PubMed | University of SussexBrighton, Universitatsklinikum Hamburg Eppendorf Hamburg, University of Nottingham, French Institute of Health and Medical Research and 10 more.
Type: | Journal: Frontiers in genetics | Year: 2016
Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behavior in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI) mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioral data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org), to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of < 0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologs of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol experience. There was a significant overall association between the human homologs of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS) during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major) of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor) of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking.
PubMed | University of Barcelona, Universitatsklinikum Hamburg Eppendorf Hamburg, University of Marburg, Paracelsus Medical University and 9 more.
Type: Journal Article | Journal: Annals of clinical and translational neurology | Year: 2014
To retrospectively determine the frequency of N-Methyl-D-Aspartate (NMDA) receptor (NMDAR) autoantibodies in patients with different forms of dementia.Clinical characterization of 660 patients with dementia, neurodegenerative disease without dementia, other neurological disorders and age-matched healthy controls combined with retrospective analysis of serum or cerebrospinal fluid (CSF) for the presence of NMDAR antibodies. Antibody binding to receptor mutants and the effect of immunotherapy were determined in a subgroup of patients.Serum NMDAR antibodies of IgM, IgA, or IgG subtypes were detected in 16.1% of 286 dementia patients (9.5% IgM, 4.9% IgA, and 1.7% IgG) and in 2.8% of 217 cognitively healthy controls (1.9% IgM and 0.9% IgA). Antibodies were rarely found in CSF. The highest prevalence of serum antibodies was detected in patients with unclassified dementia followed by progressive supranuclear palsy, corticobasal syndrome, Parkinsons disease-related dementia, and primary progressive aphasia. Among the unclassified dementia group, 60% of 20 patients had NMDAR antibodies, accompanied by higher frequency of CSF abnormalities, and subacute or fluctuating disease progression. Immunotherapy in selected prospective cases resulted in clinical stabilization, loss of antibodies, and improvement of functional imaging parameters. Epitope mapping showed varied determinants in patients with NMDAR IgA-associated cognitive decline.Serum IgA/IgM NMDAR antibodies occur in a significant number of patients with dementia. Whether these antibodies result from or contribute to the neurodegenerative disorder remains unknown, but our findings reveal a subgroup of patients with high antibody levels who can potentially benefit from immunotherapy.
PubMed | Institute fur Medizinische Diagnostik GmbH Ingelheim and Universitatsklinikum Hamburg Eppendorf Hamburg
Type: | Journal: Frontiers in cellular and infection microbiology | Year: 2015
Staphylococcus epidermidis is a usually harmless commensal bacterium highly abundant on the human skin. Under defined predisposing conditions, most importantly implantation of a medical device, S. epidermidis, however, can switch from a colonizing to an invasive life style. The emergence of S. epidermidis as an opportunistic pathogen is closely linked to the biofilm forming capability of the species. During the past decades, tremendous advance regarding our understanding of molecular mechanisms contributing to surface colonization has been made, and detailed information is available for several factors active during the primary attachment, accumulative or dispersal phase of biofilm formation. A picture evolved in which distinct factors, though appearing to be redundantly organized, take over specific and exclusive functions during biofilm development. In this review, these mechanisms are described in molecular detail, with a highlight on recent insights into multi-functional S. epidermidis cell surface proteins contributing to surface adherence and intercellular adhesion. The integration of distinct biofilm-promoting factors into regulatory networks is summarized, with an emphasis on mechanism that could allow S. epidermidis to flexibly adapt to changing environmental conditions present during colonizing or invasive life-styles.
Budnik L.T.,Universitatsklinikum Hamburg Eppendorf Hamburg |
Fahrenholtz S.,Universitatsklinikum Hamburg Eppendorf Hamburg |
Kloth S.,Universitatsklinikum Hamburg Eppendorf Hamburg |
Baur X.,Universitatsklinikum Hamburg Eppendorf Hamburg
Zentralblatt fur Arbeitsmedizin, Arbeitsschutz und Ergonomie | Year: 2011
Fumigates can enter the products and evaporate (off gassing) during unloading and storage. The major unanswered question is: Can we port, transport and warehouse workers pose health hazards due to the product emissions? Evidence suggests that import products can off gas fumigants and other toxic industrial chemicals. Spot samples in warehouses were taken to provide information about the art of possible contamination.
PubMed | Universitatsklinikum Hamburg Eppendorf Hamburg
Type: | Journal: Frontiers in aging neuroscience | Year: 2010
Healthy aging is accompanied by changes in cognitive and motor functions that result in impairment of activities of daily living. This process involves a number of modifications in the brain and is associated with metabolic, structural, and physiological changes; some of these serving as adaptive responses to the functional declines. Up to date there are no universally accepted strategies to ameliorate declining functions in this population. An essential basis to develop such strategies is a better understanding of neuroplastic changes during healthy aging. In this context, non-invasive brain stimulation techniques, such as transcranial direct current or transcranial magnetic stimulation, provide an attractive option to modulate cortical neuronal assemblies, even with subsequent changes in neuroplasticity. Thus, in the present review we discuss the use of these techniques as a tool to study underlying cortical mechanisms during healthy aging and as an interventional strategy to enhance declining functions and learning abilities in aged subjects.
PubMed | Universitatsklinikum Hamburg Eppendorf Hamburg
Type: | Journal: Frontiers in pharmacology | Year: 2012
In voltage-gated potassium (Kv) channels membrane depolarization causes movement of a voltage sensor domain. This conformational change of the protein is transmitted to the pore domain and eventually leads to pore opening. However, the voltage sensor domain may interact with two distinct gates in the pore domain: the activation gate (A-gate), involving the cytoplasmic S6 bundle crossing, and the pore gate (P-gate), located externally in the selectivity filter. How the voltage sensor moves and how tightly it interacts with these two gates on its way to adopt a relaxed conformation when the membrane is depolarized may critically determine the mode of Kv channel inactivation. In certain Kv channels, voltage sensor movement leads to a tight interaction with the P-gate, which may cause conformational changes that render the selectivity filter non-conductive (P/C-type inactivation). Other Kv channels may preferably undergo inactivation from pre-open closed-states during voltage sensor movement, because the voltage sensor temporarily uncouples from the A-gate. For this behavior, known as preferential closed-state inactivation, we introduce the term A/C-type inactivation. Mechanistically, P/C- and A/C-type inactivation represent two forms of voltage sensor inactivation.