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Archive for the ‘Geneworld’ Category

Sex differences in cognition and behavior–such as increased aggression in males–are usually thought to involve hormones, which can “masculinize” or “feminize” a brain temporarily or permanently. But now, a mouse study shows that some sex-linked genes don’t need hormones to shape male and female behavior.

 

The Y chromosome in males have been identified to contain the gene SRY (Sex determining Region Y ) that determines the formation of testicles long back, and by early ’90s scientists had learned how to breed mice whose genes and hormones function independently. Since human SRY is similar to SRY of mice, a model of SRY function has been developed in mice.

By knocking out the testes-determining SRY gene, on the Y chromosome, researchers made XY mice that churn out estrogen; and by adding SRY to females, they produce XX mice that manufacture male hormones.

With the help of such mice, it was shown that genes unrelated to hormone production also played an independent role in aggression and nurturing behaviors. This was a new revelation because, until then it was believed that only the hormones determined such behaviours.

A team led by neuroscientist Jane Taylor of Yale University was interested in habit-forming behaviors in which gender differences also have been documented. She and her colleagues trained these mice, as well as normal male and female mice, to poke their noses through one of three holes in order to obtain a food pellet. Then, some of the mice were subjected to “conditioned taste aversion”. After eating the food, they were injected with a chemical that made them sick (something like what we use in alcoholic patients to help them quit drinking.) Ordinarily, mice will quickly learn to avoid the food, but they will still eat it if they have developed an automatic habit. That happened more often for the XX mice regardless of whether they produced male or female hormones.Thus, they say, the sex difference must have something to do with genes that are not involved in the production of sex hormones.

Neurobiologist Lawrence Cahill of the University of California, Irvine, says that the study “relates very well to established sex differences in the acquisition of addictive habits.” For example, women progress from casual drug-taking to a drug habit faster than men do–a phenomenon some have attributed to hormones. Taylor says that the work also implies that women can be good multitaskers–by quickly forming habits that leave their higher brain functions free for other chores.

Blogger’s Post Script: The last piece about the study implying that women can be good multitaskers seems to be a hasty extrapolation to me, as the quoted study doesn’t provide results of any of that sort, although estrogen has been linked to many skilled activities and greater attention span. It is also important to keep in mind that the precise mechanisms of sex differentiation are still unknown and that gender differentiation is accomplished through a cascade of gene activations. Further factors are involved, then, before as well as after the SRY expression – for example the WT-1, SF-1, DAX-1, SOX-9 genes. (I’m not being chauvinistic here – just bringing to notice a bad practice in science reporting, that’s all.)

Report in Nature Neuroscience. (21 October).

News modified from Sciencenow.

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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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We have discussed what intelligence means and how it is inherited, I would like the readers to follow me thru a small digression where we will have a “zoom-in” on the exact ways by which genes work in the brain.
The technical details might be indigestible to the general reader hence an oversimplified version of the story is presented in the posts below. I should make clear at the outset that this is indeed a digression and skipping these few posts wont break the continuity of the whole thread…heh he Scientists…especially geneticists, have strange ways of naming genes and proteins that discover. Most genes are named based on the “effect” they produce in the body if they start malfunctioning. For example the now famous gene that helps in memory functions is named Amnesiac, (!??)because its mutation or absence can result severe “forgetfulness” in the carrier ! Genes like comatose and mini brain are of this kind. Another popular way of naming genes and proteins is giving the names-names of comic or epic characters or names of individuals, breeds, and even objects resembling the proteins for that matter; examples of this kind being leonardo, homer, Miranda, dachshund, slipper, sickle etc. Some scientists are fond of names from classical languages other than the “done-to death” Latin. A protein (an amide to be exact) called anandamide called so because anandam– pronounced “aanaanthom”- is the Sanskrit word for bliss or euphoria. So my readers can now speculate on the effects of this protein in brain..

Biological systems are built in order to respond to environmental stimulus. Learning takes this ability to extremes. Memory involves increasing the efficiency of how brain cells “communicate” with one another, otherwise called synaptic function.
Memories are thought to be due to lasting synaptic modifications in the brain. Repeatedly used information is processed in the brain by what is called Long term Potentiation. This mainly includes tuning the nerve cells to make them ready for repeated firing of the synapse. (a Synapse is the fancy term for the point of contact of two connected nervecells).

What is the role of genes and their protein products in these synaptic changes?

Coincidence of information from two or more modalities (for example: a baby inadvertently touching a hot iron rod) results in increased neural activity, that is, an influx of Calcium ions. Elevated amounts of Calcium ions in nerve cells cause Ca2+ to bind to a protein called Calmodulin. The Calcium-Calmodulin complex joins hands with another molecule called Adenylate Cyclase. The final combination of all three increases the cellular manufacture of a molecule known as Cyclic AMP or c-AMP for short. This molecule is called a second messenger. The job of a second messenger is to wake up genes in a cell; cAMP does just that. Thru a series of reactions subsequently, it stimulates a number of genes like CREB, Dunce, Rutagaba, Amnesiac and so on. These “activated” genes start making a lot of proteins that enhance the nerve-to-nerve connection, making the route clear for easy passage of ionic signals. The connexions thus made form the secret behind learning & memory.

Here’s a short list of some weird (!) genes and their functions in brain, to amaze your friends at the next party…

Homer : required for brain cells to control movement of limbs and body parts, and also behavioural plasticity.

Rutagaba : required for changing synaptic connexions for modifying learned things.

Dunce : destroys cAMP. And regulates amount of info stored.

Amnesiac : Needed for associating various stimuli to learned concepts.

Leonardo : Strongly associated with learning and smell, especially in fruit flies.

BALB : Makes you introverted but good at tracking back old ways.

NCS-I : Determines flexibility of learning.

BDNF : Encourages growth of nerve cells.

…you can extend this list to any number of pages…so complex is the simple task of learning..!

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We have always referred to people with exceptional abilities as “smart”, “clever” or “bright”. By doing so, we unconsciously recognize the existence of a number of different intelligence-subtypes. It has now become a commonsense notion that there exist certain types of intelligence like “arithmetic” intelligence, an “artistic” intelligence, a “commonsense” intelligence, a “cognitive” intelligence, “semantic” (vocabulary based) intelligence or “knowledge based” intelligence.

 

Such a categorization is rooted in our concept that a person who is good at one specific area should necessarily be deficient in another area. For example there are examples around us, of exceptionally brilliant scientist who are absent-minded or super mathematicians who can hardly learn a new language etc.

So how far is this notion true…?

 

Well, scientifically speaking, this notion is partly correct and partly wrong. The analysis of data from more than 400 classic databases on human intelligence research has brought to light three important findings about this:

 

a) People good at one area of intelligence tend to be good at all other areas generally!
b) Intelligence can be an expression of certain pools of interrelated abilities.
c) Though people have a tendency to be “generally intelligent”, there are sufficient evidences for specific types of intelligences and people who are good in such areas.

 

Let us examine each. Point (a) suggests that there is definitely something called “general” intelligence…some specific property of the brain that makes you “clever” on the whole.

 

What is this property of the brain ?

Extensive research into factors like “brain size”, electrical activity, its efficiency in processing visual data, and reaction time to various challenges have shown that people with higher intelligence have faster decision and response times. Such tests have concluded that intelligence correlates well with “speed of processing information”. It is curious to note that though this is the case, we don’t yet have a consensus on how exactly we‘re gonna test this “speed”!
Point (a) also suggests that our intuition about “clever” people being adept at one thing and inept at another is not exactly true.
Though there are sharply defined pools of intellectual abilities, in reality, a clever person can possess varying degrees of all these abilities. But there are compelling evidences of patients called “idiot savants” in neurology that are exceptions to this rule. These patients are a result of a phenomenon called “ Paradoxical functional facilitation”. This means that some brain related hindrances or injuries can result not only in loss or suppression of particular functions but also the enhancement of certain other abilities.
Idiot savants generally have the IQ of a 5 year old or a 10 year old child but may exhibit amazing capabilities in other areas like Calculations or Artistic works, or music.
A famous example is that of Nadia, an “autistic savant” patient who could draw more life-like illustrations than even DaVinci at the age of 8. There are similar people who can retain thousands of pages of Shakespearian literature, but can’t even find their way home after an evening walk. The theory behind this is that the birth injuries caused to their brains enhance the expansion and development of certain other unexpected areas.

Point (b) supports the “savant” theory to some extent. There are indeed inter related pools of certain intelligences, which are outlined as below.


  • Verbal Comprehension pool: consists of abilities involvingVocabulary, similarities, information processing & comprehension
  • Perceptual organization: includes abilities like completing patterns, picture sequencing, block designs and matrix reasoning.
  • Working memory: comprises faculties like digit span, letter-number sequencing, and arithmetic intelligence.
  • Processing speed: constituted by abilities like symbol search and digit-symbol decoding.


All these capacities exhibited in intelligence tests can be conveniently categorized into 8 chief mental faculties, viz.

  1. Visual perception
  2. Auditory perception
  3. Fluid intelligence
  4. Retrieval ability
  5. Crystallized intelligence
  6. Cognitive speediness
  7. General memory and learning
  8. Processing speed


In 1988, Snyderman and Rothman brought out a book on IQ controversies. They published the results of an opinion poll conducted among the specialists in cognitive psychology and allied fields.

About 99% opined that the major element of intelligence was “Abstract Thinking”. The “Ability to Solve Problems” was chosen by ~97%. And 96% of the experts considered intelligence as a product of the “Capacity to Acquire Knowledge” too. But curious enough, only 80% chose Memory as a component. Cognitive speediness was considered by 71% and General knowledge by 62%.
Still strange was the case of Creativity: hardly 60% chose this aspect as an important constituent of intelligence!!
Research data run parallel to this poll result…but we shouldn’t forsake the fact that some of the most successful scientific theories in mankind’s history were born out of sheer creativity. Examples include General Relativity, parts of QED, photonics, Planck’s theories…

   

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