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emisabella2007-blog · 5 years

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(Image caption: The researchers tracked the development of stem cells using so-called confetti reporters. © Helmholtz Zentrum München)

Brain Confetti - Why our Sense of Smell Declines in Old Age

As mammals age, their sense of smell deteriorates. In a study published in the journal ‘Cell Reports’, an interdisciplinary research team at Helmholtz Zentrum München and the University Medical Centre Mainz investigated why this is the case. For their study, the researchers tracked the development of stem cells in the brains of mice using what are known as confetti reporters. They then analysed the complex data obtained using intelligent algorithms.

In mammals, generation of new neurons (neurogenesis) is mainly limited to early childhood and occurs in adulthood only in a few regions of the forebrain. One such exception is olfactory neurons, which develop from stem cells via several intermediate stages. “The production of these neurons diminishes with advancing age. In our recent study we wanted to find out the cellular basis and what role stem cells play in the process,” says Dr. Carsten Marr, explaining the approach. He is a research group leader at the Institute of Computational Biology (ICB) of Helmholtz Zentrum München.

To shed light on this question, an interdisciplinary team of experts from the Helmholtz Zentrum München was formed that included the mathematicians Lisa Bast and Carsten Marr as well as stem cell researchers Dr. Filippo Calzolari (now Institute of Physiological Chemistry at the University Mainz) and Professor Jovica Ninkovic. “Our approach utilised what are known as confetti reporters to perform lineage tracing: In mouse brains, we induced individual stem cells and all their descendants – called clones − to light up in a specific colour”, says Filippo Calzolari. In this way, the scientists could distinguish clones over time by the different colours that give the technique its name. “In the next step, we compared clones found in young and older mice to find out what contribution individual stem cells and intermediates make to the neurogenesis of mature olfactory cells”, Calzolari adds.

Connect the Dots

However, systematic analysis of these images proved nearly impossible for humans, in that the available data were extremely heterogeneous, making a comparison of young and old brains difficult. Here the expertise of Carsten Marr and his team came into play. They are specialists in the quantification of single-cell dynamics, i.e. the study of which and how many cells of a large population make which cell fate decisions. To do so, the researchers use artificial intelligence methods, develop mathematical models and deduce algorithms to help analyse the image data.

“We compared the confetti measurements with several mathematical models of neurogenesis,” explains Lisa Bast. “We found that the ability of self-renewal declines in old age, especially in certain intermediate stages called transit amplifying progenitors.” In addition, the analysis showed that asymmetric cell division and quiescence of stem cells increased in older mice. “That means that fewer cells differentiate into olfactory cells in old age as they tend to remain in the stem cell pool and become less active. Therefore, the production comes to a halt”, says Jovica Ninkovic. The work is the first in which scientists have been able to quantitatively describe the behaviour of neural stem cells in the living mammalian brain using a mathematical model.

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emisabella2007-blog · 5 years

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this is so melancholic and pretty.

The raven

Once upon a midnight dreary, while I pondered, weak and weary,

Over many a quaint and curious volume of forgotten lore—

While I nodded, nearly napping, suddenly there came a tapping,

As of some one gently rapping, rapping at my chamber door—

"'Tis some visitor," I muttered, "tapping at my chamber door—

Only this and nothing more."

Ah, distinctly I remember it was in the bleak December;

And each separate dying ember wrought its ghost upon the floor.

Eagerly I wished the morrow;—vainly I had sought to borrow

From my books surcease of sorrow—sorrow for the lost Lenore—

For the rare and radiant maiden whom the angels name Lenore—

Nameless here for evermore.

And the silken, sad, uncertain rustling of each purple curtain

Thrilled me—filled me with fantastic terrors never felt before;

So that now, to still the beating of my heart, I stood repeating,

"'Tis some visitor entreating entrance at my chamber door—

Some late visitor entreating entrance at my chamber door;—

This it is and nothing more."

Presently my soul grew stronger; hesitating then no longer,

"Sir," said I, "or Madam, truly your forgiveness I implore;

But the fact is I was napping, and so gently you came rapping,

And so faintly you came tapping, tapping at my chamber door,

That I scarce was sure I heard you"—here I opened wide the door;—

Darkness there and nothing more.

Deep into that darkness peering, long I stood there wondering, fearing,

Doubting, dreaming dreams no mortal ever dared to dream before;

But the silence was unbroken, and the stillness gave no token,

And the only word there spoken was the whispered word, "Lenore?"

This I whispered, and an echo murmured back the word, "Lenore!"—

Merely this and nothing more.

Back into the chamber turning, all my soul within me burning,

Soon again I heard a tapping somewhat louder than before.

"Surely," said I, "surely that is something at my window lattice;

Let me see, then, what thereat is, and this mystery explore—

Let my heart be still a moment and this mystery explore;—

'Tis the wind and nothing more!"

Open here I flung the shutter, when, with many a flirt and flutter,

In there stepped a stately Raven of the saintly days of yore;

Not the least obeisance made he; not a minute stopped or stayed he;

But, with mien of lord or lady, perched above my chamber door—

Perched upon a bust of Pallas just above my chamber door—

Perched, and sat, and nothing more.

Then this ebony bird beguiling my sad fancy into smiling,

By the grave and stern decorum of the countenance it wore,

"Though thy crest be shorn and shaven, thou," I said, "art sure no craven,

Ghastly grim and ancient Raven wandering from the Nightly shore—

Tell me what thy lordly name is on the Night's Plutonian shore!"

Quoth the Raven "Nevermore."

Much I marvelled this ungainly fowl to hear discourse so plainly,

Though its answer little meaning—little relevancy bore;

For we cannot help agreeing that no living human being

Ever yet was blest with seeing bird above his chamber door—

Bird or beast upon the sculptured bust above his chamber door,

With such name as "Nevermore."

But the Raven, sitting lonely on the placid bust, spoke only

That one word, as if his soul in that one word he did outpour.

Nothing further then he uttered—not a feather then he fluttered—

Till I scarcely more than muttered "Other friends have flown before—

On the morrow he will leave me, as my hopes have flown before."

Then the bird said "Nevermore."

Startled at the stillness broken by reply so aptly spoken,

"Doubtless," said I, "what it utters is its only stock and store

Caught from some unhappy master whom unmerciful Disaster

Followed fast and followed faster till his songs one burden bore—

Till the dirges of his Hope that melancholy burden bore

Of 'Never—nevermore.'"

But the Raven still beguiling my sad fancy into smiling,

Straight I wheeled a cushioned seat in front of bird, and bust and door;

Then, upon the velvet sinking, I betook myself to linking

Fancy unto fancy, thinking what this ominous bird of yore—

What this grim, ungainly, ghastly, gaunt and ominous bird of yore

Meant in croaking "Nevermore."

This I sat engaged in guessing, but no syllable expressing

To the fowl whose fiery eyes now burned into my bosom's core;

This and more I sat divining, with my head at ease reclining

On the cushion's velvet lining that the lamp-light gloated o'er,

But whose velvet violet lining with the lamp-light gloating o'er,

She shall press, ah, nevermore!

Then, methought, the air grew denser, perfumed from an unseen censer

Swung by Seraphim whose foot-falls tinkled on the tufted floor.

"Wretch," I cried, "thy God hath lent thee—by these angels he hath sent thee

Respite—respite and nepenthe, from thy memories of Lenore;

Quaff, oh quaff this kind nepenthe and forget this lost Lenore!"

Quoth the Raven "Nevermore."

"Prophet!" said I, "thing of evil!—prophet still, if bird or devil!—

Whether Tempter sent, or whether tempest tossed thee here ashore,

Desolate yet all undaunted, on this desert land enchanted—

On this home by Horror haunted—tell me truly, I implore—

Is there—is there balm in Gilead?—tell me—tell me, I implore!"

Quoth the Raven "Nevermore."

"Prophet!" said I, "thing of evil—prophet still, if bird or devil!

By that Heaven that bends above us—by that God we both adore—

Tell this soul with sorrow laden if, within the distant Aidenn,

It shall clasp a sainted maiden whom the angels name Lenore—

Clasp a rare and radiant maiden whom the angels name Lenore."

Quoth the Raven "Nevermore."

"Be that word our sign in parting, bird or fiend!" I shrieked, upstarting—

"Get thee back into the tempest and the Night's Plutonian shore!

Leave no black plume as a token of that lie thy soul hath spoken!

Leave my loneliness unbroken!—quit the bust above my door!

Take thy beak from out my heart, and take thy form from off my door!"

Quoth the Raven "Nevermore."

And the Raven, never flitting, still is sitting, stillis sitting

On the pallid bust of Pallas just above my chamber door;

And his eyes have all the seeming of a demon's that is dreaming,

And the lamp-light o'er him streaming throws his shadow on the floor;

And my soul from out that shadow that lies floating on the floor

Shall be lifted—nevermore!

-Edgar Allan Poe

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