Time filter

Source Type

Frederiksberg, Denmark

Gerhard D.,Leibniz University of Hanover | Bremer M.,Leibniz University of Hanover | Ritz C.,Exercise and Sports

A unified modeling framework based on a set of nonlinear mixed models is proposed for flexible modeling of gene expression in real-time PCR experiments. Focus is on estimating the marginal or population-based derived parameters: cycle thresholds and ΔΔc(t), but retaining the conditional mixed model structure to adequately reflect the experimental design. Additionally, the calculation of model-average estimates allows incorporation of the model selection uncertainty. The methodology is applied for estimating the differential expression of a phosphate transporter gene OsPT6 in rice in comparison to a reference gene at several states after phosphate resupply. In a small simulation study the performance of the proposed method is evaluated and compared to a standard method. © 2013, The International Biometric Society. Source

Taube W.,University of Fribourg | Leukel C.,University of Fribourg | Leukel C.,Albert Ludwigs University of Freiburg | Nielsen J.B.,Exercise and Sports | And 3 more authors.
Cerebral Cortex

Low-frequency rTMS applied to the primary motor cortex (M1) may produce depression of motor-evoked potentials (MEPs). This depression is commonly assumed to reflect changes in cortical circuits. However, little is known about rTMS-induced effects on subcortical circuits. Therefore, the present study aimed to clarify whether rTMS influences corticospinal transmission by altering the efficiency of corticomotoneuronal (CM) synapses. The corticospinal transmission to soleus α-motoneurons was evaluated through conditioning of the soleus H-reflex by magnetic stimulation of either M1 (M1-conditioning) or the cervicomedullary junction (CMS-conditioning). The first facilitation of the H-reflex (early facilitation) was determined after M1- and CMS-conditioning. Comparison of the early facilitation before and after 20-min low-frequency (1 Hz) rTMS revealed suppression with M1- (-17 ± 4%; P = 0.001) and CMS-conditioning (-6 ± 2%; P = 0.04). The same rTMS protocol caused a significant depression of compound MEPs, whereas amplitudes of H-reflex and M-wave remained unaffected, indicating a steady level of motoneuronal excitability. Thus, the effects of rTMS are likely to occur at a premotoneuronal site - either at M1 and/or the CM synapse. As the early facilitation reflects activation of direct CM projections, the most likely site of action is the synapse of the CM neurons onto spinal motoneurons. © 2014 The Author. Published by Oxford University Press. Source

Pontoppidan P.L.,Exercise and Sports | Shen R.L.,Exercise and Sports | Petersen B.L.,Roskilde Hospital | Thymann T.,Exercise and Sports | And 4 more authors.
Experimental Biology and Medicine

Chemotherapy-induced myeloablation prior to allogeneic hematopoietic stem cell transplantation (HSCT) may be associated with severe toxicity. The current understanding of the pathophysiology of oral and gastrointestinal (GI) toxicity is largely derived from studies in rodents and very little is known from humans, especially children. We hypothesized that milk-fed piglets can be used as a clinically relevant model of GI-toxicity related to a standard conditioning chemotherapy (intravenous busulfan, Bu plus cyclophosphamide, Cy) used prior to HSCT. In study 1, dose-response relationships were investigated in three-day-old pigs (Landrace × Yorkshire × Duroc, n = 6). Pigs were given one of three different dose combinations of Bu and Cy (A: 4 days Bu, 2 × 1.6 mg/kg plus 2 days Cy, 60 mg/kg; B: 4 days Bu, 2 × 0.8 mg/kg plus 2 days Cy, 30 mg/kg; C: 2 days Bu at 2 × 1.6 mg/kg plus 1 day Cy, 60 mg/kg) and bone marrow was collected on day 11. Histology of bone marrow samples showed total aplasia after treatment A. Using this treatment in study 2, Bu-Cy pigs showed lowered spleen and intestinal weights and variable clinical signs of dehydration, sepsis, and pneumonia at tissue collection. Oral mucositis was evident as ulcers in the soft palate in 4/9 Bu-Cy pigs and villus height and brush-border enzyme activities were reduced, especially in the proximal intestine. There were no consistent effects on tissue cytokine levels (IL-8, IL-6, IL-1β, TNF-α) or blood chemistry values (electrolytes, liver transaminases, bilirubin, alkaline phosphatase), except that blood iron levels were higher in Bu-Cy pigs. We conclude that a myeloablative Bu-Cy regimen to piglets results in clinical signs comparable to those seen in pediatric patients subjected to myeloablative treatment prior to HSCT. Piglets may be used as a model for investigating chemotherapy-induced toxicity and dietary and medical interventions. © 2013 by the Society for Experimental Biology and Medicine. Source

Discover hidden collaborations