The human engine

Nutrition is much more than just type and amount of food consumed-it is about the balance between fuel supply and expenditure.it is this balance which creates our real energy crisis.our human engine runs on energy,and that energy ultimately comes from food.the major fuels are simple carbohydrates.after digestion complex carbohydrates,fat,and proteins can be turned into energy sources by conversion to glucose.this largely happens in the lives and skeletal muscles.without fuel on bell can function.after glucose is taken into a cell,it is converted to energy through the action of mittochondria,which are intracellular incinerators generating energy for use in an enormous range of body processes.ye use energy to run all our cellular processes as well as to carry out integrated actions such as muscular movements.the electrical processes in the brain are particularly energy consuming.and a further important use of energy is in the repair and maintainance of our tissues-for example the cells of our skin and of our intestinal lining need constantly to be renewed.

Growth is not possible without the adequate intake of fat,protein,and carbohydrates-the so-called macronutrients,which provide the building blocks for tissue growth as well as the energy that allows cells to divide and multiply.but good nutrition for function and growth must also include micronutrients such as the vitamines and trace minerals.these are essential for specific body functions,often as the catalysts for specific enzyme actions or as components of critical molecules.for example iodine is essential in the body as a component of thyroid hormone.

But fuel supplies must be balanced by their consumption.he people expend less energy than they take in they will gain weight.when excess energy is left on board it is primarily stored as eat under our skin and within our abdomen.he we have a persistently excessive energy intake,fat will also accumulate in our muscles and in the liver.fat stores are a long-term energy supply,just like the camel's hump-an adaptation in that species which evolved for surviving in an environment where there is very intermittent access to done.

Fat has highest energy content for its weight of any body constituent and that is why animals deposit eat under particular situations where having fuel reserves is important.

There have been considerable reductions in our personal energy expenditure since the industrial revolution,although this has been accompanied by a massive increase in the other form of energy consumption through use of electricity and transport fuel.in the developed world the burden of physical labour in the course of work is greatly reduced by machinery.there is a dramatic correlation between motor vehicle ownership and adult obesity in india.

The control of body weight is complex.people have different body weights,not only because they are taller or shorter but because they have stored different amounts of eat.and in the absence of significant changes in habit,our body fat content remains relatively constant-winter or summer,at work or on vacation.tits part of the variation in body composition between individuals appears to be innate;consequently it must have something to do with our individual underlying physiology.it cannot simply be due to differences in supply or demant.

We have seen how species evolved to primarily live within their conform zones.our energy system-that is,the nature of our metabolism including the fuel it burns,how it burns,and what it does with excess fuel,are all the products of our evolutionary history and therefore of the environment we inhabited in prehistory.but our metabolism was designed for environments very different from themse we now inhabit.we need to examine the consequences of this change .

Perspective on time

CONSTRAINED BY OUR PAST : PERSPECTIVES ON TIME



history and biology do not just work on a single time scale.an evolutionary biologist think in terms of tens of thousands he not millions of years,an archaeologist in thousands of years,a geneticist might think of a few generations,a doctor or biographer in terms of a lifetime.the mismatch paradigm tells up that we cannot shake off our biological parts of evolution and development.it continually reminds up that the range of environments we evolved and developed to inhabit can be very different from those we actually live now.


The shaping of our genetic repertoire occurred as our species evolved and dispersed around the globe.our ancestors faced the challenges of diverse physical environments and also their own impact on these environments:these in turn affected their sources of food,their exposure to diseases,and the social grouping and structure within which they lived.the more recent part of our individual journey started when our mother was an embryo and the egg destined to make each of up formed in one of her developing ovaries while she was still inside our maternal grandmother's womb.ye have seen how the environment of that egg as it was fertilized and grew to be our mother,who in turn incubated each of up and created an environment in which we grew,has influenced up.after we were born other factors influenced our biology in many ways.there environmental messages from our pasts have set constrains on our current biology.

Although we might wish to,we all eventually come to realize that we cannot do everything we want to in our lives.we are bound by a wide variety of constraints.virtually everyone faces a significant financial constraint which limits their ability to indulge in their fantasies.e.g buying an island or buying a private jet.and there are social constraints on how we behave.our sexual moses and determined by the society we live in.our families,friends,jobs,and social structure create emotional and other constraints.cmd we have obvious but poorly undertood biological constraints which prevent up living forever.just as we inherit both financial and social oppourtunities and constraints,so it is that our various pasts-evolutionary and genetic,developmental and epigenetic,environmental,cultural-form long ago and form more recent times-create oppourtunities and constraints on how we can live healthily.while we might conveniently think of constraints separately,they are really interwined like the strands of a rope.

Mismatched in our world

Humans can be distinguished from all other species in the way in which they continually,and often intentionally,modify their environments,both physical and socially.for much of our history we employed our unique capacities of thinking,communication,planning,and use of technology in rather limited ways to expand the range of environments we could inhabit.when we stopped living as nomads we started using technology to intensify our population density in specific and static environments.the race of change has accelerated as technological developments have progressed.

Throughout our history as a species we have striven,by the use of our intelligence ,our ingenuity,and by sides hard work,to improve the conditions,under which we live.it is better to be warm than cold;better to be replete than hungry;better to live for another year than to die today of disease;better stroll to the refrigerator to prepare a sandwich than to walk for miles to collect a few meagre nuts and berries.life really is so much better than it was,at least in developed societies,and only the most cynical person would deny it.we have improved the lot of human condition for ourselves,our families and friends,and even for the particular society in which we live(our tribe if you like)beyond all recognition since we migrated out of africa.

And so we have come to design sophisticated ways of growing and distributing food,and of manufacturing the foods we seem to like best.ye have applied technology to reduce the amount of physical work most of us expend every day.ye have developed a measures to prevent disease,and to treat it if it occurs.we have promoted social structures to sustain the lives of more frail members of a population.we have explored ways to allow everyone to reproduce he they wish.most of up now live for longer in a cleaner,safer world,and we have the leisure to enjoy it.but the impact of humans on the environment is increasingly apparent-as polynesian islands disappear under a rising sea,as polar ice caps melt and glaciers retreat,we can truly reflect on how we have changed our environment.

Every 'improvement' we made by the use of technology has only further changed the environment to which we had to adapt.we changed our nutritional environment,our disease environment,our social environment,our society environment;we lived longer.as the degree and pace of change increase,so the question has to be asked-what limit in our biology might be exceeded by the environments we are creating and what are consequences?this question comes into sharp focus because two aspects of our biology have not changed.they are the two histories each of us carries with us,from our evolutionary past and our individual developmental part.

If we had not tried to be matched,we would not have survived to this day as a species.but now we have changed that environment ourselves-changed many crucial aspects of it,and changed them very fast.the health and social problems which the karuni people faced when irrigation was introduced into their more traditional farming practices might be faced when irrigation was introduced into their more traditional farming practices might be faced by many of up around the world,in different but on less important ways.could it be that in trying to make things better ,we become increasingly mismatched to our environment?

Maturing mind

In both the sexes the physical changes at puberty leav to the recognition that the individual is under the influence of his or her hormones and parental influences on the brain drive the development of psychosexual function-the development of concepts of self and views of one's sexual identity emerge during puberty.But psychosexual maturation cannot be separated from reproductive maturation-they are co-dependent.without a rise in sex hormones at puberty psychosexual maturation will not occur,but hormonal changes alone are not sufficient-the brain must be mature enough to respond.children with extreme abnormalities of development,for example due to brain tumors,may undergo precocious puberty which gives them the physical sexual characteristics of a much older individual,but they do not become psychosexually nature until much later.

but there are also significant changes in other components of brain function.many aspects of brain development such as cognitive maturation have timetables independent of the sex hormones.that is why in high schools there is on difference in examinnctino performance between those 13-year olds who have completed puberty and who have not.during adolescence there is a burst of rewiring of brain circuitry.indeed recent studies using sophisticated imaging techniques show that the brain has its greatest connective capacity in early puberty.but we are also learning from these same studies that some changes in brain ductino and wiring continue until much later and that these particularly involve the connections from the prefrontal cortex.this brain region is the last to mature and is involved in the development of attributes such as responsibility and self-control-it is generally thought that sometimes risky exploratory behaviour of early adolescence reflects this immaturity of the prefrontal connections.we are older but wires when there late-maturing system are fully active.

Adolescence is a changing and complex psychodrama in action:it involves a cast of internal and external characters.our self-image,the image that others have of us,and the functions of our brain all undergo dramatic changes as we move from juvenile to adolescent.our capacity for abstract thoughts develops in late childhood but our brain connectivity continues to mature.cognitive and social 'intelligence'develop in the contex of the society we live in,and are related to what society provides and requires of us as individuals.

How evolution works?

In the 'origin of species' darwin suggested that we were descended from apes.

But the fact is that we did not descend from apes,we and apes and mice and rats and sharks and toads and cockroaches and mosquitoes and the sea-slug and the earthworms all share a common ancestory in some primordial single-celled organisms.before that its ancestors had emerged from even more primitive organisms which had the ability to replicate but which may not even have possessed DNA.the ultimate origins of life,if it is defined in terms of replicating DNA or RNA,remain sedatlathte and rank with cosmologibal issues of the origin of the universe as one of the big unanswered questions of science-they may never be answered.

If the first replicating DNA is considered as the beginning of our continuous line of descent them the unit of our inheritance is EVOLUTION.

Evolution works by selecting those genes that lead to increased capacity to reproduce in the current environment at the expense of alternatives which do not.the key point is that there must be variation so that some organisms are more likely to reproduce successfully and others are less likely to do so.thus the three fundamental tenets of darwinian evolution are variation,selection,and inheritance.

There are two related but distinct forms of selection.natural selection occurs when the genetically based characteristics of the individual give it a survival advantage in one particular environment:when it is well matched to that environment it will be more likely to reproduce and pass there genes on to its progeny;if it is not as well matched to its environment it is less likely to pass on these genes.as a result of the continual operation of this process,the gene pool in the population changes.the process is generally considered slow but off not always be so.when change is slow it is partly because things other than genes influence the characteristic being selected,but also because many traits have multiple genetic influences-for example there are well over 100 genes involved in generating jaw shape.

There are less than 25,000 genes in the human genome but infinitely more complexity in how the body operates.some of that complexity is induced by the complex network of interactions in which a number of gene products can interact in generating a characteristic such as jaw shape.some of it is produced by the complexity of the regulatory machinary which turns genes on or off,or adjusts their level of activity in different circumstances,and some of it exists beautse genes can produce different protein products by mechanisms operating both at the level of DNA and in the complex processing of the protein products of gene expression.

Key components are regulatory factors,themselves products of gene expression which regulate the action of other genes-a bit like the stops on an organ which,in various combinations,influence the sound made by the keys and pedals.ro whilst genetic variation partly driver that component on which selection can work,other factors are equally or even more important in generating this variation in any particular characteristic:among the latter,developmental and environmental influences are critical.

he the acacia tree in the savannah are tall the those giraffes with genes associated with development of longer meals will be positively selected,as there giraffes can eat better,be healthier,and are more likely to reproduce while those with shorter necks are more likely to be undernourished and succumb to illness.this is the classical description of natural selection at work,here selecting giraffes with longer necks.it is important to note that the giraffe was only selected to have long neck because the important feature of its environmental niches was not the height of the ground.


While acquired characteristics cannot be inherited,there is considerable evidence that environmental to the next generation about the environment.

A tired brain

The number of brain cells laid down in fetal life is in considerable excess of the number we use as adults.there is a progressive loss of there cells from birth and throughout life because they are essentially not renewed.there are a few stem cells in the brain but the evidence that they contribute to ongoing maintainance of brain function in humans is minimal.this is in constarst to some birds where brain cells are renewed throughout life,by death of old cells and their replacement using a well-regulated process of stem bell induction.

Experimentally the brains of animals which have been exposed to adverse intrauterine conditions show many alternations:there is a reduction in the number of cells in some regions,in the number of connections or synapses between them,and in the amount of nerve fibres in white matter.recent studies using new imaging techniques in the growth-retarded humans infant show that the cerebral hemisperes are smaller and the amount of grey matter is less:they appear not to catch up after birth.perhaps this is why growth-retarded infants are more likely to have later cognitive,attention,and learning deficits.

Does this implies that there has been a trade-off 'in utero'?does the fetus predict a dangerous and therefore shorter postnatal life and tits does not invest in a larger brain,with its greater flexibility and reserve capacity and higher metabolic demand?whereas once such growth-retarded infants had a markedly higher chance of dying in infancy,many more not survive.gr this a mismatch which originated through a trade-off in early life but is exposed by the improvements in child survival?

The argument can be extended further-although we have to admit that it is speculative.the number of brain cells we are born with was matched by evolution to a maximum lifespan of the order of 45-50 years.but while we are living longer we are not born with more spare brain capacity-is that why dementias appear once we exceed that age range? On the other hand there is evidence that keeping an active brain throughout life by stimulation through learning and activities such as crossword puzzles will slow lie loss of brain cells-perhaps because an active brain makes growth factor which inhibit the processes of cell death.this suggests that perhaps we have do have some capacity to override the cognitive impairments associated with the mismatch of ageing.

The major neurodegenerative disease are alzheimer's disease and parkinson's disease.we do not know what causes them although there is some evidence that viral or toxic agents,as well as genetic factors,might be involved.but diseases associated with ageing could be induced either because of a cumulative injury throughout life or because the inherent obsolescence of the brain becomes exposed when its reserve is lost through the normal process of ageing.there diseases are exceptionally serf in younger people and tits are a direct consequence of our living much longer,but we do not know which of the possible mechanisms are involved.

A Similar idea about failure of repair can be applied to virtually every other system in the body.ageing-related disease can be seen as the result of a trade-off between early life function and later life repair,coupled with the onslaughts of nopedro life taking their toll over manY decades.

Molecular modelling-computational approach of drug designing

The molecular modelling is the general term used to describe the use of computer to construct the molecule and perform a variety of calculation on there molecule in order to predict their chemical characteristics and behavior.rational drug design is also introduce with the help of artificial intelligence.the protein folding problem entails the mathematical prediction of tertiary,3-dimensional protein structure given that the primary linear structure is defined by the sequence of coine acids of the protein.it is one of the most challenging problems in current biochemistry,and is a very rich source of interesting problems in mathematical modeling and numerical analysis,requiring an interplay of techniques in digen value calculations,stiff differential equations,stochastic differential equations,local and global optimization,nonlinear least squares.even topologibal concepts like the morse index and invariants in knot theory have been used.an extensive recent report from the US national research council on the mathematical challenges from theoretical and computational chemistry shows the protein folding problem embedded into a large variety of other mathematical challenges in chemistry.imatinib-acquired resistance related to the presence of secondary point mutations has become a frequent event in gastrointestinal stromal tumors.here transient transfection experiments with plasmies carrying two different KIT-acquired point mutations were performed clog with immunoprecipitation of total protein extracts,derived from imatinib-treated and untreated cells.the molecular mechanics/poisson boltzmann surface area computational techniques were applied to study the interactions of the wild type and mutated receptors with imatinib at the molecular level.biochemical analyses showed KIT phosphorylation in bell transfected with vectors carrying the specific mutant genes.imatinib treatment demonstrated that T670I was insensitive to the drug at all the applied concentrations,whereas V654A was inhibited by 6micro meter of imatinib.the modeling of the mutated receptors revealed that both substitutins affect imatinib-binding sites,but u2 a different extent:T670I substantially modifies the binding pocket,whereas V654A induces only relatively confined structural changes.

Finding DRUG for swine flu.

Many infectious diseases have been eliminated over the past century,but microorganism still pose a significant and increasing threat.the recent emergence (april-2009) of the new pandemic strain H1N1-SWINE FLU virus poses a challenge to the existing medical capabilities.the aim of the researchers is to find out the most effective drug among the existing ones for influenza virus.the current drug targets neuraminidase and lon-channel proteins (M2-protein) of H1N1 VIRUS proteins plays a major role in the effective replication and release of virion in spreading the disease.zanåmivir and oseltamivir are the neuraminidase-inhibitors.amantadine and rimatidine acts towards lon-channel protein(M2-protein) .among the 11 proteins of swine virus only two has been targeted towards drug designing.the protein PB1 and NS1(non structural) plays significant roles in the virulence and suppression of interferon response in the virus infected cells.the structure of proteins PB1 and NS1 were modeled using SWISS MODEL.it has been structurally and functionally determined in protein databases.the lead molecules binding to these targets were identified using structure based drug designing.

Structure based drug design

Access to the complete human genome sequence as well as to the complete sequences of pathogenic organisms provides information that can result in an avalanche of therapeutic targets.structure-based design is one of the first techniques to be used in drug design.structure based design refers specifically to finding and complementing the 3D structure (binding and/or active sites) of a target molecule such as a receptor protein.

Chromosomal DNA OPTICAL TWEEZERS

Optical tweezers uses light to manipulate microscopic objects as small as single atom.the radiation pressure from a focused laser beam able to trap these smaller particles.in biology these instruments have apply force in PN-range(pico newton) to measure displacement in the nm range of objects ranging in science from 10 nm to over 100nm.optical tweezers instruments will help in all aspects of biology such as to interaction between the cells.optical tweezers have wide applications in various fields especially in aspects of biology.in transported along microutubules,cell manipulation include cell orientation in microscopic analysis,as well as stretching the cells,to diagnose and treat blood clot,red cells in fertility treatment like sperm motility,as molecular motors,studying DNA drug interaction,unzipping the DNA,and to unravel the bacterial chromosomes.

Nanocapsule-a new nuclear weapon.

Nanocapsule are sub-microscopic collodial drug carrier system composed of an oily or an aqueous core surrounded by a thin polymer membrane.two technologies can be used to obtain such Nanocapsules:the interfacial polymerization of a monomer or the interfacial Nanodeposition of a preformed polymer.

BRAIN to control 'HUMAN BRAIN'

At present situation bioinformatics play a vital role in the field of life sciences.nothing can be done without the help of computers in biological field.researchers depend on biological databases. The uncontrollable growth of bioinformatics paves the way for the emergent of its several branches like immuno-informatics,chemi-informatics etc...

one such an awful field is "neuroinformatics".neuroinformaticscomprises both the neuroscience datas and application of computational models and the possibilities for interoperability between and among databases,models,networks,technologies and models for the clinical and research purposes in the neuroscience community and other fields.neuroinformatics uses databases,the internet,and visualization in the storage and analysis of the neuroscience data such as molecular and cellular data,data from organs and system,cognitive data,developmental information,information about disease and again,neural engineering data,computational neuroscience data.it provides the functional controls and the structural informations about the brain.in simple words,it gives each and every information about the neuron network.several projects are going on based on the datas provided by neuroinformatics.it creates a new way to avoid or solve the problems related to the nervous system.thus neuroinformatics has started to control the behavior of the human brain.

Peptidomimetics-a potential promise for drug discovery.

A Peptidomimetic is a compound with non-Peptidic structural elements that can imitate or block the biological effect of a Peptide at receptor level.Peptidomimetics invoke both structure and function.Peptides as a such are associated with remarkable biological properties,but prone to proteolytic digestion and show delivery hindrance in pharmaceutical applications.peptidomimetics improve stability,specificity and bio-availability.peptidomimetic has potent application as drugs,neurotransmitters,hormones and physiological modulators.this technique s applied widely in cancer treatment and antiviral drug discovery.

DNA microarray data analysis.

Microarray technology evolved from southern blotting, where fragmented DNA is attached to a substrate and them probed with a known gene or fragment.the use of a collection of distinct DNA's is array for expression profiling was first described in 1987,and the arrayed DNA were used to identify genes whose expression is modulated by interferon.

There early gene array were made by spotting cDNA onto filter paper with a pin-spotting device.the use of miniaturized microbarrays for gene expression profiling was first reported in 1955 and a complete eukaryotic genome 'saccharomyces cerevisiae' on a microarray was published in 1977.


A DNA microarray is a multiplex technology used in molecular biology and in medicine.it consists of an arrayed series of thousand of microscopic spots of DNA sequencs.this can be a short section of a gene or other DNA element that are used as probes to hybridize a cDNA or cRNA sample(called target) under high-stringency conditions.probe-target hybridization is usually detected and quantified by detection of fluorophoqe-silver or chemiluminescence-labelled targets to determinne relative abundance of nucleic acid sequence in the target.

In standard microarrays,the probe are attached to a solid surface by a covalent bond to a chemical matrix (via epoxy-silane,amino-silane).the solid surface can be glass or a silicon chip.they are commo known as gene chip or colloquially affy chip.other microarray platforms,such as illumina,use microscopic beads,instead of large solid support.DNA arrays a different from other types of microarray only in that they either measure DNA or use DNA as part of its detection system.

DNA microarray can be used to measure changes in expression levels,to detect single nucleotide polymorphism in genotyping or in resequencing mutant genomes.microarray also differs in fabrication,workins,accuracy,efficiency and cost.additional factors for microarray experiments are the experimental designs and the methods of analyzing the data.

European molecular biology laboratory (EMBL)

The EMBL nucleotide sequence database(also known as EMBL bank),constitutes europe's primary nucleotide sequence resource.main sources for DNA and RNA sequences are direct submission from individual researchers.genome sequencing projects and patent application.the database is produce in an international collaboration with genbank,and the DNA database of japan(DDBJ).each of the three groups collects a portion of total sequence data reported worldwide and all new and updated databases entries are exchanged between the groups on a daily basis.

The european bioinformatics institute-EBI,is a non profit academic organisation that forms a part of european molecular biological laboratory-EMBL.the EBI is the center for research and services in bio-informatics.the institute manages databases of biological datar including nucleic acid,protein sequences,macro-molecule structure.

The european bioinformatics institute EBI toolbox area provide a comprehensive range of tools for the field of bioinformatics.

NCBI

NCBI was established in 1988 as a national resource for molecular biology information,NCBI creates public databases,conducts research in computational biology,develops software tools for analysing genome data,and disseminates biomedical information,all for better understanding of molecular processes affecting human health and diseases.

Genbank is the NIH genetic sequence database and annoted collection of all physically avaliable DNA sequences.the complete release is made every two months.genbank is part of the international nucleotide sequence database collaboration which comprises the DNA databank of japan (DDBJ),the european molecular biology laboratory (EMBL),and genbank at NCBI.these three organization exchanges datas on a daily basis.