorders, including nonsyndromic X-linked mental retardation, sometimes associated with epilepsy, as well as syndromic forms with brain abnormalities and abnormal genitalia. Furthermore, ARX mutations have been described in a few patients with autism or autistic features. In this study, we screened the ARX gene in 226 male patients with autism spectrum disorders and mental retardation; 42 of the patients had epilepsy. The mutation analysis was performed by direct sequencing of all exons and flanking regions. No ARX mutations were identified in any of the patients tested. These findings indicate that mutations in the ARX gene are very rare in autism.
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| 6. |
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| 7. |
- Coleman, Mary, et al.
(författare)
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The Autisms
- 2012
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Bok (övrigt vetenskapligt/konstnärligt)
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| 8. |
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| 9. |
- Danaei, Goodarz, et al.
(författare)
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Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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| 10. |
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| 11. |
- Gillberg, Christopher, 1950, et al.
(författare)
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Autism and medical disorders: a review of the literature.
- 1996
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Ingår i: Developmental Medicine and Child Neurology. - 0012-1622. ; 38:3, s. 191-202
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Tidskriftsartikel (refereegranskat)abstract
- The authors reviewed all the population studies on autism published in the English language with particular reference to the rate of medical disorders. Seven studies met criteria for inclusion in the survey. The mean of possibly autism-related medical disorders in persons with autism across these studies was 24.4%. There was a trend for higher rates of medical disorders among subjects with severe mental retardation. The evidence in respect of atypical autism was equivocal, and the overall prevalence of medical disorders in this group was similar to that found in typical autism.
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| 12. |
- Gillberg, Christopher, 1950, et al.
(författare)
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The Neurobiology of Autism
- 2019
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Ingår i: Autism and Pervasive Developmental Disorders, 3rd Ed. Fred R. Volkmar (red.). - Cambridge : Cambridge University Press. - 9781108297769 ; , s. 129-157
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Jamain, Stephane, et al.
(författare)
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Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism
- 2003
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 34:1, s. 27-29
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Tidskriftsartikel (refereegranskat)abstract
- Many studies have supported a genetic etiology for autism. Here we report mutations in two X-linked genes encoding neuroligins NLGN3 and NLGN4 in siblings with autism-spectrum disorders. These mutations affect cell-adhesion molecules localized at the synapse and suggest that a defect of synaptogenesis may predispose to autism.
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| 14. |
- Leblond, Claire S, et al.
(författare)
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Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments.
- 2014
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.
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| 15. |
- Philippe, Anne, et al.
(författare)
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Analysis of ten candidate genes in autism by association and linkage
- 2002
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Ingår i: American Journal of Medical Genetics. - : Wiley. - 0148-7299. ; 114:2, s. 125-128
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Tidskriftsartikel (refereegranskat)abstract
- We studied the possible involvement of ten candidate genes in autism: proenkephalin, prodynorphin, and proprotein convertase subtilisin/kexin type 2 (opioid metabolism); tyrosine hydroxylase, dopamine receptors D2 and D5, monoamine oxidases A and B (monoaminergic system); brain-derived neurotrophic factor, and neural cell adhesion molecule (involved in neurodevelopment). Thirty-eight families with two affected siblings and one family with two affected half-siblings, recruited by the Paris Autism Research International Sibpair Study (PARIS), were tested using the transmission disequilibrium test and two-point affected sib-pair linkage analysis. We found no evidence for association or linkage with intragenic or linked markers. Our family sample has good power for detecting a linkage disequilibrium of 0.80. Thus, these genes are unlikely to play a major role in the families studied, but further studies in a much larger sample would be needed to highlight weaker genetic effects.
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| 16. |
- Philippe, Anne, et al.
(författare)
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Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study.
- 1999
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 8:5, s. 805-812
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Tidskriftsartikel (refereegranskat)abstract
- Family and twin studies have suggested a genetic component in autism. We performed a genome-wide screen with 264 microsatellites markers in 51 multiplex families, using non-parametric linkage methods. Families were recruited by a collaborative group including clinicians from Sweden, France, Norway, the USA, Italy, Austria and Belgium. Using two-point and multipoint affected sib-pair analyses, 11 regions gave nominal P-values of 0.05 or lower. Four of these regions overlapped with regions on chromosomes 2q, 7q, 16p and 19p identified by the first genome-wide scan of autism performed by the International Molecular Genetic Study of Autism Consortium. Another of our potential susceptibility regions overlapped with the 15q11–q13 region identified in previous candidate gene studies. Our study revealed six additional regions on chromosomes 4q, 5p, 6q, 10q, 18q and Xp. We found that the most significant multipoint linkage was close to marker D6S283 (maximum lod score = 2.23, P= 0.0013)
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| 17. |
- Scheid, Isabelle, et al.
(författare)
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Heterozygous FA2H mutations in autism spectrum disorders
- 2013
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background Widespread abnormalities in white matter development are frequently reported in cases of autism spectrum disorders (ASD) and could be involved in the disconnectivity suggested in these disorders. Homozygous mutations in the gene coding for fatty-acid 2-hydroxylase (FA2H), an enzyme involved in myelin synthesis, are associated with complex leukodystrophies, but little is known about the functional impact of heterozygous FA2H mutations. We hypothesized that rare deleterious heterozygous mutations of FA2H might constitute risk factors for ASD. Methods We searched deleterious mutations affecting FA2H, by genotyping 1256 independent patients with ASD genotyped using Genome Wide SNP arrays, and also by sequencing in independent set of 186 subjects with ASD and 353 controls. We then explored the impact of the identified mutations by measuring FA2H enzymatic activity and expression, in transfected COS7 cells. Results One heterozygous deletion within 16q22.3-q23.1 including FA2H was observed in two siblings who share symptoms of autism and severe cognitive impairment, axial T2-FLAIR weighted MRI posterior periventricular white matter lesions. Also, two rare non-synonymous mutations (R113W and R113Q) were reported. Although predictive models suggested that R113W should be a deleterious, we did not find that FA2H activity was affected by expression of the R113W mutation in cultured COS cells. Conclusions While our results do not support a major role for FA2H coding variants in ASD, a screening of other genes related to myelin synthesis would allow us to better understand the role of non-neuronal elements in ASD susceptibility.
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| 18. |
- Tabet, Anne-Claude, et al.
(författare)
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Complex nature of apparently balanced chromosomal rearrangements in patients with autism spectrum disorder.
- 2015
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Ingår i: Molecular autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Apparently balanced chromosomal rearrangements can be associated with an abnormal phenotype, including intellectual disability and autism spectrum disorder (ASD). Genome-wide microarrays reveal cryptic genomic imbalances, related or not to the breakpoints, in 25% to 50% of patients with an abnormal phenotype carrying a microscopically balanced chromosomal rearrangement. Here we performed microarray analysis of 18 patients with ASD carrying balanced chromosomal abnormalities to identify submicroscopic imbalances implicated in abnormal neurodevelopment. METHODS: Eighteen patients with ASD carrying apparently balanced chromosomal abnormalities were screened using single nucleotide polymorphism (SNP) arrays. Nine rearrangements were de novo, seven inherited, and two of unknown inheritance. Genomic imbalances were confirmed by fluorescence in situ hybridization and quantitative PCR. RESULTS: We detected clinically significant de novo copy number variants in four patients (22%), including three with de novo rearrangements and one with an inherited abnormality. The sizes ranged from 3.3 to 4.9 Mb; three were related to the breakpoint regions and one occurred elsewhere. We report a patient with a duplication of the Wolf-Hirschhorn syndrome critical region, contributing to the delineation of this rare genomic disorder. The patient has a chromosome 4p inverted duplication deletion, with a 0.5 Mb deletion of terminal 4p and a 4.2 Mb duplication of 4p16.2p16.3. The other cases included an apparently balanced de novo translocation t(5;18)(q12;p11.2) with a 4.2 Mb deletion at the 18p breakpoint, a subject with de novo pericentric inversion inv(11)(p14q23.2) in whom the array revealed a de novo 4.9 Mb deletion in 7q21.3q22.1, and a patient with a maternal inv(2)(q14.2q37.3) with a de novo 3.3 Mb terminal 2q deletion and a 4.2 Mb duplication at the proximal breakpoint. In addition, we identified a rare de novo deletion of unknown significance on a chromosome unrelated to the initial rearrangement, disrupting a single gene, RFX3. CONCLUSIONS: These findings underscore the utility of SNP arrays for investigating apparently balanced chromosomal abnormalities in subjects with ASD or related neurodevelopmental disorders in both clinical and research settings.
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| 19. |
- Toro, Roberto, et al.
(författare)
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Key role for gene dosage and synaptic homeostasis in autism spectrum disorders.
- 2010
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Ingår i: Trends in Genetics. - : Elsevier BV. - 0168-9525. ; 26:8, s. 363-372
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Forskningsöversikt (refereegranskat)abstract
- Autism spectrum disorders (ASD) are characterized by impairments in reciprocal social communication, and repetitive, stereotyped verbal and non-verbal behaviors. Genetic studies have provided a relatively large number of genes that constitute a comprehensive framework to better understand this complex and heterogeneous syndrome. Based on the most robust findings, three observations can be made. First, genetic contributions to ASD are highly heterogeneous and most probably involve a combination of alleles with low and high penetrance. Second, the majority of the mutations apparently affect a single allele, suggesting a key role for gene dosage in susceptibility to ASD. Finally, the broad expression and function of the causative genes suggest that alteration of synaptic homeostasis could be a common biological process associated with ASD. Understanding the mechanisms that regulate synaptic homeostasis should shed new light on the causes of ASD and could provide a means to modulate the severity of the symptoms.
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| 20. |
- Wiedorn, Max O., et al.
(författare)
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Megahertz serial crystallography
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a beta-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.
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| 21. |
- Zhou, Bin, et al.
(författare)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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