Cell Differentiation Quotes

You could make iPS cells by introducing just four genes into a differentiated cell.

It’s incredible to think that mammalian cells carry about 20,000 genes, and yet it only takes four to turn a fully differentiated cell into something that is pluripotent.

mental activity such as directing attention, actually shape the structure of the brain?” As we’ve seen, experience means neural firing. When neurons fire together, the genes in their nuclei—their master control centers—become activated and “express” themselves. Gene expression means that certain proteins are produced. These proteins then enable the synaptic linkages to be constructed anew or to be strengthened. Experience also stimulates the production of myelin, the fatty sheath around axons, resulting in as much as a hundredfold increase in the speed of conduction down the neuron’s length. And as we now know, experience can also stimulate neural stem cells to differentiate into wholly new neurons in the brain. This neurogenesis, along with synapse formation and myelin growth, can take place in response to experience throughout our lives. As discussed before, the capacity of the brain to change is called neuroplasticity We are now discovering how the careful focus of attention amplifies neuroplasticity by stimulating the release of neurochemicals that enhance the structural growth of synaptic linkages among the activated neurons.

It was as if she had just discovered the irreversible process. It astonished her to think that so much could be lost, even the quantity of hallucination belonging just to the sailor that the world would bear no further trace of. She knew, because she had held him, that he suffered DT’s. Behind the initials was a metaphor, a delirium tremens, a trembling unfurrowing of the mind’s plowshare. The saint whose water can light lamps, the clairvoyant whose lapse in recall is the breath of God, the true paranoid for whom all is organized in spheres joyful or threatening about the central pulse of himself, the dreamer whose puns probe ancient fetid shafts and tunnels of truth all act in the same special relevance to the word, or whatever it is the word is there, buffering, to protect us from. The act of metaphor then was a thrust at truth and a lie, depending where you were: inside, safe, or outside, lost. Oedipa did not know where she was. Trembling, unfurrowed, she slipped sidewise, screeching back across grooves of years, to hear again the earnest, high voice of her second or third collegiate love Ray Glozing bitching among “uhs” and the syncopated tonguing of a cavity, about his freshman calculus; “dt,” God help this old tattooed man, meant also a time differential, a vanishingly small instant in which change had to be confronted at last for what it was, where it could no longer disguise itself as something innocuous like an average rate; where velocity dwelled in the projectile though the projectile be frozen in midflight, where death dwelled in the cell though the cell be looked in on at its most quick. She knew that the sailor had seen worlds no other man had seen if only because there was that high magic to low puns, because DT’s must give access to dt’s of spectra beyond the known sun, music made purely of Antarctic loneliness and fright. But nothing she knew of would preserve them, or him.

[W]hen food is placed at the start and end points of the maze, the slime mold withdraws from the dead-end corridors and shrinks its body to a tube spanning the shortest path between food sources. The single-celled slime solves the maze in this way each time it is tested.”23 Toshiyuki Nakagaki, the researcher conducting the study, commented that Even for humans it is not easy to solve a maze. But the plasmodium of true slime mold, an amoeba-like organism, has shown an amazing ability to do so. This implies that an algorithm and a high computing capacity are included in the unicellular organism.24 This capacity for mathematical differentiation and computation is wide spread. All self-organized biological systems possess it. One of the more amazing examples is the Clark’s Nutcracker.

How does this work? Rodents produce pheromonal odors with individual signatures, derived from genes called the major histocompatibility complex (MHC). This is a super variable gene cluster that produces unique proteins that form a signature for an individual. This was first studied by immunologists. What does the immune system do? It differentiates between you and invaders—“self” and “nonself”—and attacks the latter. All your cells carry your unique MHC-derived protein, and surveillance immune cells attack any cell lacking this protein password.

Tshepo reckons that it is inevitable that one’s circle of friends will become smaller as one grows older. He reasons that when we begin we are similar, like two glasses of water sitting side by side on a clean tray. There is very little that differentiates us. We are simple beings whose interests do not extend beyond playing touch and kicking balls. However, like the two glasses of water forgotten on a tray in the reading room, we start to collect bits. Bits of fluff, bits of a broken beetle wing, bits of bread, bits of pollen, bits of shed epithelial cells, bits of hair, bits of toilet paper, bits of airborne fungal organisms, bits of bits. All sorts of bits. No two combinations the same. Just like with the glasses of water, Environment, jealous of our fundamentality, bombards our basic minds with complexity. So we become frighteningly dissimilar, until there is very little that holds us together.

Stem cells, as you probably know, are capable of turning into any mature cell. They are the progenitors of all the other cells in your body, whether bone, skin, brain, or muscle. Neural stem cells (NSCs) are just slightly more differentiated: they can become any type of cell found in the nervous system, including any variety of neuron in the brain.

The differentiation of organ systems, organ parts, etc, is a stepwise affair which has been compared to the way a sculptor carves a statue out of a block of wood. With each step in the development the functions assigned to each group of cells become more precise, and more of its genetic potential is suppressed-until in the end most cells lose even their basic freedom to divide. By the time the fertilized ovum has developed into an adult organism, the individual cell has been reduced from totipotentiality to almost nullipotentiality. It still carries the coded blue-print of the whole organism in its chromosomes, but all, except that tiny fraction of the code which regulates its specialized activities, has been permanently switched off.

Different types of cells (brain cells, muscle cells, etc.) differ from each other in the structure and chemistry of their cell-bodies. The differences are due to the interaction between gene-complex cell-body and the cell's environment. In each growing and differentiating tissue a different portion of the total gene-complex is active-only that branch of the gene-hierarchy which is concerned with the functions assigned to the tissue in question; the remainder of teh genes is 'switched off'. And if we inquire into the nature of the agency which switches genes on and off, we find once more the familiar devices of triggers and feedbacks. The 'triggers' are the chemical 'inducers', 'organisers', 'operators' and 'repressors', etc. already mentioned.

And yet how much more human is the dangerous insecurity that drives those prisoners in Poe’s stories to feel out the shapes of their horrible dungeons and not be strangers to the unspeakable terror of their cells. We, however, are not prisoners. No traps or snares have been set around us, and there is nothing that should frighten or upset us. We have been put into life as into the element we most accord with, and we have, moreover, through thousands of years of adaptation, come to resemble this life so greatly that when we hold still, through a fortunate mimicry we can hardly be differentiated from everything around us. We have no reason to harbor any mistrust against our world, for it is not against us. If it has terrors, they are our terrors; if it has abysses, these abysses belong to us; if there are dangers, we must try to love them. And if only we arrange our life in accordance with the principle which tells us that we must always trust in the difficult, then what now appears to us as the most alien will become our most intimate and trusted experience.

What would fly researchers discover at the tips of the reproductive structures? In the immediate environment in which the GSC (germline stem cells) sit? Shangri-La. [...] The experimental biologist J.J. Trentin proposed in 1970 that within the bone marrow and other home locations, there exists 'hematopoietic inductice microenvironment' with the unique ability to serve as a home location for blood stem cells. In the later 1970s, another blood cell expert, R. Schofield, referred to this specialized microenvironment as a 'niche', introducing the term that would stick and eventually, become widely applied to describe the microenvironment surrounding any type of stem cell. Fly biologist H. Lin describes a stem cell niche as 'the Shangri-La, the idyllic hideaway' in which these cells reside. Nestled in the niche, Lin states, stem cells 'thrive to self-renew and to produce numerous daughter cells that will differentiate and age as they leave the paradise'. In other words, the niche is the place that a stem cell is granted its two wishes - allowing it both to remain and to become something else.

Looking back on all my interviews for this book, how many times in how many different contexts did I hear about the vital importance of having a caring adult or mentor in every young person’s life? How many times did I hear about the value of having a coach—whether you are applying for a job for the first time at Walmart or running Walmart? How many times did I hear people stressing the importance of self-motivation and practice and taking ownership of your own career or education as the real differentiators for success? How interesting was it to learn that the highest-paying jobs in the future will be stempathy jobs—jobs that combine strong science and technology skills with the ability to empathize with another human being? How ironic was it to learn that something as simple as a chicken coop or the basic planting of trees and gardens could be the most important thing we do to stabilize parts of the World of Disorder? Who ever would have thought it would become a national security and personal security imperative for all of us to scale the Golden Rule further and wider than ever? And who can deny that when individuals get so super-empowered and interdependent at the same time, it becomes more vital than ever to be able to look into the face of your neighbor or the stranger or the refugee or the migrant and see in that person a brother or sister? Who can ignore the fact that the key to Tunisia’s success in the Arab Spring was that it had a little bit more “civil society” than any other Arab country—not cell phones or Facebook friends? How many times and in how many different contexts did people mention to me the word “trust” between two human beings as the true enabler of all good things? And whoever thought that the key to building a healthy community would be a dining room table? That’s why I wasn’t surprised that when I asked Surgeon General Murthy what was the biggest disease in America today, without hesitation he answered: “It’s not cancer. It’s not heart disease. It’s isolation. It is the pronounced isolation that so many people are experiencing that is the great pathology of our lives today.” How ironic. We are the most technologically connected generation in human history—and yet more people feel more isolated than ever. This only reinforces Murthy’s earlier point—that the connections that matter most, and are in most short supply today, are the human-to-human ones.

These autonomous, self-regulating properties of holons within the growing embryo are a vital safeguard; they ensure that whatever accidental hazards arise during development, the end-product will be according to norm. In view of the millions and millions of cells which divide, differentiate, and move about in the constantly changing environment of fluids and neighbouring tissues-Waddington called it 'the epigenetic landscape'-it must be assumed that no two embryos, not even identical twins, are formed in exactly the same way. The self-regulating mechanisms which correct deviations from the norm and guarantee, so to speak, the end-result, have been compared to the homeostatic feedback devices in the adult organism-so biologists speak of 'developmental homeostasis'. The future individual is potentially predetermined in the chromosomes of the fertilised egg; but to translate this blueprint into the finished product, billions of specialized cells have to be fabricated and moulded into an integrated structure. The mind boggles at the idea that the genes of that one fertilised egg should contain built-in provisions for each and every particular contingency which every single one of its fifty-six generations of daughter cells might encounter in the process. However, the problem becomes a little less baffling if we replace the concept of the 'genetic blueprint', which implies a plan to be rigidly copied, by the concept of a genetic canon of rules which are fixed, but leave room for alternative choices, i.e., flexible strategies guided by feedbacks and pointers from the environment. But how can this formula be applied to the development of the embryo?

It may seem paradoxical to claim that stress, a physiological mechanism vital to life, is a cause of illness. To resolve this apparent contradiction, we must differentiate between acute stress and chronic stress. Acute stress is the immediate, short-term body response to threat. Chronic stress is activation of the stress mechanisms over long periods of time when a person is exposed to stressors that cannot be escaped either because she does not recognize them or because she has no control over them. Discharges of nervous system, hormonal output and immune changes constitute the flight-or-fight reactions that help us survive immediate danger. These biological responses are adaptive in the emergencies for which nature designed them. But the same stress responses, triggered chronically and without resolution, produce harm and even permanent damage. Chronically high cortisol levels destroy tissue. Chronically elevated adrenalin levels raise the blood pressure and damage the heart. There is extensive documentation of the inhibiting effect of chronic stress on the immune system. In one study, the activity of immune cells called natural killer (NK) cells were compared in two groups: spousal caregivers of people with Alzheimer’s disease, and age- and health-matched controls. NK cells are front-line troops in the fight against infections and against cancer, having the capacity to attack invading micro-organisms and to destroy cells with malignant mutations. The NK cell functioning of the caregivers was significantly suppressed, even in those whose spouses had died as long as three years previously. The caregivers who reported lower levels of social support also showed the greatest depression in immune activity — just as the loneliest medical students had the most impaired immune systems under the stress of examinations. Another study of caregivers assessed the efficacy of immunization against influenza. In this study 80 per cent among the non-stressed control group developed immunity against the virus, but only 20 per cent of the Alzheimer caregivers were able to do so. The stress of unremitting caregiving inhibited the immune system and left people susceptible to influenza. Research has also shown stress-related delays in tissue repair. The wounds of Alzheimer caregivers took an average of nine days longer to heal than those of controls. Higher levels of stress cause higher cortisol output via the HPA axis, and cortisol inhibits the activity of the inflammatory cells involved in wound healing. Dental students had a wound deliberately inflicted on their hard palates while they were facing immunology exams and again during vacation. In all of them the wound healed more quickly in the summer. Under stress, their white blood cells produced less of a substance essential to healing. The oft-observed relationship between stress, impaired immunity and illness has given rise to the concept of “diseases of adaptation,” a phrase of Hans Selye’s. The flight-or-fight response, it is argued, was indispensable in an era when early human beings had to confront a natural world of predators and other dangers. In civilized society, however, the flight-fight reaction is triggered in situations where it is neither necessary nor helpful, since we no longer face the same mortal threats to existence. The body’s physiological stress mechanisms are often triggered inappropriately, leading to disease. There is another way to look at it. The flight-or-fight alarm reaction exists today for the same purpose evolution originally assigned to it: to enable us to survive. What has happened is that we have lost touch with the gut feelings designed to be our warning system. The body mounts a stress response, but the mind is unaware of the threat. We keep ourselves in physiologically stressful situations, with only a dim awareness of distress or no awareness at all.

Laughter itself is more often than not a vital abreaction to the disgust we feel for the monstrous mixing and promiscuity that confront us. But for all that we may gag on the absence of differentiation, it still fascinates us. We love to mix everything up, even if it simultaneously repels us. The reaction whereby the organism seeks to preserve its symbolic integrity is a vital one, even if the price paid is life itself (as in the rejection of a transplanted heart). Why would bodies not resist the arbitrary swapping of organs and cells? Also: why do cells, in cancer, refuse to carry out their assigned functions?

Every one of our cells has the same DNA, of course, so what differentiates a nerve cell from a skin cell is the epigenome, the collective term for the control systems and cellular structures that tell the cell which genes should be turned on and which should remain off. And this, far more than our genes, is what actually controls much of our lives.

An interesting point: A cell in your brain and a cell in your kidney contain the exact same DNA. And while in utero (in the womb), the nascent (emerging, developing) cells differentiate into either a brain cell or a kidney cell only when crucial epigenetic processes turn the right genes on or off. So God has designed perfectly timed epigenetic signals to switch on in the womb as the baby is developing. “Before I formed you in the womb I knew you” (Jer. 1:5). Our

At the lab my professor suggested that, since it was such an amazing day, perhaps I could take the exam outside in the wetland wilderness reserve that surrounded the lab. The view of the swamp was stunning! Somehow it had never seemed beautiful to me before. She asked that I take my notebook and pencil out. “Please draw for me the complete development of the chick from fertilization to hatching. That is the only question.” I gasped, “But that is the entire course!” “Yes, I suppose it is, but make-up exams are supposed to be harder than the original, aren’t they?” I couldn’t imagine being able to regurgitate the entire course. As I sat there despondently, I closed my eyes and was flooded with grief. Then I noticed that my inner visual field was undulating like a blanket that was being shaken at one end. I began to see a movie of fertilization! When I opened my eyes a few minutes later, I realized that the movie could be run forward and back and was clear as a bell in my mind’s eye, even with my physical eyes open. Hesitantly, I drew the formation of the blastula, a hollow ball of cells that develops out of the zygote (fertilized egg). As I carefully drew frame after frame of my inner movie, it was her turn to gape! The tiny heart blossomed. The formation of the notochord, the neural groove, and the beginnings of the nervous system were flowing out of my enhanced imagery and onto the pages. A stupendous event—the animated wonder of embryonic growth and the differentiation of cells—continued at a rapid pace. I drew as quickly as I could. To my utter amazement, I was able to carefully and completely replicate the content of the entire course, drawing after drawing, like the frames of animation that I was seeing as a completed film! It took me about an hour and a quarter drawing as fast as I could to reproduce the twenty-one-day miracle of chick formation. Clearly impressed, my now suddenly lovely professor smiled and said, “Well, I suppose you deserve an A!” The sunlight twinkled on the water, the cattails waved in the gentle breeze, and the gentle wonder of life was everywhere. Reports:

Terminology and classification Leukaemias are traditionally classified into four main groups: • acute lymphoblastic leukaemia (ALL) • acute myeloid leukaemia (AML) • chronic lymphocytic leukaemia (CLL) • chronic myeloid leukaemia (CML). In acute leukaemia there is proliferation of primitive stem cells leading to an accumulation of blasts, predominantly in the bone marrow, which causes bone marrow failure. In chronic leukaemia the malignant clone is able to differentiate, resulting in an accumulation of more mature cells. Lymphocytic and lymphoblastic cells are those derived from the lymphoid stem cell (B cells and T cells). Myeloid refers to the other lineages, i.e. precursors of red cells, granulocytes, monocytes and platelets (see Fig. 24.2, p. 989). The diagnosis of leukaemia is usually suspected from an abnormal blood count, often a raised white count, and is confirmed by examination of the bone marrow. This includes the morphology of the abnormal cells, analysis of cell surface markers (immunophenotyping), clone-specific chromosome abnormalities and molecular changes. These results are incorporated in the World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues; the subclassification of acute leukaemias is shown in Box 24.47. The features in the bone marrow not only provide an accurate diagnosis but also give valuable prognostic information, allowing therapy to be tailored to the patient’s disease.

Meiosis is an elegant process but in any organism errors in meiosis sometimes occur. These errors may be the result of mistakes in separation of the chromosomes during division or of an incorrect exchange of genetic information during chiasma formation. Many genetic disorders in humans can be traced back to errors in the formation of the gametes in meiosis. Mistakes in meiosis can result in an abnormal number of chromosomes in an egg or sperm cell. If this egg or sperm is then involved in fertilization, the zygote will exhibit an abnormal number of chromosomes. The child produced from this zygote (following mitosis and differentiation) will have cells with too few or too many chromosomes

It is a scandal—or, rather, it should be a scandal and one wonders why it isn’t—that the US prison population, after reaching a postwar low in the early 1970s, has since grown more than 500 percent. The United States locks up a higher percentage of its own population than any other nation in the world. Even with extraordinary prison construction projects over the last decades, the cells are still overfull. This massive expansion cannot be explained by a growing criminality of the US population or the enhanced efficiency of law enforcement. In fact, US crime rates in this period have remained relatively constant. The scandal of US prison expansion is even more dramatic when one observes how it operates along race divisions. Latinos are incarcerated at a rate almost double that of whites, and African Americans at a rate almost six times as high. The racial imbalance of those on death row is even more extreme. It is not hard to find shocking statistics. One in eight black US males in their twenties, for instance, is in jail or prison on any given day. The number of African Americans under correctional control today, Michelle Alexander points out, is greater than the number of slaves in the mid-nineteenth century. Some authors refer to the racially skewed prison expansion as a return to elements of the plantation system or the institution of new Jim Crow laws. Keep in mind that this differential racial pattern of imprisonment is not isolated to the United States. In Europe and elsewhere, if one considers immigrant detention centers and refugee camps as arms of the carceral apparatus, those with darker skin are disproportionately in captivity.

Human embryonic development during the first 10 weeks. Organ systems are most vulnerable to teratogens during this time, when cells are dividing and differentiating.

Cell differentiation can turn neurons into everything from clocks that control circadian rhythms to photoreceptors that convert light into electrical-chemical impulses or decision makers that tally votes and decide courses of action. In the retina (often used as a case study because it can be directly and naturally stimulated), there are at least fifty different kinds of neurons specialized to different tasks, such as looking for motion, recognizing colors, detecting objects in low light, and measuring brightness and contrast. In the brain as a whole, there may be as many as 10,000 different kinds of neurons, each contributing to a different aspect of mental life.

Though words are often described as tools, they may be more properly regarded as the cells of a complex living structure, units quickly mobilized in orderly formations to function on particular occasions for particular uses. Every member of the community has access to this linguistic organization and can use it up to the capacities of his experience and intelligence, his emotional responsiveness, and his insight. At no point, except by the invention of writing, has language ever been the monopoly of a dominant minority, despite class differentiations of usage; while the medium itself is so complex and so subtle that no centralized system of control was ever, even after the invention of writing, completely effective.

The energies of the electromagnetic spectrum include microwaves, radio waves, x-rays, extremely low-frequency waves, sound harmonic frequencies, ultraviolet rays, and even infrared waves. Specific frequencies of electromagnetic energy can influence the behavior of DNA, RNA, and protein synthesis; alter protein shape and function; control gene regulation and expression; stimulate nerve-cell growth; and influence cell division and cell differentiation, as well as instruct specific cells to organize into tissues and organs. All of these cellular activities influenced by energy are part of the expression of life. And

Can the trees and flowers which we see all around us at all times have themselves formed such perfect systems as to bring about a phenomenon such as photosynthesis, some parts of which are still not fully understood, in their own bodies? Did plants choose to use carbon dioxide (CO2), of the gases in the air, to produce food? Did they themselves determine the amount of CO2 they would use? Could plants have designed those mechanisms which make up the root system and which enable them to take the materials necessary for photosynthesis from the soil? Did plants bring about a transport system where different types of tubes are used for transporting nutrients and water? As ever, defenders of the theory of evolution searching for an answer 16 The solar energy trapped by the chlorophyll in the leaf, carbon-dioxide in the air, and water in the plant go through various processes and are used to produce glucose and oxygen. These complex processes do not take place in a factory, but in special structures like those in the leaf in the picture, and which measure only one thousandth of a millimeter across. Sunlight Chlorophyll Glucose 6H2O Water Light Chlorophyll Carbon dioxide + Water Glucose + Oxygen 6CO2 Carbon dioxide 6O2 Oxygen C6 H12O 6 to the question of how plants emerged have resorted to "chance" as their only re m e d y. They have claimed that from one species of plant which came about by chance, an infinite variety of plants have emerged, again by chance, and that features such as smell, taste, and colour, particular to each species, again came about by chance. But they have been unable to give any scientific proof of these claims. Evolutionists explain moss turning into a strawberry plant, or a poplar, or a rose bush, by saying that conditions brought about by chance differentiated them. Whereas when just one plant cell is observed, a system so complex will be seen as could not have come about by minute changes over time. This complex system and other mechanisms in plants definitively disprove the coincidence scenarios put forward as evolutionist logic. In this situation just one result emerges.

While a 'cure' for HIV would, in effect, decrease Gilead's market share, PrEP not only allows for the capture of those who are HIV+ but has transformed all those who are not into consumers - market saturation as a way of life. Because of PrEP's prohibitive cost, many of those most impacted by HIV, namely young Black, Indigenous, and/or Latinx trans women and MSM as well as IV drug users, have limited, if any, access. The ongoing legacies of colonial medical disinformation swirls with transphobic epidemiology and the homicidal stigmatization of IV drug use that results in the uninterruption of the pandemic for some, while the end of AIDS is habitually proclaimed for others. In a lethal irony, it is the logic of the patent - the argument that innovation is only spurred by the security of private property - that replicates the virus and its differential death. Put plainly, the HIV cells of those taken without their informed consent or compensation, housed in the NIH reagent bank and also laboring in publicly funded labs that produced PrEP, are withheld from the same populations, and perhaps the same people from whom they were initially extracted. The theft of their viral labor helped grow Gilead's incalculable wealth, which includes $36.2 billion in earnings off Truvada alone.

deglycyrrhizinated Licorice root (DGL) DGL is a popular and substantially studied, natural compound that provides flavonoids shown to heal the gastric lining. Many different mechanisms have been demonstrated with regard to its restorative properties, including stimulation and differentiation of glandular cells, mucous formation and secretion, and the growth and regeneration of the stomach and intestinal cells.1 2 3 4

So when breakpoints come for you, remember how you’ve been reassuring the team and take your own advice: know they’re coming and get ready. Talk to your mentor. Understand what your job should look like well before every transition and plan for it. And always remember that change is growth and growth is opportunity. Your company is an organism; its cells need to divide to multiply, they need to differentiate to become something new. Don’t worry about what you’re going to lose—think about what you’re going to become.

Despite the restriction of stem cells to just two regions of the mammalian central nervous system (CNS)—the lateral ventricle linings and the dentate gyrus—it is possible to grow neural stem cells in tissue culture from a much wider range of brain regions than this. The stem cells grow in a form called neurospheres. These are clumps of cells, up to 0.3 mm wide, that grow in suspension culture in a medium containing two specific growth factors (EGF and FGF). The cultures can be initiated from any part of the foetal CNS and often from parts of the adult CNS as well, even regions not thought to undergo continuous renewal. Neurospheres are thought each to contain a few neural stem cells, which are capable of self-renewal, plus a certain number of transit amplifying cells, that have finite division potential. When neurospheres are plated on an adhesive surface in the presence of serum, they will differentiate and form the three cell types normally generated by neuronal stem cells, which are neurons, and two types of glial cells: astrocytes and oligodendrocytes. If neurospheres are dissociated into single cells, a few per cent of these cells can establish new neurospheres, with similar properties to the original. Repeated cycles of dissociation and growth can provide substantial expansion capacity. The phenomenon of neurospheres is an example of the fact that cells may behave in a different manner in tissue culture from in vivo. Neurospheres have created enormous interest because, unlike haematopoietic stem cells, they are expandable in vitro, and because there is a hope that they might be used for cell therapy of the very intractable neurodegenerative diseases involving widespread neuronal death.

There are also some potential safety concerns with grafts derived from pluripotent cells. Although Parkinson’s disease is a distressing condition that causes much suffering, it does not greatly reduce lifespan, so the period of time available for the development of complications is quite long, perhaps about 20 years on average. For any cell therapy derived from pluripotent stem cells there is always an issue about the possibility of persistence of a few pluripotent cells in the graft which might give rise to teratomas. Although the animal experiments indicate that the teratoma risk is very low, the long survival time of Parkinson’s patients does make even a very small cancer risk seem significant. Moreover, the differentiation protocols for pluripotent stem cells never produce 100 per cent of the desired cell type. Even if all the pluripotent cells are gone there will certainly be other types of neuron and glial cell present and these may generate unwanted effects. For example, the uncontrolled movement problems seen in some of the foetal midbrain graft recipients has been ascribed to the presence of other types of neuron which make inappropriate connections.

Stem cells are the undifferentiated group of cells, they are unspecified and have a great potential for proliferation, differentiation and migration. Stem Cells are vital. They can rise specialized cells for body repair. Moreover, stem cell treatment has witnessed exceptional growth and development in past few years. Their consistency, self-repairing properties and profound healing response have led to the immense popularity of Stem Cell Therapy in South Africa.

She’s old an’ she’s ornery,’’ he said gravely. “I gave the whole thing a good goin’-over ’fore we bought her. Didn’ listen to the fella talkin’ what a hell of a bargain she was. Stuck my finger in the differential an’ they wasn’t no sawdust. Opened the gear box an’ they wasn’t no sawdust. Test’ her clutch an’ rolled her wheels for line. Went under her an’ her frame ain’t splayed none. She never been rolled. Seen they was a cracked cell in her battery an’ made the fella put in a good one. The tires ain’t worth a damn, but they’re a good size. Easy to get. She’ll ride like a bull calf, but she ain’t shootin’ no oil. Reason I says buy her is she was a pop’lar car. Wreckin’ yards is full a Hudson Super-Sixes, an’ you can buy parts cheap. Could a got a bigger, fancier car for the same money, but parts too hard to get, an’ too dear. That’s how I figgered her anyways.

Faith speaks to the soul and asks us to purify our soul. When faith gives guidelines about body, it is to make sure that the body hosting the soul should become pure by cleanliness and by being non- injurious to others. Even if we have evolved through a physical process to get our current physical form, it does not matter in the faith based worldview since the faith based worldview attributes every creature’s origin and creation to the Ultimate Creator. But, we humans in our current form and nature have been given a strong ability to differentiate right from wrong actions. This ability is not within our chemical composition. We might be having same colonies of bacteria and cells like other animals. This is the chemical description of our body, i.e. the host which embodies the human soul and spirit. The ability to differentiate right from wrong is in our conscience. We like to act in ways that are essentially good and virtuous and dislike acts which are wrong and unjust. Yet, this world is not fair. Belief in afterlife accountability actualizes the cause and effect in moral matters. It will give deterministic results to every act of goodness and every act of evil. That makes life meaningful and purposeful. That enables us to look beyond our survival instincts in organizing life on the basis of moral values of justice, fairness, honesty, sacrifice and cooperation.

The properties of the renewal tissues enabled the original definition of stem cell behaviour in terms of the ability to self-renew and to generate differentiated progeny. But the most famous stem cell of them all is now the embryonic stem cell (ES cell). In one sense, the ES cell is the iconic stem cell. It is the type of stem cell that has attracted all of the ethical controversy, and it is what lay people are thinking of when they refer to ‘stem cell research’. But ironically, the embryonic stem cell does not exist in nature. It is a creature that has been created by mankind and exists only in the world of tissue culture: the growth of cells in flasks in the laboratory, kept in temperature-controlled incubators, exposed to controlled concentrations of oxygen and carbon dioxide, and nourished by complex artificial media. Cells grown in culture are often referred to by the Latin phrase in vitro (in glass, since the relevant containers used to be made of glass) and distinguished from in vivo (inside the living body).

The stagnancy of energy, lack of interest in life and creativity, unproductiveness and mediocrity which beset so many people is not the consequence of their genetic and biological programming but of parental and social conditioning. The great Otto Rank acknowledged this and correctly rectified Freud's Thanatos concept. He, like several humanist and existential philosophers and psychologists who came later, realized that our Death Instinct or drive manifests itself in the very repression addressed throughout this book. Repression is a form of violence against the Self. Rank and his followers also realized that man's blind conformity to social norms and lack of differentiation from crowd-consciousness also serves to deaden creativity and productivity. They understood that the robotic organization man, behind his cubicle or on his cell-phone, slaving for some faceless corporation, fully embodies the Death Instinct.

It’s incredible to think that mammalian cells carry about 20,000 genes, and yet it only takes four to turn a fully differentiated cell into something that is pluripotent. With just four genes Professor Yamanaka was able to push the ball right from the bottom of one of Waddington’s troughs, all the way back up to the top of the landscape.

Professor Jaenisch and his colleagues created mice carrying a genetically engineered version of the X Inactivation Centre (an X Inactivation Centre transgene). This was 450kb in size, and included the Xist gene plus other sequences on either side. They inserted this into an autosome (non-sex chromosome), created male mice carrying this transgene, and studied ES cells from these mice. The male mice only contained one normal X chromosome, because they have the XY karyotype. However, they had two X Inactivation Centres. One was on the normal X chromosome, and one was on the transgene on the autosome. When the researchers differentiated the ES cells from these mice, they found that Xist could be expressed from either of the X Inactivation Centres. When Xist was expressed, it inactivated the chromosome from which it was expressed, even if this was the autosome carrying the transgene16. These experiments showed that even cells that are normally male (XY) can count their X chromosomes. Actually, to be more specific, it showed they could count their X Inactivation Centres. The data also demonstrated that the critical features for counting, choosing and initiation were all present in the 450kb of the X Inactivation Centre around the Xist gene.

miRNAs play major roles in control of pluripotency and control of cellular differentiation. ES cells can be encouraged to differentiate into other cell types by changing the culture conditions in which they’re grown. When they begin to differentiate, it’s essential that ES cells switch off the gene expression pathways that normally allow them to keep producing additional ES cells (self-renewal). There is a miRNA family called let-7 which is essential for this switch-off process

But some mRNAs can take a long time to break down in a cell. This means that when a stem cell starts to differentiate, there will be a period when it still contains many of the stem cell mRNAs. Happily, when the stem cell starts differentiating, it switches on a new set of miRNAs. These target the residual stem cell mRNAs and accelerate their destruction. This rapid degradation of the pre-existing mRNAs ensures that the cell moves into a differentiated state as quickly and irreversibly as possible

All the reprogramming of the genome in early development has multiple effects. It allows two highly differentiated cell types to fuse and form one pluripotent cell. It balances out the competing demands of the maternal and paternal genomes, and ensures that this balancing act can be re-established in every generation. Reprogramming also prevents inappropriate epigenetic modifications being passed from parent to offspring. This means that even if cells have accumulated potentially dangerous epigenetic changes, these will be removed before they are passed on. This is why we don’t normally inherit acquired characteristics. But there are certain regions of the genome, such as IAP retrotransposons, that are relatively resistant to reprogramming. If we want to work out how certain acquired characteristics – responses to vinclozolin or responses to paternal nutrition, for example – get transmitted from parent to offspring, these IAP retrotransposons might be a good place to start looking.

What holds cells in this teetering position? In 2006, a group headed by Eric Lander at the Broad Institute in Boston, found at least part of the answer. A key set of genes in ES cells, the pluripotent cells we have come to know so well, were found to have a really strange histone modification pattern. These were genes that were very important for controlling if an ES cell stayed pluripotent, or differentiated. Histone H3K4 was methylated at these genes, which normally is associated with switching on gene expression. H3K27 was also methylated. This is normally associated with switching off gene expression. So, which modification would turn out to be stronger? Would the genes be switched on or off? The answer turned out to be both. Or neither, depending on which way we look at it. These genes were in a state called ‘poised’. Given the slightest encouragement – a change in culture conditions that pushed cells towards differentiation for example – one or other of these methylations was lost. The gene was fully switched on, or strongly repressed, depending on the epigenetic modification

Like the periosteum, the endosteum contains osteogenic cells that can differentiate into other bone cells.

When actively depositing matrix, osteoblasts are cube shaped. When inactive, they resemble the flattened osteogenic cells or may differentiate into bone lining cells. When the osteoblasts become completely surrounded by the matrix being secreted, they become osteocytes.

Experimental evidence suggests that a key element underlying a daughter cell's becoming an outer cell is inheritance of a patch of outer cell membrane containing microvilli and the actin microfilament-stabilizing protein, ezrin. The proteins that produce polarity in the outer cells are postulated to direct their differentiation toward the trophoblastic lineage. Common to the inside-outside hypothesis and the cell polarity model is the recognition that a cell that does not contact the surface does not differentiate into trophoblast, but rather becomes part of the inner cell mass.

Fig. 3.7 The cell polarity model of differentiation of blastomeres. A, If the plane of cleavage of a blastomere is perpendicular to the surface of the embryo, each daughter cell becomes trophoblast. B, If the plane of cleavage is parallel to the surface, the daughter blastomere located at the surface becomes trophoblast, whereas the daughter cell located on the interior becomes part of the inner cell mass. Even though by the 16-cell stage the

addition to the major types of cell that result from differentiation, similar processes can also alter the phenotype of terminally differentiated cells to subtly alter their functions. These different programmes of gene expression are often referred to as altered states of activation, or polarisation.

How can a single fertilized egg cell possibly contain all of the instructions required to construct an entire human, and then be able to carry out these instructions with such perfection? This single fertilized cell is the progenitor of trillions of cells, which differentiate along the way into different types. And each of these uncountable offspring cells need to know what to be, and where to be, to create the incomprehensibly complex universe that is a human being. But there’s more. The system has to get energy and building blocks from the outside. How do we grow from an infant to an adult? We have to convert food into parts of our bodies. Food gives us energy, yes, but it is also our only source of building material. Our bodies must extract the raw materials we need for construction from such sources as ice-cream, meatloaf, and pasta,  and then rearrange these raw materials into muscle cells, heart cells, brain cells, and so on. The idea that a single fertilized cell could successfully transform itself into an adult human, including a brain with many billions of neurons and a consciousness, is utterly ludicrous. Impossible. There is no way this could ever succeed. And yet, all of us are living proof that it does . . .

After years of painstaking research, in 2006 Yamanaka and his team discovered that proteins encoded by just four “master genes” could turn back the clock and transform any adult cell back into a stem cell. Just as a stem cell could differentiate itself forward in developmental time into a skin, blood, liver, heart, or any other of the two hundred types of human cells, these Yamanaka factors could revert any skin, blood, liver, or other type of cell back into the equivalent of an embryonic stem cell.

thing differentiating immune cells, heart cells, and brain cells is the precise pattern of gene expression that created them.

The four known for targeting humans are transmitted from person to person by Anopheles mosquitoes. These four parasites possess wondrously complicated life histories, encompassing multiple metamorphoses and different forms in series: an asexual stage known as the sporozoite, which enters the human skin during a mosquito bite and migrates to the human liver; another asexual stage known as the merozoite, which emerges from the liver and reproduces in red blood cells; a stage known as the trophozoite, feeding and growing inside the blood cells, each of which fattens as a schizont and then bursts, releasing more merozoites to further multiply in the blood, and causing a spike of fever; a sexual stage known as the gametocyte, differentiated into male and female versions, which emerge from a later round of infected red blood cells, enter the bloodstream en masse, and are taken up within a blood meal by the next mosquito; a fertilized sexual stage known as the ookinete, which lodges in the gut lining of the mosquito, each ookinete ripening into a sort of egg sac filled with sporozoites; and then come the sporozoites again, bursting out of the egg sac and migrating to the mosquito’s salivary glands, where they lurk, ready to surge down the mosquito’s proboscis into another host.

In still higher invertebrates, such as the earthworm, the diffuse nature of this intermediate net disappears, and it is now organized into a distinct nerve cord running the length of the worm. Sensory elements become even more differentiated, and the special senses—light sensitivity, smell, taste, gravitational orientation—become even more concentrated at the head end, swelling the size, capacity, and sophistication of the head ganglion even further. The sensory elements still originate in the worm’s skin, but now they send their axons directly to the central cord, without contacting any muscle cells; and for the first time distinct motor neurons appear, sending their axons out from the central cord to the muscle cells in the body. And in addition, we encounter another type of nerve cell for the first time, cells which are contained wholly within the head ganglion and the cord, cells which are neither really sensory nor motor, at last purely internuncial in their functions. They are arranged into afferent and efferent pathways, running the length of the cord towards and away from the head ganglion.

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Code was written, copied, combined, borrowed, and stolen among software producers as freely as in a primordial soup of living but only vaguely differentiated cells. Anyone who put together some code that could be executed as a useful process—like Dan Bricklin’s Visicalc in 1979—was in for a wild ride. Businesses sprouted like mushrooms, supported by the digital mycelium underneath. Corporations came and went, but successful code lived on.

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Leavitt had pointed out that all men, no matter how scientifically objective, had several built-in biases when discussing life. One was the assumption that complex life was larger than simple life. It was certainly true on the earth. As organisms became more intelligent, they grew larger, passing from the single-celled stage to multicellular creatures, and then to larger animals with differentiated cells working in groups called organs. On earth, the trend had been toward larger and more complex animals. But this might not be true elsewhere in the universe. In other places, life might progress in the opposite direction—toward smaller and smaller forms. Just as modern human technology had learned to make things smaller, perhaps highly advanced evolutionary pressures led to smaller life forms. There were distinct advantages to smaller forms: less consumption of raw materials, cheaper spaceflight, fewer feeding problems …

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Differentiated multiatomic structures become templates for the evolution of organic macromolecules. The latter build into still more complex and coherent systems: living cells. Groups of cells in turn build into multicellular organisms

Differentiated multiatomic structures become templates for the evolution of organic macromolecules. The latter build into still more complex and coherent systems: living cells. Groups of cells in turn build into multicellular organisms, and multicellular organisms build into societies and ecologies of organisms. Even anthills are coherent complex systems on the socio-ecological level, and so are tribes of chimpanzees and pods of dolphins. As it unfolds on Earth, evolution generates differentiated systems on higher and higher levels of complexity and coherence. We humans are differentiated systems on the highest—or perhaps just one of the highest—level of complexity and coherence so far attained on this planet.

制作假安哥拉身份证ID,【telegram:十852 55367074】（whatsApp:+852 55367074）『办理高仿护照 真护照，可根据客户样本制版印刷』可加急,制作假安哥拉身份证ID,制作假安哥拉身份证ID【telegram:+852 55367074】【WHATSApp:+852 55367074】『办理护照、签证、驾驶证、身份证ID、居留证、各种证明，发货速度快。』联系我们【飞机whatsapp 同号:+852 55367074】编辑丨王多鱼 排版丨水成文 在对抗癌症的战场上，CAR-T 细胞疗法犹如一柄斩向血液肿瘤的利剑，却在实体瘤面前屡屡受挫。传统体外扩增的 CAR-T 细胞仿佛被“催熟”的战士——扩增即伴随分化、耗竭。它们难以突破肿瘤组织屏障，即便侥幸潜入也存活不久。这两大难题，死死扼住了实体瘤 CAR-T 细胞疗法的咽喉。 中国医学科学院基础医学研究所黄波教授团队，另辟蹊径，借力“无形之手”——生物力学信号，成功破解了这一困局！他们首次利用生物力学信号，成功解偶联了 CAR-T 细胞的增殖与分化程序，仅需 4.5 天就在实验室中“锻造”出大批具有干细胞特性的 CAR-T 细胞（干细胞样 CAR-T 细胞）。这些细胞展现出强大的肿瘤浸润能力和瘤内长期生存本领，在杀伤实体瘤方面表现出卓越的成效。 这项里程碑式研究成果于 2025 年 8 月 8 日以：Mechanical signaling via β2 integrin decouples T cell proliferation and differentiation for generating stem cell-like CAR T cells 为题，发表在了 Immunity 期刊，黄波教授为论文通讯作者，吕家迪、王殿恒、司甜为论文共同第一作者，中国医学科学院肿瘤医院张海增教授、郑州大学第一附属医院张毅教授提供了关键的临床样本和人源 CAR-T 质粒支持。生物力学，这门由华裔物理学家冯元桢开创的交叉学科，揭示了力学信号与化学信号共同主宰生命活动的奥秘。黄波团队早在 2008 年就开展了生物力学在肿瘤和免疫领域的研究，采用软的纤维蛋白凝胶（弱的生物力学信号）实现肿瘤再生细胞（tumor-repopulating cell，TRC）凝胶内大量扩增 （Nat Mater. 2012;11:734-41）。进一步研究发现，TRC 在硬的力学微环境中进入休眠状态（Cancer Res. 2018;78:3926-37.），而已分化的肿瘤细胞在弱的生物力学信号下能够进行逆分化，重新获得干性特征（Research. 2023:6:0215）。 利用这种柔软性，黄波团队自建方法将软的和硬的细胞进行分选，证实柔软性是干性细胞的基本特征（EMBO J. 2021;40:e106123.）。

制作假法罗群岛身份证ID,【telegram:十852 55367074】（whatsApp:+852 55367074）『办理高仿护照 真护照，可根据客户样本制版印刷』可加急,制作假法罗群岛身份证ID,制作假法罗群岛身份证ID【telegram:+852 55367074】【WHATSApp:+852 55367074】『办理护照、签证、驾驶证、身份证ID、居留证、各种证明，发货速度快。』联系我们【飞机whatsapp 同号:+852 55367074】编辑丨王多鱼 排版丨水成文 在对抗癌症的战场上，CAR-T 细胞疗法犹如一柄斩向血液肿瘤的利剑，却在实体瘤面前屡屡受挫。传统体外扩增的 CAR-T 细胞仿佛被“催熟”的战士——扩增即伴随分化、耗竭。它们难以突破肿瘤组织屏障，即便侥幸潜入也存活不久。这两大难题，死死扼住了实体瘤 CAR-T 细胞疗法的咽喉。 中国医学科学院基础医学研究所黄波教授团队，另辟蹊径，借力“无形之手”——生物力学信号，成功破解了这一困局！他们首次利用生物力学信号，成功解偶联了 CAR-T 细胞的增殖与分化程序，仅需 4.5 天就在实验室中“锻造”出大批具有干细胞特性的 CAR-T 细胞（干细胞样 CAR-T 细胞）。这些细胞展现出强大的肿瘤浸润能力和瘤内长期生存本领，在杀伤实体瘤方面表现出卓越的成效。 这项里程碑式研究成果于 2025 年 8 月 8 日以：Mechanical signaling via β2 integrin decouples T cell proliferation and differentiation for generating stem cell-like CAR T cells 为题，发表在了 Immunity 期刊，黄波教授为论文通讯作者，吕家迪、王殿恒、司甜为论文共同第一作者，中国医学科学院肿瘤医院张海增教授、郑州大学第一附属医院张毅教授提供了关键的临床样本和人源 CAR-T 质粒支持。生物力学，这门由华裔物理学家冯元桢开创的交叉学科，揭示了力学信号与化学信号共同主宰生命活动的奥秘。黄波团队早在 2008 年就开展了生物力学在肿瘤和免疫领域的研究，采用软的纤维蛋白凝胶（弱的生物力学信号）实现肿瘤再生细胞（tumor-repopulating cell，TRC）凝胶内大量扩增 （Nat Mater. 2012;11:734-41）。进一步研究发现，TRC 在硬的力学微环境中进入休眠状态（Cancer Res. 2018;78:3926-37.），而已分化的肿瘤细胞在弱的生物力学信号下能够进行逆分化，重新获得干性特征（Research. 2023:6:0215）。 利用这种柔软性，黄波团队自建方法将软的和硬的细胞进行分选，证实柔软性是干性细胞的基本特征（EMBO J. 2021;40:e106123