Prolonged translation arrest correlates with delayed neuronal death of hippocampal CA1 neurons following global cerebral ischemia and reperfusion. Many previous studies investigated ribosome molecular biology, but mRNA regulatory mechanisms after brain ischemia have been less studied. Here we investigated the embryonic lethal abnormal vision/Hu isoforms HuR, HuB, HuC, and HuD, as well as expression of mRNAs containing adenine and rich uridine elements following global ischemia in rat brain. Proteomics of embryonic lethal abnormal vision immunoprecipitations or polysomes isolated from rat hippocampal CA1 and CA3 from controls or following 10 min ischemia plus 8 h of reperfusion showed distinct sets of mRNA-binding proteins, suggesting differential mRNA regulation in each condition. Notably, HuB, HuC, and HuD were undetectable in NIC CA1. At 8 h reperfusion, polysome-associated mRNAs contained 46.1% of ischemia-upregulated mRNAs containing adenine and rich uridine elements in CA3, but only 18.7% in CA1. Since mRNAs containing adenine and rich uridine elements regulation are important to several cellular stress responses, our results suggest CA1 is disadvantaged compared to CA3 in coping with ischemic stress, and this is expected to be an important contributing factor to CA1 selective vulnerability. (Data are available via ProteomeXchange identifier PXD004078 and GEO Series accession number GSE82146).Keywords Global brain ischemia and reperfusion, hippocampal CA1, adenine and rich uridine elements mRNA, embryonic lethal abnormal vision, mRNA regulation

No abstract

Many clinically relevant forms of acute injury, such as stroke, traumatic brain injury, and myocardial infarction, have resisted treatments to prevent cell death following injury. The clinical failures can be linked to the currently used inductive models based on biological specifics of the injury system. Here we contrast the application of inductive and deductive models of acute cell injury. Using brain ischemia as a case study, we discuss limitations in inductive inferences, including the inability to unambiguously assign cell death causality and the lack of a systematic quantitative framework. These limitations follow from an overemphasis on qualitative molecular pathways specific to the injured system. Our recently developed nonlinear dynamical theory of cell injury provides a generic, systematic approach to cell injury in which attractor states and system parameters are used to quantitatively characterize acute injury systems. The theoretical, empirical, and therapeutic implications of shifting to a deductive framework are discussed. We illustrate how a deductive mathematical framework offers tangible advantages over qualitative inductive models for the development of therapeutics of acutely injured biological systems.

Neuroprotection seeks to halt cell death after brain ischemia and has been shown to be possible in laboratory studies. However, neuroprotection has not been successfully translated into clinical practice, despite voluminous research and controlled clinical trials. We suggested these failures may be due, at least in part, to the lack of a general theory of cell injury to guide research into specific injuries. The nonlinear dynamical theory of acute cell injury was introduced to ameliorate this situation. Here we present a revised nonautonomous nonlinear theory of acute cell injury and show how to interpret its solutions in terms of acute biomedical injuries. The theory solutions demonstrate the complexity of possible outcomes following an idealized acute injury and indicate that a “one size fits all” therapy is unlikely to be successful. This conclusion is offset by the fact that the theory can (1) determine if a cell has the possibility to survive given a specific acute injury, and (2) calculate the degree of therapy needed to cause survival. To appreciate these conclusions, it is necessary to idealize and abstract complex physical systems to identify the fundamental mechanism governing the injury dynamics. The path of abstraction and idealization in biomedical research opens the possibility for medical treatments that may achieve engineering levels of precision.

Clinically-relevant forms of acute cell injury, which include stroke and myocardial infarction, have been of long-lasting challenge in terms of successful intervention and treatments. Although laboratory studies have shown it is possible to decrease cell death after such injuries, human clinical trials based on laboratory therapies have generally failed. We suggested these failures are due, at least partially, to the lack of a quantitative theoretical framework for acute cell injury. Here we provide a systematic study on a nonlinear dynamical model of acute cell injury and characterize the global dynamics of a nonautonomous version of the theory. The nonautonomous model gives rise to four qualitative types of dynamical patterns that can be mapped to the behavior of cells after clinical acute injuries. In addition, the concept of a maximum total intrinsic stress response, S max * , emerges from the nonautonomous theory. A continuous transition across the four qualitative patterns has been observed, which sets a natural range for initial conditions. Under these initial conditions in the parameter space tested, the total induced stress response can be increased to 2.5-11 folds of S max * . This result indicates that cells possess a reserve stress response capacity which provides a theoretical explanation of how therapies can prevent cell death after lethal injuries. This nonautonomous theory of acute cell injury thus provides a quantitative framework for understanding cell death and recovery and developing effective therapeutics for acute injury.

Latar Belakang: Kebugaran jasmani menempati peran penting dalam segala komponen tubuh manusia. Tingkat kebugaran jasmani dipengaruhi oleh berbagai faktor, salah satunya aktivitas fisik. Masih rendahnya aktivitas fisik pada anak akan berdampak pada kualitas sumber daya manusia untuk pembangunan nasional di masa yang akan datang. Objektif: Penelitian ini bertujuan untuk mengetahui hubungan aktivitas fisik dengan kebugaran jasmani siswa. Metode: Penelitian ini merupakan penelitian analitik observasional dengan pendekatan potong lintang. Teknik pengambilan sampel dilakukan dengan total sampling dan jumlah sampel sebanyak 46 orang. Pengumpulan data menggunakan Global Physical Activity Questionnaire (GPAQ) dan Tes Kebugaran Jasmani Indonesia (TKJI). Analisis data menggunakan uji korelasi Pearson. Hasil: Rerata skor aktivitas fisik dan kebugaran jasmani siswa berturut-turut adalah 4362,43 MET/minggu dan 12,83. Terdapat korelasi bermakna antara aktivitas fisik dengan kebugaran jasmani siswa dengan nilai p=0,001 dan derajat korelasi Pearson sebesar 0,464. Kesimpulan: Terdapat hubungan aktivitas fisik dengan kebugaran jasmani siswa SDN 13 Sungai Pisang.

Dalam masyarakat, perolehan hak atas tanah lebih sering dilakukan dengan peralihan hak, yaitu dengan melalui jual beli. Syarat-syarat materiil jual beli sangat menentukan akan sahnya jual beli tanah tersebut. Jika salah satu syarat materiil ini tidak dapat dipenuhi, atau dikatakan penjual bukan merupakan orang yang berhak atas tanah yang  dijualnya atau pembeli tidak memenuhi syarat menjadi pemilik hak atas tanah menurut Undang-undang atau tanah yang diperjualbelikan sedang dalam sengketa atau merupakan tanah yang tidak boleh diperjualbelikan, maka jual beli tanah tersebut adalah tidak sah. Sertifikat merupakan surat tanda hak yang kuat akan tetapi sertifikat bukan satu-satunya surat tanda bukti pemegang hak atas tanah namun masih ada bukti lain tentang kepemilikan yang mampu membuktikan ketidakabsahan sertifikat tanah tersebut. Dalam hal sertifkat hak atas tanah yang diterbitkan oleh Kantor Pertanahan Kabupaten/Kota telah berusia 5 (lima) tahun tidak berarti hak menggugatnya hilang bagi orang yang merasa dirugikan atas diterbitkannya sertifikat hak atas tanah tersebut. Semua tanah yang termasuk tanah yang telah dilekatkan hak dapat dimohonkan pembatalan apabila terdapat putusan Pengadilan yang telah berkekuatan hukum tetap maupun adanya cacat hukum administrasi.

These direct observations of growth-state dependent TE activity demonstrate that real-time live-cell imaging of evolution at the molecular level is achievable, and can be a powerful tool to address fundamental questions related to genome plasticity in stressed cells.