01 juillet 2007
three words. yes, three words, two short, another is longer, three words that should dance on the page. yet remain static, like lead soldiers. at attention. what are they guarding, and how, how can we look at them so that they will start dancing, start living, so. look at them. then, listen to them. separately at first. and then together. Line, place, Process. ….plAce … liNE…….. Capitals, or small letters, words mixed, upset, out of line, strangled.
finally they ring, and resound. the line of the horizon, or the dividing line, the strong place or else: the place of death.
but Process… … that drips, whistles, oozes sweat, that hold both sex and law. that runs down the chin like an over ripe, or over squeezed fruit. that throws you forward or forces you to slow down, to slow down so that time does its work to be patient another day, week, year. nine months, sometimes.
Process that means maturation and inevitable days and nights, and heartbeat, and feet, and arms so little with fingers at the end of palms still closed. Which speak of dreams, and sounds within, sounds within, cavernous and outside, chopped up, intimate, sounds of a romantic voice of a love song or a lamentation, and deep sounds that anSwer, deny, resPond, Argument. and the horizon that fades away: the one of dreams achieved longing waits, incandescent, secret desires in the mixture of days. over there, by the bar. one sees him leaning on his elbow, one turns his head. right before the kiss, one turns the head. one runs away. with a rounded belly. one runs away one catches the line of the horizon. one runs away he goes down the stairs. one dreams of before
frozen, here. in this place, here, overwhelmed by worrisome time buying fearful bursts, possessions that one is denied.
three words, yes, three words, two short, another is longer, the length of time to wait for the end of the kiss, or for him to leave, and leave you to dream of the abdomen that becomes rounder, in the warm place inside, in the cup of what soon, once the attachment is cut, will dig inside the void and marks all at once the separate
slowly, he goes down the stairs,
he hardly turns, hardly, listens, holding his breath, whimpering bitter tears, stopping sighs on the verge of nausea, holding back, the forbidden sob, he hardly turns around. She, looks at him, she, stares at her round abdomen all soft inside, the waves that filter through viper-like partitions, worries provoked by pleasure.
he hardly turns around, hardly listens, but notices the shiver and then the calm
so, he crosses a threshold another threshold, and says he says, to her, and to the other too in the abdomen that becomes round « don't forget, no, don't forget you are mine, you are entirely mine ! »
What are you thinking when you aim at them, tell me ?
Tell me, what are you thinking ?
Between you and the other, at that moment, when you aim at him, there is a fraction of time that could hold all of eternity, if the other knew about it.
The fraction of time between the moment when you line up the cross hairs on the head and the moment when you pull the trigger.
Everything in the world held in this time, all of the memory of the world – like a grain of sand that contains galaxies.
If you try a little, all of the memory of the world.
If you try a little, streets from childhood and fleeting love, lizards under stones and a sandy garden, steep cities and sleepless nights, girls' dresses and glasses of wine, dogs, tractors, wounds, Don Quixote, departures, father, people who fall, around, tears that are shed, confrontations, dirty fighting, other places, others, worthless life.
Or maybe a single image that lasts, a wisp of black hair on a cheek.
Nothing, of course. You think about nothing. You think about nothing at this moment because if at this moment you started to think, the fraction of time might last and your hand would start to shake.
No, these are not the right reasons, you think about nothing because thinking at this particular moment would be, how can we say, out of your control, yes, out of your control. It's stupid but it's like that, you are caught in a process that is beyond you and that you never think about because to think would be to doubt and to doubt would be to fail. You were made for that, you say, you were made like that – ah ha, made –, according to a process that would be too complex to explain here and what's more, it is none of our business to know, everyone has a right to privacy, simply the result is there and heads explode.
Yet you were once young, a child even.
How does a child become a man like you ?
When you see a child, do you ever think that he could become a man like you ?
Do you know that you could search and search again, in the deepest, darkest corners of your mind, search until the end of your life without finding justification for that ?
Tell me, do you know that ?
Yes, you know it but there is only one place you say, one place for each person. Mine, you say again, is that one, not another, this place, this place was for me, reserved, don't touch, it's not by chance, it's me, we have to do things, and this place, that place that I hold and makes heads explode, I was lead to it, every instant, every hour, days, years, made, designed for that, and things too, the others, others' stories, others' lives, their instants and their hours, for a long time, the instants and the hours all work so that things come to that, me in this place, water in a cement canal, no outlet, it was that or washing new cars as they came off the trains, without ever being able to buy one, a new car, you conclude.
But if water could spill out of the canal, no, not for you.
You, empty headed, elbows firmly planted, state of the art technique, absolute silence, holding your breath, on target, cross hairs, your finger, and the bullet flies, over there.
A fraction of time, again, but this one cannot possibly be rewound. What if the other knew, over there, the sea in winter, the texture of skin, the wind on
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Specificity and plasticity of cellular signalling networks
The signalling routes described previously are part of the dynamic systems whose components interact by molecular interactions and phosphorylation reactions.
Towards a semi-solid circuitry - The protein–protein interactions brought into play involve either modules specifically recognising phosphorylated tyrosine residues in a specific context, either by protein-rich sequences or lipids. These molecular assemblies which are like « Lego », enable a circuitry to be established where the idea of proximity between proteins seems to represent a principle as important as the passive diffusion of secondary messengers.
Cellular Specificity - One of the problems for this type of signalling is to understand how hundreds of different membrane receptors can generate specific cellular responses when there are relatively limited numbers of signaling pathways linking the membrane with the nucleus One solution to this problem resides in the fact that different specific signalling networks are used in a combinatorial way, each receptor utilizing a specific combination of « integrators ». Another possibility implies that the cellular response to a given receptor is dictated by the availability at the membrane level in the close environment of the receptor, of the components of different signaling pathways. This supposes that it is necessary to consider the existence of microdomains in the environment of the membrane and in which the traffic of proteins is limited. As has already been mentioned, the components found at the same « stages » of different signalling pathways have structural homologies but also very important functional homologies. In spite of this, we observe that each pathway is specific for a given stimulus (also the activation of the specific pathway of cellular stress will never make the cell proliferate).
Multiple combinations for specific responses Beyond this specific linear signalling from the membrane to the nucleus, it is clear that the majority of circuits are equipped with extraordinary plasticity. This property enables them to cooperate in a spatio-temporal way (MAP pathway JAK pathway) and also to activate multiple transcription factors whose simultaneous presence is necessary for the activity of numerous promoters.
Intensity of signals: notion of threshold - Conflicting observations have shown that according to the cell type, the same growth factors can induce either proliferation or differentiation. Thus, FGF ( fibroblast growth factor ) which is a powerful mitogen for numerous cell types, induces differentiation of a specific cell line ( PC12 cells). Another factor, EGF (epidermal growth factor) stimulates the proliferation of these cells. Overall, the two growth factors follow the same signalling pathways. However, a detailed analysis has enabled it to be shown that the difference observed in response to FGF is correlated with persistent activation of Ras-GTP AND MAP kinases which relocate in the nucleus for several hours. On the contrary, the proliferation of PC12 cells in response to EGF is correlated with an activation of Ras-GTP AND MAP kinases which remains localized in the cytoplasm. Thus, the modulation of the intensity and/or of the duration of the activation caused by two growth factors seems to represent an important component of the final cellular response. This concept highlights the effects of threshold, well known in developmental biology, where gradual variations in the concentration of ligand or that of a nuclear factor cause fundamental differences in gene expression.
Towards a multitude of signalling networks - The techniques of molecular biology have recently revealed the existence of new protein homologues of kinase proteins of the MAP kinase cascade. These results have enabled the elucidation of several parallel pathways of signal transduction which, by activating kinase proteins in a sequential way, function in a manner analogous to the classic mitogenic pathway.These types of signalling modules were set up very early in the evolutionary process since they exist in yeast. It should be noted that the MAP kinase pathway is activated by the majority of growth factors and plays a role in cellular proliferation and activation of other pathways. This is observed in response to factors which « stress » the cell, such as ultraviolet rays, thermal shocks, changes in osmolarity or the exposure to inhibitors of protein synthesis.