Effects of the implementation of the inflation targeting regime on economic growth

This research study is focused on the examination of the influence of the introduction and implementation of the monetary Inflation Targeting (IT) regime: the level of the inflation rate and the Gross Domestic Product (GDP) growth rate, as well as inflation and the GDP volatility. Conditional variance is calculated by fitting an empirical Generalized Autoregressive Conditional Heteroskedasticity (GARCH) model to an annualized quarterly date for the period from 1993Q1 to 2020Q3, all in order to assess volatility. The results of the regression model showed that there was a positive statistical significance between the instability of inflation and the instability of the growth rate of the GDP in the three analyzed countries (namely in Albania, Turkey and the Republic of Serbia). The result of introducing the IT regime when the GDP growth rate volatility is concerned is statistically significant in Serbia and Turkey and led to reduction in the GDP volatility and stabilization. However, the applied regression model indicated that, in the case of Albania and Romania, the introduction of the IT regime did not have a statistically significant impact on the GDP growth rate volatility

Functional Development of Principal Neurons in the Anteroventral Cochlear Nucleus Extends Beyond Hearing Onset

Sound information is transduced into graded receptor potential by cochlear hair cells and encoded as discrete action potentials of auditory nerve fibers. In the cochlear nucleus, auditory nerve fibers convey this information through morphologically distinct synaptic terminals onto bushy cells (BCs) and stellate cells (SCs) for processing of different sound features. With expanding use of transgenic mouse models, it is increasingly important to understand the in vivo functional development of these neurons in mice. We characterized the maturation of spontaneous and acoustically evoked activity in BCs and SCs by acquiring single-unit juxtacellular recordings between hearing onset (P12) and young adulthood (P30) of anesthetized CBA/J mice. In both cell types, hearing sensitivity and characteristic frequency (CF) range are mostly adult-like by P14, consistent with rapid maturation of the auditory periphery. In BCs, however, some physiological features like maximal firing rate, dynamic range, temporal response properties, recovery from post-stimulus depression, first spike latency (FSL) and encoding of sinusoid amplitude modulation undergo further maturation up to P18. In SCs, the development of excitatory responses is even more prolonged, indicated by a gradual increase in spontaneous and maximum firing rates up to P30. In the same cell type, broadly tuned acoustically evoked inhibition is immediately effective at hearing onset, covering the low- and high-frequency flanks of the excitatory response area. Together, these data suggest that maturation of auditory processing in the parallel ascending BC and SC streams engages distinct mechanisms at the first central synapses that may differently depend on the early auditory experience

A STUDY OF THE USE OF MIXED REALITY FOR CAPTURING HUMAN OBSERVATION AND INFERENCES IN PRODUCTION ENVIRONMENTS

Augmented and mixed reality is already considered as needful technology of the modern production systems. It is primarily employed to virtualize proper digital content, mainly related to 3D objects, into the human visual field allowing people to visualize and understand complex spatial shapes, their mutual relations, and positioning. Yet, the huge potential of the technology is waiting to be revealed in its usage for collecting and recording human observations and inferences about the context of the production environment. Its bi-directional interface makes it the most direct and the most efficient knowledge capturing means to date. The paper presents the challenges and benefits that come from the usage of a conceptual interface of an mixed reality application that is designed to collect data, semantics and knowledge about the production context directly from the man-in-process. As a production environment for the development, implementation, and testing of mixed reality applications for this purpose, various processes for the assembly and maintenance of medium-voltage equipment were used

Large-scale proteomics analysis of five brain regions from Parkinson’s disease patients with a GBA1 mutation

Despite being the second most common neurodegenerative disorder, little is known about Parkinson's disease (PD) pathogenesis. A number of genetic factors predispose towards PD, among them mutations in GBA1, which encodes the lysosomal enzyme acid-β-glucosidase. We now perform non-targeted, mass spectrometry based quantitative proteomics on five brain regions from PD patients with a GBA1 mutation (PD-GBA) and compare to age- and sex-matched idiopathic PD patients (IPD) and controls. Two proteins were differentially-expressed in all five brain regions whereas significant differences were detected between the brain regions, with changes consistent with loss of dopaminergic signaling in the substantia nigra, and activation of a number of pathways in the cingulate gyrus, including ceramide synthesis. Mitochondrial oxidative phosphorylation was inactivated in PD samples in most brain regions and to a larger extent in PD-GBA. This study provides a comprehensive large-scale proteomics dataset for the study of PD-GBA

Deletion of BDNF in Pax2 Lineage-Derived Interneuron Precursors in the Hindbrain Hampers the Proportion of Excitation/Inhibition, Learning, and Behavior

© 2021 Eckert, Marchetta, Manthey, Walter, Jovanovic, Savitska, Singer, Jacob, Rüttiger, Schimmang, Milenkovic, Pilz and Knipper.Numerous studies indicate that deficits in the proper integration or migration of specific GABAergic precursor cells from the subpallium to the cortex can lead to severe cognitive dysfunctions and neurodevelopmental pathogenesis linked to intellectual disabilities. A different set of GABAergic precursors cells that express Pax2 migrate to hindbrain regions, targeting, for example auditory or somatosensory brainstem regions. We demonstrate that the absence of BDNF in Pax2-lineage descendants of BdnfPax2KOs causes severe cognitive disabilities. In BdnfPax2KOs, a normal number of parvalbumin-positive interneurons (PV-INs) was found in the auditory cortex (AC) and hippocampal regions, which went hand in hand with reduced PV-labeling in neuropil domains and elevated activity-regulated cytoskeleton-associated protein (Arc/Arg3.1; here: Arc) levels in pyramidal neurons in these same regions. This immaturity in the inhibitory/excitatory balance of the AC and hippocampus was accompanied by elevated LTP, reduced (sound-induced) LTP/LTD adjustment, impaired learning, elevated anxiety, and deficits in social behavior, overall representing an autistic-like phenotype. Reduced tonic inhibitory strength and elevated spontaneous firing rates in dorsal cochlear nucleus (DCN) brainstem neurons in otherwise nearly normal hearing BdnfPax2KOs suggests that diminished fine-grained auditory-specific brainstem activity has hampered activity-driven integration of inhibitory networks of the AC in functional (hippocampal) circuits. This leads to an inability to scale hippocampal post-synapses during LTP/LTD plasticity. BDNF in Pax2-lineage descendants in lower brain regions should thus be considered as a novel candidate for contributing to the development of brain disorders, including autism.We acknowledge grants from the Deutsche Forschungsgemeins-chaft FOR 2060 project RU 713/3-2 (WS and LR), GRK 2381 (PM), SPP 1608 RU 316/12-1 (PE and LR), MI 954/3-1 (IM and SJ), KN 316/12-1 (MM and MK), BFU2016-76580-P (TS), and NIH NIMH 1R01MH106623 (MJ)

Developmental patterns of DR6 in normal human hippocampus and in Down syndrome

Background Death receptor 6 (DR6) is highly expressed in the human brain: it has been shown to induce axon pruning and neuron death via distinct caspases and to mediate axonal degeneration through binding to N-terminal β amyloid precursor protein (N-APP). Methods We investigated the expression of DR6 during prenatal and postnatal development in human hippocampus and temporal cortex by immunocytochemistry and Western blot analysis (118 normal human brain specimens; 9 to 41 gestational weeks; 1 day to 7 months postnatally; 3 to 91 years). To investigate the role of N-APP/DR6/caspase 6 pathway in the development of hippocampal Alzheimer’s disease (AD)-associated pathology, we examined DR6 immunoreactivity (IR) in the developing hippocampus from patients with Down syndrome (DS; 48 brain specimens; 14 to 41 gestational weeks; 7 days to 8 months postnatally; 15 to 64 years) and in adults with DS and AD. Results DR6 was highly expressed in human adult hippocampus and temporal cortex: we observed consistent similar temporal and spatial expression in both control and DS brain. Western blot analysis of total homogenates of temporal cortex and hippocampus showed developmental regulation of DR6. In the hippocampus, DR6 IR was first apparent in the stratum lacunosum-moleculare at 16 weeks of gestation, followed by stratum oriens, radiatum, pyramidale (CA1 to CA4) and molecular layer of the dentate gyrus between 21 and 23 gestational weeks, reaching a pattern similar to adult hippocampus around birth. Increased DR6 expression in dystrophic neurites was detected focally in a 15-year-old DS patient. Abnormal DR6 expression pattern, with increased expression within dystrophic neurites in and around amyloid plaques was observed in adult DS patients with widespread AD-associated neurodegeneration and was similar to the pattern observed in AD hippocampus. Double-labeling experiments demonstrated the colocalization, in dystrophic neurites, of DR6 with APP. We also observed colocalization with hyper-phosphorylated Tau and with caspase 6 (increased in hippocampus with AD pathology) in plaque-associated dystrophic neurites and within the white matter. Conclusions These findings demonstrate a developmental regulation of DR6 in human hippocampus and suggest an abnormal activation of the N-APP/DR6/caspase 6 pathway, which can contribute to initiation or progression of hippocampal AD-associated pathology

Silicon modifies leaf nutriome and improves growth of oak seedlings exposed to phosphorus deficiency and Phytophthora plurivora infection

Beneficial effects of silicon (Si) on plants have primarily been studied in crop species under single stress. Moreover, nutrient acquisition-based responses to combination of biotic and abiotic stresses (a common situation in natural habitats) have rarely been reported, in particular in conjunction with soil amendments with Si. Pedunculate oak (Quercus robur L.), one of the ecologically and economically most important tree species in Europe, is facing a severe decline due to combined stresses, but also problems in assisted regeneration in nurseries. Here, we studied the effect of Si supply on the leaf nutriome, root traits and overall growth of 12-weeks-old oak seedlings exposed to abiotic stress [low phosphorus (P) supply], biotic stress (Phytophthora plurivora root infection), and their combination. The application of Si had the strongest ameliorative effect on growth, root health and root phenome under the most severe stress conditions (i.e., combination of P deficiency and P. plurivora root infection), where it differentially affected the uptake and leaf accumulation in 11 out of 13 analysed nutrients. Silicon supply tended to reverse the pattern of change of some, but not all, leaf nutrients affected by stresses: P, boron (B) and magnesium (Mg) under P deficiency, and P, B and sulphur (S) under pathogen attack, but also nickel (Ni) and molybdenum (Mo) under all three stresses. Surprisingly, Si affected some nutrients that were not changed by a particular stress itself and decreased leaf Mg levels under all the stresses. On the other hand, pathogen attack increased leaf accumulation of Si. This exploratory work presents the complexity of nutrient crosstalk under three stresses, and opens more questions about genetic networks that control plant physiological responses. Practically, we show a potential of Si application to improve P status and root health in oak seedlings, particularly in nurseries

Silicon modulates root phenomics and leaf ionomics in oak under Phytophthora infection and low phosphorus conditions

Pedunculate oak (Quercus robur L.) is the most abundant deciduous tree species in Europe with high economical and ecological importance. Different species of Phytophthora are considered as one of the most important factors responsible for deterioration of oak forest, causing serious root damage not only in the forest trees, but also in the nurseries. Oak seedlings were grown in plastic pots with extremely low phosphorus (P) soil (1.5 mg kg-1 total P; no available Olsen-P detected). Silicon (Si) and P were supplied as Na2SiO3 (300 mg Si kg-1 dry soil) and KH2PO4 (180 mg P kg-1 dry soil), respectively. Four treatments (-P/-Si, -P+/Si, +P/-Si, and +P/+Si) were used in the experiment. After two months of experiment, a half of the plants in each treatment were root-inoculated with Phytophthora plurivora. After further four weeks, the first symptoms of P. plurivora infection appeared in leaves (e.g., leaf necrosis and wilting). Plants were then carefully removed from the pots, divided into roots and shoots, and the roots were scanned and analyzed by the WinRHIZO® software. Foliar concentrations of Si, P, K, Ca, Mg, B, Cu, Fe, Mn, and Zn were determined by ICP-OES, while the concentrations of N and S were determined by CHNS Analyzer. The addition of Si obviously improved root health status (e.g., decreasing de number of lesions and necrosis intensity) in the infected plants grown under -P conditions, which was followed by an increased foliar P concentration. The Si supply significantly increased the root variables (e.g., total root volume, root length, and area of thin roots) in both -P and +P plants inoculated with P. plurivora. Therefore, P. plurivora infection and supply of P and Si modulated the nutrient uptake and thereby changed the leaf ionomics, especially for infected -P plants supplied with Si (e.g., significantly increased B, Cu, and Si foliar concentrations and decreased Fe, Mn, Ca, Mg, K, and S foliar concentrations). Furthermore, Si fertilization significantly declined loses in plant dry biomass caused by P. plurivora infection and/or P deficiency, showing biomass comparable to non-infected +P plants

The Parkinson's disease VPS35[D620N] mutation enhances LRRK2 mediated Rab protein phosphorylation in mouse and human

Missense mutations in the LRRK2 and VPS35 genes result in autosomal dominant Parkinson’s disease. The VPS35 gene encodes for the cargo-binding component of the retromer complex, while LRRK2 modulates vesicular trafficking by phosphorylating a subgroup of Rab proteins. Pathogenic mutations in LRRK2 increase its kinase activity. It is not known how the only thus far described pathogenic VPS35 mutation, [D620N] exerts its effects. We reveal that the VPS35[D620N] knock-in mutation, strikingly elevates LRRK2 mediated phosphorylation of Rab8A, Rab10 and Rab12 in mouse embryonic fibroblasts. The VPS35[D620N] mutation also increases Rab10 phosphorylation in mouse tissues (lung, kidney, spleen and brain). Furthermore, LRRK2 mediated Rab10 phosphorylation is increased in neutrophils as well as monocytes isolated from three Parkinson’s patients with a heterozygous VPS35[D620N] mutation compared to healthy donors and idiopathic Parkinson’s patients. LRRK2 mediated Rab10 phosphorylation is significantly suppressed by knock-out or knock-down of VPS35 in wild type, LRRK2[R1441C] or VPS35[D620N] cells. Finally, VPS35[D620N] mutation promotes Rab10 phosphorylation more potently than LRRK2 pathogenic mutations. Available data suggest that Parkinson’s patients with VPS35[D620N] develop the disease at a younger age than those with LRRK2 mutations. Our observations indicate that VPS35 controls LRRK2 activity and that the VPS35[D620N] mutation results in a gain of function, potentially causing Parkinson’s disease through hyperactivation of the LRRK2 kinase. Our findings suggest that it may be possible to elaborate compounds that target the retromer complex to suppress LRRK2 activity. Moreover, patients with VPS35[D620N] associated Parkinson’s might benefit from LRRK2 inhibitor treatment that have entered clinical trials in humans