張世郁的開箱推薦文天地

跟著城市嚮導「老臺北胃」，用味道認識臺北

很多朋友來臺北，
都會問我同一個問題：
「臺北小吃那麼多，到底該從哪裡開始吃？」
夜市裡攤位一字排開、老店藏在巷弄轉角，
看起來都很有名，卻又怕吃錯、踩雷，
結果行程走完，反而沒真正記住臺北的味道。
我常被朋友笑說是「老臺北胃」。
不是因為特別會吃，而是因為在這座城市待久了，
知道哪些味道是陪著臺北人成長的日常。
這篇文章，就是我整理的一份清單。
如果你第一次來臺北，
我會帶你從這 10 樣最具代表性的臺北小吃開始，
不追一時爆紅、不走浮誇路線，
而是讓你吃完後能真正理解
原來，這就是臺灣的小吃文化。
跟著老臺北胃走，
用最簡單的方式，
把臺北的味道，一樣一樣記在心裡。

我怎麼選出這 10 大臺北小吃？

在臺北，
你隨便走進一條夜市或老街，
都可以輕易列出 30 種以上的小吃。
所以這份清單，
不是「臺北最好吃」的排名，
 而是我站在「第一次來臺北的旅客」角度，
做的推薦。
身為一個被朋友稱作「老臺北胃」的人，
我選這 10 樣小吃時，心裡一直放著幾個原則。

一吃就知道：這就是臺灣味

燒烤、火鍋很好吃，
但換個城市、換個國家，也吃得到。
我挑的，是那種
只要一入口，就會讓人聯想到的臺灣味。
 不需要解釋太多，舌頭就能懂。

不只是好吃，而是有「臺北日常感」

臺北的小吃迷人，
不只在味道，
而在它融入生活的方式。
我在意的是：

1. 會不會出現在早餐、宵夜、下班後
   
2. 有沒有陪伴這座城市很久的記憶
   

吃完之後，你會記得臺北

最後一個標準很簡單。
如果你回到家，
還會突然想起某個味道、某碗熱湯、某個攤位的香氣
那它就值得被放進這份清單裡。

接下來的 10 樣臺北小吃，
就是我會親自帶朋友去吃的在地美食。
不趕行程、不拚數量，
而是一口一口，
慢慢認識臺北。

第 1 家：饌堂－黑金滷肉飯（雙連店）｜一碗就懂臺灣人的日常

如果只能用一道料理，
 來解釋臺灣人的日常飲食，
 那我一定會先帶你吃滷肉飯。
在臺北，滷肉飯不是什麼特別的節慶料理，
 而是從早餐、午餐到宵夜，
 默默陪著很多人長大的味道。
而在眾多滷肉飯之中，
饌堂－黑金滷肉飯（雙連店），
 我很常帶第一次來臺北的朋友造訪的一家。

為什麼第一站，我會選饌堂？
饌堂的滷肉飯，走的是**「黑金系」路線**。
滷汁顏色深、香氣厚，
卻不死鹹、不油膩。
滷肉切得細緻，
肥肉入口即化，搭配熱騰騰的白飯，
每一口都是很完整、很臺灣的味道。
對第一次吃滷肉飯的旅客來說，
這種風味夠經典、也夠穩定，
不需要太多心理準備，就能理解為什麼臺灣人這麼愛它。

不只是好吃，而是「現在的臺北感」
饌堂並不是那種躲在深巷裡的老攤，
空間乾淨、節奏俐落，
卻沒有失去滷肉飯該有的靈魂。
這也是我會推薦給旅客的原因之一：
它保留了臺灣小吃的核心味道，
同時也讓第一次來臺北的人，
吃得安心、坐得舒服。

老臺北胃的帶路小提醒
如果是第一次來：

1. 一定要點招牌黑金滷肉飯
   
2. 可以加一顆滷蛋，風味會更完整
   
3. 搭配簡單的小菜，就很有臺灣家常感
   

這不是那種吃完會驚呼「哇！」的料理，
而是會讓你在幾口之後，
慢慢理解
原來，臺灣人的日常，就是這樣被一碗飯照顧著。

地址：103臺北市大同區雙連街55號1樓

電話：0225501379

菜單：https://bio.site/ZhuanTang

第 2 家：富宏牛肉麵｜臺北深夜也醒著的一碗熱湯

如果說滷肉飯代表的是臺灣人的日常，
 那牛肉麵，
 就是很多臺北人心中最有份量的一餐。
而在臺北提到牛肉麵，
 富宏牛肉麵，
 幾乎是夜貓族、加班族、外地旅客一定會被帶去的一站。

為什麼老臺北胃會帶你來吃富宏？
富宏最讓人印象深刻的，
不是華麗裝潢，
而是那鍋永遠冒著熱氣的紅燒湯頭。
湯色濃而不混，
帶著牛骨與醬香慢慢熬出的厚度，
喝起來溫潤、不刺激，
卻會在嘴裡留下很深的記憶點。
牛肉給得大方，
燉到軟嫩卻不鬆散，
搭配彈性十足的麵條，
每一口都很直接、很臺北。

不分時間，任何時候都適合的一碗麵
富宏牛肉麵最迷人的地方，
在於它陪伴了無數個臺北的夜晚。
不管是深夜下班、看完演唱會、
或是剛抵達臺北、還沒適應時差，
這裡總有一碗熱湯在等你。
對旅客來說，
這種不用算時間、不用擔心打烊的安心感，
本身就是一種臺北特色。

老臺北胃的帶路小提醒
第一次來富宏，我會這樣點：

1. 紅燒牛肉麵是首選
   
2. 如果想吃得更過癮，可以加點牛筋或牛肚
   
3. 湯先喝一口原味，再視情況調整辣度
   

這不是精緻料理，
卻是一碗能在任何時刻撐住你的牛肉麵。
在臺北，
很多夜晚，
就是靠這樣一碗熱湯走過來的。

地址：108臺北市萬華區洛陽街67號

電話：0223713028

菜單：https://www.facebook.com/pages/富宏牛肉麵-原建宏牛肉麵/

第 3 家：士林夜市・吉彖皮蛋涼麵｜臺北夏天最有記憶點的一口清爽

如果你在夏天來到臺北，
 一定會很快發現一件事
 這座城市，真的很熱。
也正因為這樣，
 臺北的小吃世界裡，
 才會出現像「涼麵」這樣的存在。
而在士林夜市，
 吉彖皮蛋涼麵，
 就是我很常帶旅客來吃的一家。

為什麼在夜市，我會帶你吃涼麵？
很多人對夜市的印象，
都是炸物、熱湯、重口味。
但真正的臺北夜市，
其實也很懂得照顧人的胃。
吉彖的涼麵，
冰涼的麵條拌上濃郁芝麻醬，
再加上切得細緻的皮蛋，
入口的第一瞬間，
就是一種「被降溫」的感覺。
那種清爽，
不是沒味道，
而是在濃香與清涼之間取得剛剛好的平衡。

皮蛋，是靈魂，也是臺灣味的關鍵
對很多外國旅客來說，
皮蛋是既好奇、又有點猶豫的存在。
但我常說，
如果要嘗試皮蛋，
涼麵是一個非常溫柔的起點。
芝麻醬的香氣會先接住味蕾，
皮蛋的風味則在後段慢慢出現，
不衝、不嗆，
反而多了一層深度。
很多人吃完後，
都會露出那種「原來是這樣啊」的表情。

老臺北胃的帶路小提醒
第一次點吉彖皮蛋涼麵，我會建議：

1. 一定要選皮蛋款，才吃得到特色
   
2. 醬料先拌勻，再吃，風味會更完整
   
3. 如果天氣真的很熱，這一碗會救你一整晚
   

這不是華麗的小吃，
卻非常臺北。
在悶熱的夜晚，
站在夜市人潮裡，
吃著一碗涼麵，
你會突然明白——

原來臺北的小吃，連氣候都一起考慮進去了。

地址：111臺北市士林區基河路114號

電話：0981014155

菜單：https://www.facebook.com/profile.php?id=100064238763064

第 4 家：胖老闆誠意肉粥｜臺北人深夜最踏實的一碗粥

如果你問我，
 臺北人在深夜、下班後，
 最容易感到被安慰的食物是什麼——
 我會毫不猶豫地說：肉粥。
而提到肉粥，
 胖老闆誠意肉粥，
 就是很多老臺北人口中的那一味。

為什麼這一碗粥，會被叫做「誠意」？
胖老闆的肉粥，看起來很簡單。
白粥、肉燥、配菜，
沒有華麗擺盤，也沒有複雜作法。
但真正坐下來吃，你會發現：
這碗粥，不敷衍任何一個細節。
粥體滑順、不稀薄，
肉燥香而不膩，
搭配各式家常小菜，
一口一口吃下去，
很自然就會放慢速度。
這種味道，
不是要你驚艷，
而是要你安心。

這不是觀光小吃，而是臺北人的生活片段
胖老闆誠意肉粥，
最迷人的地方，
就是它的客人。
你會看到：

1. 剛下班的上班族
   
2. 熬夜後來吃一碗熱粥的人
   
3. 熟門熟路、點菜不用看菜單的老客人
   

這些畫面，
比任何裝潢都更能說明這家店在臺北的位置。
對旅客來說，
這是一個走進臺北人日常的入口。

老臺北胃的帶路小提醒
第一次來吃，我會這樣建議：

1. 肉粥一定要點，這是主角
   
2. 配幾樣小菜一起吃，才有完整體驗
   
3. 不用急，慢慢吃，這碗粥就是要你放鬆
   

這不是為了拍照而存在的小吃，
而是那種
**會讓人記得「那天晚上，我在臺北吃了一碗很溫暖的粥」**的味道。

地址：10491臺北市中山區長春路89-3號

電話：0913806139

菜單：https://lin.ee/xxbYZyS

第 5 家：圓環邊蚵仔煎｜夜市裡最不能缺席的臺灣經典

如果要選一道
 最常出現在旅客記憶裡的臺灣小吃，
 蚵仔煎一定排得上前幾名。
而在臺北，
 圓環邊蚵仔煎，
 就是那種很多臺北人從小吃到大的存在。

為什麼蚵仔煎，這麼能代表臺灣？
蚵仔煎的魅力，
不在於精緻，
而在於它把幾種看似簡單的食材，
煎成了一種獨特的口感。
新鮮蚵仔的海味、
雞蛋的香氣、
地瓜粉形成的滑嫩外皮，
最後再淋上甜中帶鹹的醬汁，
一口下去，
就是夜市的完整畫面。
這種味道，
很難在其他國家找到替代品。

圓環邊，吃的是記憶感
圓環邊蚵仔煎，
沒有多餘的包裝，
也不刻意迎合潮流。
它留下來的原因很簡單
味道夠穩、節奏夠快、
讓人一吃就知道「對，就是這個」。
對旅客來說，
這是一家
不需要研究、不需要比較，就能安心點蚵仔煎的地方。

老臺北胃的帶路小提醒
第一次吃蚵仔煎，我會這樣建議：

1. 趁熱吃，口感最好
   
2. 不用急著加辣，先吃原味
   
3. 醬汁是靈魂，別急著把它拌掉
   

蚵仔煎不是細嚼慢嚥的料理，
它屬於人聲鼎沸、鍋鏟作響的夜市時刻。
站在人群裡，
吃著一盤熱騰騰的蚵仔煎，
你會很清楚地感受到
這，就是臺北的夜晚。

地址：103臺北市大同區寧夏路46號

電話：0225580198

菜單：https://oystera.com.tw/menu

第 6 家：阿淑清蒸肉圓｜第一次吃肉圓，就該從這裡開始

說到臺灣小吃，
 很多人腦中一定會出現「肉圓」兩個字。
但真正吃過之後才會發現，
 肉圓，從來不只有一種樣子。
在臺北，
 阿淑清蒸肉圓，
 就是我很常拿來介紹「清蒸派肉圓」的一家。

清蒸肉圓，和你想像的不一樣
不少旅客對肉圓的第一印象，
來自油炸版本，
外皮厚、口感重。
而阿淑的清蒸肉圓，
完全是另一個方向。
外皮晶瑩、滑嫩，
帶著自然的彈性，
不油、不膩，
一入口反而顯得清爽。
內餡扎實，
豬肉香氣清楚，
搭配特製醬汁，
味道層次簡單卻很乾淨。

為什麼我會推薦給第一次來臺北的旅客？
因為這顆肉圓，
不需要適應期。
它不刺激、不厚重，
即使是第一次嘗試臺灣小吃的人，
也能輕鬆接受。
對旅客來說，
這是一顆
「吃得懂、也記得住」的肉圓。

老臺北胃的帶路小提醒
第一次來阿淑，我會這樣吃：

1. 直接點一顆清蒸肉圓，吃原味
   
2. 醬汁先別全部拌開，邊吃邊調整
   
3. 放慢速度，感受外皮的口感變化
   

這不是夜市裡熱鬧喧囂的料理，
而是那種
安靜地展現臺灣小吃功夫的味道。
當你吃完這顆肉圓，
會更明白一件事
臺灣小吃的魅力，
往往藏在這些細節裡。

地址：242新北市新莊區復興路一段141號

電話：0229975505

第 7 家：胡記米粉湯｜一碗最貼近臺北早晨的味道

如果說前面幾樣小吃，
 是臺北的熱鬧與記憶，
 那麼米粉湯，
 就是這座城市最真實的日常。
而在臺北，
 胡記米粉湯，
 是很多人從小吃到大的存在。

為什麼米粉湯，這麼「臺北」？
米粉湯不是重口味料理，
它靠的不是刺激，
而是一碗清澈卻有深度的湯。
胡記的湯頭，
用豬骨慢慢熬出香氣，
喝起來清爽、不油，
卻能在喉嚨留下溫度。
米粉細軟，
吸附湯汁後入口順滑，
簡單到不能再簡單，
卻正是臺北人習以為常的早晨風景。

配菜，才是這一碗的靈魂延伸
在胡記吃米粉湯，
主角雖然是湯，
但真正讓人滿足的，
往往是那些小菜。
紅燒肉、豬內臟、燙青菜，
隨意點上幾樣，
湯一口、菜一口，
就是很多臺北人記憶中的早餐組合。
對旅客來說，
這是一種
不需要解釋，就能融入的臺北生活感。

老臺北胃的帶路小提醒
第一次來胡記，我會這樣建議：

1. 一定要點米粉湯，湯先喝
   
2. 再配 1～2 樣小菜，體驗會完整很多
   
3. 這一餐適合慢慢吃，不用趕
   

這不是為了觀光而存在的小吃，
而是一碗
每天準時出現在臺北人生活裡的湯。
當你坐在店裡，
聽著湯勺碰撞的聲音，
你會突然感覺到——
原來，臺北的早晨，
就是從這樣一碗米粉湯開始的。

地址：106臺北市大安區大安路一段9號1樓

電話：0227212120

第 8 家：藍家割包｜一口咬下的臺灣街頭記憶

如果要選一道
 外國旅客一看到就會好奇、吃完又會記住的小吃，
 割包，一定在名單裡。
而在臺北，
 藍家割包，
 就是我很放心帶旅客來認識這道經典的一站。

割包，為什麼被叫做「臺灣漢堡」？
割包的結構其實很簡單：
鬆軟的白饅頭、
燉得入味的滷五花肉、
酸菜、花生粉、香菜。
但真正迷人的，
是這些元素組合在一起時，
形成的層次感。
肉香、甜味、鹹味、清爽度，
在一口之間同時出現，
沒有誰搶戲，
卻彼此剛好。
這種平衡感，
正是臺灣小吃很迷人的地方。

藍家割包不是走浮誇路線，
它給人的感覺很直接
就是你期待中的割包樣子。
饅頭柔軟不乾，
五花肉肥瘦比例恰到好處，
入口即化卻不膩口，
花生粉的甜香收尾，
讓整體味道非常完整。
對第一次吃割包的旅客來說，
這是一個
不會出錯、也很容易愛上的版本。

老臺北胃的帶路小提醒
第一次吃藍家割包，我會這樣建議：

1. 直接點招牌割包，不要改配料
   
2. 如果有香菜，建議保留，味道會更完整
   
3. 趁熱吃，饅頭口感最好
   

割包不是精緻料理，
卻非常有記憶點。
站在街頭，
拿著一顆熱騰騰的割包，
邊走邊吃，
你會很清楚地感受到
這一口，就是臺灣的街頭生活。

地址：100臺北市中正區羅斯福路三段316巷8弄3號

電話：0223682060

菜單：https://instagram.com/lan_jia_gua_bao?utm_medium=copy_link

第 9 家：御品元冰火湯圓｜臺北夜晚最溫柔的一碗甜

吃了一整天的臺北小吃，
 到了這個時候，
 胃其實已經差不多滿了。
但只要天氣一涼，
 或夜色慢慢降下來，
 你還是會想找一碗——
 不是為了吃飽，而是為了舒服的甜點。
這時候，我通常會帶你來 御品元冰火湯圓。

為什麼叫「冰火」？這碗湯圓的關鍵就在這裡
御品元最有特色的地方，
就在於它的「冰火交錯」。
熱騰騰的湯圓，
外皮軟糯、內餡濃香，
搭配冰涼清甜的桂花蜜湯，
一口下去，
溫度在嘴裡交替出現。
不是衝突，
而是一種很細膩的平衡。
這樣的吃法，
也正是臺灣甜點很擅長的地方——
不張揚，但很有記憶點。

這是一碗，會讓人慢下來的甜點
和夜市裡熱鬧的甜品不同，
御品元的冰火湯圓，
更像是一個讓人停下腳步的存在。
你會發現，
坐在這裡吃湯圓的人，
說話聲都會不自覺地變小。
對旅客來說，
這不只是吃甜點，
而是一個
把白天的熱鬧慢慢收進回憶裡的時刻。

老臺北胃的帶路小提醒
第一次吃御品元，我會這樣建議：

1. 點招牌冰火湯圓，體驗完整特色
   
2. 先單吃湯圓，再搭配湯一起吃
   
3. 放慢速度，這一碗不適合趕時間
   

這不是為了拍照而存在的甜點，
而是一碗
會讓你記得「那天晚上在臺北，很舒服」的湯圓。

地址：106臺北市大安區通化街39巷50弄31號

電話：0955861816

菜單：https://instagram.com/lan_jia_gua_bao

第 10 家：頃刻間綠豆沙牛奶專賣店｜把臺北的味道，留在最後一口清甜

走到這一站，
 其實已經不需要再吃什麼大份量的東西了。
這時候，
 最適合的，
 是一杯不吵鬧、不張揚，
 卻會默默留在記憶裡的飲品。
頃刻間綠豆沙牛奶，
 就是我很常用來替一天畫下句點的選擇。

綠豆沙牛奶，為什麼這麼「臺灣」？
在臺灣，
飲料不只是解渴，
而是一種生活節奏。
綠豆沙牛奶看起來簡單，
但真正好喝的版本，
靠的是火候、比例，
還有耐心。
頃刻間的綠豆沙，
口感細緻、不粗顆，
甜度自然、不膩口，
牛奶的加入，
讓整杯變得柔順而溫和。
這不是衝擊味蕾的飲料，
而是一種
喝完之後，會覺得剛剛那一刻很舒服的甜。

為什麼我會用它當作最後一站？
因為它很臺北。
你可以外帶，
邊走邊喝；
也可以站在店門口，
慢慢把杯子喝空。
沒有儀式感，
卻很真實。
對旅客來說，
這杯綠豆沙牛奶，
就像是把今天吃過的所有味道，
溫柔地整理好，
帶走。

老臺北胃的帶路小提醒
第一次喝頃刻間，我會這樣建議：

1. 直接點招牌綠豆沙牛奶
   
2. 正常甜就很剛好，不用特別調整
   
3. 找個角落慢慢喝，別急著趕路
   

這一杯，
不會讓你驚呼，
卻會在回程的路上，
突然想起來。
原來，臺北的味道，是這樣結束一天的。

地址：111臺北市士林區小北街1號

電話：0228818619

菜單：https://instagram.com/chill_out_moment?igshid=YmMyMTA2M2Y=

如果只有 3 天的自助旅行在臺北，怎麼吃這 10 家？

第一次來臺北，
時間有限、胃容量也有限，
與其每一家都趕，不如照著節奏吃。
這份 3 天小吃路線，
是老臺北胃會帶朋友實際走的版本：
不爆走、不硬塞，
讓你每天都吃得剛剛好。

臺北 3 天小吃推薦行程表（老臺北胃版本）

雖然每個小吃的地點都有一點距離，但是你也知道，好吃的小吃，是值得你花一點時間前往品嘗
老臺北胃的小提醒

1. 不需要每一家都點到最滿
   
2. 留一點餘裕，才會想再回來
   
3. 臺北小吃的魅力，不在於吃多少，而在於記住了什麼味道
   

當你照著這 3 天走完，
你會發現，
臺北不是靠一兩道名菜被記住的，
而是靠這些看似日常、卻很真實的小吃。
下次再來，老臺北胃再帶你吃更深的那一輪。

老臺北胃帶路｜這 10 口，就是我心中的臺北

寫到這裡，
 其實已經不是在推薦哪一家小吃了。
而是在回頭看，
 這座城市，是怎麼用食物陪著人生活的。
滷肉飯、牛肉麵、肉粥、米粉湯，
 不是為了成為觀光名單而存在，
 而是每天默默出現在臺北人的日子裡。
夜市裡的蚵仔煎、涼麵、割包，
 熱鬧、吵雜、節奏很快，
 卻也正是臺北最真實的樣子。
而最後那碗湯圓、那杯綠豆沙牛奶，
 則是在一天結束時，
 替味蕾留下一個溫柔的句點。

如果你問我，
「這 10 家是不是臺北最好吃的小吃？」
我會說，
它們不一定是排行榜第一名，
卻是我真的會帶朋友去吃的版本。
因為它們吃得到：

1. 臺北人的日常
   
2. 巷弄裡的熟悉感
   
3. 不需要解釋，就能被理解的味道
   

如果你是第一次來臺北，
跟著這份清單走，
你不一定會吃得最飽，
但你一定會記得——
臺北，是什麼味道。
而如果有一天，
你又再回到這座城市，
走進熟悉的街口、
看到冒著熱氣的小攤，
你也會開始懂得，
為什麼老臺北胃，
總是記得這些看似平凡的滋味。
因為，真正留在心裡的，
從來不是吃過多少，
而是哪一口，讓你想起臺北。

御品元冰火湯圓不點會後悔嗎？

走完這 10 家，

你可能會發現一件事圓環邊蚵仔煎點這個對嗎？

臺北的小吃，其實不急著被你記住。

它們就安靜地存在在街角、夜市、轉彎處，藍家割包口味會太重嗎？

等你有一天，再回到這座城市。胡記米粉湯值得排隊嗎？

如果你是第一次來臺北，饌堂－黑金滷肉飯（雙連店）早上吃適合嗎？

希望這份「老臺北胃帶路」的清單，

能幫你少一點猶豫、多一點安心。

不用擔心踩雷，頃刻間綠豆沙牛奶專賣店值得排隊嗎？

也不用為了排行而奔波，阿淑清蒸肉圓會不會太油？

只要照著節奏走，

你就會吃到屬於自己的臺北味道。

而如果你已經來過臺北，

那更希望這篇文章，阿淑清蒸肉圓原味就好嗎？

能帶你走進那些

你可能錯過、卻一直都在的日常小吃。

因為真正迷人的旅行，

從來不是把清單全部打勾，

而是某一天，

你突然想起那碗飯、那口湯、那杯甜，胡記米粉湯口味會太清淡嗎？

然後在心裡對自己說一句：饌堂－黑金滷肉飯（雙連店）當點心適合嗎？

「下次再去臺北，還想再吃一次。」

把這篇文章存起來、分享給一起旅行的人，

或是在規劃行程時，再回來看看。

讓味道，成為你認識臺北的方式。

下一次來臺北，

別急著走遠。

老臺北胃，胖老闆誠意肉粥冬天適合吃嗎？

會一直在這些地方，

等你再回來。

Male mice have been preferred over female mice in neuroscience research due to the concern that the hormone cycle in females could lead to behavioral variations that could affect the accuracy of the results. However, new research from Harvard Medical School indicates that this concern may not be warranted in many experiments. Research findings reveal that female mice have more stable exploratory behavior than male mice. New research indicates that female mice show more stable exploratory behavior than male mice, despite hormone cycles The results challenge a long-held assumption that hormones have a broad effect on behavior in female mice, making them less suitable for research The findings make a strong scientific case for increasing the inclusion of female mice in neuroscience and other experiments Mice have long been a central part of neuroscience research, providing a flexible model that scientists can control and study to learn more about the intricate inner workings of the brain. Historically, researchers have favored male mice over female mice in experiments, in part due to concern that the hormone cycle in females causes behavioral variation that could throw off results. But new research from Harvard Medical School (HMS) challenges this notion and suggests that for many experiments, the concern may not be justified. According to the study, female mice, despite ongoing hormonal fluctuations, exhibit exploratory behavior that is more stable than that of their male peers. The study results were published on March 7 in the journal Current Biology. Using a strain of mice commonly studied in lab settings, the researchers analyzed how the animals behaved as they freely explored an open space. They found that the hormone cycle had a negligible effect on behavior and that differences in behavior between individual female mice were much greater. Moreover, differences in behavior were even greater for males than for females, both within and between mice. The results underscore the importance of incorporating both sexes into mouse studies, the research team said. “I think this is really powerful evidence that if you’re studying naturalistic, spontaneous exploratory behavior, you should include both sexes in your experiments — and it leads to the argument that in this setting, if you can only pick one sex to work on, you should actually be working on females,” said Sandeep Robert Datta, professor of neurobiology in the Blavatnik Institute at HMS, who co-led the study with Rebecca Shansky of Northeastern University. From Rodents to Humans: A History of Bias As neuroscientists strive to better understand the human brain, they routinely turn to the mouse, which Datta considers “the flagship vertebrate model for understanding how the brain works.” This is because mouse and human brains share a considerable amount of structural organization and genetic information, so scientists can easily manipulate the mouse genome to address specific experimental questions and to build models of human diseases. “Much of what we understand about the relationship between genes and neural circuits, and between neural activity and behavior, comes from basic research in the mouse, and mouse models are likely going to be really central tools in our fight against a broad array of neurological and psychological diseases,” Datta said. For more than 50 years, researchers have preferentially used male mice in experiments, and nowhere has this practice been more prominent than in neuroscience. In fact, a 2011 analysis found that there were over five times as many single-sex neuroscience studies of male mice than of female mice. Over time, this practice has resulted in a poorer understanding of the female brain, likely contributing to the misdiagnosis of mental and neurological conditions in women, as well as the development of drugs that have more side effects for women — issues outlined by Shansky in a 2021 perspective in Nature Neuroscience. The disparity in sex representation common in animal research has also been historically mirrored in research involving human subjects. “This bias starts in basic science, but the repercussions are rolled into drug development, and lead to bias in drugs being produced, and how drugs are suited for the different sexes,” said lead author Dana Levy, a research fellow in neurobiology at HMS. For example, Levy noted that conditions such as anxiety, depression, and pain are known to manifest differently in female mice and women than in the male mice that are more often used in early-stage drug testing. To address the problem of sex bias in scientific research, the National Institutes of Health published a policy in 2016 requiring researchers to include male and female subjects and samples in experiments. However, follow-up studies that look across scientific disciplines and examine neuroscience specifically indicate that progress has been slow. The reasons for such a long-standing bias in neuroscience are complicated, Datta said: “Part of it is just plain old sexism, and part of it is conservatism in the sense that people have studied male mice for so long that they don’t want to make a change.” Yet perhaps the biggest reason for excluding female mice, Datta said, stems from a widespread assumption that their behavior is broadly affected by cyclic variations in hormones such as estrogen and progesterone — the rodent version of a menstrual cycle, known as the estrous cycle. According to Datta and Levy, estrous status is known to have a strong effect on certain social and sexual behaviors in mice. However, data on the influence of estrous status in other behavioral contexts have been mixed, resulting in what Datta calls “a genuine disagreement in the literature.” “We wanted to measure how much the estrous cycle seemed to influence basic patterns of exploration,” Datta said. “Our question was whether these ongoing changes in the hormonal state of the mouse affect other neural circuits in a way that’s confusing for researchers.” “We assumed, like everybody else, that adding females was just going to complicate our experiments,” Levy added, “And so we said, ‘why not test this.’” Testing Assumptions The researchers studied genetically identical males and females from a common strain of lab mouse in a circular open field — a standard lab setup for behavioral neuroscience experiments. In practice, the test involved placing a mouse in a 5-gallon Home Depot bucket for 20 minutes and using a camera to record the mouse’s movements and behaviors in 3D as it freely explored the space. The researchers swabbed each female mouse to determine its estrous status and repeated the bucket test with the same individual multiple times. The team analyzed the videos with MoSeq, an artificial intelligence technology previously developed by the lab. The technology uses machine learning algorithms to break down a mouse’s movements into around 50 different “syllables,” or components of body language: short, single motions such as rearing up, pausing, stepping, or turning. With MoSeq, the researchers gathered in-depth, high-resolution data about the structure and pattern of mouse behavior during each session. The researchers found that estrous status had very little effect on exploratory behavior in female mice. Instead, patterns of behavior tended to vary much more across female mice than they did throughout the estrous cycle. “If you give me any random video from our pile, I can tell you which mouse it is. That’s how individualized the pattern of behavior is,” Datta said, which suggests that in behavioral studies, “a dominant aspect of variation in the data is the fact that individuals have subtly different life histories.” When the researchers compared female and male mice, they found something that surprised them: Males also exhibited individuality of behavior, but they had more behavioral variation within a single mouse and between mice than females. “People have been making this assumption that we can use male mice to reliably make comparisons within and across experiments, but our data suggest that female mice are more stable in terms of behavior despite the fact that they have the estrous cycle,” Datta said. A Case for Change Scientists generally agree that including female mice is important from a fairness perspective, Datta noted, yet some have remained concerned that it could complicate their research. For him, the new findings make a strong scientific case for using female mice in experiments. “The fact that female behavior is more reliable suggests that including females might actually decrease the overall variability in your data under many circumstances,” Datta said. Based on their findings, researchers in the Datta lab have already switched from male mice to mixed groups or female mice in their other experiments that involve circular, open-field testing. Datta cautioned that the study looks at only one mouse strain in one lab setup, and so the results cannot be generalized to other strains and setups without further testing. However, he noted that the strain and setup are commonly used in neuroscience research, including in early-stage drug development to test how a potential drug affects mouse locomotion. Datta said that the findings “should encourage folks who are interested in drug development in this context to include both sexes in their analysis.” Now, Datta and Levy are interested in exploring how internal states beyond hormonal status, such as hunger, thirst, pain, and illness, affect exploratory behavior in mice. “The question is, who wins in this tug-of-war between your current internal state and your individual identity,” Levy explained. They also want to delve deeper into the neural basis of the individuality of mouse behavior that they saw in the study. “I was shocked by how much stable variation between individuals we were observing — it’s like these mice really are individuals,” Datta said. “We’re used to thinking of lab mice as interchangeable widgets, but they’re not at all. So, what is controlling these individualized patterns of behavior?” “We want to understand the mechanisms of individuality: how variability between individuals comes about, how it affects behavior, what can alter it, and what brain regions support it,” Levy added. To this end, the Datta lab is examining mouse behavior from birth until death to understand how individualized patterns of behavior emerge and crystallize during development, and how they change throughout life. The researchers also hope that their work will open the door for more rigorous, quantitative research on whether and how the estrous cycle affects mouse behavior in other contexts, such as completing complex tasks. “This is a very interesting example of how assumptions that affect the way that we conduct and design our science are sometimes just assumptions — and it is important to directly test them, because sometimes they’re not true,” Levy said. Reference: “Mouse spontaneous behavior reflects individual variation rather than estrous state” by Dana Rubi Levy, Nigel Hunter, Sherry Lin, Emma Marie Robinson, Winthrop Gillis, Eli Benjamin Conlin, Rockwell Anyoha, Rebecca M. Shansky and Sandeep Robert Datta, 7 March 2023, Current Biology. DOI: 10.1016/j.cub.2023.02.035 Additional authors include Nigel Hunter, Sherry Lin, Emma Robinson, Winthrop Gillis, Eli Conlin, and Rockwell Anyoha of HMS. The research was supported by the NIH (U19NS113201; RF1AG073625; R01NS114020), the Brain Research Foundation, the Simons Collaboration on the Global Brain, the Simons Collaboration for Plasticity in the Aging Brain, the Human Frontier Science Program, and the Zuckerman STEM Leadership Program. Datta is on the scientific advisory boards of Neumora, Inc., and Gilgamesh Pharmaceuticals, which have licensed the MoSeq technology.

Hofstenia miamia, three-banded panther worms. Credit: Mansi Srivastava and Kathleen Mazza-Curll The formation of adult pluripotent stem cells in Hofstenia miamia was traced to two embryonic cells using advanced genetic tools. These findings illuminate stem cell regulation and evolutionary mechanisms. Stem cells are a remarkable biological wonder that have the ability to repair, replace and regenerate cells. In most animals and humans, stem cells are limited to generating only specific types of cells. For example, hair stem cells will only produce hair, and intestine stem cells will only produce intestines. However, many distantly-related invertebrates have stem cell populations that are pluripotent in adult animals, meaning they can regenerate virtually any missing cell type, a process known as whole-body regeneration. Despite the presence of these adult pluripotent stem cells (aPSCs) in various animal species such as sponges, hydras, planarian flatworms, acoel worms, and some sea squirts, the mechanism of how they are produced remains unknown in any species. In a new study published in the journal Cell researchers in the Department of Organismic and Evolutionary Biology at Harvard University have identified the cellular mechanism and molecular trajectory for the formation of aPSCs in the acoel worm, Hofstenia miamia. Images showing how single cells of the embryo were specifically and systematically converted to red color for this study. Credit: Julian Kimura H. miamia, also known as the three-banded panther worm, is a species that can fully regenerate using aPSCs called “neoblasts.” Chop H. miamia into pieces and each piece will grow a new body including everything from a mouth to the brain. Senior author Professor Mansi Srivastava collected H. miamia in the field many years ago because of its regenerative ability. Once back in the lab, H. miamia began to produce many embryos that could easily be studied. Transgenesis Unlocks New Avenues in Stem Cell Research In a previous study by Srivastava and co-author postdoctoral researcher Lorenzo Ricci developed a protocol for transgenesis in H. miamia. Transgenesis is a process that introduces something into the genome of an organism that is not normally part of that genome. This method allowed lead author Julian O. Kimura (Ph.D.’22) to pursue his question of how these stem cells are made. “One common characteristic among animals that can regenerate is the presence of pluripotent stem cells in the adult body,” said Kimura. “These cells are responsible for re-making missing body parts when the animal is injured. By understanding how animals like H. miamia make these stem cells, I felt we could better understand what gives certain animals regenerative abilities.” A pair of cells at the 16-cell stage embryo converted to red color. Over time, the cells divides to make more cells, go inside the embryo, and form the stem cells of the hatched worm. Credit: Julian Kimura There are some unifying features of these stem cell populations in adult animals such as the expression of a gene called Piwi. But in no species so far has anyone been able to figure out how these stem cells are made in the first place. “They’ve mostly been studied in the context of adult animals,” said Srivastava, “and in some species, we know a little bit about how they might be working, but we don’t know how they are made.” The researchers knew that worm hatchlings contain aPSCs, so reasoned they must be made during embryogenesis. Ricci used transgenesis to create a line that caused embryo cells to glow in fluorescent green due to the introduction of the protein Kaede into the cell. Kaede is photo-convertible, which means shining a laser beam with a very specific wavelength on the green will convert it to a red color. You can then zap the cells with a laser to turn individual green cells of the embryo into a red color. “Using transgenic animals with photo-conversion is a very new twist we devised in the lab to figure out the fates of embryonic cells,” said Srivastava. Kimura applied this method to perform lineage tracing by letting the embryos grow and watching what happens. A single cell at the 8-cell stage embryo converted to red color. Over time, the cell divides to make many more cells, which end up making most of the skin of the hatched worm. Credit: Julian Kimura Mapping Early Embryonic Development of Stem Cells Kimura followed the embryo’s development as it split from a single cell to multiple cells. Early division of these cells is marked by stereotyped cleavage, which means embryo-to-embryo cells divide in the exact same pattern such that cells can be named and studied consistently. This raised the possibility that perhaps every single cell has a unique purpose. For instance, at the eight-cell stage, it’s possible the top, left corner cell makes a certain tissue, while the bottom, right cell makes another tissue. To determine the function of each cell, Kimura systematically performed photo-conversion for each of the cells of the early embryo, creating a full fate map at the eight-cell stage. He then tracked the cells as the worm grew into an adult that still carried the red labeling. The repetitious process of following each individual cell again and again across many embryos made it possible for Kimura to trace where each cell was working. At the sixteen-cell stage embryo, he found a very specific pair of cells that gave rise to cells that looked to be the neoblasts. “This really excited us,” said Kimura, “but there was still the possibility that neoblasts were arising from multiple sources in the early embryo, not just the two pairs found at the sixteen-cell stage. Finding cells that simply resembled neoblasts in appearance wasn’t definitive evidence that they truly were neoblasts, we needed to show that they behaved like neoblasts as well.” To be certain, Kimura put this particular set of cells, called 3a/3b in H. miamia, on trial. In order to be the neoblasts the cells must satisfy all of the known properties of stem cells. Are the progeny of those cells making new tissue during regeneration? The researchers found that yes, the progeny of only those cells made new tissue during regeneration. Another defining property is the level of gene expression in stem cells, which must have hundreds of genes expressed. To determine if 3a/3b fit this property, Kimura took the progeny with 3a/3b glowing in red and all other cells glowing in green and used a sorting machine that separated the red and green cells. He then applied single-cell sequencing technology to ask, which genes are being expressed in the red cells and in the green cells. That data confirmed that at the molecular level, only the progeny of the 3a/3b cells matched stem cells and not the progeny of any other cell. “That was definitive confirmation of the fact that we found the cellular source of the stem cell population in our system,” said Kimura. “But, importantly, knowing the cellular source of stem cells now gives us a way to capture the cells as they mature and define what genes are involved in making them.” Single-Cell Data Sheds Light on Stem Cell Formation Kimura generated a huge dataset of embryonic development at the single-cell level detailing which genes were being expressed in all of the cells in embryos from the beginning to the end of development. He allowed the converted 3a/3b cells to develop a little bit further, but not all the way to the hatchling stage. He then captured these cells using the sorting technology. By doing this Kimura could clearly define which genes were specifically being expressed in the lineage of cells that make the stem cells. “Our study reveals a set of genes that could be very important controllers for the formation of stem cells,” said Kimura. “Homologues of these genes have important roles in human stem cells and this is relevant across species.“ “Julian started in my lab wanting to study how stem cells are made in the embryo,” said Srivastava, “and it’s an incredible story that when he graduated he had figured it out.” The researchers plan to continue digging deeper into the mechanism of how these genes are working in the stem cells of Hofstenia miamia, which will help to tell how nature evolved a way to make and maintain pluripotent stem cells. Knowing the molecular regulators of aPSCs will allow researchers to compare these mechanisms across species, revealing how pluripotent stem cells have evolved across animals. Reference: “Embryonic origins of adult pluripotent stem cells” by Julian O. Kimura, D. Marcela Bolaños, Lorenzo Ricci, and Mansi Srivastava, 8 December 2022, Cell. DOI: 10.1016/j.cell.2022.11.008

Illustration of Fsr’s catalytic site where sulfite gets reduced to sulfide. The siroheme (in pink) that binds and converts the sulfite is embedded in a cavity of the protein (gray surface) which is solvent accessible. This way, the sulfite can easily enter the protein and the produced sulfide can leave it. Credit: Max Planck Institute for Marine Microbiology Researchers at the Max Planck Institute for Marine Microbiology have uncovered how a methane-producing microbe thrives on toxic sulfite without becoming poisoned. Methanogens are tiny organisms that generate methane in an oxygen-deprived environment. Their production of methane, such as in the digestive system of ruminants, plays a significant role in the global carbon cycle as methane is a highly potent greenhouse gas. However, methane can also serve as an energy source for heating homes. A Toxic Base for Growth The object of the study now published in Nature Chemical Biology are two marine heat-loving methanogens: Methanothermococcus thermolithotrophicus (lives in geothermally heated sediments at around 65 °C) and Methanocaldococcus jannaschii (prefers deep-sea volcanos with around 85 °C). They obtain their cellular energy by producing methane and receive sulfur for growth in form of sulfide, that is present in their environments. While sulfide is a poison for most organisms, it is essential for methanogens and they can tolerate even high concentrations of it. However, their Achilles’ heel is the toxic and reactive sulfur compound sulfite, which destroys the enzyme needed to make methane. In their environments, both investigated organisms are occasionally exposed to sulfite, for example, when oxygen enters and reacts with the reduced sulfide. Its partial oxidation results in the formation of sulfite, and thus the methanogens need to protect themselves. But how can they do this? Marion Jespersen with the purified F420-dependent sulfite reductase (Fsr). The black color comes from all the iron involved in the reaction. Experiments are carried out in an anaerobic chamber and under artificial light to protect the enzyme from oxygen and daylight. Credit: Tristan Wagner/Max Planck Institute for Marine Microbiology A Molecular Snapshot of the Process Marion Jespersen and Tristan Wagner from the Max Planck Institute for Marine Microbiology in Bremen, Germany, together with Antonio Pierik from the University of Kaiserslautern, now provide a snapshot of the enzyme detoxifying the sulfite. This butterfly-shaped enzyme is known as the F420-dependent sulfite reductase or Fsr. It is capable of turning sulfite into sulfide – a safe source of sulfur that the methanogens require for growth. In the current study, Jespersen and her colleagues describe how the enzyme works. “The enzyme traps the sulfite and directly reduces it to sulfide, which can be incorporated, for example, into amino acids”, Jespersen explains, “As a result, the methanogen doesn’t get poisoned and even uses the product as its sulfur source. They turn poison into food!” It sounds simple. But in fact, Jespersen and her colleagues found that they were dealing with a fascinating and complicated overlap. “There are two ways of sulfite reduction: dissimilatory and assimilatory”, Jespersen explains. “The organism under study uses an enzyme that is built like a dissimilatory one, but it uses an assimilatory mechanism. It combines the best of both worlds, one could say, at least for its living conditions.” It is assumed that the enzymes from both the dissimilatory and the assimilatory pathways have evolved from one common ancestor. “Sulfite reductases are ancient enzymes that have a major impact on the global sulfur and carbon cycles”, adds Tristan Wagner, head of the Max Planck Research Group Microbial Metabolism at the Max Planck Institute in Bremen. “Our enzyme, the Fsr, is probably a snapshot of this ancient primordial enzyme, an exciting look back in evolution.” Biotechnological Applications In View The Fsr not only opens up evolutionary implications but also allows us to better understand the fascinating world of marine microbes. Methanogens that can grow only on sulfite circumvent the need to use the dangerous sulfide, their usual sulfur substrate. “This opens opportunities for safer biotechnological applications to study these important microorganisms. An optimal solution would be to find a methanogen that reduces sulfate, which is cheap, abundant, and a completely safe sulfur source”, says Wagner. In fact, this methanogen already exists, it is Methanothermococcus thermolithotrophicus. The researchers hypothesized that Fsr orchestrates the last reaction of this sulfate reduction pathway because one of its intermediates would be sulfite. “Our next challenge is to understand how it can transform sulfate to sulfite, to get a complete picture of the capabilities of these miracle microbes.” Reference: “Structures of the sulfite detoxifying F420-dependent enzyme from Methanococcales” by Marion Jespersen, Antonio J. Pierik and Tristan Wagner, 19 January 2023, Nature Chemical Biology. DOI: 10.1038/s41589-022-01232-y

RE98915RGPOIOKJ

富宏牛肉麵真的有誠意嗎？ 》台北美食指南｜10家餐廳值得你收藏富宏牛肉麵回訪率高嗎？ 》台北小吃人氣餐廳10選｜吃過都說讚圓環邊蚵仔煎一定要點嗎？ 》台北夜市美食10大美食推薦｜從燒肉到火鍋全攻略