Archive for the ‘Medicine’ Category


And it goes to :
Mario R. Capecchi, Martin J. Evans and Oliver Smithies for their discoveries of “principles for introducing specific gene modifications in mice by the use of embryonic stem cells”

Mario R. Capecchi, born 1937 in Italy, US citizen, PhD in Biophysics 1967, Harvard University, Cambridge, MA, USA. Howard Hughes Medical Institute Investigator and Distinguished Professor of Human Genetics and Biology at the University of Utah, Salt Lake City, UT, USA.

Sir Martin J. Evans, born 1941 in Great Britain, British citizen, PhD in Anatomy and Embryology 1969, University College, London, UK. Director of the School of Biosciences and Professor of Mammalian Genetics, Cardiff University, UK.

Oliver Smithies, born 1925 in Great Britain, US citizen, PhD in Biochemistry 1951, Oxford University, UK. Excellence Professor of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA.

Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice . It is now being applied to virtually all areas of biomedicine – from basic research to the development of new therapies.

Our DNA is packaged in chromosomes, which occur in pairs – one inherited from the father and one from the mother. Exchange of DNA sequences within such chromosome pairs increases genetic variation in the population and occurs by a process called homologous recombination.
Mario R. Capecchi demonstrated that homologous recombination could take place between introduced DNA and the chromosomes in mammalian cells. He showed that defective genes could be repaired by homologous recombination with the incoming DNA.

Oliver Smithies who worked on Blood diseases, initially tried to repair mutated genes in human cells by correcting the disease-causing mutations in bone marrow stem cells. (Bone marrow stem cells give rise to all blood cells.) In these attempts Smithies discovered that endogenous genes could be targeted and modified by homologous recombination .

The cell types initially studied by Capecchi and Smithies could not be used to create gene-targeted animals. This required another type of cell, one which could give rise to germ cells. Only then could the DNA modifications be passed on from the parent cell to the daughter cells.

Martin Evans worked with the technology of modifying Embryonic Stem cells from mouse cells genetically and for this purpose chose retroviruses. Retroviruses have the machinery to integrate their genes into the chromosome of cells they infect.
He demonstrated transfer of such retro viral DNA from Embryonic Stem cells, into the mouse germ line. Evans also applied gene targeting to develop mouse models for human diseases. He developed several models for the inherited human disease cystic fibrosis and has used these models to study disease mechanisms and to test the effects of gene therapy.

Capecchi and Smithies had demonstrated that genes could be targeted by homologous recombination in cultured cells, and Evans had contributed the necessary vehicle to the mouse germ line – the ES-cells. The next step was to combine the two.

A “KNOCK-OUT ” mouse is one in which a certain gene has been selectively inactivated. The inactivation is achieved byhomologous recombination of the mice embryonic cells with a small segment of genetic material we artificially insert into it using retroviruses.

How do we benefit?

The technology opens the opportunities to selectively shut-up mutated genes that are known to cause diseases in mammals. This helps us to study what exactly is the function of the “disease gene”. Gene targeting has helped us understand the roles of many hundreds of genes in mammalian fetal development by creating mouse models for human diseases in labs.

Gene targeting has already produced more than five hundred different mouse models of human disorders, including cardiovascular and neuro-degenerative diseases, diabetes and cancer.
Mario R. CapecchiMartin J EvansOliver Smithies

Source: nobelprize.org


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The sudden feeling of vague familiarity about certain scenes or things of life is a common phenomenon we might all have experienced one time or the other. Many of them were dream-like experiences, while some were so vivid; we almost thought it was a replay of the past.

The term “déjà vu” is believed to have been used first in 1876 by French physician Émile Boirac. Each episode last a few seconds only and is much common for Younger people to have these dream-states more often than older adults, yet people of all ages experience déjà vu, especially when they are stressed. There is a reverse of déjà vu, called jamais vu. Here, a familiar person or place is rejected as having never seen before.Many mysteries cloud this curious play of brain chemistry and many of them give rise to beliefs in rebirth, telepathy and clairvoyance. But is this strange feeling of familiarity really a message traveling thru time and space, from the light cone of our past? Or is it just some unconsciously managed memory trace that is peeking up at a second stimulus thru the same neural pathway?

Science has been tracking this question for many years but the stumbling block in investigating the phenomenon is the problem of recreating it in labs.

The Freudian psychoanalysts call déjà vu a replay of suppressed memories. They call it paramnesia. The original event was somehow linked to distress and was being suppressed from conscious recognition, no longer accessible to memory, they say. Temporal lobe epilepsy patients have been thought as good candidates, but their memories lack the true quality of déjà vu – the subject’s disbelief in the memory!

Dr. Vernon M. Neppe[/b] , the Director of the Pacific Neuropsychiatry Institute in Seattle, empirically defined the term déjà vu as: [u]

“any subjectively inappropriate impression of familiarity of a present experience with an undefined past.”[/u]

(His book titled [i]The psychology of Déjà vu: Have I been here before?[/i] has detailed out a long list of déjà vu presentations long back in the 1980s.)

In déjà vu, the subjective feeling of “replay of past” is imminently followed by a feeling of disbelief and rejection of the memory trace, as is widely documented. The act of seeing or hearing also does evoke a feeling of familiarity. It doesn’t pertain just to the memory alone. These qualities are absent in epileptic patients’ recollections and in drug-induced hallucinations. In such cases, the patient or the subject strongly “believes” in these traces of replayed “memory”. A similar phenomenon is seen in schizophrenics too (‘false recognition’). Hence many scientists believe that there should be a “non-epileptic” theory for deja vu that will encompass al the attributes of the phenomenon.


New light on an old problem

Robert Efron, in 1963 suggested the delayed vision theory. He stated that it is possible that sometimes the blending of information into the temporal lobe might not synchronize well and this may result in the deja vu episodes. Words flashed too rapidly to subjects without giving time for the conscious brain to register them were later identified as familiar by the same subjects in the pioneering experiments of Dr. Larry Jacoby in 1989. Recent simulated studies on attention and priming for attention have brought out certain correlations between gaps in attention and feelings of familiarity as in déjà vu. There are also reliable correlations between déjà vu and stress/fatigue as well as mood swings. It seems that whereas déjà vu may be triggered during times of peak tension when one is overly alert, it may be even more likely when one becomes tired and attention starts to wane. Alan Brown of the Southern Methodist Univ and Elizabeth Marsh at Duke University, ran a few tests on a group of students; based on the idea that deja vu’s originate in subliminal suggestion. They support the the diverted attention theory.

According to the theory, people sometimes see things twice in quick succession: the first time superficially or peripherally; the second time with full awareness. You might glance at a building while talking on a cell phone, for instance, and not really register it, then give it a second look a little while later after you get off the phone. You might not remember the first glance, but your brain has registered it subliminally, so the second glance may seem oddly familiar (see Dr.Brown’s new book [i]The Déjà Vu Experience[/i])

Temporal lobe – seat of Deja vu

Open brain surgery stimulations of déjà vu in temporal lobe has been done from the time of Dr. Penfield the latest being that of Dr.Bancaud.These expositions are being investigated with greater fervor, ever since the Alison R. Preston and John D.E. Gabrieli paper on the role of hippocampus as a scrap book of the brain, has come out.

….the relational/familiarity distinction predicts that patients with focal hippocampal damage would be selectively or disproportionately impaired on associative recognition, but exhibit intact or less impaired performance on single-item recognition. However, patients with selective hippocampal damage were equally impaired on the single-item and associative recognition tasks….. results suggest that the hippocampal formation contributes similarly to declarative memory tasks that require relational or familiarity processing…. the para-hippocampal gyrus differentiates between familiar and unfamiliar stimuli – and does so without having to retrieve a concrete episode from our memories.

The excitement is inexplicable, as the research has opened new ways to understand how we create a world of our own around us rather than fit ourselves into the world around. And that’s were evolutionary psychology starts taking up the issue.


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