Swine Flu Animation

Swine influenza (also swine flu) refers to influenza caused by any strain of the influenza virus endemic in pigs (swine). Strains endemic in swine are called swine influenza virus (SIV).Of the three genera of human flu, two are endemic also in swine: Influenzavirus A is common and Influenzavirus C is rare. Influenzavirus B has not been reported in swine. Within Influenzavirus A and Influenzavirus C, the strains endemic to swine and humans are largely distinct.
Swine flu is common in swine and rare in humans. People who work with swine, especially people with intense exposures, are at risk of catching swine influenza if the swine carry a strain able to infect humans. However, these strains infrequently circulate between humans as SIV rarely mutates into a form able to pass easily from human to human. In humans, the symptoms of swine flu are similar to those of influenza and of influenza-like illness in general, namely chills, fever, sore throat, muscle pains, severe headache, coughing, weakness and general discomfort.

The 2009 flu outbreak in humans is due to a new strain of influenza A virus subtype H1N1 that derives in part from human influenza, avian influenza, and two separate strains of swine influenza. The origins of this new strain are unknown, and the World Organization for Animal Health (OIE) reports that it has not been isolated in swine. It passes with apparent ease from human to human, an ability attributed to an as-yet unidentified mutation.
The H1N1 form of swine flu is one of the descendants of the Spanish flu that caused a devastating pandemic in humans in 1918–1919.As well as persisting in pigs, the descendants of the 1918 virus have also circulated in humans through the 20th century, contributing to the normal seasonal epidemics of influenza. However, direct transmission from pigs to humans is rare, with 12 cases in the U.S. since 2005.
The flu virus is perhaps the trickiest known to medical science; it constantly changes form to elude the protective antibodies that the body has developed in response to previous exposures to influenza or to influenza vaccines. Every two or three years the virus undergoes minor changes. Then, at intervals of roughly a decade, after the bulk of the world's population has developed some level of resistance to these minor changes, it undergoes a major shift that enables it to tear off on yet another pandemic sweep around the world, infecting hundreds of millions of people who suddenly find their antibody defenses outflanked. Even during the Spanish flu pandemic, the initial wave of the disease was relatively mild, while the second wave was highly lethal.

SIV strains isolated to date have been classified either as Influenzavirus C or one of the various subtypes of the genus Influenzavirus A.
Influenza A
Swine influenza is known to be caused by influenza A subtypes H1N1,H1N2, H3N1,[11] H3N2, and H2N3.
In swine, three influenza A virus subtypes (H1N1, H3N2, and H1N2) are circulating throughout the world. In the United States, the H1N1 subtype was exclusively prevalent among swine populations before 1998; however, since late August 1998, H3N2 subtypes have been isolated from pigs. As of 2004, H3N2 virus isolates in US swine and turkey stocks were triple reassortants, containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages.
Signs and symptoms
According to the Centers for Disease Control and Prevention (CDC), in humans the symptoms of swine flu are similar to those of influenza and of influenza-like illness in general. Symptoms include fever, cough, sore throat, body aches, headache, chills and fatigue. The 2009 outbreak has shown an increased percentage of patients reporting diarrhea and vomiting.
Because these symptoms are not specific to swine flu, a differential diagnosis of probable swine flu requires not only symptoms but also a high likelihood of swine flu due to the person's recent history. For example, during the 2009 swine flu outbreak in the United States, CDC advised physicians to "consider swine influenza infection in the differential diagnosis of patients with acute febrile respiratory illness who have either been in contact with persons with confirmed swine flu, or who were in one of the five U.S. states that have reported swine flu cases or in Mexico during the 7 days preceding their illness onset." A diagnosis of confirmed swine flu requires laboratory testing of a respiratory sample (a simple nose and throat swab).
Prevention of spread in humans I

nfluenza spreads between humans through coughing or sneezing and people touching something with the virus on it and then touching their own nose or mouth. Swine flu cannot be spread by pork products, since the virus is not transmitted through food. The swine flu in humans is most contagious during the first five days of the illness although some people, most commonly children, can remain contagious for up to ten days. Diagnosis can be made by sending a specimen, collected during the first five days, to the CDC for analysis.
Recommendations to prevent spread of the virus among humans include using standard infection control against influenza. This includes frequent washing of hands with soap and water or with alcohol-based hand sanitizers, especially after being out in public.Although the current trivalent influenza vaccine is unlikely to provide protection against the new 2009 H1N1 strain, vaccines against the new strain are being developed and could be ready as early as June 2009.
Experts agree that hand-washing can help prevent viral infections, including ordinary influenza and the new swine flu virus. Influenza can spread in coughs or sneezes, but an increasing body of evidence shows little particles of virus can linger on tabletops, telephones and other surfaces and be transferred via the fingers to the mouth, nose or eyes. Alcohol-based gel or foam hand sanitizers work well to destroy viruses and bacteria. Anyone with flu-like symptoms such as a sudden fever, cough or muscle aches should stay away from work or public transportation and should see a doctor to be tested.
Social distancing is another tactic. It means staying away from other people who might be infected and can include avoiding large gatherings, spreading out a little at work, or perhaps staying home and lying low if an infection is spreading in a community.
Influenza viruses bind through hemagglutinin onto sialic acid sugars on the surfaces of epithelial cells; typically in the nose, throat and lungs of mammals and intestines of birds.

Swine flu in humans

People who work with poultry and swine, especially people with intense exposures, are at increased risk of zoonotic infection with influenza virus endemic in these animals, and constitute a population of human hosts in which zoonosis and reassortment can co-occur. Transmission of influenza from swine to humans who work with swine was documented in a small surveillance study performed in 2004 at the University of Iowa. This study among others forms the basis of a recommendation that people whose jobs involve handling poultry and swine be the focus of increased public health surveillance. The 2009 swine flu outbreak is an apparent reassortment of several strains of influenza A virus subtype H1N1, including a strain endemic in humans and two strains endemic in pigs, as well as an avian influenza.
The CDC reports that the symptoms and transmission of the swine flu from human to human is much like that of seasonal flu. Common symptoms include fever, lethargy, lack of appetite and coughing, while runny nose, sore throat, nausea, vomiting and diarrhea have also been reported.
2009 swine flu outbreak

The new strain of swine influenza A (H1N1) involved in the 2009 flu outbreak in humans is a reassortment of several strains of influenza A virus subtype H1N1 that are, separately, endemic in humans, endemic in birds, and endemic in swine. Preliminary genetic characterization found that the hemagglutinin (HA) gene was similar to that of swine flu viruses present in United States pigs since 1999, but the neuraminidase (NA) and matrix protein (M) genes resembled versions present in European swine flu isolates. Viruses with this genetic makeup had not previously been found to be circulating in humans or pigs, but there is no formal national surveillance system to determine what viruses are circulating in pigs in the United States. The origins of this new strain remain unknown.
The earliest known human case, 5 year old Edgar Hernandez, was near a pig farm in La Gloria, Veracruz state, Mexico, that raises almost 1 million pigs a year. Residents of La Gloria have long complained about the clouds of flies that are drawn to the so-called 'manure lagoons' created by such mega-farms. Edgar Hernandez was thought to be suffering from ordinary influenza but laboratory testing revealed he had contracted swine flu. The boy went on to make a full recovery.
Swine influenza. (2009, April 30). In Wikipedia, The Free Encyclopedia. Retrieved 10:05, April 30, 2009, from http://en.wikipedia.org/w/index.php?title=Swine_influenza&oldid=287014883

Hormone Action

Lumbosacral plexus

The anterior divisions of the lumbar nerve, sacral nerve, and coccygeal nerves form the lumbosacral plexus, the first lumbar nerve being frequently joined by a branch from the twelfth thoracic. For descriptive purposes this plexus is usually divided into three parts: * lumbar plexus * sacral plexus * pudendal plexus

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  1. The angiopoietins are protein growth factors that promote angiogenesis, the formation of blood vessels. There are now four identified angiopoietins: Ang1, Ang2, Ang3, Ang4. In additional, there are a number of proteins that are closely related to angiopoietins (ANGPTL2, ANGPTL3, ANGPTL4, ANGPTL5, ANGPTL6, ANGPTL7). Ang1 and Ang2 are required for the formation of mature blood vessels, as demonstrated by mouse knock out studies.
    Angiopoietin receptors The tie receptors are tyrosine kinases, so named because they mediate cell signals by inducing the phosphorylation of key tyrosines, thus initiating the binding and activation of downstream, intracellular enzymes; this process is called cell signalling, and it is the method by which cells are induced to activate or inhibit key regulatory functions. It is somewhat controversial which of the Tie receptors mediate functional signals downstream of Ang stimulation - but it is clear that at least Tie-2 is capable of physiologic activation as a result of binding the angiopoietins

Structural Evolution of the Protein Kinase–Like Superfamily

A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation). Phosphorylation usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction.
The protein kinase family is large and important, but it is only one family in a larger superfamily of homologous kinases that phosphorylate a variety of substrates and play important roles in all three superkingdoms of life. We used a carefully constructed structural alignment of selected kinases as the basis for a study of the structural evolution of the protein kinase-like superfamily. The comparison of structures revealed a "universal core" domain consisting only of regions required for ATP binding and the phosphotransfer reaction. Remarkably, even within the universal core some kinase structures display notable changes, while still retaining essential activity. Hence, the protein kinase-like superfamily has undergone substantial structural and sequence revision over long evolutionary timescales. We constructed a phylogenetic tree for the superfamily using a novel approach that allowed for the combination of sequence and structure information into a unified quantitative analysis. When considered against the backdrop of species distribution and other metrics, our tree provides a compelling scenario for the development of the various kinase families from a shared common ancestor. We propose that most of the so-called "atypical kinases" are not intermittently derived from protein kinases, but rather diverged early in evolution to form a distinct phyletic group. Within the atypical kinases, the aminoglycoside and choline kinase families appear to share the closest relationship. These two families in turn appear to be the most closely related to the protein kinase family. In addition, our analysis suggests that the actin-fragmin kinase, an atypical protein kinase, is more closely related to the phosphoinositide-3 kinase family than to the protein kinase family. The two most divergent families, alpha-kinases and phosphatidylinositol phosphate kinases (PIPKs), appear to have distinct evolutionary histories. While the PIPKs probably have an evolutionary relationship with the rest of the kinase superfamily, the relationship appears to be very distant (and perhaps indirect). Conversely, the alpha-kinases appear to be an exception to the scenario of early divergence for the atypical kinases: they apparently arose relatively recently in eukaryotes. We present possible scenarios for the derivation of the alpha-kinases from an extant kinase fold. Text Ref:http://www.ncbi.nlm.nih.gov/pubmed/16244704


Osteotomy is a surgical operation whereby a bone is cut to shorten, lengthen, or change its alignment. It is sometimes performed to correct a hallux valgus, or to straighten a bone that has healed crookedly following a fracture. It is also used to correct a coxa vara, genu valgum, and genu varum. The operation is done under a general anaesthetic.
Osteotomy is one method to relieve pain in arthritis, especially of the hip and knee. It is being replaced by joint replacement in the older patient.

Knee osteotomy is commonly used to realign arthritic damage on one side of the knee. The goal is to shift the patient's body weight off the damaged area to the other side of the knee, where the cartilage is still healthy. Surgeons remove a wedge of the shinbone from underneath the healthy side of the knee, which allows the shinbone and thighbone to bend away from the damaged cartilage.

A model for this is the hinges on a door. When the door is shut, the hinges are flush against the wall. As the door swings open, one side of the door remains pressed against the wall as space opens up on the other side. Removing just a small wedge of bone can "swing" the knee open, pressing the healthy tissue together as space opens up between the thighbone and shinbone on the damaged side so that the arthritic surfaces do not rub against each other.
Osteotomy is also used as an alternative treatment to total knee replacement in younger and active patients. Because prosthetic knees may wear out over time, an osteotomy procedure can enable younger, active osteoarthritis patients to continue using the healthy portion of their knee. The procedure can delay the need for a total knee replacement for up to ten years.

Protein Synthesis-Translation

Control of Involuntary Muscle

Cardiac muscle and smooth muscle function involuntarily-beyond our conscious control. There is smooth muscle in organs of the digestive, respiratory, circulatory and urinogenital systems, while cardiac muscle is found exclusively in the heart. These muscles are controlled by the autonomic nervous system, which is composed of two opposing divisions, the sympathetic, shown in red, and the parasympathetic, shown in blue. Sympathetic nerves leaving the spinal cord lead first to nearby nerve chains before connecting the body organs, where they stimulate muscle activity. In the parasympathetic division, nerves pass from the spinal cord directly to the organs and have the opposite effect-decreasing muscle activity. This dual mechanism provides a method for maintaining the activity of the muscles within controlled limits. The sympathetic system is dominant in situations requiring rapid action. When, for example, danger threatens there is an increase in heart rate, respiration rate, blood pressure and sweat gland activity. The parasympathetic system is dominant while the body is resting-usually during sleep, when the heart rate is slower and respiration is deeper and more regular.

Exploring Alzheimer's Disease

Alzheimer's disease affects one in 10 Americans over the age of 65. Most of us will know someone in our lifetime with this disease. Leon J. Thal, M.D., Chairman, Department of Neurosciences at UCSD explains how this disease manifests and explores the latest research available.

Diabetes and Pregnancy

Steven Edelman, MD and perinatal specialist Thomas Moore, MD, discuss pregnancy planning, recommendations for keeping mother and baby healthy throughout the pregnancy, and post-delivery issues in women with pre-existing type 1 or type 2 diabetes.

Articular cartilage

Articular cartilage, also called hyaline cartilage, is the smooth, glistening white tissue that covers the surface of all the diarthrodial joints in the human body. As its name implies, articular cartilage is critical in the movement of one bone against another. Articular cartilage has an incredibly low coefficient of friction which, coupled with its ability to bear very large compressive loads, makes it ideally suited for placement in joints, such as the knee and hip.
Articular cartilage is not a homogeneous tissue. Instead, it has a very complex composition and architecture that permits it to achieve and maintain proper biomechanical function over the majority of a human lifespan. Articular cartilage is composed mainly of water (70-80% by wet weight). The solid phase of articular cartilage consists primarily of type II collagen and aggrecan, a chondroitin and keratan sulfate proteoglycan. Collagen forms a network of fibrils, which resist the swelling pressure generated by the proteoglycans. Aggrecan, because of its tendency to noncovalently interact with hyaluronic acid, forms huge aggregates that become trapped in the collagen network. Because of their numerous negatively charged sulfate groups, these proteoglycan aggregates attract cations, which in turn bring in water to minimize differences in osmotic pressure. Thus, type II collagen and proteoglycans create a swollen, hydrated tissue that resists compression.

Sense of Smell

Types of Stroke

 Ischemic stroke accounts for about 83 percent of all cases. Ischemic strokes occur as a result of an obstruction within a blood vessel supplying blood to the brain. The underlying condition for this type of obstruction is the development of fatty deposits lining the vessel walls. This condition is called atherosclerosis. These fatty deposits can cause two types of obstruction:
Cerebral thrombosis refers to a thrombus (blood clot) that develops at the clogged part of the vessel.

Cerebral embolism refers generally to a blood clot that forms at another location in the circulatory system, usually the heart and large arteries of the upper chest and neck. A portion of the blood clot breaks loose, enters the bloodstream and travels through the brain's blood vessels until it reaches vessels too small to let it pass. A second important cause of embolism is an irregular heartbeat, known as atrial fibrillation. It creates conditions where clots can form in the heart, dislodge and travel to the brain.
Hemorrhagic stroke accounts for about 17 percent of stroke cases.
It results from a weakened vessel that ruptures and bleeds into the surrounding brain. The blood accumulates and compresses the surrounding brain tissue. The two types of hemorrhagic strokes are intracerebral hemorrhage or subarachnoid hemorrhage.
Hemorrhagic stroke occurs when a weakened blood vessel ruptures. Two types of weakened blood vessels usually cause hemorrhagic stroke: aneurysms and arteriovenous malformations (AVMs).
An aneurysm is a ballooning of a weakened region of a blood vessel. If left untreated, the aneurysm continues to weaken until it ruptures and bleeds into the brain. Download more information on aneurysm.
An arteriovenous malformation (AVM) is a cluster of abnormally formed blood vessels. Any one of these vessels can rupture, also causing bleeding into the brain. Download more information on AVM.
Transient ischemic attacks
Also called TIAs, transient ischemic attacks are minor or warning strokes. In a TIA, conditions indicative of an ischemic stroke are present and the typical stroke warning signs develop. However, the obstruction (blood clot) occurs for a short time and tends to resolve itself through normal mechanisms.
Even though the symptoms disappear after a short time, TIAs are strong indicators of a possible major stroke. Steps should be taken immediately to prevent a stroke.

What is Reflex Arc

A reflex arc is the neural pathway that mediates a reflex action. In higher animals, most sensory neurons do not pass directly into the brain, but synapse in the spinal cord. This characteristic allows reflex actions to occur relatively quickly by activating spinal motor neurons without the delay of routing signals through the brain, although the brain will receive sensory input while the reflex action occurs. The main source of the reflex action is through the bottom muscles.
There are two types of reflex arc - autonomic reflex arc (affecting inner organs) and somatic reflex arc (affecting muscles).

Monosynaptic vs. polysynaptic When a reflex arc consists of only two neurons in an animal (one sensory neuron and one motor neuron), it is defined as monosynaptic. Monosynaptic refers to the presence of a single chemical synapse. In the case of peripheral muscle reflexes (patellar reflex, achilles reflex), brief stimulation to the muscle spindle results in contraction of the agonist or effector muscle.
By contrast, in polysynaptic reflex pathways, one or more interneurons connect afferent (sensory) and efferent (motor) signals. All but the most simple reflexes are polysynaptic, allowing processing or inhibition of polysynaptic reflexes within the spinal cord.
The Patella Reflex (knee jerk)
Patellar reflex: when the patellar tendon is tapped just below the knee, the patellar reflex is initiated and the lower leg kicks forward (via contraction of the quadriceps). The tap initiates an action potential in a specialised structure known as a muscle spindle located within the quadriceps. This action potential travels to the spinal cord, via a sensory axon which chemically communicates by releasing glutamate (see synapse) onto a motor nerve. The result of this motor nerve activity is contraction of the quadriceps muscle, leading to extension of the lower leg at the knee. The sensory input from the quadriceps also activates local interneurons that release the inhibitory neurotransmitter glycine onto motor neurons, blocking the innervation of the antagonistic (hamstring) muscle. The relaxation of the opposing muscle facilitates extension of the lower leg.

Sliding Filament Theory

Sliding filament theory A proposed mechanism of muscle contraction in which the actin and myosin filaments of striated muscle slide over each other to shorten the length of the muscle fibres (see sarcomere). Myosin-binding sites on the actin filaments are exposed when calcium ions bind to troponin molecules in these filaments. This allows bridges to form between actin and myosin, which requires ATP as an energy source. Hydrolysis of ATP in the heads of the myosin molecules causes the heads to change shape and bind to the actin filaments. The release of ADP from the myosin heads causes a further change in shape and generates mechanical energy that causes the actin and myosin filaments to slide over one another .

Cell Division- Meiosis

Meiosis (pronounced IPA:[maɪˈəʊsɪs]) is a process of reductional division in which the number of chromosomes per cell is halved. In animals, meiosis always results in the formation of gametes, while in other organisms it can give rise to spores. As with mitosis, before meiosis begins, the DNA in the original cell is replicated during S-phase of the cell cycle. Two cell divisions separate the replicated chromosomes into four haploid gametes or spores.
Meiosis is essential for sexual reproduction and therefore occurs in all eukaryotes (including single-celled organisms) that reproduce sexually. A few eukaryotes, notably the Bdelloid rotifers, have lost the ability to carry out meiosis and have acquired the ability to reproduce by parthenogenesis. Meiosis does not occur in archaea or bacteria, which reproduce via asexual processes such as binary fission.

During meiosis, the genome of a diploid germ cell, which is composed of long segments of DNA packaged into chromosomes, undergoes DNA replication followed by two rounds of division, resulting in four haploid cells. Each of these cells contain one complete set of chromosomes, or half of the genetic content of the original cell. If meiosis produces gametes, these cells must fuse during fertilization to create a new diploid cell, or zygote before any new growth can occur. Thus, the division mechanism of meiosis is a reciprocal process to the joining of two genomes that occurs at fertilization. Because the chromosomes of each parent undergo genetic recombination during meiosis, each gamete, and thus each zygote, will have a unique genetic blueprint encoded in its DNA. Together, meiosis and fertilization constitute sexuality in the eukaryotes, and generate genetically distinct individuals in populations.
In all plants, and in many protists, meiosis results in the formation of haploid cells that can divide vegetatively without undergoing fertilization, referred to as spores. In these groups, gametes are produced by mitosis.
Meiosis uses many of the same biochemical mechanisms employed during mitosis to accomplish the redistribution of chromosomes. There are several features unique to meiosis, most importantly the pairing and genetic recombination between homologous chromosomes.
Meiosis comes from the root -meio, meaning less.
Meiosis-phases Meiosis I
Meiosis I separates homologous chromosomes, producing two haploid cells (23 chromosomes, N in humans), so meiosis I is referred to as a reductional division. A regular diploid human cell contains 46 chromosomes and is considered 2N because it contains 23 pairs of homologous chromosomes. However, after meiosis I, although the cell contains 46 chromosomes it is only considered N because later in anaphase I the sister chromatids will remain together as the spindle pulls the pair toward the pole of the new cell. In meiosis II, an equational division similar to mitosis will occur whereby the sister chromatids are finally split, creating a total of 4 haploid cells (23 chromosomes, N) per daughter cell from the first division.
Prophase I
Homologous chromosomes pair (or synapse) and crossing over (or recombination) occurs - a step unique to meiosis. The paired and replicated chromosomes are called bivalents or tetrads, which have two chromosomes and four chromatids, with one chromosome coming from each parent. At this stage, non-sister chromatids may cross-over at points called chiasmata (plural; singular chiasma). Leptotene
The first stage of prophase I is the leptotene stage, also known as leptonema, from Greek words meaning "thin threads".During this stage, individual chromosomes begin to condense into long strands within the nucleus. However the two sister chromatids are still so tightly bound that they are indistinguishable from one another.
The zygotene stage, also known as zygonema, from Greek words meaning "paired threads", occurs as the chromosomes approximately line up with each other into homologous chromosomes. The is called the bouquet stage because of the way the telomeres cluster at one end of the nucleus.
The pachytene stage, also known as pachynema, from Greek words meaning "thick threads", contains the following chromosomal crossover. Nonsister chromatids of homologous chromosomes randomly exchange segments of genetic information over regions of homology. (Sex chromosomes, however, are not wholly identical, and only exchange information over a small region of homology.) Exchange takes place at sites where recombination nodules (the aforementioned chiasmata) have formed. The exchange of information between the non-sister chromatids results in a recombination of information; each chromosome has the complete set of information it had before, and there are no gaps formed as a result of the process. Because the chromosomes cannot be distinguished in the synaptonemal complex, the actual act of crossing over is not perceivable through the microscope.
During the diplotene stage, also known as diplonema, from Greek words meaning "two threads", the synaptonemal complex degrades and homologous chromosomes separate from one another a little. The chromosomes themselves uncoil a bit, allowing some transcription of DNA. However, the homologous chromosomes of each bivalent remain tightly bound at chiasmata, the regions where crossing-over occurred. The chiasmata remain on the chromosomes until they are severed in Anaphase I.
In human fetal oogenesis all developing oocytes develop to this stage and stop before birth. This suspended state is referred to as the dictyotene stage and remains so until puberty. In males, only spermatogonia(Spermatogenesis) exist until meiosis begins at puberty.
Chromosomes condense further during the diakinesis stage, from Greek words meaning "moving through". This is the first point in meiosis where the four parts of the tetrads are actually visible. Sites of crossing over entangle together, effectively overlapping, making chiasmata clearly visible. Other than this observation, the rest of the stage closely resembles prometaphase of mitosis; the nucleoli disappear, the nuclear membrane disintegrates into vesicles, and the meiotic spindle begins to form.
Synchronous processes
During these stages, two centrosomes, containing a pair of centrioles in animal cells, migrate to the two poles of the cell. These centrosomes, which were duplicated during S-phase, function as microtubule organizing centers nucleating microtubules, which are essentially cellular ropes and poles. The microtubules invade the nuclear region after the nuclear envelope disintegrates, attaching to the chromosomes at the kinetochore. The kinetochore functions as a motor, pulling the chromosome along the attached microtubule toward the originating centriole, like a train on a track. There are four kinetochores on each tetrad, but the pair of kinetochores on each sister chromatid fuses and functions as a unit during meiosis I.
Microtubules that attach to the kinetochores are known as kinetochore microtubules. Other microtubules will interact with microtubules from the opposite centriole: these are called nonkinetochore microtubules or polar microtubules. A third type of microtubules, the aster microtubules, radiates from the centrosome into the cytoplasm or contacts components of the membrane skeleton. 
Metaphase I.
Homologous pairs move together along the metaphase plate: As kinetochore microtubules from both centrioles attach to their respective kinetochores, the homologous chromosomes align along an equatorial plane that bisects the spindle, due to continuous counterbalancing forces exerted on the bivalents by the microtubules emanating from the two kinetochores of homologous chromosomes. The physical basis of the independent assortment of chromosomes is the random orientation of each bivalent along the metaphase plate, with respect to the orientation of the other bivalents along the same equatorial line.
Anaphase I
Kinetochore microtubules shorten, severing the recombination nodules and pulling homologous chromosomes apart. Since each chromosome has only one functional unit of a pair of kinetochores, whole chromosomes are pulled toward opposing poles, forming two haploid sets. Each chromosome still contains a pair of sister chromatids. Nonkinetochore microtubules lengthen, pushing the centrioles farther apart. The cell elongates in preparation for division down the center.
Telophase I
The last meiotic division effectively ends when the chromosomes arrive at the poles. Each daughter cell now has half the number of chromosomes but each chromosome consists of a pair of chromatids. The microtubules that make up the spindle network disappear, and a new nuclear membrane surrounds each haploid set. The chromosomes uncoil back into chromatin. Cytokinesis, the pinching of the cell membrane in animal cells or the formation of the cell wall in plant cells, occurs, completing the creation of two daughter cells. Sister chromatids remain attached during telophase I.

Cells may enter a period of rest known as interkinesis or interphase II. No DNA replication occurs during this stage.
Meiosis II
Meiosis II is the second part of the meiotic process. Much of the process is similar to mitosis. The end result is production of four haploid cells (23 chromosomes, 1N in humans) from the two haploid cells (23 chromosomes, 1N * each of the chromosomes consisting of two sister chromatids) produced in meiosis I. The four main steps of Meiosis II are: Prophase II, Metaphase II, Anaphase II, and Telophase II.
Prophase II takes an inversely proportional time compared to telophase I. In this prophase we see the disappearance of the nucleoli and the nuclear envelope again as well as the shortening and thickening of the chromatids. Centrioles move to the polar regions and arrange spindle fibers for the second meiotic division.
In metaphase II, the centromeres contain two kinetochores that attach to spindle fibers from the centrosomes (centrioles) at each pole. The new equatorial metaphase plate is rotated by 90 degrees when compared to meiosis I, perpendicular to the previous plate.
This is followed by anaphase II, where the centromeres are cleaved, allowing microtubules attached to the kinetochores to pull the sister chromatids apart. The sister chromatids by convention are now called sister chromosomes as they move toward opposing poles.
The process ends with telophase II, which is similar to telophase I, and is marked by uncoiling and lengthening of the chromosomes and the disappearance of the spindle. Nuclear envelopes reform and cleavage or cell wall formation eventually produces a total of four daughter cells, each with a haploid set of chromosomes. Meiosis is now complete and ends up with four new daughter cells that will go through the whole of the cell cycle again and again.

Sodium & Potassium pump

Cell Division- Mitosis

DNA Replication Animation


Osmosis is the diffusion of water through a semi-permeable membrane, from a solution of low solute concentration (high water potential) to a solution with high solute concentration (low water potential), up a solute concentration gradient. The simplest definition is that it is diffusion of water across a semipermeable membrane. It is a physical process in which a solvent moves, without input of energy, across a semi-permeable membrane (permeable to the solvent, but not the solute) separating two solutions of different concentrations. Net movement of solvent is from the less-concentrated (hypotonic) to the more-concentrated (hypertonic) solution, which tends to reduce the difference in concentrations. This effect can be countered by increasing the pressure of the hypertonic solution, with respect to the hypotonic. The osmotic pressure is defined to be the pressure required to maintain an equilibrium, with no net movement of solvent. Osmotic pressure is a colligative property, meaning that the property depends on the molar concentration of the solute but not on its identity.

Histone Deacetylases

Dr Joel Gottesfeld's lab in La Jolla, California (USA), is also working on heterochromatin modifiers as a potential treatment for FRDA, and Dr Gottesfeld started his talk by referencing a paper published by Richard Festenstein's group in 2003 (Nature) as the inspiration. His own work in California has supported the theory that heterochromatin gene silencing occurs in FRDA. The interaction between the active form of the frataxin gene and the inactive (silenced) form is mediated by enzymes called histone deacetylases (HDAC). To see if targeting these enzymes would result in an increase in frataxin, the researchers tested various commercially available HDAC inhibitors and found only one that was slightly active on the frataxin gene (compound BML-210). However they were then able to study derivatives of this compound and identified a compound (4B) which is active at increasing levels of frataxin mRNA and frataxin protein in cells. The next stage was to test the compound in a mouse model of FRDA, and they found that it was able to cross the blood brain barrier and enter the nervous system; it also inhibited HDAC in the brain. There are different classes of HDACs, based on whether they are zinc dependent or non-zinc dependent, and different HDAC inhibitors act on each of the different classes. It is important for research to identify which enzymes are the target, and this gives clues as to the desired chemical properties of the inhibitor. Chemical studies that his team has carried out have now suggested that the class 1 HDAC enzymes are the target for HDAC inhibitors which work on the frataxin gene, and they have identified HDAC3 as the primary target.

The pharmaceutical company Repligen is now working with the active HDAC inhibitors that have been identified, doing pharmacokinetic and toxicology studies to learn more and identify the most effective compounds. A library of derivatives that can be screened for potential treatments has been established, and toxicity studies are going well.


Diffusion, is a net transport of molecules from a region of higher concentration to one of lower concentration by random molecular motion. The result of diffusion is a gradual mixing of material. In a phase with uniform temperature, absent external net forces acting on the particles, the diffusion process will eventually result in complete mixing or a state of equilibrium.


Enzymes are biomolecules that catalyze .Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, the products. Almost all processes in a biological cell need enzymes to occur at significant rates. Since enzymes are selective for their substrates and speed up only a few reactions from among many possibilities, the set of enzymes made in a cell determines which metabolic pathways occur in that cell.
Like all catalysts, enzymes work by lowering the activation energy (Ea or ΔG‡) for a reaction, thus dramatically increasing the rate of the reaction. Most enzyme reaction rates are millions of times faster than those of comparable un-catalyzed reactions. As with all catalysts, enzymes are not consumed by the reactions they catalyze, nor do they alter the equilibrium of these reactions. However, enzymes do differ from most other catalysts by being much more specific. Enzymes are known to catalyze about 4,000 biochemical reactions. A few RNA molecules called ribozymes catalyze reactions, with an important example being some parts of the ribosome. Synthetic molecules called artificial enzymes also display enzyme-like catalysis.

Enzyme activity can be affected by other molecules. Inhibitors are molecules that decrease enzyme activity; activators are molecules that increase activity. Many drugs and poisons are enzyme inhibitors. Activity is also affected by temperature, chemical environment (e.g., pH), and the concentration of substrate. Some enzymes are used commercially, for example, in the synthesis of antibiotics. In addition, some household products use enzymes to speed up biochemical reactions Structures and mechanisms Enzymes are generally globular proteins and range from just 62 amino acid residues in size, for the monomer of 4-oxalocrotonate tautomerase, to over 2,500 residues in the animal fatty acid synthase.A small number of RNA-based biological catalysts exist, with the most common being the ribosome; these are referred to as either RNA-enzymes or ribozymes. The activities of enzymes are determined by their three-dimensional structure. However, although structure does determine function, predicting a novel enzyme's activity just from its structure is a very difficult problem that has not yet been solved.

Most enzymes are much larger than the substrates they act on, and only a small portion of the enzyme (around 3–4 amino acids) is directly involved in catalysis. The region that contains these catalytic residues, binds the substrate, and then carries out the reaction is known as the active site. Enzymes can also contain sites that bind cofactors, which are needed for catalysis. Some enzymes also have binding sites for small molecules, which are often direct or indirect products or substrates of the reaction catalyzed. This binding can serve to increase or decrease the enzyme's activity, providing a means for feedback regulation.

Like all proteins, enzymes are made as long, linear chains of amino acids that fold to produce a three-dimensional product. Each unique amino acid sequence produces a specific structure, which has unique properties. Individual protein chains may sometimes group together to form a protein complex. Most enzymes can be denatured—that is, unfolded and inactivated—by heating or chemical denaturants, which disrupt the three-dimensional structure of the protein. Depending on the enzyme, denaturation may be reversible or irreversible.


Enzymes can act in several ways, all of which lower ΔG‡:

  •       Lowering the activation energy by creating an environment in which the transition state is stabilized (e.g. straining the shape of a substrate—by binding the transition-state conformation of the substrate/product molecules, the enzyme distorts the bound substrate(s) into their transition state form, thereby reducing the amount of energy required to complete the transition).
  •       Lowering the energy of the transition state, but without distorting the substrate, by creating an environment with the opposite charge distribution to that of the transition state.
  •       Providing an alternative pathway. For example, temporarily reacting with the substrate to form an intermediate ES complex, which would be impossible in the absence of the enzyme.
  •       Reducing the reaction entropy change by bringing substrates together in the correct orientation to react. Considering ΔH‡ alone overlooks this effect.

Interestingly, this entropic effect involves destabilization of the ground state. and its contribution to catalysis is relatively small.

BD simulation of HIV protease substrate interaction

Coarse-grained Brownian dynamics (BD) simulation for the substrate peptide- HIV protease system. Transition of the peptide substrate from an unbound to a final bound state is shown, and the protein flaps have to open to allow for the substrate binding. The total simulation length in this run was 2 microsecond.

Cancer cell migration

Stages Breast Cancer Cells

Breast cancer cell division

Breast Cancer Cells

Deeplamellar endothelial keratoplasty- surgery

DLEK refers to a new method of advanced corneal surgery, wherein the dysfunctional endothelial layer of the cornea is selectively replaced with healthy donor tissue, without the need for surface incisions or sutures. This results in better refractive outcome compared to conventional corneal grafts. Moreover there is no risk of suture related complications such as infections, vascularization etc. Tectonically the cornea is much stronger following DLEK as compared to conventional full thickness corneal grafts.


Liposuction, also known as lipoplasty ("fat modeling"), liposculpture suction lipectomy or simply lipo ("suction-assisted fat removal") is a cosmetic surgery operation that removes fat from many different sites on the human body. Areas affected can range from the abdomen, thighs, buttocks, to the neck, backs of the arms and elsewhere. Liposuction is not a low-effort alternative to exercise and diet. It is a form of body contouring with significant attendant risks and is not a weight loss method. The amount of fat removed varies by doctor, method, and patient, but is typically less than 10 pounds (5 kg). There are several factors that limit the amount of fat that can be safely removed in one session. Ultimately, the operating physician and the patient make the decision. There are negative aspects to removing too much fat. Unusual "lumpiness" and/or "dents" in the skin can be seen in those patients "over-suctioned". The more fat removed the higher the surgical risk. While reports of people removing 50 pounds (22.7 kg) of fat has been claimed, the contouring possible with liposuction may cause the appearance of weight loss to be greater than the actual amount of fat removed. The procedure may be performed under general or local ("tumescent") anesthesia. The safety of the technique relates not only to the amount of tissue removed, but to the choice of anesthetic and the patient's overall health. It is ideal for the patient to be as fit as possible before the procedure and not to have smoked for several months.

Intervertebral Disc

Intervertebral discs (or intervertebral fibrocartilage) lie between adjacent vertebrae in the spine. Each disc forms a cartilaginous joint to allow slight movement of the vertebrae, and acts as a ligament to hold the vertebrae together.Discs consist of an outer annulus fibrosus, which surrounds the inner nucleus pulposus. The annulus fibrosus consists of several layers of fibrocartilage. The strong annular fibers contain the nucleus pulposus and distribute pressure evenly across the disc. The nucleus pulposus contains loose fibers suspended in a mucoprotein gel the consistency of jelly. The nucleus of the disc acts as a shock absorber, absorbing the impact of the body's daily activities and keeping the two vertebrae separated. The disc can be likened to a doughnut: whereby the annulus fibrosis is similar to the dough and the nucleus pulposis is the jelly. If one presses down on the front of the doughnut the jelly moves posteriorly or to the back. When one develops a prolapsed disc the jelly/ nucleus pulposus is forced out of the doughnut/ disc and may put pressure on the nerve located near the disc. This can give one the symptoms of sciatica. There is one disc between each pair of vertebrae, except for the first cervical segment, the atlas. The atlas is a ring around the roughly cone-shaped extension of the axis (second cervical segment). The axis acts as a post around which the atlas can rotate, allowing the neck to swivel. There are a total of twenty-three discs in the spine, which are most commonly identified by specifying the particular vertebrae they separate. For example, the disc between the fifth and sixth cervical vertabrae is designated "C5-6".

Knee Arthroscopy (Meniscectomy)

Knee arthroscopy has in many cases replaced the classic arthrotomy that was performed in the past. Today knee arthroscopy is commonly performed for treating meniscus injury, reconstruction of the anterior cruciate ligament and for cartilage microfracturing. Arthroscopy can also be performed just for diagnosing and checking of the knee; however, the latter use has been mainly replaced by magnetic resonance imaging. During an average knee arthroscopy, a small fiberoptic camera (the endoscope) is inserted into the joint through a small incision, about 4 mm (1/8 inch) long. A special fluid is used to visualize the joint parts. More incisions might be performed in order to check other parts of the knee. Then other miniature instruments are used and the surgery is performed. Recovery after a knee arthroscopy is significantly faster as compared to arthrotomy. Most patients can return home and walk using crutches the same or the next day after the surgery. Recovery time depends on the reason that surgery was needed and the patient's physical condition. Usually a patient can fully load his leg within a couple of days and after a few weeks the joint function can fully recover. It is not uncommon for athletes who have an above average physical condition to return to normal athletic activities within a few weeks. Arthroscopic surgeries of the knee are done for many reasons, but the usefulness of surgery for treating osteoarthritis is doubtful. A double-blind placebo-controlled study on arthroscopic surgery for osteoarthritis of the knee was published in the New England Journal of Medicine in 2002. In this three-group study, 180 military veterans with osteoarthritis of the knee were randomly assigned to receive arthroscopic débridement with lavage, just arthroscopic lavage, or a sham surgery, which made superficial incisions to the skin while pretending to do the surgery. For two years after the surgeries, patients reported their pain levels and were evaluated for joint motion. Neither the patients nor the independent evaluators knew which patients had received which surgery. The study reported, "At no point did either of the intervention groups report less pain or better function than the placebo group." Because there is no confirmed usefulness for these surgeries, many agencies are reconsidering paying for a surgery which seems to create risks with no benefit. A 2008 study confirmed that there was no long-term benefit for chronic pain, above medication and physical therapy.Since one of the main reasons for arthroscopy is to repair or trim a painful and torn or damaged meniscus, a recent study in the New England Journal of Medicine which shows that about 60% of these tears cause no pain and are found in asymptomatic subjects, may further call the rationale for this procedure into question.

Hepatitis C

Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV).[1] The infection is often asymptomatic, but once established, chronic infection can progress to scarring of the liver (fibrosis), and advanced scarring (cirrhosis). In some cases, those with cirrhosis will go on to develop liver failure or other complications of cirrhosis, including liver cancer. The hepatitis C virus (HCV) is spread by blood-to-blood contact. Most people have few symptoms after the initial infection, yet the virus persists in the liver in about 80% of those infected. Persistent infection can be treated with medication, such as interferon and ribavirin, and currently over half are cured overall. Those who develop cirrhosis or liver cancer may require a liver transplant, although the virus generally recurs after transplantion.

Atoms to X-rays: How Do Proteins Fold?

The machinery of life depends on proteins--large organic molecules composed of tens, hundreds or even thousands of amino acids bound together and folded into specifically shaped structures. How they fold into these three-dimensional structures is known as the second genetic code and is one of great challenges in science today. Join UCSD biophysicist Jose Onuchic, as he explores how physics, chemistry, biology and mathematics are all being applied to crack the protein folding mystery.

Biochemistry Lecture

Biochemistry lecture by Dr Marion Carroll

3 Biochemistry 4130: Chapter 1 Part 1

4 Biochemistry 4130: Chapter 1 Part 2

5 Biochemistry 4130: Chapter 2

6 Biochemistry 4130: Chapter 7


Atherosclerosis is a syndrome affecting arterial blood vessels. It is a chronic inflammatory response in the walls of arteries, in large part due to the accumulation of macrophage white blood cells and promoted by low density (especially small particle) lipoproteins (plasma proteins that carry cholesterol and triglycerides) without adequate removal of fats and cholesterol from the macrophages by functional high density lipoproteins (HDL), (see apoA-1 Milano). It is commonly referred to as a hardening or furring of the arteries. It is caused by the formation of multiple plaques within the arteries

Endocytosis & Exocytosis

Endocytosis is the process by which cells absorb material (molecules such as proteins) from outside the cell by engulfing it with their cell membrane. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma membrane or cell membrane. Exocytosis is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane. These membrane-bound vesicles contain soluble proteins to be secreted to the extracellular environment, as well as membrane proteins and lipids that are sent to become components of the cell membrane.


The Microtubule Preprophase Band (PPB)

The preprophase band is a microtubule array found in plant cells that are about to undergo cell division and enter the preprophase stage of the plant cell cycle. Besides the phragmosome, it is the first microscopically visible sign that a plant cell is about to enter mitosis. The preprophase band was first observed and described by Jeremy Pickett-Heaps and Donald Northcote at Cambridge University in 1966.
Just before mitosis starts, the preprophase band forms as a dense band of microtubules around the phragmosome and the future division plane just below the plasma membrane. It encircles the nucleus at the equatorial plane of the future mitotic spindle when dividing cells enter the G2 phase of the cell cycle after DNA replication is complete. The preprophase band consists mainly of microtubules and microfilaments (actin) and is generally 2-3 µm wide. When stained with fluorescent markers, it can be seen as two bright spots close to the cell wall on either side of the nucleus.

Plant cells lack centrosomes as microtubule organizing centers. Instead, the microtubules of the mitotic spindle aggregate on the nuclear surface and are reoriented to form the spindle at the end of prophase. It has been suggested that the preprophase band may have functions in properly orienting the mitotic spindle.

The preprophase band disappears as soon as the nuclear envelope breaks down and the mitotic spindle forms, leaving behind an actin-depleted zone. However, its position marks the future fusion sites for the new cell plate with the existing cell wall during telophase. When mitosis is completed, the cell plate and new cell wall form starting from the center along the plane occupied by the phragmosome. The cell plate grows outwards until it fuses with the cell wall of the dividing cell at exactly the spots predicted by the position of the preprophase band.

Cholesterol animation

Cholesterol is a lipidic, fat tissue found in the cell membranes and transported in the blood plasma of all animals. It is an essential component of mammalian cell membranes where it is required to establish proper membrane permeability and fluidity. Cholesterol is the principal sterol synthesized by animals, but small quantities are synthesized in other eukaryotes, such as plants and fungi. It is almost completely absent among prokaryotes, which include bacteria. Cholesterol is classified as a sterol (a contraction of steroid and alcohol).

Although cholesterol is essential for life, high levels in circulation are associated with atherosclerosis. Cholesterol can be ingested in the diet, recycled within the body through reabsorption of bile in the digestive tract, and produced de novo. For a person of about 150 pounds (68 kg), typical total body cholesterol content is about 35 g, typical daily dietary intake is 200–300 mg in the United States and societies with similar dietary patterns and 1 g per day is synthesized de novo.

The name cholesterol originates from the Greek chole- (bile) and stereos (solid), and the chemical suffix -ol for an alcohol, as François Poulletier de la Salle first identified cholesterol in solid form in gallstones, in 1769. However, it was only in 1815 that chemist Eugène Chevreul named the compound "cholesterine".


Cholesterol is required to build and maintain cell membranes; it regulates membrane fluidity over the range of physiological temperatures. The hydroxyl group on cholesterol interacts with the polar head groups of the membrane phospholipids and sphingolipids, while the bulky steroid and the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty acid chain of the other lipids. In this structural role, cholesterol reduces the permeability of the plasma membrane to protons (positive hydrogen ions) and sodium ions.

Pharmacokinetics-Drug Metabolism

Pharmacokinetics (in Greek: “pharmacon” meaning drug and “kinetikos” meaning putting in motion, the study of time dependency; sometimes abbreviated as “PK”) is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. In practice, this discipline is applied mainly to drug substances, though in principle it concerns itself with all manner of compounds ingested or otherwise delivered externally to an organism, such as nutrients, metabolites, hormones, toxins, etc.

Pharmacokinetics is often studied in conjunction with pharmacodynamics. Pharmacodynamics explores what a drug does to the body, whereas pharmacokinetics explores what the body does to the drug. Pharmacokinetics includes the study of the mechanisms of absorption and distribution of an administered drug, the rate at which a drug action begins and the duration of the effect, the chemical changes of the substance in the body (e.g. by enzymes) and the effects and routes of excretion of the metabolites of the drug.


Pharmacokinetics is divided into several areas which includes the extent and rate of Absorption, Distribution, Metabolism and Excretion. This is commonly referred to as the ADME scheme. However recent understanding about the drug-body interactions brought about the inclusion of new term Liberation. Now Pharmacokinetics can be better described as LADME.

* Liberation is the process of release of drug from the formulation.
* Absorption is the process of a substance entering the body.
* Distribution is the dispersion or dissemination of substances throughout the fluids and tissues of the body.
* Metabolism is the irreversible transformation of parent compounds into daughter metabolites.
* Excretion is the elimination of the substances from the body. In rare cases, some drugs irreversibly accumulate in a tissue in the body.

Pharmacokinetics describes how the body affects a specific drug after administration. Pharmacokinetic properties of drugs may be affected by elements such as the site of administration and the concentration in which the drug is administered. These may affect the absorption rate.

Factors Affecting Drug Distribution

Microfluidic Devices

The Thorsen group is focused on the modeling and design of microfluidic devices, primarily for cell-biology based applications. Laboratory expertise areas include multi-layer soft lithography, a process where elastomeric microdevices are produced from patterned silicon wafers, modeling of molecular processes in microchannels, nanofiber and nanoparticle synthesis, and the design of integrated microdevices to study complex biological processes (biofilm formation, respiration).


Metabolic engineering by Prof. Greg Stephanopoulos

Professor Stephanopoulos' current research focuses on metabolic engineering and its applications to the production of biochemicals and specialty chemicals, the rigorous evaluation of cell physiology using advanced isotopic methods, the metabolism and physiology of mammalian cells with emphasis on obesity and diabetes, and bioinformatics and functional genomics, whereby new genomics-based technologies are applied to the elucidation of cell physiology and metabolic engineering. Professor Stephanopoulos has co-authored or -edited 5 books and published approximately 240 papers and 19 patents. He has supervised 38 graduate and 32 post-doctoral students and is presently the editor-in-chief of the journal Metabolic Engineering and serves on the Editorial Boards of 7 scientific journals. He has been recognized with the Dreyfus Foundation Teacher Scholar Award (1982), Excellence in Teaching Award (1984), Technical Achievement Award of the AIChE (1984), PYI Award (1984), AIChE-FPBE Division Award (1997), M.J. Johnson Award of ACS (2001), and the R.H. Wilhelm Award in Chemical Reaction Engineering of the AIChE (2001). In 1992 he chaired the FPBE Division of AIChE and was elected a Founding Fellow of the American Institute for Medical and Biological Engineering. In 2002 he received the Merck Award in Metabolic Engineering and was elected to the Board of Directors of AIChE. In 2003, he was elected to the National Academy of Engineering (NAE) and recently was awarded an honorary doctorate degree (doctor technices honoris causa) by the Technical University of Denmark (2005).

Prof. Ram Sasisekharan on Glycosaminoglycans

Sasisekharan's laboratory's broad research objectives are aimed towards understanding the mechanisms governing the extracellular regulation of cell function, generating novel pharmacological approaches to modulate cell function for the treatment of diseases.

Glycosaminoglycans (GAGs), the polysaccharide component of the extracellular matrix (ECM), are the most acidic naturally occurring biopolymers. These GAGs not only hydrate the ECM, but also solubilize several transient molecules, such as growth factors, cytokines, enzymes etc. that diffuse from the outside of a tissue to the cell surface to modulate cellular function. GAGs are believed to regulate important physiological as well as pathological processes, which include morphogenesis, angiogenesis and tumor growth. At the present time, due to a lack of powerful methods and tools, there is little information as to how GAGs modulate or regulate a given biological process.

Research Focus

Using GAGs as a model system, our vision is to focus and develop on the one hand, a programmatic approach to investigate important questions addressing the biological roles and significance of these complex molecules. On the other hand, this strategy is built with the idea of plausible technological applications in mind, which include the development of much desired novel and powerful tools and agents for both diagnostic as well as therapeutic needs for unmet medical conditions.

Prof.Christine Ortiz on Nanomechanics

Biological materials, such as musculoskeletal and exoskeletal tissues, have developed amazingly complex, hierarchical, heterogeneous nanostructures over millions of years of evolution in order to function properly under the mechanical loads they experience in their environment. The Ortiz research group studies these fascinating materials using expertise in the new field of "nanomechanics"; i.e. the measurement and prediction of extremely small forces within and between nanoscale constituents in order to determine the local origins of macroscopic physical phenomena. Novel experimental and theoretical methods are employed (see Table below) in order to probe and understand fundamental nanoscale surface, bio-, and polymer physics mechanisms and design principles; i.e. how they work in tandem and what universal laws they follow to achieve a particular function.A quad-tiered approach is taken to achieve this goal which includes; nanomechanics of single cells and their pericellular matrix, individual molecules, biomimetic model systems, and in-tact tissue-level properties.

The scientific foundation being formed has relevance to both the medical and engineering fields. Nanotechnological methods applied to the field of musculoskeletal tissues and tissue engineering hold great promise for significant and rapid advancements towards tissue repair and/or replacement, improved treatments, and possibly even a cure for people afflicted with diseases such as osteoarthritis. In addition, the discovery of new nanoscale design principles and energy-dissipating mechanisms will enable the production of improved and increasingly advanced biologically-inspired structural engineering materials that exhibit "mechanical property amplification" - that is, dramatic improvements in mechanical properties (e.g. increases in strength and toughness) for a material relative to its constituents.

Paul T. Matsudaira Interview

About Speaker:
“People typically think of how a cell works in terms of chemistry,” says Paul Matsudaira. “But mechanics is just as vital. Everything in life is about movement. If it doesn’t move, it’s probably dead.”

A Whitehead Member, Matsudaira studies the more complex aspects of how cells move: how cells move in three dimensions and how ensembles of cells move together.

In 2007 scientists in the Matsudaira lab and their colleagues created the first fluorescent sensor that measures the forces involved in cell movement. Previously, researchers who wanted to know how much force is exerted when cells travel needed to place the cells on an instrument that bends or flexes, and then calculate the force. In contrast, the fluorescent sensor simply changes color to show how much force is applied.

Paul T. Matsudaira, PhD

In other recent work, scientists developed a computational model of a cell moving in three dimensions, overcoming the limits of two-dimensional models that ignore obstacles in the cell’s way.

Matsudaira also investigates how cells store energy to cause movement. He and his co-workers are studying a unique cellular mechanism that works by storing energy on the principle of a spring, instead of burning fuel like a car engine. Understanding how this and other molecular engines work may yield new insights into critical cell processes.

In 2001, Matsudaira founded the Whitehead Institute-MIT BioImaging Center. The Center is based on the belief that complex cellular processes can best be understood by seeing with sophisticated imaging techniques, and then understanding the images through powerful computational methods. It has three major thrusts: cryoelectron microscopy of cellular structures, using a custom-built, remote-controlled cryroelectron microscope; multidimensional high-resolution light microscopy; and quantitative bioimaging bioinformatics.

A professor of biology and professor of bioengineering at MIT, Matsudaira was first appointed an Associate Member of Whitehead Institute in 1985. He earned a PhD in biology from Dartmouth College in 1981. He did postdoctoral research at the Max Planck Institute in Göttingen, Germany, and at the Medical Research Council in Cambridge, England.

Prof. Douglas Lauffenburger

Molecular cell bioengineering: the application of engineering approaches to develop quantitative understanding of cell function in terms of fundamental molecular properties, and to apply this understanding for improved design of cell-based technologies. Our group focuses on elucidating important aspects of receptor-mediated regulation of mammalian blood and tissue cell behavioral functions such as proliferation, adhesion, migration, and macromolecular transport. A central paradigm of our work is development and testing of mechanistic models-- based on principles from engineering analysis and synthesis -- for receptor regulation of cell function by exploiting techniques of molecular biology to alter parameters characterizing receptor or ligand properties in well-characterized cell systems. Quantitative experimental assays are used to measure cell function and receptor/ligand interaction parameters. Problems are motivated by health care technologies of interest to pharmaceutical and biotechnological companies.

Controlling Biomolecules

Research Focus

In biology there are numerous examples of systems which far exceed any man-made machine in terms of efficiency, precision, and complexity. We would like to be able to take advantage of the engineering that Nature has done for thousands of years and directly manipulate biological molecules. Our goals are to create nanoscale interfaces to biology to control biological processes. This requires not only exploiting the unique size and material dependent properties of nanoparticles but also understanding and engineering their interface to biology, which is a crucial part of their implementation in any biological application.

1. Charactering the Nanoparticle - Protein Interface

Nanoparticle-protein conjuagtes have been utilized in numerous applications such as sensing, self-assembly, and imaging. For these purposes, conjugation needs to be site-specific and should not perturb the structure and function of the protein. However, this is difficult to achieve as both nanoparticles and proteins are complex chemical systems, which can interact by numerous non-covalent interactions, or non-specific adsorption. Furthermore, characterization of the interface between the nanoparticle and protein is difficult and straightforward assays do not exist. Consequently the interface is poorly understood and remains to be one of the major barriers in employing nanoparticles in biological applications.

Our ultimate goal is to come up with general design rules for optimal conjugation of nanoparticles with a protein. Toward this end, we are studying the interface of nanoparticles with the proteins Ribonuclease S and Cytochrome c. We have determined how to label these proteins in a way that is site-specific. Current efforts are focused on studying the effect of labeling position, as well as nanoparticle ligand, size, and material on the biophysical properties of the protein.
2. Understanding nanoparticle interfaces to DNA

We are studying the biophysical and functional behavior of DNA covalently linked to gold nanoparticles. Covalent linking of DNA to nanoparticles often results in non-specific adsorption of the DNA to the nanoparticle surface. This is problematic as it can prevent the ability of the DNA to hybridize to a target. We are exploring ways to label DNA with nanoparticles in such a way that DNA function is retained. Effect of nanoparticle size, DNA sequence and composition, and nanoparticle surface functionalization are studied. In addition, we are evaluating tools such as quantitative gel electrophoresis to quantitatively assay the DNA conformation on the nanoparticle surface, and charge of the nanoparticle-DNA conjugate.
3. Using nanoparticles to trigger drug delivery

Spatial and temporal control over release of a drug is key for increasing drug efficacy. We are studying how to exploit the ability to heat magnetic nanoparticles with an external field to achieve this in thermosensitive liposomes. Liposomes are a well studied vehicle for drug delivery as they have a large internal aqueous space which can carry a payload. Upon heating these liposomes release their contents, so encapsulation of magnetic nanoparticles along with the drug of interest could enable externally triggered release.

We are studying how to encapsulate water soluble magnetic nanoparticles in liposomes at very high densities using the reverse-evaporation (REV) method. We have found that increasing the concentration of nanoparticles in liposomes can perturb the lipid phase diagram, and thus synthesis of large unilamellar vesicles encapsulating nanoparticles requires optimization of liposome synthesis parameters.

We are developing a means of orthogonally heating nanoparticles, so that magnetic fields of one frequency could be used to heat one type of nanoparticle, and another frequency could be used to heat another independently. We have devised a way to achieve this by exploiting the size and material dependence of magnetic field heating.
4. Laser excitation of gold nanorods

We are exploiting the unique material properties of gold nanorods to control biological processes. Ultrafast laser excitation can rapidly heat gold nanorods, which can be utilized to release biomolecules. Because the optical properties of gold nanorods are size and shape tunable, this permits tailoring the nanorod for strategically controlled release.

We are developing methods for ligand exchange so that functionalization with DNA and proteins is possible. We are studying the thermal properties of gold nanorods and how it is influenced by the surface coating ligand. Transient absorption spectroscopy is utilized to examine the thermal transport between gold nanorods and the solvent.


Alan J. Grodzinsky Research

Alan J. Grodzinsky is an American scientist and Professor of Electrical, Mechanical and Biological Engineering and Director of the Center for Biomedical Engineering at MIT.

Grodzinsky graduated in Electrical Engineering from MIT in 1971, obtaining a doctorate three years later under the supervision of James Melcher, with a thesis on membrane electromechanics.

Grodzinsky was a founding Fellow of the American Institute of Medical and Biological Engineering in 1993. He received a NIH Merit Award in 1994.

Research Focus

Influence of mechanical, chemical and electrical stresses on connective tissue metabolism, growth, remodeling, repair and pathology; Cartilage tissue engineering; effects of mechanical forces on cellular regulation of gene expression, synthesis and degradation of extracellular matrix macromolecules; Molecular, cellular, and tissue biomechanics; Diagnostics and therapeutics for arthritis; Electromechanical and physicochemical properties of connective tissues and polyelectrolyte-based biomaterials. Electrically controlled hydrogel membrane permeability for drug delivery and separation processes. Fundamental study and modeling of electrical, mechanical and chemical energy conversion in natural and synthetic membranes, and in biological tissues.