Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

Introduction

Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson''s disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1).

Materials and Methods

IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated.

Results

PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters.

Discussion

Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders.     

Über Duplicitas anterior,posterior und posterior,partim cruciata bei Triton

Ohne Zusammenfassung     

Imaging gene expression in regional brain ischemia in vivo with a targeted [111in]-antisense radiopharmaceutical

The gene encoding glial fibrillary acidic protein (GFAP) is downregulated 24 hr after reversible brain ischemia, such as with a middle cerebral artery occlusion (MCAO). The in vivo imaging of decreased GFAP gene expression in cerebral ischemia was examined in the present studies using a targeted peptide nucleic acid (PNA), which was labeled with (111)In, and which hybridized to nucleotides 20-37 of the rat GFAP mRNA. The PNA was monobiotinylated, and was attached to a monoclonal antibody (MAb) to the transferrin receptor (TfR) via a biotin-streptavidin linkage. The TfR MAb enables trans-membrane transport of the PNA antisense radiopharmaceutical from blood to the cytosol of brain cells. The decreased GFAP gene expression at 24 hr after a 1-hr reversible MCAO was confirmed by immunocytochemistry. The [(111)In]-labeled PNA - MAb conjugate was administered intravenously to anesthetized rats at 24 hr after the 1-hr reversible MCAO, and the brain uptake of the targeted antisense imaging agent was decreased relative to brain regions outside of the infarct zone. These studies provide evidence that decreased expression of a target gene in brain can be imaged in vivo with a sequence-specific PNA, provided the antisense radiopharmaceutical is delivered across cell membranes with a receptor-specific targeting agent.     

Evolution under pH stress and high population densities leads to increased density-dependent fitness in the protist Tetrahymena thermophila

Abiotic stress is a major force of selection that organisms are constantly facing. While the evolutionary effects of various stressors have been broadly studied, it is only more recently that the relevance of interactions between evolution and underlying ecological conditions, that is, eco-evolutionary feedbacks, have been highlighted. Here, we experimentally investigated how populations adapt to pH-stress under high population densities. Using the protist species Tetrahymena thermophila, we studied how four different genotypes evolved in response to stressfully low pH conditions and high population densities. We found that genotypes underwent evolutionary changes, some shifting up and others shifting down their intrinsic rates of increase (r₀). Overall, evolution at low pH led to the convergence of r₀ and intraspecific competitive ability (α) across the four genotypes. Given the strong correlation between r₀ and α, we argue that this convergence was a consequence of selection for increased density-dependent fitness at low pH under the experienced high density conditions. Increased density-dependent fitness was either attained through increase in r₀, or decrease of α, depending on the genetic background. In conclusion, we show that demography can influence the direction of evolution under abiotic stress.     

Gustatory perception and metabolic utilization of sugars by<Emphasis Type="Italic"> Myrmica rubra</Emphasis> ant workers

The suitability of various nectar and honeydew sugars as a food source for the polyphagous ant species M. rubra (L.) was studied. The sugars used included monosaccharides (fructose, glucose, galactose, mannose, rhamnose), disaccharides (sucrose, maltose, trehalose, melibiose, lactose) and trisaccharides (melizitose, raffinose, erlose). Single-sugar solutions were tested on ant workers in a long-term laboratory bioassay in which acceptance of the solutions and ant survival were recorded. The acceptance of the sugars was confirmed in a second bioassay in which feeding time was established. Enzymatic hydrolysis of sucrose, maltose and melibiose was investigated through HPLC analyses of workers fed these disaccharides. Sugar acceptance and feeding time were related to ant survival. Considering the monosaccharide units of which the sugars are composed, fructose seems especially suitable as a short-term energy source, while glucose appears to be used both directly and for storage. The presence of a galactose unit appears to reduce sugar suitability. It is suggested that the workers possess invertase and maltase and to a lesser degree also galactosidase. The gustatory perception is correlated with the profitability of sugars in further metabolic processes.     

Sequentially Deposited versus Conventional Nonfullerene Organic Solar Cells: Interfacial Trap States,Vertical Stratification,and Exciton Dissociation

Bulk heterojunction (BHJ) nonfullerene organic solar cells prepared from sequentially deposited donor and acceptor layers (sq‐BHJ) have recently been shown to be highly efficient, environmentally friendly, and compatible with large area and roll‐to‐roll fabrication. However, the related photophysics at donor‐acceptor interface and the vertical heterogeneity of donor‐acceptor distribution, critical for exciton dissociation and device performance, have been largely unexplored. Herein, steady‐state and time‐resolved optical and electrical techniques are employed to characterize the interfacial trap states. Correlating with the luminescent efficiency of interfacial states and its nonradiative recombination, interfacial trap states are characterized to be about 40% more populated in the sq‐BHJ devices than the as‐cast BHJ (c‐BHJ), which probably limits the device voltage output. Cross‐sectional energy‐dispersive X‐ray spectroscopy and ultraviolet photoemission spectroscopy depth profiling directly visualize the donor–acceptor vertical stratification with a precision of 1–2 nm. From the proposed “needle” model, the high exciton dissociation efficiency is rationalized. This study highlights the promise of sequential deposition to fabricate efficient solar cells, and points toward improving the voltage output and overall device performance via eliminating interfacial trap states.     

Predation on snakes of Argentina: Effects of coloration and ring pattern on coral and false coral snakes

The occurrence of coral snake coloration among unrelated venomous and non‐venomous snake species has often been explained in terms of warning coloration and mimicry. In Argentina, no field tests have been conducted to confirm this mimetic association between one venomous coral species (Micrurus phyrrocryptus, Elapidae) and two non‐venomous snake species with a similar color pattern (Lystrophis pulcher and Oxyrhopus rhombifer, Colubridae). The aims of this work were to test for the possible aposematic or cryptic function of the ring pattern and coloration of coral snakes and false coral snakes from central Argentina, and to analyse whether the pattern is effective throughout the year. Predation on snakes was estimated by using non‐toxic plasticine replicas of ringed venomous and non‐venomous snakes and unbanded green snakes placed along transects in their natural habitat during the dry and rainy season. Ringed color pattern was attacked by predators despite the background color. One of the replica types was attacked more than expected during the dry season, suggesting that both shape and width of rings may influence the choice by predators. The reaction of predators towards replicas that mimic snake species with ringed patterns is independent of the geographical region, and we can conclude that mimicry characteristics are quite general when the true models are present in the area.     

Size matters in quantitative radar monitoring of animal migration: estimating monitored volume from wingbeat frequency

Quantitative radar studies are an important component of studying the movements of birds. Whether a bird, at a certain distance from the radar, is detected or not depends on its size. The volume monitored by the radar is therefore different for birds of different sizes. Consequently, an accurate quantification of bird movements recorded by small‐scale radar requires an accurate determination of the monitored volume for the objects in question, although this has tended to be ignored. Here, we demonstrate the importance of sensitivity settings for echo detection on the estimated movement intensities of birds of different sizes. The amount of energy reflected from a bird and detected by the radar receiver (echo power) depends not only on the bird's size and on the distance from the radar antenna, but also on the beam shape and the bird's position within this beam. We propose a method to estimate the size of a bird based on the wingbeat frequency, retrieved from the echo‐signal, independent of the absolute echo power. The estimated bird‐size allows calculation of size‐specific monitored volumes, allowing accurate quantification of movement intensities. We further investigate the importance of applying size‐specific monitored volumes to quantify avian movements instead of using echo counts. We also highlight the importance of accounting for size‐specific monitored volume of small scale radar systems, and the necessity of reporting technical information on radar parameters. Applying this framework will increase the quality and validity of quantitative radar monitoring.     

Effects of angiotensin II and its selective antagonists on inferior olivary neurones.

On the basis of biochemical and autoradiographic studies it has been shown that the inferior olivary nucleus (ION) contains predominantly angiotensin II (Ang II) receptors of the subtype 2 (AT2). In the present investigation we used microiontophoretic techniques to test the effect of Ang II on the spontaneous firing rate of rat neurones in the ION in vivo. Ang II excited the majority of histologically identified ION neurones. Furthermore, the antagonism of this angiotensin-induced excitation by selective angiotensin receptor blockers of subtype 1 and 2 (AT1 and AT2) was examined. The excitation could be blocked by low doses of the AT2-antagonists PD 123177 and CGP 42112A, whereas the AT1-antagonist DuP 753 was ineffective even at high doses. On a few occasions, however, ejection of the AT1-antagonist resulted in a potentiation of angiotensin-induced excitation. The results suggest that Ang II has an excitatory effect on a considerable number of ION neurones and that this effect is mediated by AT2-receptors.