Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1

XRCC1 protein is required for the repair of DNA single-strand breaks and genetic stability, and is essential for viability in mammals. XRCC1 functions as a scaffold protein by interacting and modulating polypeptide components of the single-strand break repair machinery, including AP endonuclease-1, DNA ligase IIIα, poly (ADP-ribose) polymerase, DNA polymerase β and human polynucleotide kinase. We show here that the E6 protein of human papillomavirus type 1, 8 and 16 directly binds XRCC1. When tested in CHO derived XRCC1 ‘knock out’ EM9 cells, co-expression of human papillomavirus 16 E6 with human XRCC1 reduced the ability of the latter protein to correct the methyl methane sulfate sensitivity of XRCC1 mutant CHO cell line EM9. These data identify a novel link between small DNA tumour viruses and DNA repair pathways, and suggest a novel explanation for the development of genomic instability in tissue cells persistently infected with papillomaviruses

Brain activation in frontotemporal and Alzheimer's dementia: a functional near-infrared spectroscopy study

BACKGROUND: Frontotemporal dementia is an increasingly studied disease, the underlying functional impairments on a neurobiological level of which have not been fully understood. Patients with the behavioral-subtype frontotemporal dementia (bvFTD) are particularly challenging for clinical measurements such as functional imaging due to their behavioral symptoms. Here, an alternative imaging method, functional near-infrared spectroscopy (fNIRS), is introduced to measure task-related cortical brain activation based on blood oxygenation. The current study investigated differences in cortical activation patterns of patients with bvFTD, Alzheimer’s dementia (AD), and healthy elderly subjects measured by fNIRS. METHOD: Eight probable bvFTD patients completed the semantic, phonological, and control conditions of a verbal fluency task. Eight AD patients and eight healthy controls were compared on the same task. Simultaneously, an fNIRS measurement was conducted and analyzed using a correction method based on the expected negative correlation between oxygenated and deoxygenated hemoglobin. RESULTS: Healthy controls show an increase in cortical activation measured in frontoparietal areas such as the dorsolateral prefrontal cortex. The activation pattern of patients with AD is similar, but weaker. In contrast, bvFTD patients show a more frontopolar pattern, with activation of Broca’s area, instead of the dorsolateral prefrontal cortex and the superior temporal gyrus. The frontoparietal compensation mechanisms, seen in the healthy elderly, were missing in bvFTD patients. CONCLUSION: Different frontoparietal cortical activation patterns may indicate a correlate of diverse pathophysiological mechanisms of AD and bvFTD during verbal fluency processing. The AD pattern is weaker and more similar to the healthy pattern, whereas the bvFTD pattern is qualitatively different, namely more frontopolar and without frontoparietal compensation activation. It adheres to a change of cortical activation during the course of the disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-016-0224-8) contains supplementary material, which is available to authorized users

Additional file 2: of Brain activation in frontotemporal and Alzheimer’s dementia: a functional near-infrared spectroscopy study

Statistical source data for Fig. 3. Contrast of two groups each concerning the contrast of phonematic condition, semantic condition, and the control condition; grey background signifies significant contrasts. AD Alzheimer’s dementia, bvFTD behavioral variant of frontotemporal dementia, CAT category (semantic) condition, HC healthy controls, LET letter (phonematic) condition, WD weekday (control) condition. (XLSX 13 kb

Additional file 1: of Brain activation in frontotemporal and Alzheimer’s dementia: a functional near-infrared spectroscopy study

Statistical source data for Fig. 2. Contrast of phonematic condition, semantic condition, and the control condition in the three groups; grey background signifies significant contrasts. AD Alzheimer’s dementia, bvFTD behavioral variant of frontotemporal dementia, CAT category (semantic) condition, HC healthy controls, LET letter (phonematic) condition, WD weekday (control) condition. (XLSX 13 kb

Insights from a laboratory and naturalistic investigation on stress, rumination and frontal brain functioning in MDD: An fNIRS study

Recent research has emphasized rumination as an important maintaining factor in various mental disorders. However, operationalization and therefore induction of rumination in experimental settings poses a major challenge in terms of ecological validity. As stress seems to play a key role in everyday situations eliciting rumination, we conducted two stress paradigms while assessing behavioral and neurophysiological measures. Aiming to replicate previous findings on induced rumination by means of the Trier Social Stress Test (TSST) and comparing them to physiological (pain) stress, a clinical sample of patients with Major Depressive Disorder (MDD; n = 22) and healthy controls (HC; n = 23) was recruited. Cortical blood oxygenation was assessed during the stress paradigms using functional near-infrared spectroscopy (fNIRS). Further, we used ecological momentary assessment (EMA) of stress, rumination and mood to be able to correlate ruminative responses during induced stress and everyday rumination. Our results showed that social stress but not physiological stress induced depressive rumination in MDD but not in HC. Further, rumination reactivity in response to social stress but not to physiological stress was significantly associated with rumination reactivity in everyday life as assessed with EMA. With respect to cortical oxygenation, MDD subjects showed hypoactivity in the Cognitive Control Network during the TSST, which mediated the differences between MDD and HC in post-stress rumination. Our findings emphasize the role of negative social triggers in depressive rumination and validate the TSST as an induction method for depressive rumination. The results inform future developments in psychotherapeutic treatment for depressive rumination