Inhibitory Role of Inducible cAMP Early Repressor (ICER) in Methamphetamine-Induced Locomotor Sensitization

BACKGROUND: The inducible cyclic adenosine monophosphate (cAMP) early repressor (ICER) is highly expressed in the central nervous system and functions as a repressor of cAMP response element-binding protein (CREB) transcription. The present study sought to clarify the role of ICER in the effects of methamphetamine (METH). METHODS AND FINDINGS: We tested METH-induced locomotor sensitization in wildtype mice, ICER knockout mice, and ICER I-overexpressing mice. Both ICER wildtype mice and knockout mice displayed increased locomotor activity after continuous injections of METH. However, ICER knockout mice displayed a tendency toward higher locomotor activity compared with wildtype mice, although no significant difference was observed between the two genotypes. Moreover, compared with wildtype mice, ICER I-overexpressing mice displayed a significant decrease in METH-induced locomotor sensitization. Furthermore, Western blot analysis and quantitative real-time reverse transcription polymerase chain reaction demonstrated that ICER overexpression abolished the METH-induced increase in CREB expression and repressed cocaine- and amphetamine-regulated transcript (CART) and prodynorphin (Pdyn) expression in mice. The decreased CART and Pdyn mRNA expression levels in vivo may underlie the inhibitory role of ICER in METH-induced locomotor sensitization. CONCLUSIONS: Our data suggest that ICER plays an inhibitory role in METH-induced locomotor sensitization

Inducible cAMP Early Repressor (ICER) and Brain Functions

The inducible cAMP early repressor (ICER) is an endogenous repressor of cAMP-responsive element (CRE)-mediated gene transcription and belongs to the CRE-binding protein (CREB)/CRE modulator (CREM)/activating transcription factor 1 (ATF-1) gene family. ICER plays an important role in regulating the neuroendocrine system and the circadian rhythm. Other aspects of ICER function have recently attracted heightened attention. Being a natural inducible CREB antagonist, and more broadly, an inducible repressor of CRE-mediated gene transcription, ICER regulates long-lasting plastic changes that occur in the brain in response to incoming stimulation. This review will bring together data on ICER and its functions in the brain, with a special emphasis on recent findings highlighting the involvement of ICER in the regulation of long-term plasticity underlying learning and memory

Deregulation of CREB Signaling Pathway Induced by Chronic Hyperglycemia Downregulates NeuroD Transcription

CREB mediates the transcriptional effects of glucose and incretin hormones in insulin-target cells and insulin-producing β-cells. Although the inhibition of CREB activity is known to decrease the β-cell mass, it is still unknown what factors inversely alter the CREB signaling pathway in β-cells. Here, we show that β-cell dysfunctions occurring in chronic hyperglycemia are not caused by simple inhibition of CREB activity but rather by the persistent activation of CREB due to decreases in protein phophatase PP2A. When freshly isolated rat pancreatic islets were chronically exposed to 25 mM (high) glucose, the PP2A activity was reduced with a concomitant increase in active pCREB. Brief challenges with 15 mM glucose or 30 µM forskolin after 2 hour fasting further increased the level of pCREB and consequently induced the persistent expression of ICER. The excessively produced ICER was sufficient to repress the transcription of NeuroD, insulin, and SUR1 genes. In contrast, when islets were grown in 5 mM (low) glucose, CREB was transiently activated in response to glucose or forskolin stimuli. Thus, ICER expression was transient and insufficient to repress those target genes. Importantly, overexpression of PP2A reversed the adverse effects of chronic hyperglycemia and successfully restored the transient activation of CREB and ICER. Conversely, depletion of PP2A with siRNA was sufficient to disrupt the negative feedback regulation of CREB and induce hyperglycemic phenotypes even under low glucose conditions. Our findings suggest that the failure of the negative feedback regulation of CREB is the primary cause for β-cell dysfunctions under conditions of pathogenic hyperglycemia, and PP2A can be a novel target for future therapies aiming to protect β-cells mass in the late transitional phase of non-insulin dependent type 2 diabetes (NIDDM)

Early phase of plasticity-related gene regulation and SRF dependent transcription in the hippocampus

Hippocampal organotypic cultures are a highly reliable in vitro model for studying neuroplasticity: in this paper, we analyze the early phase of the transcriptional response induced by a 20 \ub5M gabazine treatment (GabT), a GABA-Ar antagonist, by using Affymetrix oligonucleotide microarray, RT-PCR based time-course and chromatin-immuno-precipitation. The transcriptome profiling revealed that the pool of genes up-regulated by GabT, besides being strongly related to the regulation of growth and synaptic transmission, is also endowed with neuro-protective and pro-survival properties. By using RT-PCR, we quantified a time-course of the transient expression for 33 of the highest up-regulated genes, with an average sampling rate of 10 minutes and covering the time interval [10 3690] minutes. The cluster analysis of the time-course disclosed the existence of three different dynamical patterns, one of which proved, in a statistical analysis based on results from previous works, to be significantly related with SRF-dependent regulation (p-value<0.05). The chromatin immunoprecipitation (chip) assay confirmed the rich presence of working CArG boxes in the genes belonging to the latter dynamical pattern and therefore validated the statistical analysis. Furthermore, an in silico analysis of the promoters revealed the presence of additional conserved CArG boxes upstream of the genes Nr4a1 and Rgs2. The chip assay confirmed a significant SRF signal in the Nr4a1 CArG box but not in the Rgs2 CArG box

Comparison of efficiency of methane production from liquid muck and dung with refined glicerin addition

W pracy przedstawiono wyniki badań laboratoryjnych produktywności gnojowicy świńskiej i bydlęcej z dodatkiem gliceryny w aspekcie ich przydatności do produkcji biogazu. Gnojowica świńska bądź bydlęca są podstawowymi substratami wykorzystywanymi w biogazowni rolniczej.This article presents the results of laboratory investigations of productiveness of the liquid muck and dung with glycerin added in aspect of their usefulness to the production of biogas. The liquid muck or dung are basic substrata used in agricultural biogas-works. The obtained results affirmed that the dung is better for biogas production

Tradycyjne i energetyczne wykorzystanie buraka cukrowego. Analiza ekonomiczna

The process of intensive transformation to which the sugar beet market in the European Union has been subject in recent years in order to meet the external obligations set by the WTO Panel, has had a severe impact on sugar beet production in Poland. Two major observations have been reported, namely a significant decrease of number of sugar beet farms and a reduction in those areas of tillage surfaces intended for sugar beet cultivation. It is worth mentioning that sugar beet is highly important to crop rotation and hardly any other plant in European agriculture can replace it. There is therefore both a strong need and a great opportunity for the further support and development of sugar beet production. As the international obligation to reduce greenhouse gas emission became effective, interest in biomass usage as a viable alternative to fossil fuels increased. This study thus set out to perform an economic comparison in respect of the use of sugar beets for traditional purposes and for energy, and to conduct an economic analysis of the income obtained from the sale of electrical energy sale by a biogas facility where sugar beets were used for biogas production. The comparative analysis was carried out taking both incomes from sugar beet production for sugar and root and leaf production for biogas into consideration. The results are very promising and allow the postulation that the use of sugar beet for biogas production provides an excellent opportunity for reviving defunct sugar plants and increasing the tillage surface for sugar beet in Poland.Proces intensywnej transformacji rynku produkcji cukru, której została poddana Unia Europejska w ostatnich latach, w celu spełnienia zobowiązań zewnętrznych wyznaczonych przez panel WTO, miał poważny wpływ na produkcję buraków cukrowych w Polsce. Nastąpił znaczny spadek liczby gospodarstw uprawiających buraki cukrowe i zmniejszenie powierzchni przeznaczonej na uprawę tej rośliny. Jednakże burak cukrowy jest bardzo ważną rośliną w produkcji rolniczej, zarówno z punktu widzenia miejsca w płodozmianie, jak i opłacalności uprawy. Badania wskazują także na szerokie możliwości alternatywnego wykorzystania buraków. Istnieje zatem potrzeba wspierania rozwoju produkcji buraka cukrowego. Dzięki międzynarodowym zobowiązaniom do redukcji emisji gazów cieplarnianych, wzrosło zainteresowanie wykorzystaniem biomasy, w tym buraka cukrowego, jako alternatywy dla paliw kopalnych. Artykuł obejmuje ekonomiczne porównanie wykorzystania buraków cukrowych do produkcji cukru i alternatywnego, do produkcji energii. W pracy przeprowadzono analizę ekonomiczną dochodów uzyskanych ze sprzedaży energii elektrycznej przez biogazownię, w której buraki cukrowe były wykorzystywane do produkcji biometanu. Analiza porównawcza została przeprowadzona dla dochodów z produkcji buraków cukrowych przeznaczonych na cukier oraz z przeznaczeniem do produkcji biogazu, wykorzystując korzenie i liście. Wyniki pozwalają na stwierdzenie, że wykorzystanie buraków cukrowych do produkcji biogazu może być podstawą do zwiększenia powierzchni uprawy buraków cukrowych w Polsce, a także do zaadaptowania zamkniętych cukrowni na biogazownie

Ocena eksploatacyjno-ekonomiczna technologii przygotowania i zadawania dawki pełnoporcjowej dla bydła

The paper presents results of studies on operational and economic evaluation of three technologies used to prepare and feed total mixed ration (TMR) for cattle. The experiments were conducted on three farms in the Wielkopolska region, in which feed rations of 2662 up to 3595 kg were prepared. Mean operating output capacities for loading operations of feed mixer wagons ranged from approx. 10.5 t·h-1 for front loaders to approx. 12 t·h-1 for the telescope loader. Mean operating output capacities of feed mixer wagons ranged from 2.05 to 5.26 t·h-1. Labour outlays per 1 ton prepared and fed TMR varied, ranging from 0.21 to 0.50 rbh·t-1, while labour outlays at loading of the feed mixer wagon chamber with successive total mixed ration components were comparable, ranging from 0.09 to 0.10 rbh·t-1. The total cost of machine operations was lowest for the T1 technology, amounting to 22.53 zł·t-1, for T2 it was slightly higher at 23.92 zł·t-1, while it was the greatest for T3, amounting to 30.73 zł·t-1.W pracy przedstawiono wyniki badań dotyczące oceny eksploatacyjno-ekonomicznej trzech technologii przygotowania i zadawania dawki całkowicie kompletnej (TMR) dla bydła. Badania były realizowane w trzech gospodarstwach rolnych na terenie Wielkopolski w których jednorazowo przygotowywano dawki w ilości od 2662 do 3595 kg. Średnie wydajności eksploatacyjne załadunku wozów paszowych wynosiły od około 10,5 t·h-1 dla ładowaczy czołowych do około 12 t·h-1 dla ładowarki teleskopowej. Średnie wydajności eksploatacyjne wozów paszowych wynosiły od 2,05 do 5,26 t·h-1. Nakłady robocizny odniesione do 1 tony przygotowanej i zadanej dawki TMR były zróżnicowane i wynosiły od 0,21 do 0,50 rbh·t-1, natomiast na zbliżonym poziomie były nakłady robocizny przy załadunku zbiornika wozu paszowego kolejnymi składnikami dawki całkowicie kompletnej i wynosiły od 0,09 do 0,10 rbh·t-1. Łączny koszt wykonania prac maszynowych najmniejszy był w technologii T1 i wynosił 22,53 zł·t-1, nieznacznie większy niż w technologii T1 i wynosił 23,92 zł·t-1 a największy w technologii T3 - 30,73 zł·t-1