The fatal neurological disorder Alzheimer's disease has been linked to soluble neurotoxic oligomers of amyloid-β (Aβ) peptides. Herein we demonstrate that Cu(1+) ligated within Aβ(42) oligomers (Aβ ...sequence: DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA) possesses a highly dioxygen sensitive tetrahedral coordination geometry. The biological implications of these findings are discussed.
Complement is implicated in the pathogenesis of inflammatory disorders of the central nervous system (CNS), like multiple sclerosis, Alzheimer's disease, and trauma. The anaphylatoxins C3a and C5a ...are thought to be the major contributors to complement-mediated inflammation in the CNS, likely mediating their effects via their ability to attract and activate leukocytes and common capacity to augment inflammation. For example, in experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis, CNS-specific expression of C3a in C3a/GFAP transgenic mice renders them prone to massive cellular infiltration of the CNS and increases their mortality. In contrast, other studies have suggested that C3a can function in an anti-inflammatory fashion in the CNS, by inducing neurotrophin production and preventing NMDA-mediated neurotoxicity. To further investigate the seemingly paradoxical role of C3a in acute inflammation of the brain, we studied the pathogenesis of endotoxin shock in C3a/GFAP transgenic, C3a receptor-deficient (C3aR
−/−) and C3a/GFAP
×
C3aR
−/− mutant mice. Here we report that C3a/GFAP mice were significantly more resistant to endotoxin-induced lethality than wild-type and C3aR
−/− mice. Surprisingly, C3a/GFAP
×
C3aR
−/− hybrids were also significantly protected, indicating that C3a exerts its protective anti-inflammatory effect either directly or via an as yet unidentified non-canonical C3aR.
The presence and fate of pharmaceutically active compounds (PhACs) in agricultural fields are rarely investigated. The present study highlights that root-derived low-molecular-weight organic acids ...(LMWOAs) affect the mobility of PhACs in cultivated humic Arenosol. Sorption experiments are conducted using three PhACs characterised by different physicochemical properties: carbamazepine (CBZ), 17α-ethinylestradiol (EE2), and diclofenac-sodium (DFC). The results suggest that the adsorption of EE2 is more intense than the other two PhACs, whereas DFC and CBZ are primarily dominated by desorption. LMWOAs mainly provide additional low-energy adsorption sites for the PhACs, and slight pH changes do not significantly affect the sorption mechanism. During competitive adsorption, the high-energy sites of the adsorbents are initially occupied by EE2 owing to its high adsorption energy (∼15 kJ/mol). The new low-energy binding sites enhance the adsorption of DFC (from 8.5 % to 72.0 %) and CBZ (from 31.0 % to 70.0 %) during multicomponent adsorption. LMWOAs not only affect adsorption by modifying the pH but also provide additional binding sites that allow the PhACs to remain in the root environment for a longer period. As the concentration of LMWOAs temporarily changes, so does the availability of PhACs in the root zone. Environmental changes in the humic horizon enhance the mobility of the adsorbed PhACs, which renders them continuously available for uptake by plants, thus increasing the possibility of PhACs entering the human food chain.
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•High-energy sites of the soils were occupied first by 17α-ethinylestradiol (EE2), followed by carbamazepine (CBZ) and diclofenac (DFC).•Low-molecular-weight organic acids (LMWOAs) provided more low-energy adsorption sites for CBZ and DFC.•Statistical analysis shows that organic matter influences the impact of LMWOAs.•The sorption equilibrium of pharmaceuticals varies in time by LMWOAs.
•Relationship of shallow groundwater, precipitation and surface water is analyzed.•Dynamic factor analysis used.•Background factors in groundwater time series determined.•Spatial distribution of ...factor scores plotted.
The paper assesses the impact on the fluctuation of the shallow-groundwater table of the diversion of the Danube upstream from the Gabčikovo/Bős hydroelectric power plant in a hydraulically connected, geologically identical, and structurally not decomposable geological area in North-West Hungary. On the basis of shallow-groundwater level monitoring data the impact was traced back to the effect of the Danube’s changed flow course, and quantized for the whole study area.
To this end the influence of the river had to be separated from the effect of precipitation. The means chosen was the application of dynamic factor analysis to the registered hydrograph time series. We conclude that the originally homogeneous and dominant effect of the Danube has split and now consists of a diverted and a returning component (downstream from the power plant), and that this is a likely cause of ram-effect and river bed clogging. Furthermore the effect of precipitation ceased to be suppressed, and came to the fore.
Severe perinatal hypoxia–ischemia is an important cause of brain injury in both full-term and premature newborns, with a high risk of future behavioral and neurological deficits. The most commonly ...used animal model of neonatal hypoxia–ischemia is the unilateral ligation of the common carotid artery followed by exposure to hypoxia in 7-day-old rats. In spite of the wide use of this model, lot of contradictions and discrepancies exist between the results obtained by different laboratories regarding behavioral deficits and there are no data regarding the possible delay of the appearance of neurological reflexes and the time-course of reflex performances following neonatal hypoxic–ischemic injury in rats. In the present study we showed that neonatal hypoxia–ischemia retarded the development of somatic growth and several neurological reflexes (ear twitch, grasping, gait and negative geotaxis). Hypoxic animals also displayed retarded performance in righting, geotaxis and gait reflexes. Although hypoxic pups performed worse in most tests for motor coordination, they reached normal levels by 5 weeks of age except in the footfault test. In the open-field, hypoxic animals were generally more active, except at 3 weeks, when activity of normal pups increased enormously as well. Brain areas were significantly reduced in hypoxic animals, but no close correlation was found with behavioral deficits.
Although light-emitting diode (LED) technology has extended the research on targeted photomorphogenic, physiological, and biochemical responses in plants, there is not enough direct information about ...how light affects polyamine metabolism. In this study, the effect of three spectral compositions (referred to by their most typical characteristic: blue, red, and the combination of blue and red pink lights) on polyamine metabolism was compared to those obtained under white light conditions at the same light intensity. Although light quality induced pronounced differences in plant morphology, pigment contents, and the expression of polyamine metabolism-related genes, endogenous polyamine levels did not differ substantially. When exogenous polyamines were applied, their roborative effect were detected under all light conditions, but these beneficial changes were correlated with an increase in polyamine content and polyamine metabolism-related gene expression only under blue light. The effect of the polyamines on leaf gene expression under red light was the opposite, with a decreasing tendency. Results suggest that light quality may optimize plant growth through the adjustment of polyamine metabolism at the gene expression level. Polyamine treatments induced different strategies in fine-tuning of polyamine metabolism, which were induced for optimal plant growth and development under different spectral compositions.
The purpose of this study was to assess whether retinal microvascular or corneal nerve abnormalities occur earlier in diabetes mellitus (DM) and to identify imaging biomarkers in order to help ...prevent the subsequent irreversible retinal and corneal complications.
The study comprised 35 eyes of 35 healthy volunteers and 52 eyes of 52 patients with type 1 and type 2 DM. Swept-source optical coherence tomography (OCT), OCT angiography, and in vivo corneal confocal microscopy were performed in both groups. Corneal sub-basal nerve plexus and vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) were evaluated.
All corneal sub-basal nerve fiber parameters were decreased in patients with DM compared with healthy subjects and the difference was significant for each result except for nerve fiber width (P = 0.586). No significant correlation was obtained between any nerve fiber morphology parameters and disease duration or HbA1C. VD in SCP was significantly decreased in the superior (P < 0.0001), temporal (P = 0.001), and nasal quadrant (P = 0.003) in the diabetes group. In DCP, only superior VD (P = 0.036), decreased significantly in the diabetes group. Ganglion cell layer thickness in the inner ring showed a significantly lower value in patients with DM (P < 0.0001).
Our results implicate a more pronounced and earlier damage to the corneal nerve fibers compared to the retinal microvasculature in patients with DM.
In DM, an earlier and more pronounced damage to the corneal nerve fibers was observed compared to the retinal microvasculature.
The prevention of pre-eclampsia is difficult due to the syndromic nature and multiple underlying mechanisms of this severe complication of pregnancy. The current clinical distinction between early- ...and late-onset disease, although clinically useful, does not reflect the true nature and complexity of the pathologic processes leading to pre-eclampsia. The current gaps in knowledge on the heterogeneous molecular pathways of this syndrome and the lack of adequate, specific diagnostic methods are major obstacles to early screening and tailored preventive strategies. The development of novel diagnostic tools for detecting the activation of the identified disease pathways would enable early, accurate screening and personalized preventive therapies. We implemented a holistic approach that includes the utilization of different proteomic profiling methods of maternal plasma samples collected from various ethnic populations and the application of systems biology analysis to plasma proteomic, maternal demographic, clinical characteristic, and placental histopathologic data. This approach enabled the identification of four molecular subclasses of pre-eclampsia in which distinct and shared disease mechanisms are activated. The current review summarizes the results and conclusions from these studies and the research and clinical implications of our findings.
The purpose of our study was to determine the functional and neuroanatomic correlates of poststroke depressive symptoms.
Patients with consecutive admissions to a regional stroke center for new-onset ...unilateral hemispheric stroke who met World Health Organization and National Institute of Neurological and Communicative Disorders and Stroke criteria were eligible for inclusion in a longitudinal study. Acutely, patients underwent CT scanning, and at 3 months and 1 year after stroke, depressive symptoms were assessed by using both the Montgomery-Asberg Depression Rating Scale and the Zung Self-Rating Depression Scale. The Functional Independence Measure (FIM) served as an indication of functional outcome and was obtained at 1 month, 3 months, and 1 year after stroke, along with other demographic information. The Talairach and Tournoux stereotactic atlas was used for the primary determination of CT lesion localization. Lesion proximity to the anterior frontal pole was also measured.
Eighty-one patients participated in the longitudinal study. Stepwise linear regression analyses generated a highly significant model (F(3,76)=9.8, R(2)=28%, P<0.0005), with lower 1-month total FIM scores, living at home, and damage to the inferior frontal region predicting higher depression scores at 3 months. Similarly, lower 3-month total FIM scores correlated with higher 3-month depression scores, and lower 1-year total FIM scores correlated with higher 1-year depression scores.
Functional measures correlated with poststroke depression across time and, together with neuroanatomic measures, predicted depressive symptoms longitudinally. Although inferior frontal lesion location, irrespective of side, appeared to play a role as a risk factor in this study, the degree of functional dependence after stroke imparted the greatest risk.
Nowadays, Hungary is famous for its musical pedagogical method, the Kodaly concept, many foreign music lovers, and music teachers travel to our country to get to know and master it. But what do we ...experience in practice, what are the benefits for the musical tastes of young people? The aim of the study is to provide an insight into the attitudes of music and music in primary school youth and the surrounding social environment. We present a small slice of international research led by Dr. Judit Varadi, in which we examined the results of 4th and 6th grade pupils of five primary schools in Debrecen, 221 students in all. In the course of our research, we used a questionnaire consisting of 46 questions, which examined the family background of young people, the process of singing and music classes, listening habits, attitudes related to music classes, and music itself. Results were analyzed using SPSS 22.0 for Windows. In our observations, we found that parents’ previous music studies have a great influence on teaching their children to music. The attitudes toward class music and music and the number of classical music records in the children’s home are also positive. In our changing world, the genres of light music have gained a lot of space, the effect of which is reflected in the musical tastes of young people. How to get a full picture of the subject, and then the entire material will be processed.
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