morphogen

In the 1960s Lewis Wolpert devised a model to describe basic pattern formation in development. This model was known as the French Flag Model. It is a useful model as the formation of the three colours of the flag can be used to understand the formation of the three germ layers present in embryos. The first thing to note is that no matter what size the flag, it still maintains the same basic pattern. One third will be blue, one third white and one third red, in that order, along one axis. Second, in a line of cells with defined boundaries, each cell has the potential to differentiate into a blue, white or red cell. Wolpert set out to try and explain the mechanism behind how the cells know which colour they should differentiate into. Cells must receive some form of information to deduce where they are situated within the flag model, and then according to their genetic program interpret this information by differentiating into one of the three cell types.

There are two stages of pattern formation, first the cells have to establish their position and then they have to interpret this information. The fact that a clear distinction has been made between these two processes implies that there is no set relation between a cells position and the how it interprets the information it is sent. Thus in a different set of parameters these cells are capable of producing a completely different pattern. Wolpert devised a simple way to explain how a cell establishes its orientation, based on the gradient of a substance. If the concentration of a chemical substance decreases from one end of the flag to the other a cell could work out where exactly it was positioned in relation to the boundaries. This would be due to the amount of chemical substance the cell received. This Chemical substance is known as a Morphogen. Morphogens are described as substances in embryonic tissues that form a concentration gradient and influences morphogenesis.

In the French Flag Model we assume the concentration is greatest at one end and lowest at the opposite end and so the morphogen diffuses at a constant rate down the line of cells. It is also safe to assume that the cells respond to threshold concentrations of the morphogen. Above a particular concentration threshold blue cells will form, whilst below this concentration threshold but above another, white cells will form. Below both these concentration thresholds red cells form creating the complete French Flag pattern.

The threshold could be one of two things; the specific amount of morphogen need to bind to receptors on the cells in order to activate intracellular signalling cascades, or differing concentrations of transcription factors, which are required to activate certain genes within the cells.

This model highlights two important features of morphogenesis. Firstly, even if the length of the line of cells varies, patterns will still from in the correct proportions, as long as defined boundaries are present with constant but differing concentrations of morphogen at either end. Secondly the pattern could regenerate itself to the complete original form after being cut in half, as long as the defined boundaries and concentrations were re-established. 

[Adapted from Wolpert Principles of developmental Biology]



Retinoic acid gradient visualized for the first time in an embryo

Researchers from the RIKEN Brain Science Institute in Japan report a new technique that allows them to visualize the distribution of retinoic acid in a live zebrafish embryo, in real-time. This technique enabled them to observe two concentration gradients going in opposing directions along the head-to-tail axis of the embryo, thus providing long-awaited evidence that retinoic acid is a morphogen.

A morphogen is a substance governing the pattern of tissue development in the process of morphogenesis, and the positions of the various specialized cell types within a tissue.

Since morphogens diffuse through the tissues of an embryo during early development, concentration gradients are set up. These gradients drive the process of differentiation of unspecialised (stem) cells into different cell types, ultimately forming all the tissues and organs of the body.

Sonic Hedgehog

Arguably among the most interesting/badass things I‘ve come across while studying is the Sonic Hedgehog (Shh) morphogen. Not only is it a major player in organogenesis, but it also has the GREATEST name.

If the MCAT doesn’t test me on this I am going to be so upset.

Like, very upset.

Image: Hall, T.M., Porter, J.A., Beachy, P.A., Leahy, D.J. A potential catalytic site revealed by the 1.7-A crystal structure of the amino-terminal signalling domain of hedgehog protein.

icecreamandwhiskey asked:

could you do the oc character profile for astrid rodgers if you haven't already?

Full Name: Astrid Elianne Bianca Rodgers
Gender and Sexuality: Cis female, pan
Pronouns: She/hers
Ethnicity/Species: ¾ Human (mixed heritage, mostly North American Anglo and Western European), ¼ Centaurian
Birthplace and Birthdate: Earth, Chicago; January 7, 2340 (stardate 17018.9)
Guilty Pleasures: Pasta, vintage holonovels
Phobias: Death by explosive decompression, sudden-onset gluten intolerance, bees
What They Would Be Famous For: Developing a viral agonist designed to target and temporarily destabilize a Founder’s morphogenic enzymes, if she can ever get the RNA to resequence properly. Also for getting a gold medal at The Sector 001 All-Species Pasta-Eating Competition.
What They Would Get Arrested For: Putting an all-you-can-eat Italian buffet out of business singlehandedly. Also war crimes, if the Dominion had a say.
OC You Ship Them With: Elizabeth O'Clare
OC Most Likely To Murder Them: Elizabeth O'Clare
Favorite Movie/Book Holonovel Genre: Terran period dramas, specifically those focused around Western culture from 1500 to 1900 AD
Least Favorite Movie/Book Holonovel Cliche: Worst Aid and Instant Drama (Just Add Tracheotomy)
Talents and/or Powers: Eidetic memory, can tie a cherry stem into a double helix with her tongue, can eat her weight in pasta (possibly literally)
Why Someone Might Love Them: When she loves someone, she loves with all her being; she will always go above and beyond to help and protect the people close to her.
Why Someone Might Hate Them: She is literally always thinking about work, no matter what else is going on. She’s a champion multitasker, but that does mean she sometimes seems a bit distracted.
How They Change: 

Why You Love Them: Smarts. Sass. Spaghetti.

Superfluidity:

Kundalini awakenings are associated with a tumescence of the “blueprint” of the bodymind. Within this amplified morphogenic field the cells set about reorganizing themselves to convey the upsurge of consciousness or Spirit. During this period of increased spiritual field there is greater vibration, rhythm, correspondence and communication between atoms, cells and organs. This is tacitly undeniable to anyone going through a kundalini awakening. In fact it is this intensification of sensation and function coupled with the abrupt breakthrough into expanded states of awareness that is most disturbing about the experience of kundalini, for we are so used to living in the half-death of collective conditioning. This higher integration is concurrent with increased psychic, extrasensory abilities, such that as we integrate our internal organism, we delve more deeply into the collective interiors of the human race and the globe. Through the elevation of the personal we access the transpersonal and tune into the Global Brain.

A good word to describe this amplified of being during metamorphosis is superfluid. We can assume that cell membranes become more permeable, including the blood brain barrier. Polarities become more pronounced, increasing the ion exchange and current flow between them. The fields of the organs, plexuses, brain and the body must be greatly expanded and magnified. There must be increased nutrient and waste product exchange coupled with greatly increased enzymatic action and oxygen usage. ATP and glucose metabolism must be at an all time high, as on every level we become more “alive and awake.”
The cavity within the center of the spinal column itself both makes and contains cerebrospinal fluid. The super-charged body and expanded heart-field must act like a cyclotron on the spine. The cerebrospinal fluid probably becomes supercharged with ions and laden with neuropeptides, during awakening, accumulating to crescendo point with the inner-conjunctions. At the height of the awakening I imagine that all the cerebrospinal fluid becomes Amrita, or nectar of the Gods as it is saturated with ions, endorphins, glutamate, NO and various neurotransmitters.
Along with circulation of this fluid up the spine and around the brain cavities, the increased permeability between the cerebrospinal fluid and the blood following histamine release, could allow the elixir to flow within the bloodstream as well. After it bathes the brain and spine CSF is reabsorbed into venus sinus blood via arachnoid villi projecting into the superior sagittal sinus.
The amrita in the blood then would hyper-relax the entire bodymind and thereby energy is conserved and accumulated for the inner-conjunction. Supplanting the normal laborious flow of energy through nervous tissue this “spark,” reminiscent of lightning, zaps many volts through the organism. Like lightning the spark could comprise of wave pulses of energy between the positive and negative poles, but moving so fast as to be perceived as one ongoing current.
Changing the voltage across a neuron membrane can open channels that allow various kinds of ions (including calcium ions) to enter and leave the neuron. The membrane’s conductivity to ions is voltage dependent. The movement of ions (which constitutes an electric current) cause further changes in the membrane and so on–thus perpetuating a superfluid, supercharged state. There are references in the texts, especially those on Tantric Kriya Yoga on the magnetizing and ionizing of the cerebrospinal fluid (CSF). This ionized fluid then awakens and transforms the brain and broadens the range of conscious and sensory prehension.
Apparently breathing itself ionizes the CSF. According to Ipsalu Tantric Kriya Yoga a technique called the Cobra Breath pulls magnetic energy into the spine, ionizing the spinal fluid and allowing the kundalini to rise, bathing the brain in magnetized fluid and transforming consciousness. Most breathing techniques will aid in elevating and integrating consciousness.
Besides changes in the cell receptors other changes in the cell membranes would fuel the conflagration of superfluidity. Changes in the physio-chemical and EMF environment of the cell, along with increased temperature, hydrostatic pressure and osmotic pressure would lead to changes in the lipid composition of the cell membrane. This change in the cell membrane would in turn contribute to an upsurge in the rate/activity of cellular energy generation and metabolism. Thus creating a feedback relationship that would maintain hyperactivation until the resources necessary to perpetuate this contagion are depleted. If however lifestyle is such to maintain high cellular energy levels without damage to the cells themselves, then the alchemy of transmutation could proceed at a quickened pace indefinitely. By feeding the life harmonic - we feed our spiritual attainment.

Source:
Biology of Kundalini
Exploring the Fire of Life
Bok 1; Pg 285, Pg 286
Author: Jana Dixon

Surface Modification of 3D-Printed Porous Scaffolds via Mussel-Inspired Polydopamine and Effective Immobilization of rhBMP-2 to Promote Osteogenic Differentiation for Bone Tissue Engineering

Publication date: Available online 8 February 2016Source:Acta Biomaterialia
Author(s): Sang Jin Lee, Donghyun Lee, Taek Rim Yoon, Hyung Keun Kim, Ha Hyeon Jo, Ji Sun Park, Jun Hee Lee, Wan Doo Kim, Il Keun Kwon, Su A Park
For tissue engineering, a bio-porous scaffold which is applied to bone-tissue regeneration should provide the hydrophilicity for cell attachment as well as provide for the capability to bind a bioactive molecule such as a growth factor in order to improve cell differentiation. In this work, we prepared a three-dimensional (3D) printed polycaprolactone scaffold (PCLS) grafted with recombinant human bone morphogenic protein-2 (rhBMP2) attached via polydopamine (DOPA) chemistry. The DOPA coated PCL scaffold was characterized by contact angle, water uptake, and x-ray photoelectron spectroscopy (XPS) in order to certify that the surface was successfully coated with DOPA. In order to test the loading and release of rhBMP2, we examined the release rate for 28 days. For the In-vitro cell study, pre-osteoblast MC3T3-E1 cells were seeded onto PCL scaffolds (PCLS), DOPA coated PCL scaffold (PCLSD), and scaffolds with varying concentrations of rhBMP2 grafted onto the PCLSD 100 and PCLSD 500 (100 ng/ml and 500 ng/ml loaded), respectively. These scaffolds were evaluated by cell proliferation, alkaline phosphatase activity, and real time polymerase chain reaction with immunochemistry in order to verify their osteogenic activity. Through these studies, we demonstrated that our fabricated scaffolds were well coated with DOPA as well as grafted with rhBMP2 at a quantity of 22.7 ± 5 ng when treatment with 100 ng/ml rhBMP2 and 153.3 ± 2.4 ng when treated with 500 ng/ml rhBMP2. This grafting enables rhBMP2 to be released in a sustained pattern. In the in-vitro results, the cell proliferation and an osteoconductivity of PCLSD 500 groups was greater than any other group. All of these results suggest that our manufactured 3D printed porous scaffold would be a useful construct for application to the bone tissue engineering field.Statement of SignificanceTissue-engineered scaffolds are not only extremely complex and cumbersome, but also use organic solvents which can negatively influence cellular function. Thus, a rapid, solvent-free method is necessary to improve scaffold generation. Recently, 3D printing such as a rapid prototyping technique has several benefits in that manufacturing is a simple process using computer aided design and scaffolds can be generated without using solvents. In this study, we designed a bio-active scaffold using a very simple and direct method to manufacture DOPAcoated 3D PCL porous scaffold grafted with rhBMP2 as a means to create bone-tissue regenerative scaffolds. To our knowledge, our approach can allow for the generation of scaffolds which possessed good properties for use as bone-tissue scaffolds.
Graphical abstract

Highlights

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Redefining the induction of periodontal tissue regeneration in primates by the osteogenic proteins of the transforming growth factor‐β supergene family http://www.medworm.com/index.php?rid=164557740&cid=d_11_11_f&fid=28245&url=http%3A%2F%2Fonlinelibrary.wiley.com%2Fresolve%2Fdoi%3FDOI%3D10.1111%252Fjre.12356 DDDENT.com International Social Dental Network

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Redefining the induction of periodontal tissue regeneration in primates by the osteogenic proteins of the transforming growth factor‐β supergene family

image

The molecular bases of periodontal tissue induction and regeneration are the osteogenic proteins of the transforming growth factor‐β (TGF‐β) supergene family. These morphogens act as soluble mediators for the induction of tissues morphogenesis sculpting the multicellular mineralized structures of the periodontal tissues with functionally oriented ligament fibers into newly formed cementum. Human TGF‐β3 (hTGF‐β3) in growth factor‐reduced Matrigel® matrix induces cementogenesis when implanted in class II mandibular furcation defects surgically prepared in the non‐human primate Chacma baboon, Papio ursinus. The newly formed periodontal ligament space is characterized by running fibers tightly attached to the cementoid surface penetrating as mineralized constructs within the n…

Signaling filopodia in vertebrate embryonic development

Abstract

Next to classical diffusion-based models, filopodia-like cellular protrusions have been proposed to mediate long range signaling events and morphogen gradient formation during communication between distant cells. An increasing wealth of data indicates that in spite of variable characteristics of signaling filopodia in different biological contexts, they represent a paradigm of intercellular crosstalk which is presently being unraveled in a growing literature. Here, we summarize recent advances in investigating the morphology, cellular basis and function of signaling filopodia, with focus on their role during embryonic development in vertebrates.

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2

so they leave running.

the two of them running, running full tilt out of the room, running through the sliding plexiglas doors as soon as they open and forward still. are they the only ones running? there’s nobody else here in the hallway except for them. they can hear a security guard’s walkie talkie going off somewhere in the distance ahead of them, loud insistent direction, please all security with block D clearance, report to the morphogenic engine chambers. andrew’s knees are shrieking at him already and they’re going to completely fucking hate him for this in the morning but he runs anyway. he’s running, and he’s turning his head and asking dale something like, “did they say what hope’s ppm was,” and dale makes a sound like he’s starting to open his mouth to answer, “he-” when the noises over the radio ahead of them warp into shouting and dale falters. they both do, stumbling over their own feet for half a second mid-run as the voice rips over the radio around the corner, loud like the person is shouting over
panic?

he’s panicking?

andrew’s swallowing hard at a strange lump of nothing in his throat, some invisible all in the base of his throat, and they’re running faster. they approach the corner and turn messily around it, and the source of the noise is on the floor in front of them, a walkie talkie laying discarded. flat on its back with its owner nowhere in sight. they stop dead and the thing on the floor crackles loudly to life again, a haze of strange squealing noise. people talking in quick fast stacatto voices, loud and openly nestled on the edge of a panic, and a man on the other end shouting directly into the microphone over a background chorus of a high, wavering electrical interference, ‘ALL BLOCK D CL–RD– TO —VAC- TE TH-

'R-P–T-,

'B—CK D STA-F-’

dale tries to scoop up the radio as they start up running again but drops it, fumbles trying to grab at it again, and then just leaves it. it begins shouting something frantical behind them as they pull further away. but the interference is too great, and they’ve already moved too far away to decipher it.

they sprint away from the hall where the radio’s fallen, onward, twisting through corridors and barreling down sets of metal stairs in dead silence except for their heavy breathing, their conjoined panting as they run and run in a winding path that is entirely too long - headed for the D block, for the morphogenic engine life pod chambers, where hope is, where andrew thinks he heard the man on the radio mention. instruction to go towards. fuck. fuck.
they reach a fork, and andrew banks left, in deeper towards the pods with dale following half a step behind, running until they reach and breach through the crash doors and come racing into the huge space of the black engine’s home, a globe hanging like an insect egg, drooping down from the blackness in a clutch somewhere underground. they’re stumbling in towards the center pods, an empty chair surrounded by flashing monitors, control panels, no people.
no one is here. the alarms on the engine and its dozens of screens are all going off in an empty room.
they’ve left. everyone’s left.

all at once, andrew realizes that coming here was a mistake
the room is empty. whatever decision pod staff made, they made it long before he and dale arrived. ten minutes too late. half a minute too late. everyone is long fucking gone. this was a mistake, and there is a sudden feversweat shooting to life along the gooseflesh at the back of andrew’s neck, a feeling like cold water rising through his body, like the hairs along his flesh are raising, lifting in anticipation of a lightning strike. the air cold and clammy around him. dewy, like early morning, home, with something lifting its shiny wet head up from the cold pre dawn ground on his lawn. the prior staff left for a reason and here they are, here andrew and dale are anyway and dale is finding the will in him to break his freeze and move forward for the first time in his dumb fucking life, dale is stumbling ahead towards hope’s pod and gawking at the monitor next to it and his voice is,

“it’s holy SHIT SIX HUNDRED THOUSAND PPM AND-”

a mistake to be here,
mistake,
a split second before billy hope’s body in the tank, his ragged half naked body skewered on rods and tubes tunneling down into his bones, into his airways and stomach and the secret place where his heart lay planted, before the muscles in billy hope’s body clench and arch him hard, with his mouth opening wide and

the air around the circular tank displaces, ripples, like glassy clear water distorted by a rock plummeting through it to the bottom, like the rising of a tremendous sudden heat, and

“-coming out,” someone in the room is speaking at dale but too quietly, the adrenaline and migraine pain pounding so thick and pressurized and dizzy in andrew’s brain that he has no idea whose voice it could be, like he’s watching someone else inhabiting his own body, making the noises for him in a slow motion slur,
“something’s,

"coming out-”

before hope’s mouth gapes wide around the tubes in his throat,
and there is a thunderclap blinding explosion of bathroom fluorescent lights and nauseous migraine visuals, drunken spinning humid air, a blinding sun and black birds singing the exact same hazing insectoid squeal that comes from behind the window in andrew’s quasi-hotel room, it floods the air blank inside the whole room, erases everything from under and around andrew’s body, blots out the world into a white space, into nothing.
into a holy nuclear light
. .

. .


.