New Google product: Inbox

Googles New Inbox

On 22nd October Google announced  something new. It’s called Inbox. Years in the making, Inbox is by the same people who brought you Gmail, but it’s not Gmail: it’s a completely different type of inbox, designed to focus on what really matters. 

Email started simply as a way to send digital notes around the office. But fast-forward 30 years and with just the phone in your pocket, you can use email to contact virtually anyone in the world…from your best friend to the owner of that bagel shop you discovered last week. 

With this evolution comes new challenges: we get more email now than ever, important information is buried inside messages, and our most important tasks can slip through the cracks—especially when we’re working on our phones. For many of us, dealing with email has become a daily chore that distracts from what we really need to do—rather than helping us get those things done.

If this all sounds familiar, then Inbox is for you. Or more accurately, Inbox works for you. Here are some of the ways Inbox is at your service:

Bundles: stay organized automatically 
Inbox expands upon the categories we introduced in Gmail last year, making it easy to deal with similar types of mail all at once. For example, all your purchase receipts or bank statements are neatly grouped together so that you can quickly review and then swipe them out of the way. You can even teach Inbox to adapt to the way you work by choosing which emails you’d like to see grouped together. 

Highlights: the important info at a glance
Inbox highlights the key information from important messages, such as flight itineraries, event information, and photos and documents emailed to you by friends and family. Inbox will even display useful information from the web that wasn’t in the original email, such as the real-time status of your flights and package deliveries. Highlights and Bundles work together to give you just the information you need at a glance.

Reminders, Assists, and Snooze: your to-do’s on your own terms

Inbox makes it easy to focus on your priorities by letting you add your own Reminders, from picking up the dry cleaning to giving your parents a call. No matter what you need to remember, your inbox becomes a centralized place to keep track of the things you need to get back to. 

A sampling of Assists

And speaking of to-do’s, Inbox helps you cross those off your list by providing Assists—handy pieces of information you may need to get the job done. For example, if you write a Reminder to call the hardware store, Inbox will supply the store’s phone number and tell you if it's open. Assists work for your email, too. If you make a restaurant reservation online, Inbox adds a map to your confirmation email. Book a flight online, and Inbox gives a link to check-in.

Of course, not everything needs to be done right now. Whether you’re in an inconvenient place or simply need to focus on something else first, Inbox lets you Snooze away emails and Reminders. You can set them to come back at another time or when you get to a specific location, like your home or your office.

Get started with Inbox
Starting today, we’re sending out the first round of invitations to give Inbox a try, and each new user will be able to invite their friends. If Inbox can’t arrive soon enough for you, you can email us at inbox@google.com to get an invitation as soon as more become available. 

When you start using Inbox, you’ll quickly see that it doesn’t feel the same as Gmail—and that’s the point. Gmail’s still there for you, butInbox is something new. It’s a better way to get back to what matters, and we can’t wait to share it with you.

New Google product: Inbox

6:55 AM email, Google, inbox, new Google product

Number of eggs a woman has predicts heart attack risk

What Else An Eggs Can Say?

The number of eggs in a woman's ovaries could tell a lot more than just how fertile she is. It may provide a window onto how fast her cells are ageing and, in particular, reflect her risk of developing heart disease.

Number of Eggs and Disease Risks

Women are born with all of their eggs and, throughout their life, the number they have declines. The onset of menopause is triggered by this decline.

After menopause hits, the risk of heart disease increases. Women who experience it early – before the age of 46 – are at twice the risk of developing heart disease in later life as women who go through menopause at a typical age.

Several factors that coincide with menopause compound this risk, including a shift in the type of cholesterol the body produces, the redistribution of body fat and increased blood pressure. The drop in oestrogen levels is also thought to play a role as the hormone helps keeps blood vessels elastic. ButMarcelle Cedars at the University of California, San Francisco, wondered if the increased risk to women who experience early menopause might have a more fundamental cause. "Perhaps women who go through menopause early are intrinsically aging at a different rate," says Cedars.

Telling telomeres

To find out, Cedars' team took blood samples from 1100 non-menopausal women aged 25 to 45 and measured their amount of anti-Müllerian hormone (AMH), an indicator of how many eggs are in the ovaries. They confirmed the number of eggs by counting the pockets of fluid, called follicles, around each egg using an ultrasound.

To measure the women's biological age, the researchers looked at the length of telomeres in their white blood cells. Telomeres are the dangly bits at the end of chromosomes that shorten every time a cell divides. Their length is considered a measure of cellular age.

Between three and five years later, 250 of the women came back so researchers could calculate their risk of developing heart disease in the next decade – known as their Framington score. This takes account of risk factors such as cholesterol levels, blood pressure and body weight.

As expected, the team found that women with lower egg counts had higher Framington scores, but they also had shorter telomeres. Previous studies have suggested that shorter telomeres are linked with heart disease,dementia and cancer, and also with a shorter lifespan. So women with fewer eggs may also be at higher risk of other age-related diseases, although epidemiological studies will be needed to bolster this link.

Early warning

"We think the ovary may be more sensitive to the processes of aging," says Cedars, making it like a canary in a coal mine for a general state of accelerated aging.

"It is a very promising hypothesis that reproductive ageing could serve as a window into cardiovascular health and the cellular aging process," says JoAnn Manson, an epidemiologist at Harvard School of Public Health in Boston, Massachusetts.

Confirming that number of eggs, as well as age at menopause, is associated with risk of cardiovascular disease is important because heart disease is thenumber one cause of death for women around the world. Women are often diagnosed later than men and also tend to have a worse prognosis after being diagnosed, so finding ways to identify those at higher risk is crucial, says Cedars. Many women undergo AMH testing for fertility purposes and those with low egg counts could be monitored for cardiovascular health and advised to make lifestyle changes at a relatively young age, she says.

The researchers presented their findings this week at the annual meeting of the American Society for Reproductive Medicine in Honolulu, Hawaii.

Number of eggs a woman has predicts heart attack risk

2:48 PM Disease Risk, Heart Attack prediction

Anticlotting Medical Device : Inspired By Pitcher Plant

Technology Inspired By Nature : New Medical Device

Dialysis and implanted arteries widely used in medical industry to keep people alive. The major concern with these devices are blood clotting and infection due to adhered pathogens. Clotting of blood was  handled by treating blood with anticlotinng agents like Heparin. But this method have its own risk;by interfering with clotting, they can cause potentially deadly bleeding.

The New Dialysis Device

Recently, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University looked to the carnivorous pitcher plant for guidance. The plant’s structure includes wells with surfaces too slippery for insects to crawl out of. Those surfaces inspired the development of a coating so slippery that it prevents blood and bacteria from sticking.

The team tested the coating on the interiors of tubes and catheters attached to pigs. They demonstrated that the coating did not degrade, and that blood kept flowing without clotting, for eight hours. Blood usually starts to clot in tubes in an hour. The study is in the journal Nature Biotechnology. [Daniel C. Leslie et al, A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling]

The researchers also tested whether a gecko could latch onto the coating with its notoriously sticky footpads. But not even the gecko could get a grip. 

Liquid-infused, Porous Surface (SLIPS) approach

SLIPS was inspired by the Nepenthes pitcher plant, which uses a layer of liquid water to create a low friction surface that prevents attachment of insects. The SLIPS technology creates omniphobic slippery surfaces by infiltrating porous or roughened substrates with various liquid perfluorocarbons (LPs) that prevent adhesion to the underlying substrate through formation of a stably immobilized, molecularly smooth, liquid overlayer. However, existing medical-grade materials, such as polycarbonate, polysulfone and polyvinyl chloride (PVC), have highly smooth surfaces. Thus, to create nonadhesive, antithrombogenic surfaces that might be useful for clinical medicine in the near-term, we set out to modify the SLIPS technology so that it can be applied to these smooth surfaces. This was accomplished by covalently binding a flexible molecular perfluorocarbon layer, or tethered perfluorocarbon (TP), on the material surface and then coating it with a mobile layer of an LP (perfluorodecalin) that has been used extensively in medicine for applications such as liquid ventilation, ophthalmic surgery and as an US Food and Drug Administration (FDA)-approved blood substitute.

Anticlotting Medical Device : Inspired By Pitcher Plant

4:58 PM Dialysis, featured, medical device, Nepenthes, perfluorocarbons, Pitcher plant., SLIPS

SSL 3.0 The 18 year Old Vulnarebility : The POODLE

The POODLE

Google researchers announced  that it has discovered a vulnerability (referred to as POODLE) in SSL version 3.0. Bodo Möller of the Google Security Team found the issue along with fellow Googlers Thai Duong and Krzysztof Kotowicz. Makers of web browsers, including Google, are working on a fix.

The exploit first allows attackers to initiate a “downgrade dance” that tells the client that the server doesn’t support the more secure TLS (Transport Layer Security) protocol and forces it to connect via SSL 3.0. From there a man-in-the-middle attack can decrypt secure HTTP cookies. Google calls this the POODLE (Padding Oracle On Downgraded Legacy Encryption) attack.

In other words, your data is no longer encrypted. Google researchers Bodo Möller, Thai Duong and Krzysztof Kotowicz recommend disabling SSL 3.0 on servers and in clients. The server and client will default to the more secure TSL and the exploit won’t be possible.

TLS_FALLBACK_SCSV And Chromium Patcha

For end users, if your browser supports it, disable SSL 3.0 support or better yet use tools that support TLS_FALLBACK_SCSV (Transport Layer Security Signalling Cipher Suite Value), it prevents downgrade attacks. Google says that it will begin testing Chrome changes that disable using SSL 3.0 fallback and it will remove SSL 3.0 support completely from all its products in the coming months. In fact, there’s already a Chromium patch available that disables SSL 3.0 fallback.

Mozilla's Plan

In response to today’s news, Mozilla plans to turn off SSL 3.0 in Firefox. “SSLv3 will be disabled by default in Firefox 34, which will be released on Nov 25,” said Mozilla in a post. The code to disable the protocol will be available tonight via Nightly.

SSL Version Control

Anyone interested in disabling SSL 3.0 right now can do so with the SSL Version Control add on for Firefox.

Introduced in 1996, SSL protocol is supposed to allow for communication without fear of eavesdropping because the information being shared is encrypted. When a client (browser, apps etc,) pings a server they engage in a security handshake that creates keys to encrypt and decrypt information sent back and forth.

Microsoft had this to say:

Microsoft is aware of detailed information that has been published describing a new method to exploit a vulnerability in SSL 3.0. This is an industry-wide vulnerability affecting the SSL 3.0 protocol itself and is not specific to the Windows operating system. All supported versions of Microsoft Windows implement this protocol and are affected by this vulnerability. Microsoft is not aware of attacks that try to use the reported vulnerability at this time. Considering the attack scenario, this vulnerability is not considered high risk to customers.

We are actively working with partners in our Microsoft Active Protections Program (MAPP) to provide information that they can use to provide broader protections to customers.

Upon completion of this investigation, Microsoft will take the appropriate action to help protect our customers. This may include providing a security update through our monthly release process or providing an out-of-cycle security update, depending on customer needs.

This POODLE bites: exploiting the SSL 3.0 fallback [Google]

SSL 3.0 The 18 year Old Vulnarebility : The POODLE

1:45 PM Chromium patch, google reserch, poodle, SSL 3.0, TLS_FALLBACK_SCSV

Ebola Gorilla Vaccine Could Prevent Human Outbreak

Ebola The Deadly Virus

In a podcast on today 13^th Oct 2014 on Scientific America by David Biello, stating the possibility of preventing Ebola outbreaks in Human by vaccinating Gorilla against Ebola. The first line of statement is little odd but on continue listening, I understood the meaning behind the statement.

Vaccination For Ebola

Humans are not only the victim of deadly Ebola virus. Chimps and Gorillas are also susceptible to the disease.  He stated that, the current Ebola epidemic may have started with the butchering of an infected          fruit bat.  But we cannot avoid the possibility from Chimpanzee, which found dead in the forest and eaten by people, who cannot afford to pass up a free meat.

Connection Between Ebola And Apes

Ebola has killed thousands of great apes. Some 95 percent of gorillas who become infected die. Several previous outbreaks of Ebola in central Africa stemmed from dead gorillas or chimps found in the forest and butchered for food. All it takes to start an epidemic is infected blood getting in a person’s eye, mouth or open wound.

That's why veterinarians from the Wildlife Conservation Society and other conservation organizations may prove to be the front line for defending humans against Ebola.

  

Like their physician counterparts, vets are hoping to develop a vaccine, perhaps to be administered orally. At the very least, monitoring Ebola outbreaks in apes could provide early warning for potential human outbreaks. By saving the apes we may be saving ourselves.

Ebola Gorilla Vaccine Could Prevent Human Outbreak

4:58 PM EBOLA cure, Ebola Vaccination, Preventing Ebola

STEM Cells , A Basic Introduction

What Are STEM Cells

"An undifferentiated cell of a multicellular organism that is capable of giving rise to indefinitely more cells of the same type, and from which certain other kinds of cell arise by differentiation"

Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

Stem cells are distinguished from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions.

Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. The functions and characteristics of these cells will be explained in this document. Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem cell-like state. This new type of stem cell, called induced pluripotent stem cells (iPSCs), will be discussed in a later section of this document.

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lungs, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.

Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine.

Laboratory studies of stem cells enable scientists to learn about the cells’ essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.

Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.

What are the unique properties of all stem cells?

Stem cells differ from other kinds of cells in the body. All stem cells—regardless of their source—have three general properties: they are capable of dividing and renewing themselves for long periods; they are unspecialized; and they can give rise to specialized cell types.

Stem cells are capable of dividing and renewing themselves for long periods. Unlike muscle cells, blood cells, or nerve cells—which do not normally replicate themselves—stem cells may replicate many times, or proliferate. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.

Scientists are trying to understand two fundamental properties of stem cells that relate to their long-term self-renewal:

1. Why can embryonic stem cells proliferate for a year or more in the laboratory without differentiating, but most non-embryonic stem cells cannot; and
2. What are the factors in living organisms that normally regulate stem cellproliferation and self-renewal?

Discovering the answers to these questions may make it possible to understand how cell proliferation is regulated during normal embryonic development or during the abnormal cell division that leads to cancer. Such information would also enable scientists to grow embryonic and non-embryonic stem cells more efficiently in the laboratory.

The specific factors and conditions that allow stem cells to remain unspecialized are of great interest to scientists. It has taken scientists many years of trial and error to learn to derive and maintain stem cells in the laboratory without them spontaneously differentiating into specific cell types. For example, it took two decades to learn how to grow human embryonic stem cells in the laboratory following the development of conditions for growing mouse stem cells. Likewise, scientists must first understand the signals that enable a non-embryonic (adult) stem cell population to proliferate and remain unspecialized before they will be able to grow large numbers of unspecialized adult stem cells in the laboratory.

Stem cells are unspecialized. One of the fundamental properties of a stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. For example, a stem cell cannot work with its neighbors to pump blood through the body (like a heart muscle cell), and it cannot carry oxygen molecules through the bloodstream (like a red blood cell). However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells.

Stem cells can give rise to specialized cells. When unspecialized stem cells give rise to specialized cells, the process is called differentiation. While differentiating, the cell usually goes through several stages, becoming more specialized at each step. Scientists are just beginning to understand the signals inside and outside cells that trigger each step of the differentiation process. The internal signals are controlled by a cell's genes, which are interspersed across long strands of DNA and carry coded instructions for all cellular structures and functions. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment. The interaction of signals during differentiation causes the cell's DNA to acquire epigenetic marks that restrict DNA expression in the cell and can be passed on through cell division.

Many questions about stem cell differentiation remain. For example, are the internal and external signals for cell differentiation similar for all kinds of stem cells? Can specific sets of signals be identified that promote differentiation into specific cell types? Addressing these questions may lead scientists to find new ways to control stem cell differentiation in the laboratory, thereby growing cells or tissues that can be used for specific purposes such as cell-based therapies or drug screening.

Adult stem cells typically generate the cell types of the tissue in which they reside. For example, a blood-forming adult stem cell in the bone marrow normally gives rise to the many types of blood cells. It is generally accepted that a blood-forming cell in the bone marrow—which is called a hematopoietic stem cell—cannot give rise to the cells of a very different tissue, such as nerve cells in the brain. Experiments over the last several years have purported to show that stem cells from one tissue may give rise to cell types of a completely different tissue. This remains an area of great debate within the research community. This controversy demonstrates the challenges of studying adult stem cells and suggests that additional research using adult stem cells is necessary to understand their full potential as future therapies.

What are embryonic stem cells?

A. What stages of early embryonic development are important for generating embryonic stem cells?

Embryonic stem cells, as their name suggests, are derived from embryos. Most embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro—in an in vitro fertilization clinic—and then donated for research purposes with informed consent of the donors. They are not derived from eggs fertilized in a woman's body.

B. How are embryonic stem cells grown in the laboratory?

Growing cells in the laboratory is known as cell culture. Human embryonic stem cells (hESCs) are generated by transferring cells from a preimplantation-stage embryo into a plastic laboratory culture dish that contains a nutrient broth known as culture medium. The cells divide and spread over the surface of the dish. In the original protocol, the inner surface of the culture dish was coated with mouse embryonic skin cells specially treated so they will not divide. This coating layer of cells is called afeeder layer. The mouse cells in the bottom of the culture dish provide the cells a sticky surface to which they can attach. Also, the feeder cells release nutrients into the culture medium. Researchers have now devised ways to grow embryonic stem cells without mouse feeder cells. This is a significant scientific advance because of the risk that viruses or other macromolecules in the mouse cells may be transmitted to the human cells.

The process of generating an embryonic stem cell line is somewhat inefficient, so lines are not produced each time cells from the preimplantation-stage embryo are placed into a culture dish. However, if the plated cells survive, divide and multiply enough to crowd the dish, they are removed gently and plated into several fresh culture dishes. The process of re-plating or subculturing the cells is repeated many times and for many months. Each cycle of subculturing the cells is referred to as a passage. Once the cell line is established, the original cells yield millions of embryonic stem cells. Embryonic stem cells that have proliferated in cell culture for for a prolonged period of time without differentiating, and are pluripotent are referred to as an embryonic stem cell line. At any stage in the process, batches of cells can be frozen and shipped to other laboratories for further culture and experimentation.

C. What laboratory tests are used to identify embryonic stem cells?

At various points during the process of generating embryonic stem cell lines, scientists test the cells to see whether they exhibit the fundamental properties that make them embryonic stem cells. This process is called characterization.

Scientists who study human embryonic stem cells have not yet agreed on a standard battery of tests that measure the cells' fundamental properties. However, laboratories that grow human embryonic stem cell lines use several kinds of tests, including:

• Growing and subculturing the stem cells for many months. This ensures that the cells are capable of long-term growth and self-renewal. Scientists inspect the cultures through a microscope to see that the cells look healthy and remainundifferentiated.
• Using specific techniques to determine the presence of transcription factors that are typically produced by undifferentiated cells. Two of the most important transcription factors are Nanog and Oct4. Transcription factors help turn geneson and off at the right time, which is an important part of the processes of celldifferentiation and embryonic development. In this case, both Oct 4 and Nanog are associated with maintaining the stem cells in an undifferentiated state, capable of self-renewal.
• Using specific techniques to determine the presence of particular cell surface markers that are typically produced by undifferentiated cells.
• 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 re-grown, or subcultured, after freezing, thawing, and re-plating.
• 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 cells characteristic of the three germ layers; or 3) injecting the cells into a mouse with a suppressed immune system to test for the formation of a benign tumor called a teratoma. Since the mouse’s immune system is suppressed, the injected human stem cells are not rejected by the mouse immune system and scientists can observe growth and differentiation of the human stem cells. 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 appropriate 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).

Figure 1. Directed differentiation of mouse embryonic stem cells. 

 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 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, Duchenne's muscular dystrophy, heart disease, and vision and hearing loss.

What are adult stem cells?

An adult stem cell is thought to be an undifferentiated cell, found among differentiated cells in a tissue or organ.  The adult stem cell can renew itself and can differentiate to yield some or all of 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. Scientists also use the term somatic stem cell instead of adult stem cell, where somatic refers to cells of the body (not the germ cells, sperm or eggs). Unlike embryonic stem cells, which are defined by their origin (cells from thepreimplantation-stage embryo), the origin of adult stem cells in some mature tissues is still under investigation.

Research on adult stem cells has 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 researchers and clinicians to ask whether adult stem cells could be used for transplants. In fact, adult hematopoietic, or blood-forming, stem cells from bone marrow have been used in transplants for more than 40 years. Scientists now have evidence that stem cells exist in the brain and the heart, two locations where adult stem cells were not at first expected to reside. If the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of transplantation-based therapies.

The history of research on adult stem cells began more than 60 years ago. In the 1950s, 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 stem cells (also calledmesenchymal stem cells, or skeletal stem cells by some), were discovered a few years later. These non-hematopoietic stem cells make up a small proportion of the stromal cell population in the bone marrow and can generate bone, cartilage, and fat cells that support the formation of blood and fibrous connective tissue.

In the 1960s, scientists who were studying rats discovered two regions of the brain that contained dividing cells that ultimately become nerve cells. Despite these reports, most scientists believed that the adult brain could not generate new nerve cells. 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 andoligodendrocytes, 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, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis. They are thought to reside in a specific area of each tissue (called a "stem cell niche"). In many tissues, current evidence suggests that some types of stem cells are pericytes, cells that compose the outermost layer of small blood vessels. Stem cells may remain quiescent (non-dividing) for long periods of time until they are activated by a normal need for more cells to maintain tissues, or by disease or tissue injury.

Typically, there is a very small number of stem cells in each tissue and, once removed from the body, their capacity to divide is limited, making generation of large quantities of stem cells difficult. Scientists in many laboratories are trying to find better ways to grow large quantities of adult stem cells in cell culture and to manipulate them to generate specific cell types so they can be used to treat injury or disease. Some examples of potential treatments include regenerating bone using cells derived from bone marrow stroma, developing insulin-producing cells for type 1 diabetes, and repairing damaged heart muscle following a heart attack with cardiac muscle cells.

B. What tests are used to identify adult stem cells?

Scientists often use one or more of the following methods to identify adult stem cells: (1) label the cells in a living tissue with molecular markers and then determine the specialized cell types they generate; (2) remove the cells from a living animal, label them in cell culture, and transplant them back into another animal to determine whether the cells replace (or "repopulate") their tissue of origin.

Importantly, scientists must demonstrate that a single adult stem cell can generate a line of genetically identical cells that then gives rise to all the appropriate differentiated cell types of the tissue. To confirm experimentally that a putative adult stem cell is indeed a stem cell, scientists tend to show either that the cell can give rise to these genetically identical cells in culture, and/or that a purified population of these candidate stem cells can repopulate or reform the tissue after transplant into an 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.

Normal differentiation pathways of adult stem cells. In a living animal, adult stem cells are available to divide, when needed, 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) that have been demonstrated in vitro or in vivo.

Figure 2. Hematopoietic and stromal stem cell differentiation.

• 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, and macrophages.
• Mesenchymal stem cells have been reported to be present in many tissues. Those from bone marrow (bone marrow stromal stem cells, skeletal stem cells) give rise to a variety of cell types: bone cells (osteoblasts and osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and stromal cells that support blood formation. However, it is not yet clear how similar or dissimilar mesenchymal cells derived from non-bone marrow sources are to those from bone marrow stroma.
• 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 andoligodendrocytes.
• 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.

Transdifferentiation. A number of experiments have reported that certain adult stem cell types can differentiate into cell types seen in organs or tissues other than those expected from the cells' predicted lineage (i.e., brain stem cells that differentiate into blood cells or blood-forming cells that differentiate into cardiac muscle cells, and so forth). This reported phenomenon is called transdifferentiation.

Although isolated instances of transdifferentiation have been observed in some vertebrate species, whether this phenomenon actually occurs in humans is under debate by the scientific community. Instead of transdifferentiation, the observed instances may involve fusion of a donor cell with a recipient cell. Another possibility is that transplanted stem cells are secreting factors that encourage the recipient's own stem cells to begin the repair process. Even when transdifferentiation has been detected, only a very small percentage of cells undergo the process.

In a variation of transdifferentiation experiments, scientists have recently demonstrated that certain adult cell types can be "reprogrammed" into other cell types in vivo using a well-controlled process of genetic modification (see Section VI for a discussion of the principles of reprogramming). This strategy may offer a way to reprogram available cells into other cell types that have been lost or damaged due to disease. For example, one recent experiment shows how pancreatic beta cells, the insulin-producing cells that are lost or damaged in diabetes, could possibly be created by reprogramming other pancreatic cells. By "re-starting" expression of three critical beta cell genes in differentiated adult pancreatic exocrine cells, researchers were able to create beta cell-like cells that can secrete insulin. The reprogrammed cells were similar to beta cells in appearance, size, and shape; expressed genes characteristic of beta cells; and were able to partially restore blood sugar regulation in mice whose own beta cells had been chemically destroyed. While not transdifferentiation by definition, this method for reprogramming adult cells may be used as a model for directly reprogramming other adult cell types.

In addition to reprogramming cells to become a specific cell type, it is now possible to reprogram adult somatic cells to become like embryonic stem cells (induced pluripotent stem cells, iPSCs) through the introduction of embryonic genes. Thus, a source of cells can be generated that are specific to the donor, thereby increasing the chance of compatibility if such cells were to be used for tissue regeneration. However, like embryonic stem cells, determination of the methods by which iPSCs can be completely and reproducibly committed to appropriate cell lineages is still under investigation.

D. 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?
• How do adult stem cells evolve during development and how are they maintained in the adult? Are they "leftover" embryonic stem cells, or do they arise in some other way?
• Why do stem cells remain in an undifferentiated state when all the cells around them have differentiated? What are the characteristics of their “niche” that controls their behavior?
• Do adult stem cells have the capacity to transdifferentiate, and is it possible to control this process to improve its reliability and efficiency?
• If the beneficial effect of adult stem cell transplantation is a trophic effect, what are the mechanisms? Is donor cell-recipient cell contact required, secretion of factors by the donor cell, or both?
• What are the factors that control adult stem cell proliferation and differentiation?
• What are the factors that stimulate stem cells to relocate to sites of injury or damage, and how can this process be enhanced for better healing?

STEM Cells , A Basic Introduction

12:25 PM cell division, embryonic stem cells, Medicine, Potency, STEM cells