| 1. |
- Satizabal, Claudia L., et al.
(author)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Journal article (peer-reviewed)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 2. |
- Schiller, D, et al.
(author)
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The Human Affectome
- 2024
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In: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
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Journal article (peer-reviewed)
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| 3. |
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| 4. |
- Moshammer, R., et al.
(author)
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Few-photon multiple ionization of Ne and Ar by strong free-electron-laser pulses
- 2007
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 98:20, s. 203001-
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Journal article (peer-reviewed)abstract
- Few-photon multiple ionization of Ne and Ar atoms by strong vacuum ultraviolet laser pulses from the free-electron laser at Hamburg was investigated differentially with the Heidelberg reaction microscope. The light-intensity dependence of Ne2+ production reveals the dominance of nonsequential two-photon double ionization at intensities of I < 6x10(12) W/cm(2) and significant contributions of three-photon ionization as I increases. Ne2+ recoil-ion-momentum distributions suggest that two electrons absorbing "instantaneously" two photons are ejected most likely into opposite hemispheres with similar energies.
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| 5. |
- Rolles, D., et al.
(author)
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Femtosecond x-ray photoelectron diffraction on gas-phase dibromobenzene molecules
- 2014
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In: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 47:12
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Journal article (peer-reviewed)abstract
- We present time-resolved femtosecond photoelectron momentum images and angular distributions of dissociating, laser-aligned 1,4-dibromobenzene (C6H4Br2) molecules measured in a near-infrared pump, soft-x-ray probe experiment performed at an x-ray free-electron laser. The observed alignment dependence of the bromine 2p photoelectron angular distributions is compared to density functional theory calculations and interpreted in terms of photoelectron diffraction. While no clear time-dependent effects are observed in the angular distribution of the Br(2p) photoelectrons, other, low-energy electrons show a pronounced dependence on the time delay between the near-infrared laser and the x-ray pulse.
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| 6. |
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| 7. |
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| 8. |
- Seibert, M. Marvin, et al.
(author)
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Single mimivirus particles intercepted and imaged with an X-ray laser
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 470:7332, s. 78-81
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Journal article (peer-reviewed)abstract
- X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions(1-4). Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma(1). The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval(2). Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a noncrystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source(5). Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000 K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.
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| 9. |
- Blaschke, Stefan J., et al.
(author)
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Early Blood–Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice
- 2024
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In: International Journal of Molecular Sciences. - 1661-6596. ; 25:9
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Journal article (peer-reviewed)abstract
- Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice. Longitudinal behavioral assessments were conducted for up to seven days afterward, alongside the evaluation of structural cerebral integrity by in vivo magnetic resonance imaging (MRI, 9.4 T), and validated ex vivo by histology. Blood–brain barrier (BBB) integrity was analyzed by means of fluorescent dextran- as well as immunoglobulin G (IgG) extravasation, and neuroinflammatory processes were characterized both in vivo by positron emission tomography (PET) using [18F]DPA-714 and ex vivo using immunohistochemistry. While a single CBI resulted in a defined, subacute neuropsychiatric phenotype, longitudinal cognitive testing revealed a marked decrease in spatial cognition, most pronounced in mice subjected to CBI at high frequency (every 48 h). Functional deficits were correlated to a parallel disruption of the BBB, (R2 = 0.29, p < 0.01), even detectable by a significant increase in hippocampal uptake of [18F]DPA-714, which was not due to activation of microglia, as confirmed immunohistochemically. Featuring a mild but widespread disruption of the BBB without evidence of macroscopic damage, this model induces a characteristic neuro-psychiatric phenotype that correlates to the degree of BBB disruption. Based on these findings, the BBB may function as both a biomarker of CBI severity and as a potential treatment target to improve recovery from concussion.
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| 10. |
- Bussy, Aurélie, et al.
(author)
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Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
- 2023
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 44:7, s. 2684-2700
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Journal article (peer-reviewed)abstract
- Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.
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| 11. |
- Osswald, S., et al.
(author)
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EVIS 2014 : 3rd Workshop on Electric Vehicle Information Systems
- 2014
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In: AutomotiveUI 2014 - 6th International Conference on Automotive User Interfaces and Interactive Vehicular Applications, in Cooperation with ACM SIGCHI - Adjunct Proceedings. - New York, NY, USA : ACM. - 9781450307253 ; , s. 93-98
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Conference paper (peer-reviewed)abstract
- The effort to push the electric vehicle development worldwide is continuously rising. Production sites for electric vehicle components are built, billions are invested to create new battery electric vehicle concepts (BEV) and new players are entering the market. The information systems of electric vehicles (EVIS) need to cope with a variety of new features that are related to changes of vehicle components and driving behavior, but also with changes and new systems that are silently introduced into the vehicles. Sustainability, mobility concepts and smart mobility are just a few points out of many that can be attributed to the "silent" category. With this workshop, we continue to bring together researchers, designers and practitioners to explore the related field and generate a state of the art perspective on EVIS.
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| 12. |
- Schroeter, Elena R., et al.
(author)
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Deep Time Paleoproteomics : Looking Forward
- 2022
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 21:1, s. 9-19
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Research review (peer-reviewed)abstract
- The goal of paleoproteomics is to characterize proteins from specimens that have been subjected to the degrading and obscuring effects of time, thus obtaining biological information about tissues or organisms both unobservable in the present and unobtainable through morphological study. Although the description of sequences from Tyrannosaurus rex and Brachylophosaurus canadensis suggested that proteins may persist over tens of millions of years, the majority of paleoproteomic analyses have focused on historical, archeological, or relatively young paleontological samples that rarely exceed 1 million years in age. However, recent advances in methodology and analyses of diverse tissues types (e.g., fossil eggshell, dental enamel) have begun closing the large window of time that remains unexplored in the fossil history of the Cenozoic. In this perspective, we discuss the history and current state of deep time paleoproteomics (DTPp), here defined as paleoproteomic study of samples ∼1 million years (1 Ma) or more in age. We then discuss the future of DTPp research, including what we see as critical ways the field can expand, advancements in technology that can be utilized, and the types of questions DTPp can address if such a future is realized.
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| 13. |
- Schweitzer, Mary Higby, et al.
(author)
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Paleoproteomics of Mesozoic Dinosaurs and Other Mesozoic Fossils
- 2019
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In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 19:16
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Research review (peer-reviewed)abstract
- Molecular studies have contributed greatly to our understanding of evolutionary processes that act upon virtually every aspect of living organisms. However, these studies are limited with regard to extinct organisms, particularly those from the Mesozoic because fossils pose unique challenges to molecular workflows, and because prevailing wisdom suggests no endogenous molecular components can persist into deep time. Here, the power and potential of a molecular approach to Mesozoic fossils is discussed. Molecular methods that have been applied to Mesozoic fossils—including iconic, non-avian dinosaurs— and the challenges inherent in such analyses, are compared and evaluated. Taphonomic processes resulting in the transition of living organisms from the biosphere into the fossil record are reviewed, and the possible effects of taphonomic alteration on downstream analyses that can be problematic for very old material (e.g., molecular modifications, limitations of on comparative databases) are addressed. Molecular studies applied to ancient remains are placed in historical context, and past and current studies are evaluated with respect to producing phylogenetically and/or evolutionarily significant data. Finally, some criteria for assessing the presence of endogenous biomolecules in very ancient fossil remains are suggested as a starting framework for such studies.
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| 14. |
- Terhal, Paulien A., et al.
(author)
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A Study of the Clinical and Radiological Features in a Cohort of 93 Patients with a COL2A1 Mutation Causing Spondyloepiphyseal Dysplasia Congenita or a Related Phenotype
- 2015
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In: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 167A:3, s. 461-475
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Journal article (peer-reviewed)abstract
- Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that are commonly associated with orthopedic, ocular, and hearing problems. However, the frequency of many clinical features has never been determined. We retrospectively investigated the clinical, radiological, and genotypic data in a group of 93 patients with molecularly confirmed SEDC or a related disorder. The majority of the patients (80/93) had short stature, with radiological features of SEDC (n=64), others having SEMD (n=5), Kniest dysplasia (n=7), spondyloperipheral dysplasia (n=2), or Torrance-like dysplasia (n=2). The remaining 13 patients had normal stature with mild SED, Stickler-like syndrome or multiple epiphyseal dysplasia. Over 50% of the patients had undergone orthopedic surgery, usually for scoliosis, femoral osteotomy or hip replacement. Odontoid hypoplasia was present in 56% (95% CI 38-74) and a correlation between odontoid hypoplasia and short stature was observed. Atlanto-axial instability, was observed in 5 of the 18 patients (28%, 95% CI 10-54) in whom flexion-extension films of the cervical spine were available; however, it was rarely accompanied by myelopathy. Myopia was found in 45% (95% CI 35-56), and retinal detachment had occurred in 12% (95% CI 6-21; median age 14 years; youngest age 3.5 years). Thirty-two patients complained of hearing loss (37%, 95% CI 27-48) of whom 17 required hearing aids. The ophthalmological features and possibly also hearing loss are often relatively frequent and severe in patients with splicing mutations. Based on clinical findings, age at onset and genotype-phenotype correlations in this cohort, we propose guidelines for the management and follow-up in this group of disorders.
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| 15. |
- Ullmann, Paul V., et al.
(author)
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Molecular tests support the viability of rare earth elements as proxies for fossil biomolecule preservation
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- The rare earth element (REE) composition of a fossil bone reflects its chemical alteration during diagenesis. Consequently, fossils presenting low REE concentrations and/or REE profiles indicative of simple diffusion, signifying minimal alteration, have been proposed as ideal candidates for paleomolecular investigation. We directly tested this prediction by conducting multiple biomolecular assays on a well-preserved fibula of the dinosaur Edmontosaurus from the Cretaceous Hell Creek Formation previously found to exhibit low REE concentrations and steeply-declining REE profiles. Gel electrophoresis identified the presence of organic material in this specimen, and subsequent immunofluorescence and enzyme-linked immunosorbant assays identified preservation of epitopes of the structural protein collagen I. Our results thereby support the utility of REE profiles as proxies for soft tissue and biomolecular preservation in fossil bones. Based on considerations of trace element taphonomy, we also draw predictions as to the biomolecular recovery potential of additional REE profile types exhibited by fossil bones.
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| 16. |
- Wolf, S., et al.
(author)
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Ala228 variant of trail receptor 1 affecting the ligand binding site is associated with chronic lymphocytic leukemia, mantle cell lymphoma, prostate cancer, head and neck squamous cell carcinoma and bladder cancer
- 2006
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In: Int J Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 118:7, s. 1831-5
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Journal article (peer-reviewed)abstract
- Allelic loss of chromosome 8p21-22 is a frequent event in various human cancers including mantle cell lymphoma (MCL), prostate cancer, head and neck squamous cell carcinoma (HNSCC) and bladder cancer. The tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptors, including TNFRSF10A and TNFRSF10B, are located within this chromosomal region. Since recent studies demonstrate that chronic lymphocytic leukemia (CLL) and prostate cells are TRAIL induced apoptosis, TRAIL-receptors are strong tumor suppressor candidate genes in human cancers exhibiting loss of chromosomal material in 8p21.3. However, no mutation of the TRAIL receptor genes has been reported in CLL, MCL, prostate cancer, HNSCC so far. In this study we analyzed the complete coding region of TNFRSF10A and TNFRSF10B in a series of 32 MCL and 101 CLL samples and detected a single nucleotide polymorphism (SNP) in TNFRSF10A (A683C) with tumor specific allele distribution. We examined allele distribution in 395 samples of different tumor entities (prostate cancer, n = 43; HNSCC, n = 40; bladder cancer, n = 179) and compared them to 137 samples from healthy probands. We found the rare allele of TNFRSF10A is more frequent in CLL, MCL, prostate cancer, bladder cancer and HNSCC. The A683C polymorphism did not cosegregate with other TNFRSF10A polymorphisms previously described. Thus screening for 683A-->C nucleotide exchanges may become important in diagnosis and/or treatment of these malignancies.
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