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中文翻譯日文

在此之前，在涉及上述各種帕金森氏症的基因間，沒有顯明份子聯系關系性。” Khurana暗示：「他們認為，上述方式可能為將來研發特定病患的療法鋪路。」

帕金森氏症(PD)及其他“突觸核蛋白病”已知，與神經元中的α突觸核卵白錯誤折疊有關翻譯透過人類遺傳學的闡明，較不清晰的是，此毛病摺疊如何觸及帕金森氏症中，增多遭連累的基因數量。

在發表於先行網路版《細胞系統》期刊的兩篇研究中，附屬美國麻省理工學院及懷特海德生物醫學研究所的研究人員們解釋了，他們若何利用一套新的生物暨計算方法，來說明上述問題。

“Among them were multiple genes known to predispose individuals to Parkinson’s—so we show that various genetic forms of Parkinson’s are directly related to alpha-synuclein. Moreover, the results showed that many effects of alpha-synuclein have been conserved across a billion years of evolution from yeast to human,” said Khurana, former Visiting Scientist at the Whitehead Institute.

“In the second paper, we created a spatial map of alpha-synuclein, cataloging all the proteins in living neurons that were in close proximity to the protein,” explained Chee Yeun Chung翻譯社 former Whitehead Institute Senior Research Scientist翻譯社 who co-led both studies with Khurana.

懷特海德生物醫學研究所前客座科學家，Khurana宣稱：「其中多個是已知，使個別易得帕金森氏症的基因，因此他們證實，帕金森氏症的各種遺傳情勢，直接與α突觸核卵白有關翻譯此外，這些研究成效證實了，α突觸核卵白的諸多作用，在經歷十億年的演化中，從酵母菌到人類一向是守恆的。」

入手下手，他們設計了兩種有系統繪製活細胞內α突觸核卵白足跡圖的方法翻譯這兩篇研究的重要暨配合通信撰文人，Vikram Khurana诠釋：「第一篇論文中，在麵包酵母細胞樣本中，他們利用了強有力且不偏不倚的遺傳東西，來確認332個影響α突觸核卵白毒性的基因。」

為了證實他們的研究，此些研究人員從具有分歧帕金森氏症遺傳情勢的患者產生了神經元翻譯他們證實，從其闡明圖產生的分子圖，使他們得以確認此些不同形式帕金森氏症中，共有的異常。

“The result was TransposeNet, a new suite of computational tools that uses machine learning algorithms to visualize patterns and interaction networks based on genes that are highly conserved from yeast to humans—and then makes predictions about the additional genes that are part of the alpha-synuclein toxicity response in humans.”

This analysis produced networks that mapped out how alpha-synuclein is related to other Parkinson’s genes through well-defined molecular pathways. “We now have a system to look at how seemingly unrelated genes come together to cause Parkinson’s and how they are related to the protein that misfolds in this disease,” said Khurana.

Prior to this翻譯社 there was no obvious molecular connection between the genes implicated in these varieties of PD. "We believe these methods could pave the way for developing patient-specific treatments in the future,” Khurana observed.

The mapping was achieved without disturbing the native environment of the neuron, by tagging alpha-synuclein with an enzyme—APEX—that allowed proteins less than 10 nanometers away from synuclein to be marked with a trackable fingerprint.

“It turns out the mechanisms of toxicity of the misfolded protein are closely related to which proteins it directly interacts with翻譯社 and that these interactions can explain connections between different Parkinson’s genetic risk factors翻譯社” said Khurana, now a Principal Investigator within the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital and the Harvard Stem Cell Institute.

原文網址：http://wi.mit.edu/news/archive/2017/new-clues-basis-parkinson-s-disease-and-other-synucleinopathies

此分析產生了，精確顯示出α突觸核蛋白若何透過明確分子路子，而與其他帕金森氏症的基因有關翻譯Khurana傳播鼓吹：「今朝，他們擁探討看似不相幹基因，如何一起引發帕金森氏症及此些基因如何與該疾病中，毛病摺疊卵白質有聯系關系的方式。」

Finally翻譯社 the authors addressed two major challenges for any study that generates large data-sets of individual genes and proteins in model organisms like yeast: How to assemble the data into coherent maps? And how to integrate information across species翻譯社 in this case from yeast to human?

目前是美國麻薩諸塞州波士頓市布里根婦女醫院Ann Romney神經病學疾病中心，及哈佛大學醫學院幹細胞研究所重要查詢拜訪研究員的Khurana傳播鼓吹：「這證實了，毛病摺疊的卵白質毒性機理，與其直接交互感化的蛋白質有密切聯系關系，並且此些交互感化能诠釋，帕金森氏症分歧遺傳風險因子間的關聯性。」

Enter computational biologist Jian Peng, former Visiting Scientist at Whitehead Institute and postdoctoral researcher at MIT. “First, we had to figure out much better methods to find human counterparts of yeast genes, and then we had to arrange the humanized set of genes in a meaningful way,” explained Peng, now Assistant Professor of Computer Sciences at University of Illinois, Urbana-Champaign.

In two studies published in the advance online edition of Cell Systems, researchers affiliated with Whitehead Institute and Massachusetts Institute of Technology (MIT) explain how they used a suite of novel biological and computational methods to shed light on the question. 

今朝是美國麻薩諸塞州劍橋市Yumanity Therapeutics生物手藝公司的科學配合開創人兼副總監的Chung強調：「了局，他們首度能在完整腦細胞的生理狀況下，以極微小標准視覺化該卵白質的位置翻譯」

翻譯：許東榮

與Khurana配合領導這兩項研究的懷特海德生物醫學研究所，前資深研究科學家Chee Yeun Chung解釋：「在第二篇論文中，他們設計了α突觸核卵白的空間圖，來將活神經元中特別很是接近該蛋白的所有蛋白質編入目次中。」

Parkinson’s disease (PD) and other “synucleinopathies” are known to be linked to the misfolding of alpha-synuclein protein in neurons. Less clear is how this misfolding relates to the growing number of genes implicated in PD through analysis of human genetics.

Remarkably, the maps derived from these two processes were closely related and converged on the same Parkinson’s genes and cellular processes. Whether in a yeast cell or in a neuron, alpha synuclein directly interfered with the rate of production of proteins in the cell, and the transport of proteins between cellular compartments.

懷特海德生物醫學研究所前客座科學家，及麻省理工學院博士後研究員的較量爭論生物學家，今朝是美國伊利諾大學厄巴納-香檳分校計較機科學助理傳授，Jian Peng解釋：「起首，他們必須想出更好的方式，來找出酵母基因的人類對應物，然後必需以有意義的方式，來整理具有人類屬性的基因組翻譯」

To start翻譯社 they created two ways to systematically map the footprint of alpha-synuclein within living cells. “In the first paper翻譯社 we used powerful and unbiased genetic tools in the simple Baker’s yeast cell to identify 332 genes that impact the toxicity of alpha-synuclein,” explained Vikram Khurana翻譯社 first and co-corresponding author on the studies.

To confirm their work, the researchers generated neurons from Parkinson’s patients with different genetic forms of the disease. They showed that the molecular maps generated from their analyses allowed them to identify abnormalities shared among these distinct forms of Parkinson’s.

惹人注視的是，這些源自上述兩種方法的圖是密切相關的，且集中於相同帕金森氏症的基因及細胞變化過程。不論於酵母細胞或神經元中，α突觸核卵白皆直接干擾此細胞諸卵白質的產生速度，及細胞分室間的卵白質輸送。

“As a result, for the first time, we were able to visualize the protein’s location翻譯社 at minute scale翻譯社 under physiologic conditions in an intact brain cell翻譯社” noted Chung翻譯社 who is now Scientific Co-founder and Associate Director at Yumanity Therapeutics in Cambridge. 

藉由使用一種，使距離突觸核蛋白不及10奈米的卵白質得以，利用可追蹤酶解圖譜被標識表記標幟的酵素(APEX)，來符號α突觸核卵白。上述圖的繪製，是在沒有擾亂神經元天然情況下告竣的。

最後，此些撰文者們面對了，有關在雷同酵母菌的模型生物中，產生大量個別基因及卵白質數據集之任何研究的兩項重大挑戰：若何將此些數據組合成協調的圖？及若何整合此事例中，從酵母菌到人類的跨物種資訊？

「成績是轉置網(TransposeNet：一套根據從酵母到人類是高度守恆的基因，利用進修演算法的機械來視覺化模式及互動網絡，然後作出猜測有關，屬人類α突觸核卵白毒性反映一部份之額外基因的新計算工具。」