The influence of brain iron and myelin on magnetic susceptibility and effective transverse relaxation - A biochemical and histological validation study.

Quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2*) mapping are both highly sensitive to variations in brain iron content. Clinical Magnetic Resonance Imaging (MRI) studies report changes of susceptibilities and relaxation rates in various neurological diseases which are often equated with changes in regional brain iron content. However, these mentioned metrics lack specificity for iron, since they are also influenced by the presence of myelin.

Underlying mechanism of subcortical brain protection during hypoxia and reoxygenation in a sheep model - Influence of α1-adrenergic signalling.

While the cerebral autoregulation sufficiently protects subcortical brain regions during hypoxia or asphyxia, the cerebral cortex is not as adequately protected, which suggests that regulation of the cerebral blood flow (CBF) is area-specific. Hypoxia was induced by inhalation of 5% oxygen, for reoxygenation 100% oxygen was used. Cortical and subcortical CBF (by laser Doppler flowmetry), blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were constantly monitored.

Arginine Methylation by PRMT2 Controls the Functions of the Actin Nucleator Cobl.

The complex architecture of neuronal networks in the brain requires tight control of the actin cytoskeleton. The actin nucleator Cobl is critical for neuronal morphogenesis. Here we reveal that Cobl is controlled by arginine methylation.

Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.

Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (r = 0.

Time course of the response to navigated repetitive transcranial magnetic stimulation at 10 Hz in chronic neuropathic pain.

Objective This prospective study evaluated the time to response and outcomes of navigated repetitive transcranial magnetic stimulation (TMS) at a frequency of 10 Hz in patients with chronic neuropathic pain. Methods This prospective study included patients with unilateral chronic neuropathic pain. All patients received motor cortex stimulation at 10 Hz over nine consecutive days using repetitive TMS.

Long-lived rodents reveal signatures of positive selection in genes associated with lifespan.

The genetics of lifespan determination is poorly understood. Most research has been done on short-lived animals and it is unclear if these insights can be transferred to long-lived mammals like humans. Some African mole-rats (Bathyergidae) have life expectancies that are multiple times higher than similar sized and phylogenetically closely related rodents.

Improving stomach content based death time determination by maximum probability estimation.

Stomach content based death time estimation (SCE), is a well-known technique in forensic sciences. Among more qualitatively oriented approaches the content percentage based method SCE by Tröger, Baur and Spann yields quantitative results and gives stochastic error measures for its outputs. This is possible since the methods estimator, which we call transformed expectation estimator (TEE) as well as the probability distribution of the time between last meal and death are determined numerically, though in SCE the estimator and confidence intervals are presented graphically only.

Detection of HPV16 in Esophageal Cancer in a High-Incidence Region of Malawi.

This study was designed to explore the role of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC). Fifty-five patients receiving diagnostic upper gastrointestinal endoscopy at Zomba Central Hospital or Queen Elizabeth Hospital in Blantyre (Malawi) in 2010, were included in our study. Formalin-fixed paraffin-embedded biopsies were collected for histopathological diagnosis.

Comparison of metabolic adaptations between endurance- and sprint-trained athletes after an exhaustive exercise in two different calf muscles using a multi-slice P-MR spectroscopic sequence.

Measurements of exercise-induced metabolic changes, such as oxygen consumption, carbon dioxide exhalation or lactate concentration, are important indicators for assessing the current performance level of athletes in training science. With exercise-limiting metabolic processes occurring in loaded muscles, P-MRS represents a particularly powerful modality to identify and analyze corresponding training-induced alterations. Against this background, the current study aimed to analyze metabolic adaptations after an exhaustive exercise in two calf muscles (m.

Functional Analyses of RUNX3 and CaMKIINα in Ovarian Cancer Cell Lines Reveal Tumor-Suppressive Functions for CaMKIINα and Dichotomous Roles for RUNX3 Transcript Variants.

(1) Background: Epithelial ovarian cancer (EOC) is the most lethal cancer of the female reproductive system. In an earlier study, we identified multiple genes as hypermethylated in tumors of patients with poor prognosis. The most promising combination of markers to predict a patient's outcome was and .

Fully automatic CT-histogram-based fat estimation in dead bodies.

Post-mortem body cooling is the foundation of temperature-based death time estimations (TDE) in homicide cases. Forensic science generally provides two types of p.m.

Beta HPV38 oncoproteins act with a hit-and-run mechanism in ultraviolet radiation-induced skin carcinogenesis in mice.

Cutaneous beta human papillomavirus (HPV) types are suspected to be involved, together with ultraviolet (UV) radiation, in the development of non-melanoma skin cancer (NMSC). Studies in in vitro and in vivo experimental models have highlighted the transforming properties of beta HPV E6 and E7 oncoproteins. However, epidemiological findings indicate that beta HPV types may be required only at an initial stage of carcinogenesis, and may become dispensable after full establishment of NMSC.

Cobl-like promotes actin filament formation and dendritic branching using only a single WH2 domain.

Local actin filament formation powers the development of the signal-receiving arbor of neurons that underlies neuronal network formation. Yet, little is known about the molecules that drive these processes and may functionally connect them to the transient calcium pulses observed in restricted areas in the forming dendritic arbor. Here we demonstrate that Cordon-Bleu (Cobl)-like, an uncharacterized protein suggested to represent a very distantly related, evolutionary ancestor of the actin nucleator Cobl, despite having only a single G-actin-binding Wiskott-Aldrich syndrome protein Homology 2 (WH2) domain, massively promoted the formation of F-actin-rich membrane ruffles of COS-7 cells and of dendritic branches of neurons.

Deciphering caveolar functions by KO-mediated impairment of caveolar invagination.

Several human diseases are associated with a lack of caveolae. Yet, the functions of caveolae and the molecular mechanisms critical for shaping them still are debated. We show that muscle cells of KO mice show severe reductions of caveolae reminiscent of human caveolinopathies.

Validation of Reference Genes for Expression Studies in Human Meningiomas under Different Experimental Settings.

Quantitative polymerase chain reaction (qPCR) is a sensitive technique for the quantitative analysis of gene expression levels. To compare mRNA transcripts across tumour and non-pathological tissue, appropriate reference genes are required for internal standardisation. Validation of these reference genes in meningiomas has not yet been reported.

Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs.

Background: Prenatal glucocorticoid administration alters the activity of the fetal hypothalamic-pituitary-adrenocortical axis (HPAA), and correspondingly the adenocorticotropic hormone (ACTH) and cortisol levels after birth. The dosages required for these effects are critically discussed. Activation of the HPAA is related to metabolic syndrome and diabetes mellitus.

Assessment of intra- and inter-regional interrelations between GABA+, Glx and BOLD during pain perception in the human brain - A combined H fMRS and fMRI study.

To explore brain activity and the related neurochemical processes, current research focuses increasingly on the combined acquisition of H MR spectra and fMRI data to investigate potential associations between local metabolite resting state levels and stimulus-induced BOLD signal changes. In this study, whole-brain fMRI measurements and localized functional H MEGA-PRESS MRS scans were conducted at 3T in healthy subjects prior to and during acute pain stimulation to quantify resting state GABA+/tCr and Glx/tCr levels in the insular cortex together with their stimulus-induced changes and to explore associations between these neurochemical parameters with intra-regional but also inter-regional BOLD responses. Inter-regionally, a significant negative correlation between the BOLD signal of a cluster in the supplementary motor area with overlap to the mid-cingulate cortex (R = -0.

Viral-Cellular DNA Junctions as Molecular Markers for Assessing Intra-Tumor Heterogeneity in Cervical Cancer and for the Detection of Circulating Tumor DNA.

The development of cervical cancer is frequently accompanied by the integration of human papillomaviruses (HPV) DNA into the host genome. Viral-cellular junction sequences, which arise in consequence, are highly tumor specific. By using these fragments as markers for tumor cell origin, we examined cervical cancer clonality in the context of intra-tumor heterogeneity.

A Simple Procedure for the Evaluation of Bone Vitality by Staining with a Tetrazolium Salt.

Presently, no intra-operative method for a direct assessment of bone vitality exists. Therefore, we set out to test the applicability of tetrazolium-based staining on bone samples. The explanted femoral heads of 37 patients were used to obtain either cancellous bone fragments or bone slices.

How gastrin-releasing peptide receptor (GRPR) and αβ integrin expression reflect reorganization features of tumors after hyperthermia treatments.

The outcome of tumor treatment via hyperthermia in the clinic has been reported to be heterogeneous. Here, we assessed how the presence of gastrin-releasing peptide receptor (GRPR) and αβ integrin together with the morphology of the vascularization reflects the growth behavior of tumors after hyperthermia treatment. MDA-MB-231 tumor bearing mice were treated either with high (46 °C) or low dose (42 °C) water hyperthermia for 60 min.

Influence of hypo- and hyperthermia on death time estimation - A simulation study.

Numerous physiological and pathological mechanisms can cause elevated or lowered body core temperatures. Deviations from the physiological level of about 37°C can influence temperature based death time estimations. However, it has not been investigated by means of thermodynamics, to which extent hypo- and hyperthermia bias death time estimates.

Quantitative susceptibility mapping (QSM) and R in the human brain at 3T: Evaluation of intra-scanner repeatability.

Quantitative susceptibility mapping (QSM) and the effective transverse relaxation rate (R*) can be used to monitor iron and myelin content in brain tissue, which are both subject to changes in many neurological diseases but also during healthy aging. In this study, we quantitatively assessed the repeatability of QSM and R* by applying four independent scans in eight young healthy, female subjects on a 3T MRI scanner. Since QSM does not yield absolute values for bulk magnetic susceptibilities, we additionally investigated the influence of the choice of a reference brain region for susceptibility by computing susceptibility differences with respect to five different brain structures (whole brain, frontal white matter (fWM), internal capsule (IC), cerebrospinal fluid (CSF) in the lateral ventricle, cortical gray matter (cGM)).

Quantification of mitral regurgitation during percutaneous mitral valve repair: added value of simultaneous hemodynamic and 3D echocardiographic assessment.

The objective of this study was to investigate the usefulness of intraprocedural hemodynamic monitoring for MR evaluation during pMRV. Assessment of mitral regurgitation (MR) during percutaneous mitral valve repair (pMVR) procedure is challenging. 3D color Doppler allows exact quantification of MR, but is technically demanding.

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling.

Background: Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage.

Methods: Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry.

Calibration and parameter variation using a finite element model for death time estimation: The influence of the substrate.

The most established method for temperature based death time estimation is based on an empirical double exponential model. New physically based approaches using numerical simulation techniques are subject of current research. A major advantage of such models is the possibility to incorporate non-standard boundary conditions.