Publications by authors named "Lena Schmid"

9 Publications

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Different forms of African cassava mosaic virus capsid protein within plants and virions.

Virology 2019 03 17;529:81-90. Epub 2019 Jan 17.

University of Stuttgart, Institute of Biomaterials and Biomolecular Systems, Department of Molecular Biology and Plant Virology, Pfaffenwaldring 57, 70550 Stuttgart, Germany.

One geminiviral gene encodes the capsid protein (CP), which can appear as several bands after electrophoresis depending on virus and plant. African cassava mosaic virus-Nigeria CP in Nicotiana benthamiana, however, yielded one band (~ 30 kDa) in total protein extracts and purified virions, although its expression in yeast yielded two bands (~ 30, 32 kDa). Mass spectrometry of the complete protein and its tryptic fragments from virions is consistent with a cleaved start M1, acetylated S2, and partial phosphorylation at T12, S25 and S62. Mutants for additional potentially modified sites (N223A; C235A) were fully infectious and formed geminiparticles. Separation in triton acetic acid urea gels confirmed charge changes of the CP between plants and yeast indicating differential phosphorylation. If the CP gene alone was expressed in plants, multiple bands were observed like in yeast. A high turnover rate indicates that post-translational modifications promote CP decay probably via the ubiquitin-triggered proteasomal pathway.
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http://dx.doi.org/10.1016/j.virol.2019.01.018DOI Listing
March 2019

s exerts developmental stage-specific effects in human hematopoiesis.

Haematologica 2018 08 22;103(8):e336-e340. Epub 2018 Mar 22.

Pediatric Hematology and Oncology, Martin-Luther-University Halle-Wittenberg, Halle, Germany

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http://dx.doi.org/10.3324/haematol.2018.191338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068023PMC
August 2018

Dysfunction of Somatostatin-Positive Interneurons Associated with Memory Deficits in an Alzheimer's Disease Model.

Neuron 2016 Oct 15;92(1):114-125. Epub 2016 Sep 15.

Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany. Electronic address:

Alzheimer's disease (AD) is characterized by cognitive decline and neuronal network dysfunction, but the underlying mechanisms remain unknown. In the hippocampus, microcircuit activity during learning and memory processes is tightly controlled by O-LM interneurons. Here, we investigated the effect of beta-amyloidosis on O-LM interneuron structural and functional connectivity, combining two-photon in vivo imaging of synaptic morphology, awake Ca imaging, and retrograde mono-transsynaptic rabies tracing. We find severely impaired synaptic rewiring that occurs on the O-LM interneuron input and output level in a mouse model of AD. Synaptic rewiring that occurs upon fear learning on O-LM interneuron input level is affected in mice with AD-like pathology. This process requires the release of acetylcholine from septo-hippocampal projections. We identify decreased cholinergic action on O-LM interneurons in APP/PS1 mice as a key pathomechanism that contributes to memory impairment in a mouse model, with potential relevance for human AD.
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http://dx.doi.org/10.1016/j.neuron.2016.08.034DOI Listing
October 2016

Association of cortical thickness and neurological soft signs in patients with chronic schizophrenia and healthy controls.

Neuropsychobiology 2015 7;71(4):225-33. Epub 2015 Aug 7.

College of Education, Shanghai Normal University, Shanghai, China.

Background: Neurological soft signs (NSS), i.e. subtle neurological abnormalities, have been frequently found in schizophrenia. Neuroimaging studies in schizophrenia have shown abnormal cortical thickness changes across the cortical mantle. However, few studies have examined relationships between NSS and cortical thickness abnormalities in schizophrenia.

Method: A sample of 18 patients with chronic schizophrenia and 20 age-matched healthy controls were included. Cortical thickness was assessed on high-resolution 3-tesla magnetic resonance imaging by using FreeSurfer software and NSS were rated on the Heidelberg Scale.

Results: Significant negative correlations between NSS and cortical thickness were found in the prefrontal, inferior temporal, superior parietal, postcentral, and supramarginal cortices in the schizophrenia patients. In the controls, however, this negative correlation was found in the anterior cingulate, pericalcarine and superior/middle temporal regions.

Conclusion: Our results not only confirmed the association between NSS and cortical thickness in chronic schizophrenia but also indicated that patients and controls have different anatomical substrates of NSS.
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http://dx.doi.org/10.1159/000382020DOI Listing
May 2016

Neuropsychology, autobiographical memory, and hippocampal volume in "younger" and "older" patients with chronic schizophrenia.

Front Psychiatry 2015 21;6:53. Epub 2015 Apr 21.

Section of Geriatric Psychiatry, Department of General Psychiatry, University of Heidelberg , Heidelberg , Germany ; Institute of Gerontology, University of Heidelberg , Heidelberg , Germany.

Despite a wide range of studies on neuropsychology in schizophrenia, autobiographical memory (AM) has been scarcely investigated in these patients. Hence, less is known about AM in older patients and hippocampal contribution to autobiographical memories of varying remoteness. Therefore, we investigated hippocampal volume and AM along with important neuropsychological domains in patients with chronic schizophrenia and the respective relationships between these parameters. We compared 25 older patients with chronic schizophrenia to 23 younger patients and an older healthy control group (N = 21) with respect to AM, additional neuropsychological parameters, and hippocampal volume. Personal episodic and semantic memory was investigated using a semi-structured interview. Additional neuropsychological parameters were assessed by using a battery of standard neuropsychological tests. Structural magnetic resonance imaging data were analyzed with an automated region-of-interest procedure. While hippocampal volume reduction and neuropsychological impairment were more pronounced in the older than in the younger patients, both groups showed equivalent reduced AM performance for recent personal episodes. In the patient group, significant correlations between left hippocampal volume and recent autobiographical episodes as well as personal semantic memories arose. Verbal memory and working memory were significantly correlated with right hippocampal volume; executive functions, however, were associated with bilateral hippocampal volumes. These findings underline the complexity of AM and its impairments in the course of schizophrenia in comparison to rather progressive neuropsychological deficits and address the importance of hippocampal contribution.
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http://dx.doi.org/10.3389/fpsyt.2015.00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404739PMC
May 2015

Comparison of grey matter volume and thickness for analysing cortical changes in chronic schizophrenia: a matter of surface area, grey/white matter intensity contrast, and curvature.

Psychiatry Res 2015 Feb 22;231(2):176-83. Epub 2014 Dec 22.

Section of Geriatric Psychiatry, Department of Psychiatry, University of Heidelberg, Germany; Institute of Gerontology, University of Heidelberg, Germany. Electronic address:

Grey matter volume and cortical thickness are the two most widely used measures for detecting grey matter morphometric changes in various diseases such as schizophrenia. However, these two measures only share partial overlapping regions in identifying morphometric changes. Few studies have investigated the contributions of the potential factors to the differences of grey matter volume and cortical thickness. To investigate this question, 3T magnetic resonance images from 22 patients with schizophrenia and 20 well-matched healthy controls were chosen for analyses. Grey matter volume and cortical thickness were measured by VBM and Freesurfer. Grey matter volume results were then rendered onto the surface template of Freesurfer to compare the differences from cortical thickness in anatomical locations. Discrepancy regions of the grey matter volume and thickness where grey matter volume significantly decreased but without corresponding evidence of cortical thinning involved the rostral middle frontal, precentral, lateral occipital and superior frontal gyri. Subsequent region-of-interest analysis demonstrated that changes in surface area, grey/white matter intensity contrast and curvature accounted for the discrepancies. Our results suggest that the differences between grey matter volume and thickness could be jointly driven by surface area, grey/white matter intensity contrast and curvature.
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http://dx.doi.org/10.1016/j.pscychresns.2014.12.004DOI Listing
February 2015

Long-term in vivo imaging of dendritic spines in the hippocampus reveals structural plasticity.

J Neurosci 2014 Oct;34(42):13948-53

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

Hippocampal function is important for learning and memory. During memory processing, hippocampal CA1 neurons play a crucial role by integrating excitatory synaptic input from CA3 and the entorhinal cortex. These neurons receive excitatory input almost exclusively on dendritic spines. The formation and elimination--structural plasticity--of dendritic spines reflect wiring changes within the hippocampal network. Despite the relevance of the hippocampus in learning and memory, most in vivo data on structural plasticity derive from cortical regions. We established a chronic hippocampal window approach using two-photon microscopy to visualize dendritic spines throughout all CA1 hippocampal layers and over a time course of weeks. Moreover, even granule cells in dentate gyrus could be reliably detected. We found that the spine density in stratum radiatum (∼1.1 per micrometer) remained stable over weeks. However, a small fraction (3.4%) of spines were formed and eliminated between imaging sessions, which demonstrated that spines of CA1 neurons exhibit structural plasticity in adult mice. In addition, we tested for possible inflammatory or behavioral side effects of hippocampal window implantation. Mice exhibited a transient increase in microgliosis and astrogliosis, which declined within a few weeks. We did not detect any difference in behavioral performance in an open-field and contextual fear-conditioning paradigm. In conclusion, hippocampal long-term two-photon imaging revealed structural plasticity of dendritic spines in CA1 pyramidal neurons. This approach may provide a powerful tool to analyze changes in neuronal network rewiring during hippocampal learning and memory processes in health and disease.
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http://dx.doi.org/10.1523/JNEUROSCI.1464-14.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705298PMC
October 2014

Hippocampal volume reduction and autobiographical memory deficits in chronic schizophrenia.

Psychiatry Res 2013 Mar 14;211(3):189-94. Epub 2012 Nov 14.

Section of Geriatric Psychiatry, University of Heidelberg, Voßstr. 4, 69115 Heidelberg, Germany.

Although autobiographical memory (AM) deficits and hippocampal changes are frequently found in schizophrenia, their actual association remained yet to be established. AM performance and hippocampal volume were examined in 33 older, chronic schizophrenic patients and 21 healthy volunteers matched for age, gender and education. Psychopathological symptoms and additional neuropsychological parameters were assessed by using appropriate rating scales; magnetic resonance imaging (MRI) 3-T data were analyzed via an automated region-of-interest procedure. When compared with the control subjects, patients showed significantly decreased left anterior and posterior hippocampal volumes. Episodic but not semantic AM performance was significantly lower in the patients than in the healthy controls. Both episodic and semantic AM deficits were significantly correlated with volume of the left hippocampus in the patient group. In contrast, deficits in verbal memory, working memory and remote semantic memory observed in the patients did not relate to hippocampal volume. Our findings indicate that AM deficits in chronic schizophrenia are associated with hippocampal volume reductions and underline the importance of this pathology in schizophrenia.
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http://dx.doi.org/10.1016/j.pscychresns.2012.04.002DOI Listing
March 2013

Reduced gray to white matter tissue intensity contrast in schizophrenia.

PLoS One 2012 15;7(5):e37016. Epub 2012 May 15.

Structural Neuroimaging Group, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany.

Background: While numerous structural magnetic resonance imaging (MRI) studies revealed changes of brain volume or density, cortical thickness and fibre integrity in schizophrenia, the effect of tissue alterations on the contrast properties of neural structures has so far remained mostly unexplored.

Methods: Whole brain high-resolution MRI at 3 Tesla was used to investigate tissue contrast and cortical thickness in patients with schizophrenia and healthy controls.

Results: Patients showed significantly decreased gray to white matter contrast in large portions throughout the cortical mantle with preponderance in inferior, middle, superior and medial temporal areas as well as in lateral and medial frontal regions. The extent of these intensity contrast changes exceeded the extent of cortical thinning. Further, contrast changes remained significant after controlling for cortical thickness measurements.

Conclusions: Our findings clearly emphasize the presence of schizophrenia related brain tissue changes that alter the imaging properties of brain structures. Intensity contrast measurements might not only serve as a highly sensitive metric but also as a potential indicator of a distinct pathological process that might be independent from volume or thickness alterations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037016PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352852PMC
January 2013