Discovering RNA-Protein Interactome by Using Chemical Context Profiling of the RNA-Protein Interface

SummaryRNA-protein (RNP) interactions generally are required for RNA function. At least 5% of human genes code for RNA-binding proteins. Whereas many approaches can identify the RNA partners for a specific protein, finding the protein partners for a specific RNA is difficult. We present a machine-learning method that scores a protein’s binding potential for an RNA structure by utilizing the chemical context profiles of the interface from known RNP structures. Our approach is applicable even when only a single RNP structure is available. We examined 801 mammalian proteins and find that 37 (4.6%) potentially bind transfer RNA (tRNA). Most are enzymes involved in cellular processes unrelated to translation and were not known to interact with RNA. We experimentally tested six positive and three negative predictions for tRNA binding in vivo, and all nine predictions were correct. Our computational approach provides a powerful complement to experiments in discovering new RNPs

<原著>Heat shockの阻血腎移植モデルに対する効果

体温の上昇に伴い細胞に特有の反応がみられ, Heat shock response (HSR) と呼ばれている. この HSR が種々の侵襲に対し, 一過性の生体防御機構を担っているといわれており, 我々は, 出血性及び Anoxic shock による混阻血腎を用いた腎移植モデルにおける HSR の効果について検討した. 雑種豚を用い, 実験群を以下の2群に分けた. 1群 (control 群): donor を急速脱血し血圧 50 mmHg 以下に10分間維持した後, 気管内挿管チューブをクランプした anoxic shock を作製した群, 2群 (heat shock 群): donor の体温を heat exchanger を用い, 15分間 42. 5℃ に維持した後, 4 - 6時間の常温期聞をおいた後, 1群同様の出血性及び Anoxic shock を作製した群とした. 両群とも計90分間の温阻血後腎摘出, 20時間低温持続潅流し, recipient の両側腎摘出, 阻血腎を異所性に移植し, 免疫抑制剤投与のもと, 術後経過を行った. 術後10日までの生存率は, 1群 4/8 (50%) に対し, 2群7. 8 (87. 5%) であった. 術後7日自の血清クレアチニン値は, 1群 11. 2±4. 0 mg/dl に対し, 2群 3. 7±2. 7 mg/dl と有意な差 (p<0. 01) を認めた. 病理学的にも, 細胞障害は1群に比べ2群ではより軽度であった. 今回の実験結果では, HSR が, 阻血腎に対する防御作用を認め, 重度ショック豚腎の移植が可能であることが示唆された. Heat shock により正常の蛋白の合成低下と Heat shock proteins (HSP) と呼ばれる一群の蛋白合成が誘導されることが知られている. そして, HSR の生体防御機構と HSP の合成能の消長が相関するともいわれており, 今後, さらに詳しい HSR の生理学的意義とともに, HSP 自体の細胞・遺伝子レベノレでの機能解析を通じて, その臨床への応用も可能なものと考えている

Estimating the Clinical and Economic Impact of Switching from the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) to Higher-Valent Options in Greek Infants

In June 2010, Greece introduced the 13-valent pneumococcal conjugate vaccine (PCV13) for pediatric vaccination and has since observed a large decrease in pneumococcal disease caused by these vaccine serotypes, yet the disease prevalence of non-vaccine serotypes has increased. Two higher-valent conjugate vaccines, a 15-valent (PCV15) and a 20-valent (PCV20), were developed to improve serotype coverage and combat serotype replacement. A decision-analytic model was adapted to the Greek setting using historical pneumococcal disease trends from PCV13 to forecast future clinical and economic outcomes of higher-valent PCVs over a 10-year period (2023–2033). The model estimated outcomes related to invasive pneumococcal disease (IPD), hospitalized and non-hospitalized pneumonia, and otitis media (OM) resulting from a switch in vaccination programs to PCV15 in 2023 or switching to PCV20 in 2024. Cost-effectiveness was evaluated from the third-party payer’s perspective in the Greek healthcare system. Compared to implementing PCV15 one year earlier, switching from PCV13 to PCV20 in 2024 was estimated to be a cost-saving strategy by saving the Greek health system over EUR 50 million in direct medical costs and averting over 250 IPD cases, 54,800 OM cases, 8450 pneumonia cases, and 255 deaths across all ages over a 10-year period

Preoperative stress conditioning prevents paralysis after experimental aortic surgery: Increased heat shock protein content is associated with ischemic tolerance of the spinal cord

AbstractBackground: All forms of surgical therapy are stressful and injurious. The problems of paralysis, renal dysfunction, and colonic ischemia associated with aortic occlusion are due to acute ischemia-reperfusion injury at the cellular level. Acute-anterior spinal cord ischemia is the most devastating outcome of these iatrogenic-ischemic events. The majority of surgical procedures are performed electively and therefore provide an opportunity to preoperatively condition the patient to minimize these ischemia-related morbidities. Objectives: We sought to determine whether acute spinal cord injury associated with aortic occlusion can be prevented by induction of the cellular stress response by means of preoperative administration of whole-body hyperthermia or stannous chloride. Methods: The study consisted of an experimental rabbit model of infrarenal aortic occlusion for 20 minutes at normothermic body temperature. Results: Control rabbits experienced an 88% (7/8) incidence of paralysis after spinal cord ischemia induced by 20 minutes of aortic occlusion, whereas animals treated preoperatively with either whole-body hyperthermia (0/9) or stannous chloride (0/4) never became paralyzed (P <.001 for control vs treated groups). Ischemic protection of the spinal cord was associated with increased content of stress proteins within tissues of pretreated animals. Conclusion: Prior induction of the heat shock response in the whole animal will increase the content of stress proteins within the spinal cord and other tissues and result in the prevention of hind-limb paralysis associated with aortic occlusion. We have designated the preoperative induction of the cellular stress response for the prevention of ischemic tissue injury stress conditioning. We suggest that stress-conditioning protocols represent the opportunity to practice preventative medicine at the molecular level.J Thorac Cardiovasc Surg 2002;124:162-7

Improving acute skin-flap survival through stress conditioning using heat shock and recovery

We present our initial experience with a new method of increasing the survival of acute skin flaps through stress conditioning using heat shock and recovery. The heat-shock response is a basic form of stress response that exists on the cellular level. When cultured cells or whole organisms are exposed to supraphysiologic levels of heat, they respond by synthesizing a number of highly conserved proteins known as heat-shock proteins. These proteins have been shown to offer the cell or organism a survival advantage over nonstressed controls.The study demonstrates a significant survival advantage in acute dorsal skin flaps of Sprague-Dawley rats (p = 0.001). Study animals (n = 10) were subjected to a heating blanket set at 45°C for 30 minutes and were allowed 6 hours' recovery before developing the flaps. Heat-shock protein was demonstrated in immunohisto-chemically stained sections of skin from the study animals but not in control animal skin (n = 14).We postulate that through stress conditioning a latent mechanism present within all cells was activated, thereby allowing the cells of our experimental flaps to better survive the stress of the acute flap model