Databases of Virology

This is a collection of internet based databases of virology in which you can find virological bioprotocols, pathways, solution recipes, animations, knowledge source, education ebooks, videos, pictures, and healthcare information. 

The Journal of Virology Online - http://jvi.asm.org/

Online version of the Journal of Virology, the premier journal for peer-reviewed papers on virology research. 

Retrovirology - http://www.retrovirology.com
A peer reviewed journal that publishes reviews and original research on retroviruses. 

Virus Databases Online - http://www.ictvdb.rothamsted.ac.uk/
A comprehensive index of viruses provided by the International Committee on Taxonomy of Viruses. Also provides a picture gallery, identification tool and software tools.

All the Virology on the WWW - http://www.virology.net/ 

Links to virology information, collection of virus pictures, virology bookshop, jobs, and course notes. 

UK Clinical Virology Network - http://www.clinical-virology.org
News, clinical tests, and current viruses in circulation. 

HIV Sequence Database - http://www.hiv.lanl.gov/content/index
Collection HIV and related genetic sequence data and computer analyses - from the Los Alamos Natl. Lab. 

American Society for Virology - http://www.asv.org/
A forum for investigators of human, animal, insect, plant, fungal and bacterial viruses in areas such as clinical, ecological, biological or biochemical research. 

Paramyxoviruses - http://en.wikipedia.org/wiki/Paramyxovirus
Information from Wikipedia on these negative-sense single-stranded RNA viruses, responsible for a number of human and animal diseases, including their taxonomy, morphology and pathogenesis. 

Poxvirus Bioinformatics Resource - http://www.poxvirus.org
The Poxvirus Bioinformatics Resource Center has been established to provide resources to the scientific community for basic research and to facilitate the development of novel antiviral therapies and vaccines against human orthopoxvirus infections as well as approaches for environmental detection of virions and the rapid diagnosis of disease. 

Viral Replication - http://en.wikipedia.org/wiki/Viral_replication
Information from Wikipedia on the attachment, entry, and expression of viral genomic material in host cells. 

Wadsworth Center - New York State Department of Health - http://www.wadsworth.org/databank/viruses.htm
Information and images regarding; Rabies virus, Herpes virus, Enteroviruses, Norwalk virus, Human Parvovirus B19 and Rotavirus. 

Virology Down Under - http://www.uq.edu.au/vdu/
An Australian based portal and educational site providing links and information on human viruses and related areas of science. 

Hidden Killers--Deadly Viruses - http://library.thinkquest.org/23054/gather/index.shtml
Basics about viruses, our bodies' immune systems, information about specific viruses, and how these 'hidden killers' could potentially be used as bio-weapons. There are also weekly/bi-weekly feature articles on various facets that involve viruses. 

A New Germ Theory - http://www.theatlantic.com/issues/99feb/germs.htm
The dictates of evolution virtually demand that the causes of some of humanity's chronic and most baffling "noninfectious" illnesses will turn out to be pathogens -- that is the radical view of a prominent evolutionary biologist. 

EVA: European Virus Archive - http://www.european-virus-archive.com
Project aiming to create a European network of high calibre laboratories with the expertise to collect, amplify, characterise, standardise, authenticate, distribute and track all viruses. 

Viper: Virus Particle Explorer - http://mmtsb.org/viper/
Descriptions of icosahedral virus capsid structures, along with structural and computational analysis. 

VirHostNet - http://pbildb1.univ-lyon1.fr/virhostnet
Knowledgebase for virus-host and protein-protein interaction networks. 

National Collection of Pathogenic Viruses - http://www.ukncc.co.uk/html/members/ncpv/ncpv.htm
NCPV preserves well-characterised, authenticated human pathogenic viruses in a secure facility. The agents or nucleic acids derived from these viruses are supplied to the worldwide scientific community according to national and international guidelines. 

Baculovirus.com - http://www.baculovirus.com
Technical knowledge, information, newsgroup, helpful in using the Baculovirus expression vector system and insect cell expression. 

Virology - http://www.elsevier.com/locate/issn/0042-6822
This journal publishes the results of basic research in all branches of virology, including the viruses of vertebrates and invertebrates, plants, bacteria, and yeasts/fungi. 

What the Heck is a Virus? - http://people.ku.edu/~jbrown/virus.html
Provides a relatively easy to understand answer to this question. 

Virusys Corporation - http://www.virusys.com
Specialists in the design and manufacture of virus related antibodies and antigens. A full range of laboratory services is available that includes infectious dose determination, viral protein purification and custom antibody production. 

Blogging for Bacteriophages - http://www.phagehunter.org/
Blog by Tim Sampson who takes a look at recent developments in the world of microbiology. 

The Molecules of HIV - http://www.mcld.co.uk/hiv/
The life cycle, immune response, and schematic diagram of the human immuno-deficiency virus. 

Plant Virology - http://www.bioinvision.dk/plantvir1.html
Introduction to virus structure, transmission, and transport. 

The Phage Phorum - http://www.phages.org
A place to find general information regarding biophages and an open discussion of topics related to biophages. 

Veterinary Virology - http://www.pitt.edu/~super1/lecture/lec3351/001.htm
Lecture presentation on the replication of viruses within animals cells. 

Viral Replication - http://www.epidemic.org/theFacts/viruses/viralReplication.html
Description of the hepatitis virus replication process. 

Medical Virology - http://www.medicalvirology.com
Scientific findings, clinical therapies research, and public health aspects on viruses of medical importance. 

GeneJohnson Inc. - http://www.genejohnson.net
HIV genomic data storage and analysis systems. HIVBase allows one to organize HIV sequence data, perform complex statistical analysis, and collaborate data all in one program. 

Viralman - http://viralman.110mb.com
Educational site for students provided by H.Niazmand at Azad University of Kazeroun, with downloads and an image gallery. 

Hepadnavirus Testing, Inc. - http://www.hvtinc.com 

The site describes the services provided by Hepadnavirus Testing, Inc., which uses HBV and DHBV to evaluate disinfectants, inactivation processes, and antiviral drugs for the biotechnology and pharmaceutical industries. 

Antiviral Intelistrat - http://www.antiviralintelistrat.com/
Database of antiviral drugs and vaccines. It regroups over 1700 product files containing detailed information on compounds and vaccines related to the prevention or treatment of viral diseases. Subscription needed. 

Chicken Flu: Recombinant Genes on the Loose - http://www.synapses.co.uk/science/fluvirus.html
Information regarding viral genes, replication, and strain evolution. Written in 1997 but updated in 2005. 

Seminars in Virology - http://www.sciencedirect.com/science?...... 

Review journal dedicated to keeping scientists informed of developments in the  

field of virology on a topic by topic basis. 

Virus Ultrastructure - http://web.uct.ac.za/depts/mmi/stannard/linda.html
This page is designed primarily as an introductory manual for students of virology,but anyone who is interested is invited to take a brief "peep" at some of the inhabitants of the microbial Lilliput Land. 

Journal of General Virology - http://www.sgm.ac.uk/JGVDirect/
Archive of downloadable PDF virus journals. 

大陆房地产绝密“潜规则”购房者欲哭无泪

红网12日报导，该报一名记者卧底做一名售楼员，揭示卖楼之前首先是“卖自己”：不仅穿着、谈吐要做好包装，还要迅速磨掉你性格中的那些菱角。而干这一行，“潜规则”、“不习惯”，是必不可少的，但赚到钱、学到策略才是王道。理论上，你能把房子卖好，就能卖好一切东西——这个行业特有的生态环境决定了售楼员的业绩就是整个销售行业的技术高度。

报导说，但是，没人会把这当做荣耀，因为，站在他们身后的开发商才是一切游戏规则最终的操盘手。而购房者欲哭无泪，这里是房地产业十大绝密“潜规则”

绝密一:现在你们知道炒房团怎么炒了吧？

绝大多数人都以为是开盘之后温州人和山西人以市场价买进。那你就错了，炒房团深知开发商的软肋——缺钱!巨额资金的介入，会让开发商眼前一亮，头晕目眩。
因为，说实在话，几亿、十几亿从银行得到贷款，远不是想像的那么容易。炒房团，就是有钱人组成团，给房地产开发商提供巨额资金。
目的一：帮助房地产商，使其光环维持和光大。房地产行业，时刻在风口狼尖上，不进则退，不活则死。
目的二：使城市房屋（包括商、住）价格狂飙，彻底激活消费者买涨不买跌的心理。
目的三：盘活房地产开发商的资金链，使其银行巨额贷款的困难逐步消化，分解给刚性购房群体和中产阶层（绝大部份都是银行按揭）。
实际上，投资性购房者可以说是像狗一样地在吃人家丢的骨头。
显而易见，房地产的泡沫是由：1、愚民的政府政策；2、贪婪的商业银行；3、无德的富人阶层；4、无辜的中华文明（安家立业是成年标志）这四个条件促成的。

绝密二:房子究竟值多少钱？

你说它值多少钱它就值多少钱！既然买房子对所有人来说都是投资，那么它的价格与成本之间小幅度或大幅度的波动，都应该认为是正常的。
没有涨和跌反而是不正常的，涨的越快，应该跌的越猛。
公众期盼的是：1、富人应该有社会公德，不应该为高房价推波助澜；2、国家政策应该明确，你鼓动高房价就是与缩小贫富差距相悖；3、商业银行应该为关乎民族命运的科教文卫和制造业发展提供服务，为热衷于虚拟经济的降降温。

绝密三：房地产行业的潜规则：

官商勾结成大事。不与官（至少是涉及的所有主管部门一把手）勾结寸步难行。想勾结出感情，不动大手笔免谈。
噱头必不可少。要么是海外投资的旗号（其实是老虎皮），要么是浙闽大亨的来头。奔驰车和保时捷排量越大越有感召力，宣传册子、广告语越霸气越能打动中国人。

绝密四：说说散户炒房。

1、100万资金首付30%，按揭3套100万的期房，总价300万，支出90万。
2、两年后交房，当天交房屋维修基金和契税3.5%。两年期间已归还银行贷款30万。当你收到房子时，你已经累计支出130.5万元。
3、此时，房价已经过两年的共20%的上涨，市场上你的3套房总价已达360万。通过你在房屋中介公司挂牌销售，你可能有幸按360万全部脱手，获利29.5万。
4、实际获利与银行存款相比，100万元银行2年期存款利息可达12万元（大额存款是高利息），你实际比银行存款利息多得17.5万元。
5、如果中介在1年内才把你的3套房出手，你实际获利比存款利息还要少3.5万元（多还一年房贷15万元）。
6、若恰逢国家房地产政策调控，或者你贪婪地捂到5年后出手，你自己计算吧。到那时候，你就死去吧。不仅仅是sb。
那时候，银行会一天一个函催你还款。你实在挺不住了，把“夏利”车也卖了，把16岁的女儿也早早嫁人，甚至你老婆会到广州街头“站街”帮你赚钱还债。也许你会跳楼。即使你不跳楼，法院会把你领进小黑屋。如果你跳楼，那就是中国房地产崩盘了。

绝密五：再说说炒房团。

资金从哪里来？
山西煤老板：非法开采国家资源，廉价使用劳动力，因陋就简的采掘设备和安全技术措施，结伙入盟哄抬煤炭价格，以极快的速度实现资本积累。
温州客：没有文化的个体户出身，小手工作坊仿冒国际名牌产品，在全国各地（特别是西部偏远落后地区）开设销售网点，春江水暖鸭先知把握了市场经济形势，早期敛财速度惊人。大资金动辙数千万、数亿、数十亿。
福建客：房地产热之前（2005年之前），全国70%的公路、铁路、电站隧道工程几乎被福建人一手独揽，采取不正当的手段榨取民工血汗，钻营中国央企施工企业（说白了就是给央企领导投资），很快发达。要知道隧道工程资金流量巨大，比如一项工程总投资3个亿，赚5,000万利润是最笨的福建老板。另外，早年的走私之流，能让杨钰莹这样的名女人都投怀送抱，可见走私资本积累速度也是很罕见的。

绝密六：炒房的暴利究竟有多大？

以楼上为例，提前与房地产董事长暗地协议，以2,200元/平方米抢购巨量房源（至少300套），鼓动市场价超过7,000元，并力挺10,000元/平，逐步随售楼部销售出手，资金逐步回笼，在中共政府的目前政策形势下，回笼的越慢，反而利益收获就越大。大到多少？
当二、三线城市的平均房价达到10,000元/平的时候，炒房团的收益完全可以达到500%！炒房团扑向一个城市，是同时扑向所有楼盘。这样一来，一个城市的房价飙升已成定势！以去年底的海南岛为例，炒房团可以让海南的房价一天一个价，一夜一个行情，造就一个又一个真实的梦！
其实，炒房团的组成人员，绝大多数都是高中没读完的，自己签个名字都歪歪扭扭。炒房的技术含量确实很低，真的很低，会用加减乘除足矣，甚至连加权平均都不用。更不用看什么各类权威的什么CPI、PPI、GDP。投入了一些钱，3个月后赚多少钱？6个月后赚多少？1年后赚多少？

绝密七：房地产会崩盘吗？

崩盘是什么概念呀？房价崩盘了，中国就乱了。
那时候说不清人民币究竟会升值还是贬值，反正银行要不会倒闭，但存款取现困难，30%的央企倒闭，60%的中小民企消失。但房价必须下跌，跌30～40%一点也不过分，到这个水平，银行依然不吃亏，已买房自住的跟这几乎没关系，想买房的肯定喜上眉梢。炒房团或投资性购房的散户，为国家和社会做点贡献合情合理。

绝密八：房市四大傻

1、自住房买涨不买跌的心理害人又害己，是一大傻；
2、不要以为买房子从银行贷款手续简单就很方便。银行的还款计划是前2年先把它的利息大部份回收，银行是贪婪的，也是不可靠的。贷款180万、25年还贷期是二大傻；
3、如果你是城镇户口，没有迁移户口的需求，现在买房子是大笨蛋。
买房自住的叫“房奴”，前世来生都得还，“出来混，总是要还的”。每个月还银行几千元，你从今往后的生活就谈不上质量。城镇居民买高价房是三大傻；
4、有人说，买得起高价房是男人成功标志，这里我要说，买高价房的人都是四大傻。
建议：真的要住城市，租房（当然要稳定的租价和租期）是最好的选择。

绝密九：知道什么是“房虫”吗

在北方，街上练摊的，都要请些哥们朋友来捧场，造成人头攒动的声势，名字叫“托儿”。房地产行业的“托儿”有个专用名称叫“房虫”。
1、楼盘开盘当天，你要去买房子排队买号，你也许排在第500位的号，然而等你出手敲定一套房子，等你签定合约时，你会发现你的合约编号是第0030号。
你明白了吗？你前面后面排队的数百人、上千人，都是人家花小费请来的“房虫”！
2、还有一类“房虫”，是真的交定金、签合同。然而1～3个月后，一旦房价飙涨，他们会成批成批地退房。他们是打“假球”，真正目的是把球传给刚性购买群体。当然，他们与房地产老板的合同与你的合同有关键性的差别：不存在退房扣5%的违约金！
肯定啦，买房时的定金是房地产老板提前给的。还有，不瞎忙，参与本次房虫活动，每个操作员都有5,000～20,000的“辛苦费”。你相信吗？

绝密十：究竟有多少人在真正关心房价？

1、政府官员：关心自己的仕途;关心本界政绩;关心本辖区的GDP，能创造越多的地王，本地经济越繁荣。
2、商业银行：历来发愁货币贷款任务完不成。放贷越多，收益越大。存款准备金或贸易逆差是北京总部的事（各商业银行在全国的市级分行网点至少5,000个，具体小政策自己灵活机动掌握）。
3、经济学家：是读书到博士、评职称到正教授级、写书给省部级刊物，顺理成章到所谓的“发展研究中心”上班，每天8小时上班，业余时间保养下身体，否则头发会掉光。不可忽视的是，相当一部份经济学家已经依附于财团，持有的某些观点是为了赚得一些小实惠。
4、富人阶层（仅流动资金就超过500万人民币）：早就对房子这个东西没有激情啦（早有豪华居所）。
5、中产阶层（固定资本超100万，流动资本低于100万）：可能介入炒股、炒房，会迅速步入富人阶层或沦为贫民阶层。
6、贫民阶层（上班族或个体业主，家庭月收入低于10000，存款低于10万）：是刚性消费群体，对房价涨跌敏感，有强烈的改善住房需求，是忠实房奴。
7、贫困阶层（家庭月收入低于3,000，比如即将倒闭的企业职工，频繁跳槽的年轻大学生，还有农民及农民工，存款低于20,000）：有饭吃、饿不死的一族，城市买房几乎是梦。
8、特困阶层（家庭月总收入低于1,000，天旱没水吃，下雨屋漏雨）：是政府救济对象，听买房子像听天书。

最后问一句你属于哪个阶层呢。

You are never too old

Keep Active as You Age

We’ve all heard that exercise is good for you. Did you know that it’s as true for older people as it is for any age group? You’re never too old to get moving, get stronger and improve your health.

Fitting exercise and physical activity into your day can enhance your life in so many ways. Regular physical activity can improve your balance and boost or maintain your strength and fitness. It may also improve your mood and help you manage or lessen the impact of conditions like diabetes, heart disease, osteoporosis and depression.

Despite these proven benefits, exercise and physical activity rates among older people are surprisingly low. Only about 30% of people ages 45 to 64 say they engage in regular leisure-time physical activity. This falls to 25% of those between the ages of 65 and 74 and 11% of people age 85 and older.

Experts recommend 4 types of exercise for older adults: endurance, balance, strength and flexibility. Brisk walking, dancing and other endurance exercises improve the health of your heart, lungs and circulatory system. These exercises can make it easier for you to mow the lawn, climb stairs and do other daily activities. Strength exercises include lifting weights or using resistance bands. They can increase muscle strength to help with activities such as carrying groceries or lifting grandchildren. Balance exercises can help prevent falls—a major health risk for older adults. Stretching, or flexibility exercises, can give you more freedom of movement for bending to tie your shoes or looking over your shoulder as you back out of the driveway.

“Even if you haven’t been active previously, it’s important to get started and stay active,” says Dr. Richard J. Hodes, director of NIH’s National Institute on Aging. “We know that people want to live independently for as long as they possibly can. By exercising regularly and including more physical activity in their daily routine, older people can preserve their physical function, which is key to doing the everyday things they want to do.”

To help you get started and keep moving, NIH brought together some of the nation’s leading experts on aging, exercise and motivation. They developed a guide to exercise for older adults. The guide serves as the basis for a new national exercise and physical activity campaign for people ages 50 and older. It’s called Go4Life.

“Older adults can exercise safely, even those who have physical limitations,” Hodes says. “Go4Life is based on studies showing the benefits of exercise and physical activity for older people, including those with chronic health conditions.”

Stem Cells and Diseases

The Promise of Stem Cells

Studying stem cells will help us understand how they transform into the dazzling array of specialized cells that make us what we are. Some of the most serious medical conditions, such as cancer and birth defects, are due to problems that occur somewhere in this process.

A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions.

Another potential application of stem cells is making cells and tissues for medical therapies. Today, donated organs and tissues are often used to replace those that are diseased or destroyed. Unfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantation. Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat a myriad of diseases, conditions, and disabilities including Parkinson's and Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid arthritis.

Have human embryonic stem cells successfully treated any human diseases?

Scientists have been able to do experiments with human embryonic stem cells (hESC) only since 1998, when a group led by Dr. James Thomson at the University of Wisconsin developed a technique to isolate and grow the cells. Moreover, Federal funds to support hESC research have been available since only August 9, 2001, when President Bush announced his decision on Federal funding for hESC research. Because many academic researchers rely on Federal funds to support their laboratories, they are just beginning to learn how to grow and use the cells. Thus, although hESC are thought to offer potential cures and therapies for many devastating diseases, research using them is still in its early stages.

Adult stem cells, such as blood-forming stem cells in bone marrow (called hematopoietic stem cells, or HSCs), are currently the only type of stem cell commonly used to treat human diseases. Doctors have been transferring HSCs in bone marrow transplants for over 40 years. More advanced techniques of collecting, or "harvesting," HSCs are now used in order to treat leukemia, lymphoma and several inherited blood disorders.

The clinical potential of adult stem cells has also been demonstrated in the treatment of other human diseases that include diabetes and advanced kidney cancer. However, these newer uses have involved studies with a very limited number of patients.

Participating in Research Studies

Scientists are testing the abilities of adult stem cells to treat certain diseases. You can search for clinical trials using stem cells (or other methods) to treat a specific disease at ClinicalTrials.gov.

（Source：The National Institutes of Health resource for stem cell research）

Stem Cell Basics (2)

examining the chromosomes under a microscope. This is a method to assess whether the chromosomes are damaged or if the number of chromosomes has changed. It does not detect genetic mutations in the cells.

determining whether the cells can be subcultured after freezing, thawing, and replating.

testing whether the human embryonic stem cells are pluripotent by 1) allowing the cells to differentiate spontaneously in cell culture; 2) manipulating the cells so they will differentiate to form specific cell types; or 3) injecting the cells into an immunosuppressed mouse to test for the formation of a benign tumor called a teratoma. Teratomas typically contain a mixture of many differentiated or partly differentiated cell types—an indication that the embryonic stem cells are capable of differentiating into multiple cell types.

D. How are embryonic stem cells stimulated to differentiate?

As long as the embryonic stem cells in culture are grown under certain conditions, they can remain undifferentiated (unspecialized). But if cells are allowed to clump together to form embryoid bodies, they begin to differentiate spontaneously. They can form muscle cells, nerve cells, and many other cell types. Although spontaneous differentiation is a good indication that a culture of embryonic stem cells is healthy, it is not an efficient way to produce cultures of specific cell types.

So, to generate cultures of specific types of differentiated cells—heart muscle cells, blood cells, or nerve cells, for example—scientists try to control the differentiation of embryonic stem cells. They change the chemical composition of the culture medium, alter the surface of the culture dish, or modify the cells by inserting specific genes. Through years of experimentation scientists have established some basic protocols or "recipes" for the directed differentiation of embryonic stem cells into some specific cell types (Figure 1). (For more examples of directed differentiation of embryonic stem cells, see Chapters 5–9 and Appendices B and C of the NIH report Stem Cells: Scientific Progress and Future Research Directions.)

If scientists can reliably direct the differentiation of embryonic stem cells into specific cell types, they may be able to use the resulting, differentiated cells to treat certain diseases at some point in the future. Diseases that might be treated by transplanting cells generated from human embryonic stem cells include Parkinson's disease, diabetes, traumatic spinal cord injury, Purkinje cell degeneration, Duchenne's muscular dystrophy, heart disease, and vision and hearing loss.

IV. What are adult stem cells?

An adult stem cell is an undifferentiated cell found among differentiated cells in a tissue or organ, can renew itself, and can differentiate to yield the major specialized cell types of the tissue or organ. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found. Some scientists now use the term somatic stem cell instead of adult stem cell. Unlike embryonic stem cells, which are defined by their origin (the inner cell mass of the blastocyst), the origin of adult stem cells in mature tissues is unknown.

Research on adult stem cells has recently generated a great deal of excitement. Scientists have found adult stem cells in many more tissues than they once thought possible. This finding has led scientists to ask whether adult stem cells could be used for transplants. In fact, adult blood forming stem cells from bone marrow have been used in transplants for 30 years. Certain kinds of adult stem cells seem to have the ability to differentiate into a number of different cell types, given the right conditions. If this differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of therapies for many serious common diseases.

The history of research on adult stem cells began about 40 years ago. In the 1960s, researchers discovered that the bone marrow contains at least two kinds of stem cells. One population, called hematopoietic stem cells, forms all the types of blood cells in the body. A second population, called bone marrow stromal cells, was discovered a few years later. Stromal cells are a mixed cell population that generates bone, cartilage, fat, and fibrous connective tissue.

Also in the 1960s, scientists who were studying rats discovered two regions of the brain that contained dividing cells, which become nerve cells. Despite these reports, most scientists believed that new nerve cells could not be generated in the adult brain. It was not until the 1990s that scientists agreed that the adult brain does contain stem cells that are able to generate the brain's three major cell types—astrocytes and oligodendrocytes, which are non-neuronal cells, and neurons, or nerve cells.

A. Where are adult stem cells found and what do they normally do?

adult stem cells have been identified in many organs and tissues. One important point to understand about adult stem cells is that there are a very small number of stem cells in each tissue. Stem cells are thought to reside in a specific area of each tissue where they may remain quiescent (non-dividing) for many years until they are activated by disease or tissue injury. The adult tissues reported to contain stem cells include brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin and liver.

Scientists in many laboratories are trying to find ways to grow adult stem cells in cell culture and manipulate them to generate specific cell types so they can be used to treat injury or disease. Some examples of potential treatments include replacing the dopamine-producing cells in the brains of Parkinson's patients, developing insulin-producing cells for type I diabetes and repairing damaged heart muscle following a heart attack with cardiac muscle cells.

B. What tests are used for identifying adult stem cells?

Scientists do not agree on the criteria that should be used to identify and test adult stem cells. However, they often use one or more of the following three methods: (1) labeling the cells in a living tissue with molecular markers and then determining the specialized cell types they generate; (2) removing the cells from a living animal, labeling them in cell culture, and transplanting them back into another animal to determine whether the cells repopulate their tissue of origin; and (3) isolating the cells, growing them in cell culture, and manipulating them, often by adding growth factors or introducing new genes, to determine what differentiated cells types they can become.

Also, a single adult stem cell should be able to generate a line of genetically identical cells—known as a clone—which then gives rise to all the appropriate differentiated cell types of the tissue. Scientists tend to show either that a stem cell can give rise to a clone of cells in cell culture, or that a purified population of candidate stem cells can repopulate the tissue after transplant into an animal. Recently, by infecting adult stem cells with a virus that gives a unique identifier to each individual cell, scientists have been able to demonstrate that individual adult stem cell clones have the ability to repopulate injured tissues in a living animal.

C. What is known about adult stem cell differentiation?

As indicated above, scientists have reported that adult stem cells occur in many tissues and that they enter normal differentiation pathways to form the specialized cell types of the tissue in which they reside. Adult stem cells may also exhibit the ability to form specialized cell types of other tissues, which is known as transdifferentiation or plasticity.

Normal differentiation pathways of adult stem cells. In a living animal, adult stem cells can divide for a long period and can give rise to mature cell types that have characteristic shapes and specialized structures and functions of a particular tissue. The following are examples of differentiation pathways of adult stem cells (Figure 2).

Hematopoietic stem cells give rise to all the types of blood cells: red blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes, macrophages, and platelets.

Bone marrow stromal cells (mesenchymal stem cells) give rise to a variety of cell types: bone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and other kinds of connective tissue cells such as those in tendons.

Neural stem cells in the brain give rise to its three major cell types: nerve cells (neurons) and two categories of non-neuronal cells—astrocytes and oligodendrocytes.

Epithelial stem cells in the lining of the digestive tract occur in deep crypts and give rise to several cell types: absorptive cells, goblet cells, Paneth cells, and enteroendocrine cells.

Skin stem cells occur in the basal layer of the epidermis and at the base of hair follicles. The epidermal stem cells give rise to keratinocytes, which migrate to the surface of the skin and form a protective layer. The follicular stem cells can give rise to both the hair follicle and to the epidermis.

Adult stem cell plasticity and transdifferentiation. A number of experiments have suggested that certain adult stem cell types are pluripotent. This ability to differentiate into multiple cell types is called plasticity or transdifferentiation. The following list offers examples of adult stem cell plasticity that have been reported during the past few years.

Hematopoietic stem cells may differentiate into: three major types of brain cells (neurons, oligodendrocytes, and astrocytes); skeletal muscle cells; cardiac muscle cells; and liver cells.

Bone marrow stromal cells may differentiate into: cardiac muscle cells and skeletal muscle cells.

Brain stem cells may differentiate into: blood cells and skeletal muscle cells.

Current research is aimed at determining the mechanisms that underlie adult stem cell plasticity. If such mechanisms can be identified and controlled, existing stem cells from a healthy tissue might be induced to repopulate and repair a diseased tissue (Figure 3).

C. What are the key questions about adult stem cells?

Many important questions about adult stem cells remain to be answered. They include:

How many kinds of adult stem cells exist, and in which tissues do they exist?

What are the sources of adult stem cells in the body? Are they "leftover" embryonic stem cells, or do they arise in some other way? Why do they remain in an undifferentiated state when all the cells around them have differentiated?

Do adult stem cells normally exhibit plasticity, or do they only transdifferentiate when scientists manipulate them experimentally? What are the signalsthat regulate the proliferation and differentiation of stem cells that demonstrate plasticity?

Is it possible to manipulate adult stem cells to enhance their proliferation so that sufficient tissue for transplants can be produced?

Does a single type of stem cell exist—possibly in the bone marrow or circulating in the blood—that can generate the cells of any organ or tissue?

What are the factors that stimulate stem cells to relocate to sites of injury or damage?

V. What are the similarities and differences between embryonic and adult stem cells?

Human embryonic and adult stem cells each have advantages and disadvantages regarding potential use for cell-based regenerative therapies. Of course, adult and embryonic stem cells differ in the number and type of differentiated cells types they can become. Embryonic stem cells can become all cell types of the body because they are pluripotent. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, some evidence suggests that adult stem cell plasticity may exist, increasing the number of cell types a given adult stem cell can become.

Large numbers of embryonic stem cells can be relatively easily grown in culture, while adult stem cells are rare in mature tissues and methods for expanding their numbers in cell culture have not yet been worked out. This is an important distinction, as large numbers of cells are needed for stem cell replacement therapies.

A potential advantage of using stem cells from an adult is that the patient's own cells could be expanded in culture and then reintroduced into the patient. The use of the patient's own adult stem cells would mean that the cells would not be rejected by the immune system. This represents a significant advantage as immune rejection is a difficult problem that can only be circumvented with immunosuppressive drugs.

Embryonic stem cells from a donor introduced into a patient could cause transplant rejection. However, whether the recipient would reject donor embryonic stem cells has not been determined in human experiments.

VI. What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized?

There are many ways in which human stem cells can be used in basic research and in clinical research. However, there are many technical hurdles between the promise of stem cells and the realization of these uses, which will only be overcome by continued intensive stem cell research.

Studies of human embryonic stem cells may yield information about the complex events that occur during human development. A primary goal of this work is to identify how undifferentiated stem cells become differentiated. Scientists know that turning genes on and off is central to this process. Some of the most serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation. A better understanding of the genetic and molecular controls of these processes may yield information about how such diseases arise and suggest new strategies for therapy. A significant hurdle to this use and most uses of stem cells is that scientists do not yet fully understand the signals that turn specific genes on and off to influence the differentiation of the stem cell.

Human stem cells could also be used to test new drugs. For example, new medications could be tested for safety on differentiated cells generated from human pluripotent cell lines. Other kinds of cell lines are already used in this way. Cancer cell lines, for example, are used to screen potential anti-tumor drugs. But, the availability of pluripotent stem cells would allow drug testing in a wider range of cell types. However, to screen drugs effectively, the conditions must be identical when comparing different drugs. Therefore, scientists will have to be able to precisely control the differentiation of stem cells into the specific cell type on which drugs will be tested. Current knowledge of the signals controlling differentiation fall well short of being able to mimic these conditions precisely to consistently have identical differentiated cells for each drug being tested.

Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. Today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including Parkinson's and Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.

For example, it may become possible to generate healthy heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart disease. Preliminary research in mice and other animals indicates that bone marrow stem cells, transplanted into a damaged heart, can generate heart muscle cells and successfully repopulate the heart tissue. Other recent studies in cell culture systems indicate that it may be possible to direct the differentiation of embryonic stem cells or adult bone marrow cells into heart muscle cells.

In people who suffer from type I diabetes, the cells of the pancreas that normally produce insulin are destroyed by the patient's own immune system. New studies indicate that it may be possible to direct the differentiation of human embryonic stem cells in cell culture to form insulin-producing cells that eventually could be used in transplantation therapy for diabetics.

To realize the promise of novel cell-based therapies for such pervasive and debilitating diseases, scientists must be able to easily and reproducibly manipulate stem cells so that they possess the necessary characteristics for successful differentiation, transplantation and engraftment. The following is a list of steps in successful cell-based treatments that scientists will have to learn to precisely control to bring such treatments to the clinic. To be useful for transplant purposes, stem cells must be reproducibly made to:

Proliferate extensively and generate sufficient quantities of tissue.

Differentiate into the desired cell type(s).

Survive in the recipient after transplant.

Integrate into the surrounding tissue after transplant.

Function appropriately for the duration of the recipient's life.

Avoid harming the recipient in any way.

Also, to avoid the problem of immune rejection, scientists are experimenting with different research strategies to generate tissues that will not be rejected.

To summarize, the promise of stem cell therapies is an exciting one, but significant technical hurdles remain that will only be overcome through years of intensive research.

The NIH has a wide array of new scientific programs designed to support research that uses embryonic stem cell lines.

VII. Where can I get more information?

You can start with other sections of this Info Center. For a more detailed discussion of stem cells, see Stem Cells: Scientific Progress and Future Research Directions. Check the Frequently Asked Questions page for quick answers to specific queries. The navigation table at right can connect you to the information you need.

The following Web sites, which are not part of the NIH Stem Cell site, also contain information about stem cells. The NIH is not responsible for the content of these sites.

http://www.news.wisc.edu/packages/stemcells/
The University of Wisconsin's Web site about stem cells, written for general audiences.

http://www.eurekalert.org
EurekAlert! is a publicly accessible science news site run by the American Association for the Advancement of Sciences. Search for "stem cells."

http://scitechdaily.com/
A site that offers a range of news articles, features, and commentaries about science and technology topics. Search for "stem cells."

http://www.sciam.com/
The Web site for Scientific American. Search for "stem cells."

http://today.reuters.com/news/newssearchresults.aspx?srch=stem%20cell&searchtype=a
Searches the Reuters news site for stories about stem cells.

http://www.stemcellresearchnews.com/
A commercial, online newsletter that features stories about stem cells of all types.

（Source：NIH， In Stem Cell Information）