HHMI meeting Day 1

It’s been a while since my last post about science.

Today is the first evening of the three day Howard Hughes meeting at Janelia.

I’m here for the science and I’m on a mission of a first look at my next project in a different lab.

The highlight of this evening, in my opinion, was Hopi Hoekstra’s presentation. They did a fantastic job of establishing deer mice as a model organism for social and mating behavior. They did some really elegant genetics identifying loci contributed to monogmy, which I think is pretty cool.

Had some inspiring chat with Chris Walsh and Hugo Bellen. Not a bad start.

To be continued…

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EYE_LIZ

P.S. 掐指一算, 还能再看到这双眼三次.

<啪嗒>
清透的茶色湖水 环绕着
灰白的月光 轻抚着
走向看不见的尽头 催眠着

她的眼 是午夜的沙滩
静静的 一个 一个浪头
重复中 明白了世间一切的道理

伸手不见五指 摸索着
门后的光 诱惑着
听得到天堂的召唤 虔诚着

她的眼 是贴满玻璃色彩的教堂
没有审判 没有对错
穹顶倾泻的白光下 无拘无束的忏悔

黑得静默 却水晶般清澈透亮
白得无瑕 却容纳了所有的情感

她的眼 是一个世界
甚至可以包容得下我的世界
她的眼 总在期盼
任凝视再久也不会收回

只是…

猫的脖子

tara不见了.

tara是只猫.一只摸不到脖子的小猫.

所以tara的消失毫不意外.

tara住在同一座公寓的二楼一间屋里.平时每天走正门进出的时候看不见那间屋,只有在走向公寓院子尽头的停车位的路上才会经过. 每次开车回来都很晚,<啪嗒>一声停好车,一转身抬头,二楼的那间房间立刻一览无余.房间很宽敞,很空,帘子总是开着,时而开着嫩黄的顶灯.猫便窝在窗缝上,盘踞着俯看窗外.开灯的时候,猫是虎皮黄色的;屋里熄灯的时候,外头惨淡的路灯照出一个黑色的剪影, 玻璃弹子一样的眼睛嵌在黑影里, 发出和脚下摩擦沙地的刺刺声——猜是这声音,从车子的距离何至于能听见二楼房里眼珠摩擦眼眶的声音.

于是这成了一个场景,一个有固定套路的布景. 刹车.拉闸.开门.关门.上锁.转身.仰头.确认剪影.确认摩擦的声音.确认完每一个步骤,完成整个仪式,僵硬的身躯才能放松下来,自如的走过回公寓的小路.

tara没有表情.不咧嘴.也不打哈欠.眼睛也没有特别的表情.没有贵气逼人.也没有楚楚动人.慢慢的,虎皮色的花斑身子成了漆黑的硬纸板剪影,玻璃弹子的眼珠成了熬不过冬天印在墙上的爬山虎. 但是仪式成了习惯,愈发显出每个步骤确认的重要.

习惯成了自然以后, 有时候也能开始读到tara并非不存在的表情. 会歪头.会踱步.会瘫倒. 会笑. 会好奇. 会想要更多. 会撒娇. 会不耐烦. 会语重心长…尾巴扬起是一个意思,半弯着是另一个意思. 躺着握爪是一个意思,蜷缩着握爪又是另一个意思.即使表达同一种情绪,可以用胡子,用虎牙,还可以用抬头纹. 如此丰富,却又无比新奇,轻松的细节表达能力, 让人羡慕,着迷,无可救药的上瘾.

现在这份独一无二随着tara的消失也一并无处可觅了. 是如此的突然, 毫无预兆的无影无踪了——世界上大多数的失踪大抵都是这般突然的罢. 于是仪式不复存在,残破的一半不知该怎么办.身躯重归僵硬.脚底摩擦沙地的刺刺声,也变回了<梆梆>的恐龙一步一个坑印. 强大得沉重感到达极点,以至于变得很轻,很轻. 活像冥王星脱离太阳引力轨道,飞向外太空. 活像做了一个无比清纯的梦,醒来一天都沉在其中不能释怀的感觉.又好像熬了一夜恍如隔世,仿佛世界不曾存在过,而自己为什么在这里.

这种心情的下场, 和碎了一地摊在街上的酒瓶一样. 第一天, 还能闻到没散尽的酒味. 第二天, 碎片干巴巴的躺在地上,一脸无辜. 第三天, 上面开始沾了灰尘. 一个礼拜, 人们已经习惯了绕着经过. 最好突然有一天, 全都不见了. 不见得是如此的彻底和突然, 以至于想不起来是今天不见的还是之前已经没有了. 总之是全都干净了,何苦去想哪一天哪一点钟是谁拾起了碎片,包好处理掉了呐.

tara不见了.

我会难过好一阵子.

还没有摸过她的脖子.

my most hated words in 2015

“Thank you Sooo much”

When has it become trendy to say this, genuinely and sincerely, when someone’e being helped on some trivial matter?

“Can you pass me some napkins””Yup””Thank you so much”
“What time is it””12:15””Thank you so much”
“Hey can you keep an eye on my stuff for a sec””Sure””Thank you so much”

It’s everyday, everywhere and in nearly every conversation. The richness of the whole phrase make me nausea. It reminds me of the voice in the “next big thing” ads by samsung: “our phone allows us to do amaaaazing things” “the next big thing is here”. Those seemingly friendly and pure tones cannot hide the fact that they’ve been carefully calibrated and crafted, one syllabus a time, to magically convey their messages to the innocent audience. I almost think they’ve consulted a dozen psychologists so that the tones, the messages and the visual can fully grab the weakness of human nature. So are those banners and posters with one or two all-captalized catchphrases. All those Steve Jobs’ type of presentation and visualization are unnaturally unhealthy and deceiving. Nothing can be summarized in one phrase. Everything is complicated. A bold, catching slogan sells good, but it doesn’t actually make the product better, especially when everybody is doing it.

What about a simple and snappy “Thanks” or a formal and less emotionally engaged “Thank you” for such subtlety? I guess you’d never say those two words. What if I saved your life from an angry hippo at the zoo? How are you going to thank me for that? What are you going to say so that I feel I deserve this? I guess you’d run out of your repertoire of expressing gratitude. sometimes it’s not even something grateful. It’s more of a pet phrase, something slipped out of the mouth subconciously to make people feel you care about them, to end a conversation, or just to be cute. Well, perhaps no reason for such behavior.

If over-modesty is a sickness of Asians, over-politeness is becoming a pandemic among modern citizens in America. And both make me nausea, for a long time. Adding a “so much” tag at the end of a sentence doesn’t bond people closer. The over-polite conversation balls tossed back and forth are sarcastically sad, because beneath the web knitted by them, in stark contrast, is the absurd nature of desolated individuality and the lack of understanding and trust. They are just there, all the time, cold, isolated and hard. Anything we try to build in the layer above it not only does not help, but even worse, makes the facts down below opaque and inaccessible.

Say “Thanks” when it should be said. Then feel the warmth and coldness of human connection when it’s presented, truly and transparently.

小说家的操守

今天看到一段让自己脸红的话。是周国平援引昆德拉对小说职责的一段评论:

“一个小说家必须具备存在的眼光,看到比现实更多的东西。然而许多小说家都没有此种眼光,他们或者囿于局部的现实,或者习惯于对现实作某种本质主义的抽象”。。。
“这种情况,借用海德格尔的概念,就是“存在的被遗忘””。如此写出来的小说,不过是小说化的情欲,忏悔,自传,披露隐私罢了。“

这段话应该批评了世界上百分之九十九点九的小说家,包括所有经典文学,所有故事童话,以及所谓的<哲学小说>———-那不过是在用小说的形式上哲学课罢了。

But ya’ know what, I don’t care. 我就是那种倾全部注意力于当下瞬间细节的描绘者—-语言的摄影师,说的高尚点。我就是把一切情欲,忏悔,道德和无奈小说化的那种人——主要是情欲。我就是那种描绘记忆中的现实,不揭示任何存在的花间派。为此我乐此不疲。

另一位评论家Rebecca Solnit最近在一篇virginia woolf 的文章里写道:”writers have to be by nature optimists…it’s the job of writers and explorers to see more, to travel light when it comes to preconception, to go into the dark with their eyes open.”

Which I totally disagree. 我写任何我想写的东西。笔者不应对读者对社会负有任何责任感和导向型。我们的职责只有写任何我们感兴趣,我们觉得值得探讨的话题。文字本身没有开导读者,给读者以信心的责任。而我写作,仅仅是体验一种不一样的可能性罢了,而且凑巧大部分时候是及其消极晦暗的。我不认为这就是没有价值的。相反,文字应该是把世界原原本本的摊平了展现在人们面前的介质。

历史上的今天:
2011年7月8日 写一首给朋友的分手歌

夜幕的守望者

我是一个城市人。生于城市。长于城市。现在我是一个彻头彻尾的城市的外乡人。

曾经转角的小吃店,消失了;曾经熟悉的青石板,也不再了;曾经的楼房,被更高的楼房挡住了;曾经的人们,被另一群人代替了。

城市的味道变得复杂了,多了石灰味,少了青草味;多了一点躁动,少了一点平和;多了光亮,少了夜色温柔。我像一条狗,拖着疲惫的四条腿,努力分辨那熟悉的气味的方向。却总因为太过模糊而不得不时而停下,这里嗅嗅,那里嗅嗅,一脸茫然的向人们摇摇尾巴。

闭上眼,我好像知道在哪里;顺着模糊的记忆,我却找不到我要的回忆。 Continue reading “夜幕的守望者”

second night in hong kong

我的头还有点疼.鼻尖还有残留的机舱里刺鼻的冰冷气息.

食指揉了揉发胀的太阳穴.定了定神,努力把眼睛对着前面. 毫无预兆的,是什么呢?

<啪嗒> 是了, 今天遇见了个百分之百的女孩.在这百分之百的夏日里.

毫无征兆的,好像熬了一夜的清晨,惺忪双眼,套着睡裤吹着口哨走在已经有声音的街上,拐角路过早点店,毫无预兆的,街角一抬头看到了日出的阳光.庄严.绚丽.不由得屏住呼吸,心跳的紧张起来,让人只想驻足原地,对着它行注目礼,直到仪式结束.仿佛一道电流,一束光,这一时刻生命改变了轨迹. Continue reading “second night in hong kong”

reference organizer

ReadCube, the reference manager software from Nature Publishing Group, has recently released major update/re-development, which finally makes it a usable gadget and a legitimate competitor of Mendeley, my favorite one in this category.

Since my early days in science (2008 ish), I’ve always wanted a perfect file manager that organizes and displays my pdfs——-something like the “Papers” on Mac, but works on PC, has a cloud storage and is free.

After several months’ searching and comparing, I settled down on Mendeley and have used it ever since.

Mendeley has everything I need. Concise UI, automatic metadata fetching, great PDF display, notes, highlights and tags. The free version offers 1G (2G now) of cloud storage, which is a decent amount for PDF files, and sync between the desktop version and the web. It also has a web importer bookmarklet which allows instant paper import to the library when the metadata is able to be extracted from the current webpage. This works on PubMed and most of the journal websites. It has something beyond my expectation. It introduces the “watched folders”, in which every PDF stored are automatically listed and updated in the software library. Even better, you have the option to let Mendeley rename your files based on key metadata information such as “author”,”journal” and “year”. Last but not least, it’s also an Endnote. Easy reference import and bibliography generation in office word, open office and libre office.

The only two minor flaws in my opinion is: the font size of the library display is too small (~10.5 pt) and cannot be changed, which makes it hard to browse from a 15” laptop. This later becomes less of an issue when I more and more rely on searching with tags and authors and basically not use the main library display anymore. The other downside of Mendeley is the memory allocation. I’ve experienced, when the library contains over 1,000 PDF files, severe lag and poor performance of the software. Since then, I reduced the number of actual PDFs saved on my disk, instead saved most of them only in metadata format.

Back to ReadCube. ReadCube was first introduced, I believe, sometime in 2012. I gave it a try because of its stunning UI and the ability to fetch reference hyperlinks and supplemental information from the paper. The user interface is very Mac like: simplicity, nice button effects and awesome colors. For some of the papers that are “enhanceable”, ReadCube can automatically extract reference and supplemental information from the paper, which is great. But ReadCube at the time did not offer many other useful features like what Mendeley does: web importer, write-and-cite tool, cloud and file renaming. What was the worst and essentially prevented me using ReadCube was the display: it has three columns, the library info panel on the left, references/abstract/supplemental on the right, and the actual PDF in the middle. The two panels on either side cannot be closed/hidden and therefore the effective reading space is greatly reduced, and on my 15.5” laptop, too small a font to read. You can zoom in, but everything became a mess to navigate. Also, the addition of references and supplemental often times makes the software running slow and easy to crash.

But everything’s changed in this recent major re-make from last week. The two cumbersome panels can be removed during reading mode, which makes the actual size of reading space equivalent to that of Mendeley’s. Everything is smoother and quicker. I can finally enjoy reading a paper without having worry about the font size and potential crashes. It also introduces web importer and citation tool for Word. On the other hand, you have to pay for cloud space (though unlimited) and watched folder option for $5/mo. And it still doesn’t have tags and file-renaming. And for some reason (perhaps because of my customized font rendering), fonts in ReadCube do not look as sharp as in Mendeley.

So, Mendeley is still my go-to reference manager and paper organizer, although ReadCube has had some great features and improvement. Something I think could be useful is the online Mendeley community. You can invite friends and colleagues and share ideas and papers; you can see other people’s recommendation and comments on papers, sort of like F1000, but clearly less matured. I haven’t tested either of those because I have only one friend in my Mendeley account and we haven’t talked since February of 2011.

chemogenomics

I was about to write something about this study led by Guri Giaever’s group from my beloved U of T MoGen department, when I saw the update from Derek Lowe’s blog on the same subject, where he and a few fellow chemists have spotted some silly chemistry mistakes.

First, they appear to recognize N-phenylbenzylamine and it’s biologically equivalent tautomer as two chemicals and apparently target two distinct cellular pathways.

Then there’s this issue with imidazole and protonated imidazole, which shouldn’t exist at all in a physiological buffer system.

And this one is particularly funny: they have this cyclohexa-2,4-dien-1-one

which should just be phenol indeed.

And there’s a few more examples of mis-nomenclature and small molecules invalid in a biological system like those.

What a shame on the authors! What a shame on the reviewers! and on Ron David, who is in the authorship list and whom I respect a lot.

PS. a note on Guri. Apparently she’s not at U of T anymore. She and her husband, another MoGen faculty, Corey Nislow have joined UBC since last year. Interesting move.

Cysteine and Huntington’s disease: a very ambiguous link

This paper is interesting. It’s not substantial.

I take it as a grain of salt. No, I don’t like it at all.

They were seeing reduced level of an metabolic enzyme Cystathionine γ-lyase (CSE), which makes cysteine and hydrogen sulfide in three models of huntington’ disease: cell lines, mouse models and post-mortem patient samples. And CSE KO mice exhibits certain behavior deficits resembling HD symptoms. Replenishing cysteine in diet alleviates these behavior deficits and increases survival.

First of all, it’s an interesting observation of a reduced level of CSE in HD models——perhaps among hundreds of other random proteins. There is no evidence suggesting CSE activity loss or global reduction in cysteine level, in any way, contributes to disease onset/progression.

Actually they can’t tell if cysteine is the culprit here. CSE makes both cysteine and hydrogen sulfide, and we know that H2S is an important second messenger in signaling in the brain and periphery. That cysteine rescue experiment does not rule out H2S function in the disease state.

The biggest problem I have with this study is all the behavior assay. They were trying to use a few of the standard motor tests to model HD, which is just not nearly satisfying at all. Who knows what causes these deficits when you deplete one of the nine essential amino acids ? It totally doesn’t have to be, in any way, Huntington-dependent, and these tests are not at all good means to monitor HD pathophysiology.

What should they do? Well, since it’s just too vague a connection between CSE expression and some random motor behavior tests, anything in between is essential and the more, the better. At least they should’ve looked at some cellular phenotypes including cell death, inclusion body aggregates and neurodegeneration. Some metabolic profiling and behavior are also welcomed.