關於 journal article structure ，我們在網路上蒐集到這些相關的討論、資訊與評價

你在路上應該沒看過跟你長一模一樣的人吧？👤👤

人類基因不會百分百遺傳，主要是因為人類的 #遺傳多樣性 靠父母染色體的配對跟互換，當🧬DNA互換不完美時就會發生基因變異。其中，DNA互換時負責在旁邊加油添醋，阿不是，是加油打氣的催化酵素叫做 ⭐DMC1⭐

雖然父母染色體的DNA序列很相似，卻不完全相同，但是DMC1卻可以協助不完美的DNA配對並完成完美互換！為什麼DMC1可以做到呢？㊙中研院的秘密武器 #高解析度冷凍電子顯微鏡 最近看穿這一套戲法！

🎯中研院與臺大研究團隊透過冷凍電顯技術，解出 #原子級解析度 的DMC1-DNA複合體結構，看到DMC1蛋白和DNA彼此相互作用時的分子細節。發現在DNA錯誤配對的位置，DMC1藉由結構上較大的空間與支持，允許DNA不完美配對與互換。

此發現未來對於因DMC1突變造成的不孕，及染色體分配不均而導致的疾病，可望提供分子層次上的解釋。

#中研院 #臺灣大學 #生化所 #何孟樵 #蔡明道 #冀宏源 #李弘文 #遺傳 #染色體 #冷凍電顯
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🔬幫劃重點：沒有這一台，可能就看不到了🔬
高解析度冷凍電子顯微鏡（cryo-EM）是現今結構生物研究最具發展潛力的技術，能在 #原子尺度，快速且不破壞性地觀察生物分子。簡單來說，一般光學顯微鏡頂多百倍，冷凍電顯則能看到十萬倍。

📍還是不懂？ https://research.sinica.edu.tw/tsai-ming-daw-cryo-electron-microscope/
📍論文連結：https://www.nature.com/articles/s41467-020-20258-1

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Genetic diversity is a key driving force of evolution. During homologous recombination, chromosomes from father and mother will pair together to exchange the genetic material leading to genetic diversity. In the process of chromosome pairing, the DMC1 protein is the key enzyme that catalyzes the DNA exchange reaction. What puzzles scientists is that although the chromosomal DNA sequences of the father and mother are similar, they are not completely the same. How DMC1 can tolerate the imperfection? What is the underlying mechanism? The research teams from National Taiwan University and Academia Sinica used a newly established cryo-electron microscopy facility and biochemical experiments to show that the DMC1 protein possesses a unique structure to accommodate imperfect pairing. The research results were published in the top-tier journal Nature Communications in January, 2021.

‧Article: https://www.nature.com/articles/s41467-020-20258-1

《原來臍帶除了臍帶血還有臍帶膜？》

有不少讀者都對臍帶的醫療用途有興趣，上回跟大家分享完臍帶血後，今日跟大家講講比較少人聽過的「臍帶膜」。

上回提到過去小Baby出生後，臍帶大多被當做醫療廢物，在過去的三十年臍帶血持續發展，透過幹細胞治療血液類疾病。而近年，除了臍帶血外，科學家發現了原來臍帶外層的膜（Lining）也有潛在的醫療用途。

【何謂臍帶膜（Umbilical Cord Lining Membrane）】

在講解臍帶膜前，先講解一下臍帶的歷史背景。

17世紀英國醫學家Thomas Wharton發現臍帶組織（Stroma）含有一種啫喱狀的物質，將其命名為Wharton's jelly。這層啫喱的作用為防止臍帶血管（靜脈和動脈）交叉（clumping）和提供臍帶的彈性。1991年科學家McElreavey從Wharton's jelly中分離出類似纖維母細胞的細胞（Fibroblast-like cells）[1]，而這些Fibroblast-like cells在2004年被發現是幹細胞的一種 - 間質幹細胞（Mesenchymal Stem Cells MSCs） [2]。自此臍帶不同的組織便成為科學家的研究對象。

隨著臍帶研究的發展，近年科學家發現能夠利用CellOptimaTM 技術從臍帶外層的組織（臍帶膜）裡提取更多的幹細胞 - 除了間質幹細胞（Mesenchymal Stem Cells MSCs）外，還可提取上皮幹細胞（Epthelial Stem Cells EpSCs）［3］。

那麼，這些EpSCs和MSCs幹細胞跟臍帶血的造血幹細胞（Hematopoietic Stem Cells HSCs）有什麼分別呢？

臍帶血的造血幹細胞主要作用是生成為不同的血液細胞，如之前文章提及到的紅血球、白血球和血小板，可用作治療個別血液類疾病如血癌和個別免疫系統疾病。

MSCs幹細胞則可生成為一些組成不同器官如皮膚、軟骨組織、腦部、心臟和肌肉等等的細胞。

EpSCs幹細胞則可生成為一些組成皮膚或空心（Hollow Structure）的器官如腸臟、氣管、膀胱和子宮等等的細胞。

由於MSCs跟EpSCs幹細胞有生成作不同器官的潛能，近年不少科學家紛紛收集臍帶進行研究。

研究發現MSCs幹細胞有以下潛能並正在對這些疾病進行動物實驗和臨床試驗。[4]

1. 心血管疾病如心肌梗塞和心肌無力症
2. 腦神經系統疾病如腦退化症、多發性硬化症和脊柱神經受傷等等
3. 自體免疫系統疾病如一型糖尿病、自體免疫性肝炎、潰瘍性結腸炎、紅斑狼瘡和類風濕性關節炎等等

令人鼓舞的是，根據目前的臨床試驗公怖結果，在自體免疫系統疾病和內分泌疾病方面，移植MSCs幹細胞後，病情有顯著的改善。同時有研究亦發現MSCs幹細胞有較低的免疫原性（Immunogenicity）、相當較能避開人體免疫系統的識別，減低移植排斥反應。現時不少的臨床研究制用此特性，探討將MSCs幹細胞用作異體移植（Allogeneic Transplantation）例如近親甚至免疫不相容（HLA-Mismatch）的外人等[8]， MSCs幹細胞的移植技術的研究開始了二十多年，目前的研究成果相當正面，其低免疫原性的特質在未來能夠怎樣應用在免疫不相容的病人身上實在值得我們期待。[2][5][8]

而EpSCs幹細胞方面，研究發現或許有以下潛在臨床應用 [6][7]

1. 燒傷治療和傷口癒合
2. 一型糖尿病
3. 肝臟衰竭

不過由於有關臍帶膜的研究，並不被歸納為醫療系統常用的治療，現有的應用均為實驗性質。雖然目前研究仍處床試驗階段，但隨著移植的個案越來越多，臍帶膜的幹細胞似乎有著不少的發展潛力。

跟上回提到臍帶血一樣，從收集臍帶膜到儲存臍帶膜及臨床實驗性應用都有嚴謹的要求，例如運送的時間、過程、儲存系統以及國際認證。

近年不少提供臍帶血儲存服務的生物科技公司同時有提供儲存臍帶膜的服務[2]。跟臍帶血一樣，目前並非醫療系統會資助的常見項目，故對一般家庭來可謂一筆大開支。

正在考慮儲存臍帶血或膜的孕婦宜先充分調查不同臍帶生物科技公司的背景、財政狀況、過去的移植紀錄、使用的儲存技術等等。同時，如有任何疑問務必諮詢專家或醫生意見以作informed decision。

【Reference】
[1] Isolation, Culture and Characterisation of Fibroblast-Like Cells Derived From the Wharton's Jelly Portion of Human Umbilical Cord. Stem Cell Biochemical Society Transaction. https://portlandpress.com/biochemsoctrans/article/19/1/29S/81930/Isolation-culture-and-characterisation-of

[2] The Therapeutic Potential, Challenges and Future Clinical Directions of Stem Cells From the Wharton's Jelly of the Human Umbilical Cord. Stem Cell Reviews and Reports. https://link.springer.com/article/10.1007/s12015-012-9418-z

[3] Epithelial and Mesenchymal Stem Cells From the Umbilical Cord Lining Membrane. Cell Transplant.
https://pubmed.ncbi.nlm.nih.gov/24636188/

[4] Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy. Stem Cells international. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019943/

[5]Immunogenicity and Immunomodulatory Properties of Umbilical Cord Lining Mesenchymal Stem Cells. Cell Transplant. https://pubmed.ncbi.nlm.nih.gov/21054940/

[6] Short review on human umbilical cord lining epithelial cells and their potential clinical applications. Stem Cell Research & Therapy. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634865/#CR40

[7] Longitudinal In-Vivo Volumetry Study for Porcine Liver Regeneration From CT Data. 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. https://ieeexplore.ieee.org/document/6944684

[8] The Importance of HLA Assessment in “Off-the-Shelf” Allogeneic Mesenchymal Stem Cells Based-Therapies. International Journal of Molecular Sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888380/

Photo: Internet Photo

#研究分析 #科普系列 #臍帶膜 #上皮幹細胞 #間質幹細胞 #CellOptima #MesenchymalStemCells #EpthelialStemCells

🇩🇰 這是一篇深度報導，來自歐洲現存最古老的報紙：丹麥Weekendavisen，題目是從香港抗爭運動、香港聯繫加泰羅尼亞的集會，前瞻全球大城市的「永久革命」。一篇報導訪問了世界各地大量學者，我也在其中，雖然只是每人一句，加在一起，卻有了很完整的圖像。

以下為英譯：

Protest! The demonstrations in Hong Kong were just the beginning. Now there are unrest in big cities from Baghdad to Barcelona. Perhaps the stage is set for something that could look like a permanent revolution in the world's big cities.

A world on the barricades

At the end of October, an hour after dark, a group of young protesters gathered at the Chater Garden Park in Hong Kong. Some of them wore large red and yellow flags. The talk began and the applause filled the warm evening air. There were slogans of independence, and demands of self-determination - from Spain. For the protest was in sympathy with the Catalan independence movement.

At the same time, a group of Catalan protesters staged a protest in front of the Chinese Consulate in Barcelona in favor of Hong Kong's hope for more democracy. The message was not to be mistaken: We are in the same boat. Or, as Joshua Wong, one of the leading members of the Hong Kong protest movement, told the Catalan news agency: "The people of Hong Kong and Catalonia both deserve the right to decide their own destiny."

For much of 2019, Hong Kong's streets have been ravaged by fierce protests and a growing desperation on both sides, with escalating violence and vandalism ensuing. But what, do observers ask, if Hong Kong is not just a Chinese crisis, but a warning of anger that is about to break out globally?

Each week brings new turmoil from an unexpected edge. In recent days, attention has focused on Chile. Here, more than 20 people have lost their lives in unrest, which has mainly been about unequal distribution of economic goods. Before then, the unrest has hit places as diverse as Lebanon and the Czech Republic, Bolivia and Algeria, Russia and Sudan.

With such a geographical spread, it is difficult to bring the protests to any sort of common denominator, but they all reflect a form of powerlessness so acute that traditional ways of speaking do not seem adequate.

Hardy Merriman, head of research at the International Center for Nonviolent Conflict in Washington, is not in doubt that it is a real wave of protest and that we have not seen the ending yet.

"I have been researching non-violent resistance for 17 years, and to me it is obvious that there are far more popular protest movements now than before. Often the protests have roots in the way political systems work. Elsewhere, it is about welfare and economic inequality or both. The two sets of factors are often related, ”he says.

Economic powerlessness

Hong Kong is a good example of this. The desire among the majority of Hong Kong's seven million residents to maintain an independent political identity vis-à-vis the People's Republic of China is well known, but the resentment of the streets is also fueled by a sense of economic powerlessness. Hong Kong is one of the most unequal communities in the world, and especially the uneven access to the real estate market is causing a stir.

According to Lee Chun-wing, a sociologist at Hong Kong Polytechnic University, the turmoil in the city is not just facing Beijing, but also expressing a daunting showdown with the neoliberal economy, which should diminish the state's role and give the market more influence, but in its real form often ends with the brutal arbitrariness of jungle law.

'The many protests show that neoliberalism is unable to instill hope in many. And as one of the world's most neoliberal cities, Hong Kong is no exception. While the protests here are, of course, primarily political, there is no doubt that social polarization and economic inequality make many young people not afraid to participate in more radical protests and do not care whether they are accused of damage economic growth, 'he says.

The turmoil is now so extensive that it can no longer be dismissed as a coincidence. Something special and significant is happening. As UN Secretary General António Guterres put it last week, it would be wrong to stare blindly at the superficial differences between the factors that get people on the streets.
“There are also common features that are recurring across the continents and should force us to reflect and respond. It is clear that there is growing distrust between the people and the political elites and growing threats to the social contract. The world is struggling with the negative consequences of globalization and the new technologies that have led to growing inequality in individual societies, "he told reporters in New York.

Triggered by trifles

In many cases, the riots have been triggered by questions that may appear almost trivial on the surface. In Chile, there was an increase in the price of the capital's subway equivalent to 30 Danish cents, while in Lebanon there were reports of a tax on certain services on the Internet. In both places, it was just the reason why the people have been able to express a far more fundamental dissatisfaction.

In a broad sense, there are two situations where a population is rebelling, says Paul Almeida, who teaches sociology at the University of California, Merced. The first is when more opportunities suddenly open up and conditions get better. People are getting hungry for more and trying to pressure their politicians to give even more concessions.

“But then there is also the mobilization that takes place when people get worse. That seems to be the overall theme of the current protests, even in Hong Kong. People are concerned about various kinds of threats they face. It may be the threat of inferior economic conditions, or it may be a more political threat of erosion of rights. But the question is why it is happening right now. That's the 10,000-kroner issue, ”says Almeida.

Almeida, who has just published the book Social Movements: The Structure of Social Mobilization, even gives a possible answer. A growing authoritarian, anti-democratic flow has spread across the continents and united rulers in all countries, and among others it is the one that has now triggered a reaction in the peoples.

“There is a tendency for more use of force by the state power. If we look at the death toll in Latin America, they are high considering that the countries are democracies. This kind of violence is not usually expected in democratic regimes in connection with protests. It is an interesting trend and may be related to the authoritarian flow that is underway worldwide. It's worth watching, 'he says.

The authoritarian wave

Politologists Anna Lürhmann and Staffan Lindberg from the University of Gothenburg describe in a paper published earlier this year a "third autocratic wave." Unlike previous waves, for example, in the years before World War II, when democracy was beaten under great external drama , the new wave is characterized by creeping. It happens little by little - in countries like Turkey, Nicaragua, Venezuela, Hungary and Russia - at such a slow pace that you barely notice it.

Even old-fashioned autocrats nowadays understand the language of democracy - the only acceptable lingua franca in politics - and so the popular reaction does not happen very often when it becomes clear at once that the electoral process itself is not sufficient to secure democratic conditions. Against this backdrop, Kenneth Chan, a politician at Hong Kong Baptist University, sees the recent worldwide wave of unrest as an expression of the legitimacy crisis of the democratic regimes.

“People have become more likely to take the initiative and take part in direct actions because they feel that they have not made the changes they had hoped for through the elections. In fact, the leaders elected by the peoples are perceived as undermining the institutional guarantees of citizens' security, freedom, welfare and rights. As a result, over the past decade, we have seen more democracies reduced to semi-democracies, hybrid regimes and authoritarian regimes, ”he says.

"Therefore, we should also not be surprised by the new wave of resistance from the people. On the surface, the spark may be a relatively innocent or inconsiderate decision by the leadership, but people's anger quickly turns to what they see as the cause of the democratic deroute, that is, an arrogant and selfish leadership, a weakened democratic control, a dysfunctional civil society. who are no longer able to speak on behalf of the people. ”The world is changing. Anthony Ince, a cardiff at Cardiff University who has researched urban urban unrest, sees the uprisings as the culmination of long-term nagging discontent and an almost revolutionary situation where new can arise.

"The wider context is that the dominant world order - the global neoliberalism that has dominated since the 1980s - is under pressure from a number of sides, creating both uncertainty and at the same time the possibility of change. People may feel that we are in a period of uncertainty, confusion, anxiety, but perhaps also hope, ”he says.
Learning from each other.

Apart from mutual assurances of solidarity the protest movements in between, there does not appear to be any kind of coordination. But it may not be necessary either. In a time of social media, learning from each other's practices is easy, says Simon Shen, a University of Hong Kong political scientist.

“They learn from each other at the tactical level. Protesters in Hong Kong have seen what happened in Ukraine through YouTube, and now protesters in Catalonia and Lebanon are taking lessons from Hong Kong. It's reminiscent of 1968, when baby boomers around the globe were inspired by an alternative ideology to break down rigid hierarchies, 'he says.
But just as the protest movements can learn from each other, the same goes for their opponents. According to Harvard political scientist Erica Chenoweth, Russia has been particularly active in trying to establish cooperation with other authoritarian regimes, which feel threatened by riots in the style of the "color revolutions" on the periphery of the old Soviet empire at the turn of the century.

"It has resulted in joint efforts between Russian, Chinese, Iranian, Venezuelan, Belarusian, Syrian and other national authorities to develop, systematize and report on techniques and practices that have proved useful in trying to contain such threats," writes Chenoweth in an article in the journal Global Responsibility to Protect.

Max Fisher and Amanda Taub, commentators at the New York Times, point to the social media as a double-edged sword. Not only are Twitter and Facebook powerful weapons in the hands of tech-savvy autocrats. They are also of questionable value to the protesting grass roots. With WhatsApp and other new technologies, it is possible to mobilize large numbers of interested and almost-interested participants in collective action. But they quickly fall apart again.

The volatile affiliation is one of the reasons why, according to a recent survey, politically motivated protests today only succeed in reaching their targets in 30 percent of cases. A generation ago, the success rate was 70 percent. Therefore, unrest often recurs every few years, and they last longer, as Hong Kong is an example of. Perhaps the scene is set for something that might resemble a permanent revolution in the world's big cities - a kind of background noise that other residents will eventually just get used to.

"Since there is still no obvious alternative to neoliberalism, the polarization that led to the protests initially will probably continue to apply," says Lee of Hong Kong Polytechnic University. "At the same time, this means that the anger and frustration will continue to rumble in society."