8,314 research outputs found
Circadian rhythm and epilepsy
No full textAdvances in diagnostic technology, including chronic intracranial EEG recordings, have confirmed the clinical observation of different temporal patterns of epileptic activity and seizure occurrence over a 24-h period. The rhythmic patterns in epileptic activity and seizure occurrence are probably related to vigilance states and circadian variation in excitatory and inhibitory balance. Core circadian genes BMAL1 and CLOCK, which code for transcription factors, have been shown to influence excitability and seizure threshold. Despite uncertainties about the relative contribution of vigilance states versus circadian rhythmicity, including circadian factors such as seizure timing improves sensitivity of seizure prediction algorithms in individual patients. Improved prediction of seizure occurrence opens the possibility for personalised antiepileptic drug-dosing regimens timed to particular phases of the circadian cycle to improve seizure control and to reduce side-effects and risks associated with seizures. Further studies are needed to clarify the pathways through which rhythmic patterns of epileptic activity are generated, because this might also inform future treatment options
Cortical neuronal loss and hippocampal sclerosis are not detected by voxel-based morphometry in individual epilepsy surgery patients
No full textVoxel-based morphometry (VBM) has detected differences between brains of groups of patients
with epilepsy and controls, but the sensitivity for detecting subtle pathological changes in single subjects
has not been established. The aim of the study was to test the sensitivity of VBM using statistical parametric
mapping (SPM5) to detect hippocampal sclerosis (HS) and cortical neuronal loss in individual patients.
T1-weighted volumetric 1.5 T MR images from 13 patients with HS and laminar cortical neuronal loss
were segmented, normalised and smoothed using SPM5. Both modulated and non-modulated analyses
were performed. Comparisons of one control subject against the rest (n ¼ 23) were first performed to ascertain
the smoothing level with the lowest number of SPM changes in controls. Each patient was then compared
against the whole control group. The lowest number of SPM changes in control subjects was found
at a smoothing level of 10 mm full width half maximum for modulated and non-modulated data. In the
patient group, no SPM abnormalities were found in the affected temporal lobe or hippocampus at this
smoothing level. At lower smoothing levels there were numerous SPM findings in controls and patients.
VBM did not detect any abnormalities associated with either laminar cortical neuronal loss or HS. This
may be due to normalisation and smoothing of images and low statistical power in areas with larger interindividual
differences. This suggests that the methodology may currently not be suitable to detect particular
occult abnormalities possibly associated with seizure onset zone in individual epilepsy patients with
unremarkable standard structural MRI
Atom chip for BEC interferometry
No full textWe have fabricated and tested an atom chip that operates as a matter wave interferometer. In this communication we describe the fabrication of the chip by ion-beam milling of gold evaporated onto a silicon substrate. We present data on the quality of the wires, on the current density that can be reached in the wires and on the smoothness of the magnetic traps that are formed. We demonstrate the operation of the interferometer, showing that we can coherently split and recombine a Bose–Einstein condensate with good phase stability
Increased expression of the Hutchinson–Gilford progeria syndrome truncated lamin A transcript during cell aging
No full textMost cases of the segmental progeroid syndrome, Hutchinson-Gilford progeria syndrome (HGPS), are caused by a de novo dominant mutation within a single codon of the LMNA gene. This mutation leads to the increased usage of an internal splice site that generates an alternative lamin A transcript with an internal deletion of 150 nucleotides, called lamin A Delta 150. The LMNA gene encodes two major proteins of the inner nuclear lamina, lamins A and C, but not much is known about their expression levels. Determination of the overall expression levels of the LMNA gene transcripts is an important step to further the understanding of the HGPS. In this study, we have performed absolute quantification of the lamins A, C and A Delta 150 transcripts in primary dermal fibroblasts from HGPS patients and unaffected age-matched and parent controls. We show that the lamin A Delta 150 transcript is present in unaffected controls but its expression is >160-fold lower than that in samples from HGPS patients. Analysis of transcript expression during in vitro aging shows that although the levels of lamin A and lamin C transcripts remain unchanged, the lamin A Delta 150 transcript increases in late passage cells from HGPS patients and parental controls. This study provides a new method for LMNA transcript analysis and insights into the expression of the LMNA gene in HGPS and normal cells
Correction to: Genetic diversity and signatures of selection in Icelandic horses and Exmoor ponies (BMC Genomics, (2024), 25, 1, (772), 10.1186/s12864-024-10682-8)
No full textGenetic diversity and signatures of selection in Icelandic horses and Exmoor ponies
No full textBackgroundThe Icelandic horse and Exmoor pony are ancient, native breeds, adapted to harsh environmental conditions and they have both undergone severe historic bottlenecks. However, in modern days, the selection pressures on these breeds differ substantially. The aim of this study was to assess genetic diversity in both breeds through expected (HE) and observed heterozygosity (HO) and effective population size (Ne). Furthermore, we aimed to identify runs of homozygosity (ROH) to estimate and compare genomic inbreeding and signatures of selection in the breeds.ResultsHO was estimated at 0.34 and 0.33 in the Icelandic horse and Exmoor pony, respectively, aligning closely with HE of 0.34 for both breeds. Based on genomic data, the Ne for the last generation was calculated to be 125 individuals for Icelandic horses and 42 for Exmoor ponies. Genomic inbreeding coefficient (FROH) ranged from 0.08 to 0.20 for the Icelandic horse and 0.12 to 0.27 for the Exmoor pony, with the majority of inbreeding attributed to short ROHs in both breeds. Several ROH islands associated with performance were identified in the Icelandic horse, featuring target genes such as DMRT3, DOCK8, EDNRB, SLAIN1, and NEURL1. Shared ROH islands between both breeds were linked to metabolic processes (FOXO1), body size, and the immune system (CYRIB), while private ROH islands in Exmoor ponies were associated with coat colours (ASIP, TBX3, OCA2), immune system (LYG1, LYG2), and fertility (TEX14, SPO11, ADAM20).ConclusionsEvaluations of genetic diversity and inbreeding reveal insights into the evolutionary trajectories of both breeds, highlighting the consequences of population bottlenecks. While the genetic diversity in the Icelandic horse is acceptable, a critically low genetic diversity was estimated for the Exmoor pony, which requires further validation. Identified signatures of selection highlight the differences in the use of the two breeds as well as their adaptive trait similarities. The results provide insight into genomic regions under selection pressure in a gaited performance horse breed and various adaptive traits in small-sized native horse breeds. This understanding contributes to preserving genetic diversity and population health in these equine populations
Festschrift in honour of Professor Neville Stanton: A lone crusader in a world of driving simulators
No full textThe automotive future has always pointed to a world of intelligent co-pilots and robot cars, but perhaps no more so than Knight Rider. In this 1980's television series the fictional Knight Industries Two Thousand (KITT) was a supercomputer on wheels with 1000 megabytes of memory. The protagonist was Michael Knight, a young loner on a crusade to champion the cause of the innocent and the helpless. This was a shadowy flight into the trials and tribulations of different levels of automation, re-claiming control when automation failed, and a wilful, chatty computer co-driver. An amusing metaphor, perhaps, for the research impact made by Neville Stanton in the field of vehicle automation. Without question – to paraphrase the Knight Rider outro – “one man can make a difference”. This festschrift in Neville's honour tells the story of how
How Many Danish Jobs Can (Potentially) Be Done Elsewhere?
No full textThis paper employs a new survey technique to arrive at estimates of the proportion of jobs with the characteristic that they can be performed elsewhere than currently, in particular in other countries. The results from the survey which was carried out in November 2008 indicate that the proportion of current jobs with offshorability characteristics in Denmark is in the 20 to 30 percent range. Danish jobs that could potentially be carried out elsewhere are primarily found in the services sector (financial and business services) and they are typically performed by employees from the middle of the wage distributionJobs; offshorability; outsourcing
Genetic and serological characteristics of tissue-specific autoimmune disease
No full textThe immune system has evolved to protect us from infectious disease and not to overreact to our own tissues or commensal flora. Immune system attack directed against self-tissue is referred to as autoimmune disease, a group of diseases that affect more than 5% of the population. Hypothyroidism and type 1 diabetes are well-known examples, resulting from the destruction of the thyroid gland, and of the insulin-producing beta cells in the pancreatic islets, respectively. Autoimmunity is also the predominant cause of primary adrenal failure, known as Addison’s disease, where the adrenal cortex is destroyed by the immune system. All four studies in this thesis were aimed to improve our understanding of autoimmune disease in terms of genetic risk factors, serological biomarkers, and tolerance mechanisms. Despite its high heritability, little is known about the genetic background of Addison’s disease. Paper I and II address the heritable risk factors in Addison’s disease and discover novel genetic risk variants. Early recognition of the rare syndrome autoimmune polyendocrine syndrome type I (APS1) is essential for prevention of its potentially lethal complications. By identifying four previously undiagnosed patients with APS1, Paper III is a proof-of-concept study showing that serological screening of patients with Addison’s disease can identify otherwise undiagnosed APS1 patients. Paper IV studies peripheral immune tolerance by investigating the serologic repertoire in patients with mutations in FOXP3, lacking regulatory T lymphocytes. Autoantibodies against a set of structurally unrelated enterocyte antigens are demonstrated, including tissue-specific nuclear receptors. In summary, this thesis takes on several aspects of autoimmunity. Both genetic, serological and clinical studies are integrated to explore new characteristics of tissue-specific autoimmune disease.List of scientific papersI. Eriksson D, Bianchi M, Landegren N, Nordin J, Dalin F, Mathioudaki A, Nordling Eriksson G, Hultin-Rosenberg L, Dahlqvist J, Zetterqvist H, Karlsson Å, Hallgren Å, Farias F. H. G, Murén E, Ahlgren K. M, Lobell A, Andersson G, Tandre K, Dahlqvist S. R, Söderkvist P, Rönnblom L, Hulting A.-L, Wahlberg J, Ekwall O, Dahlqvist P, Meadows J. R. S, Bensing S, Lindblad-Toh K, Kämpe O, Rosengren Pielberg G. Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison’s disease. Journal of Internal Medicine. 2016, 280(6): 595–608. https://doi.org/10.1111/joim.12569 II. Eriksson D, Bianchi M, Landegren N, Dalin F, Skov J, Hultin-Rosenberg L, Mathioudaki A, Nordin J, Hallgren Å, Andersson G, Tandre K, Dahlqvist S, Söderkvist P, Rönnblom L, Hulting A-L, Wahlberg J, Dahlqvist P, Ekwall O, Meadows J, Lindblad-Toh K, Bensing S, Rosengren Pielberg G, Kämpe O. Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison’s disease. [Manuscript]III. Eriksson D, Dalin F, Nordling Eriksson G, Landegren N, Bianchi M, Hallgren Å, Dahlqvist P, Wahlberg J, Ekwall O, Winqvist O, Catrina SB, Rönnelid J, The Swedish Addison Registry Study Group, Hulting AL, Lindblad-Toh K, Alimohammadi M, Husebye E. S, Knappskog P. M, Rosengren Pielberg G, Bensing S, Kämpe O. Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1. Journal of Clinical Endocrinology and Metabolism. 2018, 103(1): 179-186. https://doi.org/10.1210/jc.2017-01957 IV. Eriksson D, Bacchetta R, Gunnarsson H. I, Chan A, Barzaghi F, Ehl S, Hallgren Å, van Gool F, Sardh F, Laakso S. M, Rönnblom A, Ekwall O, Mäkitie O, Bensing S, Husebye E. S, Anderson M, Kämpe O, Landegren N. Patients deficient in regulatory T cells target enterocyte antigens. [Manuscript]</p
Body size at birth is associated with food and nutrient intake in adulthood
No full textBACKGROUND: Small body size at birth is associated with an increased risk of cardiovascular disease and type 2 diabetes. Dietary habits are tightly linked with these disorders, but the association between body size at birth and adult diet has been little studied. We examined the association between body size at birth and intake of foods and macronutrients in adulthood.METHODOLOGY/PRINCIPAL FINDINGS: We studied 1797 participants, aged 56 to 70, of the Helsinki Birth Cohort Study, whose birth weight and length were recorded. Preterm births were excluded. During a clinical study, diet was assessed with a validated food-frequency questionnaire. A linear regression model adjusted for potential confounders was used to assess the associations. Intake of fruits and berries was 13.26 g (95% confidence interval [CI]: 0.56, 25.96) higher per 1 kg/m(3) increase in ponderal index (PI) at birth, and 83.16 g (95% CI: 17.76, 148.56) higher per 1 kg higher birth weight. One unit higher PI at birth was associated with 0.14% of energy (E%) lower intake of fat (95% CI: -0.26, -0.03) and 0.18 E% higher intake of carbohydrates (95% CI: 0.04, 0.32) as well as 0.08 E% higher sucrose (95% CI: 0.00, 0.15), 0.05 E% higher fructose (95% CI: 0.01, 0.09), and 0.18 g higher fiber (95% CI: 0.02, 0.34) intake in adulthood. Similar associations were observed between birth weight and macronutrient intake.CONCLUSIONS: Prenatal growth may modify later life food and macronutrient intake. Altered dietary habits could potentially explain an increased risk of chronic disease in individuals born with small body size
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