呵呵呵呵。

A report on the 47th ASCB annual meeting, Washington DC, Dec 1-5, 2007

(note, the below text is a draft, I'll come back and edit it when I have time.)

Part III - Stem Cells, their niches, and aging

The Stem cell niches minisymposium is one of the last platform sessions of the conference. I was, am and will be very interested in germline stem cells and their niches. So I enthusiastically attended the symposium. Turns out, a lot of the talks are very good and inspiring. I hope every reader knows about (or heard of) stem cells. These are the cells with potential to proliferate and differentiate into other types of cells.They're not only important for the maintenance of our body, but also have great therapeutic potentials. The stem cell niche, is the microenvironment, which a stem cell is found. Niches are very important in regulating stem cell self-renewal (without this ability, normal cells simply get old and die), supporting stem cells, controlling stem cell differentiation. I would say this is an exiting topic, but today I will only briefly introduce three talks which I think grabbed my attention.

(i) Stem cell-niche interaction: A mutant stem cell can replace the wild type stem cell in the stem cell niche by "pushing" it out. This study was done using the Drosophila ovary model. The mutation, bam, causes increase in E-Cadherin expression in the mutant cells, and therefore have stronger interaction with the niche, forcing the wild type stem cells out.

(ii) Material exchange between stem cells and their niche: A amazing live cell imaging video (work done at NIH) showed that Hematopoietic stem cells (HSC) are quite dynamic and try to make contact with their niche, the osteoblastic cells. Material transfers from HSC to the niche (both lipid and protein components) are observed. Cell-cell contact is required for the transfer and the transfer is done NOT by a proteolytic-based or a vesicle-based mechanism. Further study suggest endocytosis may play a role. It is not surprising that material exchange happens between stem cells and their niches, but what is the physiological significance of material transfer from a stem to the niche?

(iii) Aging and stem cell niche: Studies on Drosophila germline stem cell (GSC) of old males revealed that GSC in old males decrease in number and the division of the GSC also decreased. But can we reverse the situation by simply introducing more stem cells? No exactly. When the males get older, the hub cell (part of the male GSC niche) is also aging. The GSC self-renewal signals (e.g. Upd) produced by the hub cell is decreased. DE-Cadherin expression is also decreased. There is an overall decrease of the JAK-STAT signaling, which is a important signaling for male GSC in Drosophila. These results really urges us to consider the condition when considering possible stem cell therapies. Well, we are all going to age. Nothing can reverse this process. Why not live happily and let nature take its act!

The above three talks highlighted the importance of the stem cell niche. They also remind us that a multi-cellular organism is an entity that although formed by individual cells, these cells interact to create a bonding rule. Studying a single cell or studying an organism as a whole could be quite different. Therefore one must be very cautious when creating models for a living system.

亮堂堂才六十多天，3－6月的衣服穿在身上已经嫌小了。所以猪爸猪妈给他取小名叫：“衣服阿诺舒华辛迪加”，取衣服终结者之意（不是指他的体魄像施瓦州长）。看来过元旦节时要给猪儿八买新衣服了。

我的一个Dissertation Committee member Susan曾经语重心长地教育过我们，说她在生第一个宝宝的时候太激动，结果存货赶不上宝宝发育的形势，好多东西买来根本没有用。所以给宝宝买东西，要因时而宜，兵来将挡，水来土淹，千万不要冲动。省下钱来，宝宝花钱的地方多。我们一开始没有听从，也是犯了这个毛病，猪猪猪的衣服和尿不湿之类的存了好多。有的衣服一包三件，只穿了一件，别的还没有用过，就已经穿不得了。早知道就干脆留下来，送人也好，拆开了就只有自己留着做纪念了。

小雨天约会是浪漫的，冬日里的雨把空气弄得湿湿的，对干燥的北方来讲，吸一口气，很舒服，更不用说这是第一次约会。（海飞丝广告：“第一次约会，碰到下雨，本来是很浪漫的，可是我的头皮屑。）

猪爸和猪妈今天双双把班逃了，相约在Farragut Square中央的塑像下接头，猪妈撑一把蓝色的伞，暗号是“猪！”。

碰头后我们一起去参观Corcoran Gallery of Art的Ansel Adams/Annie Leibovitz的摄影展。没想到人真多，可能是大家都想赶在1月展出结束之前一睹而后快吧。摄影展很好，看完后，我们稍绕道从白宫前走过，看灯火灿烂的National Christmas Tree，也感受一下节日的气氛。

好久没有过过二人世界了，两人跷班出门走走，也叫浪漫。

大学同学小暴送我一本书，叫30,000 Years of Art: The story of human creativity across time and space. 全书一千多页，12X12X2.9英寸，12.9镑。跟我们家猪儿差不多重。阅读起来颇要费消耗一些卡路里。减肥与新知同部进行，好书啊好书！此书以时间为序，罗列了世界各地各文化各时代的代表性美术作品（绘画，雕塑）1000种。每页皆是精美的大幅图片，加之一段描述性介绍。不失为一本有趣的参考书。我翻了翻了，其中不少物件我在各地博物馆里见到过，还有一些在DC附近的博物馆中，有机会还可以亲去观赏。比如说我印象很深的唐代“镶金兽首玛瑙杯 ”，我在西安的陕西历史博物馆看到过。这回在书中看到，又勾起我对西安-华山游的回忆起来。感谢小暴同学的友情赠送。人说千里送鹅毛，这回是千里赠巨书，友情之深，犹如马里亚纳海沟，不可测矣！

呵呵。

小孩子皮肤粉嬾粉嬾的，不过如果维护不好，很容易干燥，出疹子。一身滑的皮肤很快可以变得如象皮一般。天天包着尿不湿的屁股也不小心也可能长尿疹。以下是几种婴儿用品我们用过，非常有效：

1. 擦屁股用的：A+D Original Ointment，可以防止尿片疹和保护皮肤。我们家猪猪用了它，屁股上从来没有出过疹子。唯一的缺点是这种油膏有一种特别的气味，全身擦了不好闻。Target的售价好象比别的地方都便宜。4 Oz一支的才3块多。

2. 擦身上用的：天气不太干燥的时候用Aveeno Baby Daily Moisture Lotion，无色无味，没有刺激性，擦过后皮肤很舒服。不贵，12 FL Oz.的带pump的瓶只要不到5块钱。不过天气干燥后就不够油了。在冬天开了暖气后，连用加湿器湿度也才35%左右，这时一般的lotion就不顶用了。要用很油的油膏。儿科医生建议了Cetaphil和Aquaphor，我们试用过Aquaphor Healing Ointment不错，所以我去买了一大瓶14 Oz的油膏（这东西很油，大盒用起来比软管和pump方便得多，而且价格要比小支软管便宜一半以上）。这种油膏对干燥起皮的皮肤非常有效（大人也可以用），几乎可以说是擦一次就见效，坚持几次宝宝的皮肤就又恢复粉嬾嬾的状态了，而且可以保护比较轻微的抓伤（小宝宝的猪爪爪很利害，稍微晚剪一次指甲脸上立即就有印子，好在小孩子愈合极快）。而且这种油膏可以擦嘴唇。

3. 擦脸上用的：上述Aquaphor Healing Ointment可以用来擦脸，但是弄在脸上就显得太油了。我们用国产的成都老名牌"春娟宝宝霜”，香喷喷的，温和，而对脸部皮肤有奇效。

4. 紫草油：不要小看中医药的水平，紫草用生菜籽油（没有用一般菜籽油代替也可）浸出后，外用，对湿疹，烧伤，麻疹，热病癍疹，湿疹，疮疡，丹毒等皮肤毛病有特效。宝宝身上长红疙瘩的时候，用紫草油擦，只一次红色就消去，再连续擦两次，基本就好了。

他是谁？当然是我们黄八斤小儿。宝宝过了八周，就会有意识地笑了。娃娃笑真是利害的武器，你看着他笑，心就醉了。这几天过节，我一定要好好在家和猪猪猪玩一玩。

今天是冬至节，大家吃了羊肉，喝了羊肉汤没？成都的习俗是冬至这一天，一定要喝羊肉汤。冬天寒，一碗羊肉汤下肚，鲜味足还暖身，最好不过。四川羊肉出名的地界是简阳。在成都，原来老青石桥有两家卖羊肉汤的馆味道极好。我们04年冬天回国的时候还专程跑去喝汤，一家馆子隔壁卖白面锅盔，买来就着羊肉汤吃，到现在我还能回味。

昨天猪妈把猪婆婆猪公公带去Mall里看剩蛋节日的气氛，结果看到一场好戏。可惜可惜，猪爸好几年没有看过打架的场面，这一次生生错过了。据说，在Mall里面，先是有一家人同一照相的服务员争吵，围了一大群人。他们站在二楼看着，突然人群一个收缩动作，迅速向争吵中心涌去，原来突然冲来一人，同先前那位服务员打起来。于是乎叫好声，鼓掌声忙成一片。我听猪妈讲述，就象中学时学过的一篇课文：《口技》。错过了热闹，不知道下一回什么时候可以赶到。

宝宝两个月体检，要接种五种疫苗：白百破（DTaP），B型流感嗜血杆菌（Hib），脊髓灰质炎（IPV），肺炎链球菌（Pneumococcal Conjugate），轮状病毒（Rotavirus）。前四种打针，最后一种口服。这一回是把猪儿子打痛了，两根大腿一边两针，一针下去就大哭起来，还流了眼泪（第一次流泪！）。听得看得我好心痛。打完后敢紧搂宝宝到怀里，轻轻地拍他的背。亮堂堂还是很勇敢的，哭几声后就不哭了。一脸委屈样，眼角还挂着泪痕。我对八斤说，男子汉流血不流泪哦，哭相太难看，以后找不到漂漂妹妹哦。一句话把他逗笑了。咯咯咯地。猪猪猪又长胖了，现在是13镑14盎司；身高有24英寸半。俨然是个大娃娃了。

发一张放在car seat里准备出门时照的片片以飨众猪粉丝们。

妈的，又忍不住在深更半夜读鬼故事，看得我刷牙的时候都不敢照镜子，害怕背后突然钻出个人来 -- 老婆经常搞这个台子，无声无息地站到我身后，我低头吐一口水，抬头就看到镜子里多了一个人。唉。

Peptide fragments of prostatic acidic phosphatase, which can form fiber clusters (amyloid fibrils) found in semen can boost HIV transmission by 30 to 400,000-fold. (Münch, J. et al. 2007, Cell 131:1059-1071).

http://www.chinachairproject.com/

Some of the pieces are interesting.

A report on the 47th ASCB annual meeting, Washington DC, Dec 1-5, 2007 (Cont. Part II)
(note, the below text is a draft, I'll come back and edit it when I have time.).

Part II. Single-cell organism interests:

In the second day of the meeting, the prokaryotes sessions are pretty interesting. After all these years, these tiny single-cells organisms are still useful and also help us understand what is life?

(i) Does nature roll a dice?
The randomness in life is always an intriguing question. There are fine examples of this, if we look at a population of cells or organisms, especially in prokaryotes. How do they make the decision? Why under similar conditions, only a fraction of the cells took a route completely different from the others. Here are some examples:
  1) Competence of Bacillus. Bacteria cells sometime can take up DNA from their environment easily. These cells are called competent cells. In Bacillus, competence is controlled by a gene called ComK. Once ComK expresses, it will turn on about 100 genes, including itself, which forms a positive feadback loop to enhance the competence of the cell. But in a bacteria culture, only a portion of the cells can become competent. Competent cells have the advantage of taking up foreign DNA, which means they may gain beneficial genes, such as antibiotic resistance. But at the same time, cells at competent state, will temporarily stop growing.
  2) Sporalation of Bacillus. Starvation will trigger the bacteria to form a spore, which could survive very hush conditions. SpoOA is a critical gene that controls this process. When SpoOA is turned on, there is a time window during which the cell could determine whether to undergo the asymmetric division (after this step, sporalation will be irreversible). Again, only a small portion of the cells will turn to a SpoOA-on state upon nutrient limitation. Interestingly, The SpoOA-on cells will also release peptide toxins to kill the surrounding SpoOA-off cells. The dead SpoOA-off cells release nutrients to support the SpoOA-on cells. It is an amazing example of how cells deal with the future uncertainty.
  3) Biofilm formation. Sometime bacteria cells can held themselves together with extracellular matrix and thus forming biofilms. The matrix opreons are controlled by a gene called SinR (an inhibiter), which is negatively regulated by SinI. In the cell population, the number of SinR molecules is about 20 times of the number of the SinI molecules. Which explains why not all cells form biofilms. But why? SinI is regulated by SpoOA. As mentioned in 2), only a portion of the cells express SpoOA.

What do these examples tell us? If we look at an individual cell, its behavior or fate could be either A or B, but that does not determine the behavior or the fate of the entire population.

(ii) Synthetic Biology
Synthetic Biologists aim to build an "artificial biological systems for engineering applications". Which is something we've been doing for decades. Single-cell organisms, such as a bacterium, a yeast etc. are the simplest to manipulate. Let's not talk about this any further. But instead talking about one interesting engineering effort:

With global warming and energy problem, the international society are take great effort searching for alternative energy source. The big issue for us, is biofuel. But how to produce clean alternative energy source with good enough energy balance? How about Hydrogen? Hydrogen can be produced by engineered E coli bacteria using formic acid as original material, which can be produced by engineered yeasts. Let's see whether this scheme works out and the missing links filled.

This weekend I watched to DVDs: Superbad and Bridge to Terabithia. It's a weird combination. But I think both movies worth my praise. Superbad seems real and funny. I like the funny part a lot. You don't see cheap jokes in this movie, which is really, really amazing. If you like Knocked Up, you'll certainly love Superbad because it is even better than the former. (Don't forget to watch the end credits, you'll see those ingenious penis drawings, supposedly by young Seth. They're not gross at all.) Bridge to Terabithia is a very touching film adapted from a famous novel. Two worlds were unfolded in the film, the real world and the world out of imagination, as with another wonderful film, Pan's Labyrinth. I am surprised that a children's movie could also inspire adults. Very well, it is true that we should "keep our minds WIDE open". The world and our lives are in deed beautiful. And if we embrace more, we'll enjoy more.

买了一堆乱七八糟的东西。选了这段时间最冷的一天出门，好在天气很好，下午出门的时候竟然出大太阳，风依然很大。猪儿八还是像往常一样听话，在猪爸怀里睁着两眼到处瞅。到后来不舒服了，才哼了两声。我们买了几株小植物来替换掉上周干死的那盆。还买了一张阳台上用的小铁圆桌，加上一盏蜡烛灯，阳台上突然有节日氛了。猪妈从明天开始上班。可怜的猪猪猪只好吃冻过的奶了。只有他小子知道，还是鲜奶好吃。今天我们几个大人，几乎是轮流抱着他玩了一下午。宠，也就这一回了。再过几个月上Day Care，猪宝宝要更独立才好。

有几天没有发亮堂堂的照片了。猪肉粉丝们是不是等急了？猪爸在晚上拍了几张。如下：

RT

A report on the 47th ASCB annual meeting, Washington DC, Dec 1-5, 2007

(note, the below text is a draft, I'll come back and edit it when I have time.)

It's kind of interesting that two physicists took the keynote platform for the ASCB annual meeting this year. As I mentioned before, this may signals a growing urge of some Biologist to introduce solid mathematics into biological models, if not building the whole new structure using mathematics. The conference is huge and diverse. This is expected. Actually, few talks in the meeting are related to my research project. But I am interested in many fields of Biological Sciences. I have to say that I didn't see many new ideas, rather, a lot of the "new concepts" emerged in the meeting were sophisticated re-development of old ideas. Below are summaries and thoughts about some of the sessions I attended during the meeting. Hopefully these words are informative. Any feedback is welcome.

Part I - Imaging

Fluorescent microscopy (FM) has revolutionized cell biology. We have seen wonderful works done with antibody-based FM. GFP fusion proteins enabled us to track protein in a living cell. And live-cell imaging flourished. With technical advancement, we're pretty good at observing at single cell level as well as constructing 3D images of the cell. So what's next?

In this year's meeting. I attended two mini-symposia focusing imaging. Seems to me researchers in this field are concerning about how to better label and track proteins inside a live cell.

The two techniques I mentioned previously have limitations: for antibody-based targeting, it works only on cell surface proteins unless labeled antibodies are micro-injected into the cell (or we have to fix/kill the cell and permeabilize it); GFP itself is a huge protein, therefore GFP-fusion sometimes affects protein function. In both cases, it is hard to control the fluorescence. To over come the difficulties, researchers have explored using organic fluorophores, quantum dot, and photo activatable fluorescence chemicals etc (all of them are much smaller). The goal, of course, is to have minimum effect on tagged proteins, while having maxim flexibility in controlling the labels.

(i) Ligase mediated protein labeling
Tsien et al. developed FLASH, using small peptide-based labeling. However it is less specific and sensitive. Ligase mediated protein labeling is a more promising labeling technique (Fernandez-Suarez et al., NBT Dec 2007). This method covalently tags protein with small-molecule probes (such as alkyl azide) using engineered lipoic acid ligase. The tagged protein can then be visualized with cyclo-octyne conjugates (also see their previous work on biotin ligase labeling). 

(ii) Photoactivation
In my blog, I talked about photoactivatable GFP. Here is another type of photoactivatable molecules. A nature protein, Phototropin (from plant), has a LOV domain that act as a light sensor. The protein labels can be activated by a specific wavelength of light at a desired time and at a desired sub-cellular location of the cell. This so called "Caging Technology" (name not confirmed) has limitations (proteins needs heavy bio-engineering), but it can be a powerful tool in spatio-temperal analysis of proteins.

多事之冬。十二月还未过半，美国大陆上就接连发生了三起枪击事件。死亡人数不少，而且性质恶劣。

12月5日，Omaha, Nebraska的一个购物广场中，一个19岁青年开枪射杀八人伤五人后自杀。

12月9日，科罗拉多州，一个24岁青年在请求教堂帮助未遂后开枪杀人，12小时后又到65英里外的另一教堂报复杀人，两处死4人伤5人。该人在第二处被警卫击伤后开枪自杀。

12月11日，拉斯维加斯某学校外，有人用枪射击刚下校车的学生，造成2人重伤，4人轻伤。

商场，教堂，学校。不知道还需要有多少类似的事件发生，才会又有人重提禁枪的话题。难道今后人人都要全副武装去商场，去教堂，去学校？幼儿园怎么办？是不是要给宝宝穿上防弹衣，然后一人配一把枪？

周末有点忙。要过节了，活动也多了起来。逛街购物时间太花时间，没有空给亮堂堂照片片。他小子乖还是乖，不过临时变“丑”起来，长得象猪爸。宝宝到这个年龄，力气也大，打起人来非疼，也开始发声学语来。