543 research outputs found
Subnormothermic Perfusion in the Isolated Rat Liver Preserves the Antioxidant Glutathione and Enhances the Function of the Ubiquitin Proteasome System.
The reduction of oxidative stress is suggested to be one of the main mechanisms to explain the benefits of subnormothermic perfusion against ischemic liver damage. In this study we investigated the early cellular mechanisms induced in isolated rat livers after 15 min perfusion at temperatures ranging from normothermia (37°C) to subnormothermia (26°C and 22°C). Subnormothermic perfusion was found to maintain hepatic viability. Perfusion at 22°C raised reduced glutathione levels and the activity of glutathione reductase; however, lipid and protein oxidation still occurred as determined by malondialdehyde, 4-hydroxynonenal-protein adducts, and advanced oxidation protein products. In livers perfused at 22°C the lysosomal and ubiquitin proteasome system (UPS) were both activated. The 26S chymotrypsin-like (β5) proteasome activity was significantly increased in the 26°C (46%) and 22°C (42%) groups. The increased proteasome activity may be due to increased Rpt6 Ser120 phosphorylation, which is known to enhance 26S proteasome activity. Together, our results indicate that the early events produced by subnormothermic perfusion in the liver can induce oxidative stress concomitantly with antioxidant glutathione preservation and enhanced function of the lysosomal and UPS systems. Thus, a brief hypothermia could trigger antioxidant mechanisms and may be functioning as a preconditioning stimulus
PENTINGNYA PEMBANGUNAN SARANA PRASARANA TRANSPORTASI SEBAGAI UPAYA MEMBANGUN DESA DI KABUPATEN MINAHASA UTARA PROVINSI SULAWESI UTARA
Pembangunan desa merupakan hal yang penting untuk meningkatkan taraf hidup masyarakat kawasan perdesaan. Salah satu faktor yang menunjang pergerakan aksesibilitas masyarakat desa adalah tersedianya sarana dan prasarana transportasi. Ketersediaan jaringan jalan sebagai kebutuhan masyarakat desa merupakan hal yang sangat penting. Oleh sebab itu pemerintah melalui Kementerian Desa, Pembangunan Daerah Tertinggal dan Transmigrasi Republik Indonesia melakukan studi sebagai upaya untuk membangun desa sebagai salah satu bagian dari Nawacita Pemerintah Indonesia. Provinsi Sulawesi Utara merupakan salah satu Provinsi yang terpilih sebagai lokasi pelaksanaan studi ini. Melalui pemerintah Provinsi Sulawesi Utara ditetapkanlah Kabupaten Minahasa Utara sebagai tempat pelaksanaan studi kawasan perdesaan.Kebutuhan Prasarana dan Sarana Kawasan Perdesaan berdasarkan Standar (Pedoman Penentuan Standar Pelayanan Minimal sesuai dengan Keputusan Menteri Permukiman dan Prasarana Wilayah No. 534/KPTS/M/2001), Bidang Pelayanan Pemukiman Perdesaan pentingnya kebutuhan akan jaringan jalan perdesaan yang dibagi dalan 2 (dua) bagian yakni Kebutuhan akan jaringan jalan desa dan kebutuhan akan jalan setapak desa. Hasil perencanaan sarana prasarana kebutuhan masyarakat baik infrastruktur maupun kebutuhan akan jasa pelayanan kepada masyarakat, terutama masyarakat perdesaan harus direalisasikan dalam bentuk pembangunan kesejahteraan masyarakat.Berikut ini adalah beberapa langkah strategis dalam rangka peningkatan pembangunan kawasan perdesaan dalam hal ini pembangunan sarana prasarana transportasi kawasan perdesaan: Penggunaan dana desa untuk kebutuhan pembangunan prasarana transportasi jalan desa, pembangunan dengan swadaya masyarakat desa, usulan pembangunan melalui Musrembang di tingkat desa diusulkan ke Musrembang Kecamatan untuk selanjutnya diusulkan ke Tingkat Kabupaten untuk diusulkan dalam APBD Kabupaten.Kata kunci : Pembangunan Desa, Musrembang, APBD Kabupaten.
ANALISIS GAYA KEPEMIMPINAN DALAM UPAYA MEMPERCEPAT PENANGANAN PENGADUAN MASYARAKAT PADA DINAS LINGKUNGAN HIDUP KABUPATEN LAMPUNG SELATAN
Penelitian ini berjudul Analisis Gaya Kepemimpinan Dalam Upaya Mempercepat Penanganan Pengaduan Masyarakat Pada Dinas Lingkungan Hidup Kabupaten Lampung Selatan yang dilakukan berdasarkan pengamatan dan wawancara mendalam. Kepala Dinas Lingkungan Hidup Kabupaten Lampung Selatan salah satu tugasnya dalam rangka meningkatkan kualitas pelayanan kepada masyarakat terkait perlindungan dan pengelolaan lingkungan hidup. Hasil pengamatan pada Dinas Lingkungan Hidup Lampung Selatan didapatkan kurangnya kemampuan bawahan dalam bekerja atau kehandalan para karyawan terhadap tugas yang diberikan oleh pimpinan, penguasaan sebagian bawahan terhadap bidang tupoksi belum memahami, lamban/kurangnya inisiatif karyawan dalam menanggapi pengaduan masyarakat dan lemahnya koordinasi serta sinergitas antar bidang terkait. Dalam organisasi publik, bawahan bekerja selalu tergantung pada pimpinan. Berdasarkan permasalahan tersebut, penelitian ini bertujuan untuk menganalisis gaya kepemimpinan Kepala Dinas Lingkungan Hidup Lampung Selatan berdasarkan teori Ronald Lippitt dan Ralph K. White yang dikategorikan menjadi tiga gaya kepemimpinan yaitu otokratis, demokratis, dan laissez-faire. Penelitian yang digunakan dengan teknik pengumpulan data dilakukan secara kualitatif, yaitu wawancara mendalam dan observasi. Berdasarkan hasil penelitian yang dilakukan dapat disimpulkan bahwa Kepala Dinas Lingkungan Hidup Lampung Selatan dengan gaya kepemimpinan demokratis dalam kepemimpinannya dapat mempercepat pelayanan pengaduan masyarakat di Dinas Lingkungan Hidup Kabupaten Lampung Selatan
The MPI bioinformatics Toolkit as an integrative platform for advanced protein sequence and structure analysis.
The MPI Bioinformatics Toolkit (http://toolkit.tuebingen.mpg.de) is an open, interactive web service for comprehensive and collaborative protein bioinformatic analysis. It offers a wide array of interconnected, state-of-the-art bioinformatics tools to experts and non-experts alike, developed both externally (e.g. BLAST+, HMMER3, MUSCLE) and internally (e.g. HHpred, HHblits, PCOILS). While a beta version of the Toolkit was released 10 years ago, the current production-level release has been available since 2008 and has serviced more than 1.6 million external user queries. The usage of the Toolkit has continued to increase linearly over the years, reaching more than 400 000 queries in 2015. In fact, through the breadth of its tools and their tight interconnection, the Toolkit has become an excellent platform for experimental scientists as well as a useful resource for teaching bioinformatic inquiry to students in the life sciences. In this article, we report on the evolution of the Toolkit over the last ten years, focusing on the expansion of the tool repertoire (e.g. CS-BLAST, HHblits) and on infrastructural work needed to remain operative in a changing web environment
Extracellular ferritin contributes to neuronal injury in an in vitro model of ischemic stroke
Previous clinical and experimental studies have shown that neurological decline and poor functional outcome after acute ischemic stroke in humans are associated with high ferritin levels in serum and cerebrospinal fluid (CSF) within 24 h of ischemic stroke onset. The aim of the present study was to find out if and how high extracellular ferritin concentrations can increase the excitotoxicity effect in a neuronal cortical culture model of stroke. Extracellular ferritin (100 ng/ml) significantly increased the excitotoxic effect caused by excessive exogenous glutamate (50 µM and 100 µM) by leading to an increase in lipid peroxidation, a reduction in mitochondrial membrane potential, and a decrease in neuron viability. Extracellular apoferritin (100 ng/ml), the iron-free form of the protein, does not increase the excitotoxicity of glutamate, which proves that iron was responsible for the neurotoxic effect of the exogenous ferritin. We present evidence that extracellular ferritin iron exacerbates the neurotoxic effect induced by glutamate excitotoxicity and that the effect of ferritin iron is dependent of glutamate excitotoxicity. Our results support the idea that body iron overload is involved in the severity of the brain damage caused by stroke and reveal the need to control systemic iron homeostasis.Peer ReviewedPostprint (author's final draft
Optimization of input parameters to a CN neuron model to simulate its activity during and between epileptic absence seizures
Peer reviewe
Oxidative Stress and Antioxidant Activity in Hypothermia and Rewarming. Can RONS Modulate the Beneficial Effects of Therapeutic Hypothermia?
Hypothermia is a condition in which core temperature drops below the level necessary to maintain bodily functions. The decrease in temperature may disrupt some physiological systems of the body, including alterations in microcirculation and reduction of oxygen supply to tissues. The lack of oxygen can induce the generation of reactive oxygen and nitrogen free radicals (RONS), followed by oxidative stress, and finally, apoptosis and/or necrosis. Furthermore, since the hypothermia is inevitably followed by a rewarming process, we should also consider its effects. Despite hypothermia and rewarming inducing injury, many benefits of hypothermia have been demonstrated when used to preserve brain, cardiac, hepatic, and intestinal function against ischemic injury. This review gives an overview of the effects of hypothermia and rewarming on the oxidant/antioxidant balance and provides hypothesis for the role of reactive oxygen species in therapeutic hypothermia
Combining machine learning and simulations of a morphologically realistic model to study modulation of neuronal activity in cerebellar nuclei
Abstract from 23rd Annual Computational Neuroscience Meeting: CNS 2014 © 2014 Alva et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Epileptic absence seizures are characterized by synchronized oscillatory activity in the cerebral cortex that can be recorded as so-called spike-and-wave discharges (SWDs) by electroencephalogram. Although the cerebral cortex and the directly connected thalamus are paramount to this particular form of epilepsy, several other parts of the mammalian brain are likely to influence this oscillatory activity. We have recently shown that some of the cerebellar nuclei (CN) neurons, which form the main output of the cerebellum, show synchronized oscillatory activity during episodes of cortical SWDs in two independent mouse models of absence epilepsy [1]. The CN neurons that show this significant correlation with the SWDs are deemed to “participate” in the seizure activity and are therefore used in our current study designed to unravel the potential causes of such oscillatory firing patternsPeer reviewe
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