Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities

<p>Abstract</p> <p>Background</p> <p>PEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity.</p> <p>Results</p> <p>We report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls.</p> <p>Conclusion</p> <p>We found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning.</p

Pengaruh Iradiasi Gamma pada Konversi Biomassa Lignoselulosa Sabut Kelapa Menjadi Bioetanol

Sabut kelapa adalah salah satu limbah lignoselulosa yang dapat dikonversikan menjadi bioetanol. Konversi bioetanol pada penelitian ini dilakukan melalui beberapa tahapan yaitu proses pre-treatment, proses Saccharification and Simultaneous Fermentation (SSF), dan proses pemurnian. Proses pre-treatment sebagai proses pemecahan ikatan lignoselulosa menjadi poin utama dalam proses konversi biomassa lignoselulosa. Penelitian ini dilakukan untuk mengetahui pengaruh iradiasi gamma terhadap pemecahan ikatan lignoselulosa pada proses pre-treatment tersebut. Proses iradiasi gamma divariasikan pada dosis sebesar 0 kGy, 100 kGy, 150 kGy, 200 kGy, 250 kGy dan dilanjutkan pre-treatment secara kimia menggunakan NaOH 4%. Kemudian dilanjutkan proses pemurnian setelah proses SSF selama 72 jam. Kadar bioetanol yang diperoleh setelah proses pemurnian diukur menggunakan metode refraktometri dan piknometri. Pada penelitian ini diperoleh kadar bioetanol tertinggi pada dosis iradiasi gamma 200 kGy, yaitu 35,15% untuk metode refraktometri, dan 36,77% untuk metode piknometri. Hasil tersebut jauh lebih tinggi bila dibandingkan dengan kadar bioetanol tanpa iradiasi gamma yaitu 2,45% untuk metode refraktometri, dan 6,92% untuk metode piknometri. Penelitian ini menunjukkan bahwa metode pre-treatment dengan iradiasi gamma dapat menghasilkan kadar bioetanol yang lebih tinggi dibandingkan tanpa menggunakan iradiasi gamma.Coconut husk is one of lignocellulosic wastes that can be converted into bioethanol. Bioethanol conversion in this study was carried out through several stages, namely the pre-treatment process, the Saccharification and Simultaneous Fermentation (SSF) process, and the purification process. The pre-treatment process as the process of breaking lignocellulosic bonds becomes the main point in the process of lignocellulosic biomass conversion. This research was conducted to determine the effect of gamma irradiation to breaking lignocellulosic bonds on the pre-treatment process. Gamma irradiation process was varied in doses of 0 kGy, 100 kGy, 150 kGy, 200 kGy, 250 kGy and continued with chemical pre-treatment using 4% NaOH. Then the purification process was continued after the SSF process for 6 days. Bioethanol levels obtained after the purification process were measured using refractometry and picnometry methods. In this study, the highest levels of bioethanol were obtained at a gamma irradiation dose of 200 kGy, namely 34.93% for the refractometry method, and 26.67% for the picnometry method, respectively. These results are much higher when compared to bioethanol levels without gamma irradiation, which is 2.25% for the refractometry method, and 5.49% for the picnometry method, respectively. This study shows that the pre-treatment method with gamma irradiation can produce higher levels of bioethanol than without using gamma irradiation

Deletion of the Coffin–Lowry Syndrome Gene Rsk2 in Mice is Associated With Impaired Spatial Learning and Reduced Control of Exploratory Behavior

Coffin-Lowry Syndrome (CLS) is an X-linked syndromic form of mental retardation associated with skeletal abnormalities. It is caused by mutations of the Rsk2 gene, which encodes a growth factor regulated kinase. Gene deletion studies in mice have shown an essential role for the Rsk2 gene in osteoblast differentiation and function, establishing a causal link between Rsk2 deficiency and skeletal abnormalities of CLS. Although analyses in mice have revealed prominent expression of Rsk2 in brain structures that are essential for learning and memory, evidence at the behavioral level for an involvement of Rsk2 in cognitive function is still lacking. Here, we have examined Rsk2-deficient mice in two extensive batteries of behavioral tests, which were conducted independently in two laboratories in Zurich (Switzerland) and Orsay (France). Despite the known reduction of bone mass, all parameters of motor function were normal, confirming the suitability of Rsk2-deficient mice for behavioral testing. Rsk2-deficient mice showed a mild impairment of spatial working memory, delayed acquisition of a spatial reference memory task and long-term spatial memory deficits. In contrast, associative and recognition memory, as well as the habituation of exploratory activity were normal. Our studies also revealed mild signs of disinhibition in exploratory activity, as well as a difficulty to adapt to new test environments, which likely contributed to the learning impairments displayed by Rsk2-deficient mice. The observed behavioral changes are in line with observations made in other mouse models of human mental retardation and support a role of Rsk2 in cognitive function