transmembrane

Story time

When I was young (17) and just starting to explore my gender identity I made the same foolish mistakes many people do. I was in a rush to stop using an ace bandage to bind and bought a binder from Amazon, a horrible idea. It was a tight fit and not made for someone of my build but instead of returning it I kept wearing it. I wore it for almost a year and rarely ever took it off or loosened it from the tightest setting. I see post of people sharing their stories about binder dangers and such but I didn’t listen.

Over the next year my health slowly failed me. First it was just hard to breath but since I have life long bronchitis I didn’t think much of it. Then my ribs began to hurt but since I was hit by a car almost 3 years ago I didn’t think much of it. It wasn’t till my heart started giving out that I took notice. Ever beat of it hurt and sometimes my chest would light up with pain as my heart fluttered. It was horrible. It got to the point where I thought I was actually dying and I my boyfriend wanted to take me to the hospital. At that point I finally took the bloody thing off but it was to late the damage was done. I can no longer wear a binder. The one I own and wear casually is far too big and does nothing in terms of compression I only wear it as an undershirt and just for the comforting feeling of knowing I’m wearing a binder of sorts but it does nothing to stop my dysphoria. But if I had worn that old binder another week or two i wouldn’t of woken up again.

GPCR signalling. Here are three examples of transmembrane signalling through G-protein-coupled receptors, with a little bit on their specific modes of regulation.

Adrenergic receptors couple to heterotrimeric G-proteins, which can be either stimulatory or inhibitory on adenylate cyclase, depending on the exact receptor: beta ARs stimulate AC; alpha ARs inhibit it. AC makes cAMP, the secondary messenger. cAMP binds protein kinase A, causing dissociation of its regulatory subunits and activation of the enzyme. cAMP is degraded to AMP by action of phosphodiesterase. Receptors are homologously desensitised by action of beta AR kinase, which phosphorylates cryptic phosphorylation sites on beta AR when adrenaline is bound. They are heterologously desensitised by downstream kinases which are only on when PKA is active.

The thrombin receptor is activated by N-terminal cleavage by thrombin. This reveals a TRAP sequence in the receptor, which acts as its own ligand. Phospholipase C beta is activated through a heterotrimeric G protein. (Note that phospholipate C gamma is activated through receptor tyrosine kinases.) PLC beta makes IP3, which releases calcium ions from the SR, ER, and/or cell exterior. Calcium ions activate protein kinase C. Calcium is removed from the cell by SERCA and PMCA ATPase calcium pumps.

The rhodopsin receptor in light-sensitive rod cells contains retinal, which undergoes a cis/trans isomerisation on incident light. Transducin carries the signal to phosphodiesterase, which extinguishes the second messenger cGMP. Loss of cGMP causes closure of cGMP-gated ion channels and stops calcium and sodium ion influx. This stops glutamate release, which allows the membrane to hyperpolarise, delivering the signal to the bipolar cell. Recoverin modulates the activity of guanylyl cyclase, which makes cGMP, by responding to the cellular calcium level. This allows the signal pathway to work in a range of ambient light conditions.

Abbreviations: Adr = adrenaline; GPCR = G-protein-coupled receptor; AR = adrenergic receptor; G = G-protein; AC = adenylate cyclase; ATP = adenosine triphosphate; cAMP = cyclic adenosine monophosphate; reg = regulatory subunit; cat = catalytic subunit; PKA = protein kinase A; beta ARK = beta adrenergic receptor kinase; Thr = thrombin; TRAP = thrombin receptor activatory peptide; PLC = phospholipase C; PIP2 = phosphatidylinositol 4,5-bisphosphate; IP3 = inositol 1,4,5-trisphosphate; DAG = diacylglycerol; SR = sarcoplasmic reticulum; ER = endoplasmic reticulum; PKC = protein kinase C; h = Planck’s constant; nu = frequency of light; PDE = phosphodiesterase; GC = guanylyl cyclase; GTP = guanosine triphosphate; cGMP = cyclic guanosine monophosphate; GMP = guanosine monophosphate; Glu = glutamate.


Signalling through G-protein-coupled receptors von Ayraethazide ist lizenziert unter einer Creative Commons Namensnennung - Weitergabe unter gleichen Bedingungen 4.0 International Lizenz.

My twin just posted on my Facebook timeline that she accepts that I want to be a boy and that I identify myself as a boy and called me by my “new” name and she loves having a twin brother and she wishes the best for me and will always be proud of me I’m actually crying that you sister. I love you

Action waves in the brain

A new theoretical model describes the nervous impulse as an electromechanical wave

Two researchers from Princeton University have developed a theoretical model describing the nervous impulse as an electromechanical wave that travels along nerve fibres, explaining curious experimental observations and challenging basic assumptions about how the brain works. The mechanism of the nervous impulse was made clear in a series of experiments carried out by Alan Hodgkin and Andrew Huxley from the late 1930s onwards. They prepared segments of giant squid axon, placed them in salt water solution, and then impaled them with microelectrodes, with which they could both inject electrical current into the fibre and record its voltage. This enabled them to control the voltage across the membrane and also measure the movements of current responsible for producing the impulse. Resting nerve cells have a lower concentration of sodium ions, and a higher concentration of potassium ions, than the spaces surrounding them, so that the inside of the membrane is negatively charged with respect to the outside. This transmembrane voltage is called the resting potential; most nerve cells have a resting potential of about -70 millivolts. Hodgkin and Huxley discovered that the nervous impulse is caused by the flow of sodium ions into the cell, followed almost immediately by the flow of potassium ions out. The ions move in and out through channel proteins that traverse the membrane, and open briefly in response to changes in membrane voltage, allowing first one ion species in, then the other out, in just one thousandth of a second. The influx of sodium ions reverses the transmembrane voltage, but then the potassium ion efflux quickly reverts it to its resting state. Hence, neuroscientists refer to nervous impulses as action potentials.

(via Action waves in the brain | Science | The Guardian)

An overview of two signal transduction pathways involving insulin: insulin release in response to rising blood glucose level; and the action of insulin to release GluT4 to lower blood glucose levels.

The response of β cells to high glucose is by oscillating calcium levels in the β cell, the islet, and the entire pancreas. It is thought that by oscillating, the cells do not desensitise to the signal of high glucose level.

The action of insulin is to translocate GluT4 receptors to the plasma membrane to increase uptake of glucose into the cell. This is done by an PIP3 signalling pathway. There also exists a PIP3-independent pathway, but this isn’t so well understood.


Insulin signalling by Ayraethazide is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

My twin just posted on my Facebook timeline that she accepts that I want to be a boy and that I identify myself as a boy and called me by my “new” name and she loves having a twin brother and she wishes the best for me and will always be proud of me I’m actually crying that you sister. I love you

[ Authors ]
Markus Basan, Timon Idema, Martin Lenz, Jean-François Joanny, Thomas Risler
[ Abstract ]
Contact inhibition is the process by which cells switch from a motile growing state to a passive and stabilized state upon touching their neighbors. When two cells touch, an adhesion link is created between them by means of transmembrane E-cadherin proteins. Simultaneously, their actin filaments stop polymerizing in the direction perpendicular to the membrane and reorganize to create an apical belt that colocalizes with the adhesion links. Here, we propose a detailed quantitative model of the role of the cytoplasmic $\beta$-catenin and $\alpha$-catenin proteins in this process, treated as a reaction-diffusion system. Upon cell-cell contact, the concentration in $\alpha$-catenin dimers increases, inhibiting actin branching and thereby reducing cellular motility and expansion pressure. This model provides a mechanism for contact inhibition that could explain previously unrelated experimental findings on the role played by E-cadherin, $\beta$-catenin and $\alpha$-catenin in the cellular phenotype and in tumorigenesis. In particular, we address the effect of a knockout of the adenomatous polyposis coli tumor suppressor gene. Potential direct tests of our model are discussed.

C-type Lectin Receptors

aka CLRs

they are transmembrane receptors 

a type of carbohydrate-bindingprotein domainknown as a lectin.[2]The C-type designation is from their requirement for calcium for binding.[3]Proteins that contain C-type lectin domains have a diverse range of functions including cell-cell adhesion, immune response to pathogens and apoptosis

they help to catch the lymphocytes, macrophages and etc on the walls of the endothelial cells on the inside of blood vessel and then cause them to adhere to then eventually go through the endothelial wall and to the site of infection. 

Molecular Structure, Function, and Assembly of the ATP Synthases: International Seminar free ebook ,

Molecular Structure, Function, and Assembly of the ATP Synthases: International Seminar

<p>English | 1989 | ISBN: 1461278821 | PDF | pages: 271 | 6,9 mb<br /> <br /> In recent years, the ATP synthase (H+ATPase, FoFrATPase) has been the subject of intensive IDvestigations in many laboratories. The major reason for this lies in the fact that this enzyme complex catalyses one of the most important reactions in living cells, namely the synthesis of ATP utilizing the energy from an electrochemical transmembrane H+ gradient, generated by the cellular respiratory chain or by the light reactions of photosynthetic organisms. The mechanism by which the H+ motive force is utilized to drive the synthesis of ATP is one of the major unsolved problems in biochemistry. Thus, the fundamental information concerning the-molecular structure and the mechanism of assembly of the ATP synthase is of major significance in cell biology. A seminar/workshop on the Molecular Structure, Function and Assembly of the ATP synthases was held in April, 1987 at the EastWest Center, University of Hawaii, Honolulu, Hawaii, to promote exchange of information between laboratories actively engaged in the study of the A TP synthases, and to provide a forum for discussion and coordination of data derived from molecular, genetic and biochemical approaches used in different laboratories. This volume summarizes the result of the seminar/workshop, in the form of a collection of papers presented at the meeting, and provides an overvIew of current work in this rapidly progressing area of research.</p>

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Intravenous immunoglobulin (IVIg) dampens neuronal toll-like receptor-mediated responses in ischemia.

Intravenous immunoglobulin (IVIg) dampens neuronal toll-like receptor-mediated responses in ischemia.

J Neuroinflammation. 2015 Apr 15;12(1):73

Authors: Lok KZ, Basta M, Manzanero S, Arumugam TV

Abstract
BACKGROUND: Ischemic stroke causes a high rate of deaths and permanent neurological damage in survivors. Ischemic stroke triggers the release of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1), which activate toll-like receptors (TLRs) and receptor for advanced glycation endproducts (RAGE) in the affected area, leading to an exaggerated inflammatory response and cell death. Both TLRs and RAGE are transmembrane pattern recognition receptors (PRRs) that have been shown to contribute to ischemic stroke-induced brain injury. Intravenous immunoglobulin (IVIg) preparations obtained by fractionating human blood plasma are increasingly being used as an effective therapeutic agent in the treatment of several inflammatory diseases. Its use as a potential therapeutic agent for treatment of stroke has been proposed, but little is known about the direct neuroprotective mechanisms of IVIg. We therefore investigate whether IVIg exerts its beneficial effects on the outcome of neuronal injury by modulating HMGB1-induced TLR and RAGE expressions and activations.
METHODS: Primary cortical neurons were subjected to glucose deprivation or oxygen and glucose deprivation conditions and treated with IVIg and recombinant HMGB1. C57/BL6J mice were subjected to middle cerebral artery occlusion, followed by reperfusion, and IVIg was administered intravenously 3 h after the start of reperfusion. Expression of TLRs, RAGE and downstream signalling proteins in neurons and brain tissues were evaluated by immunoblot.
RESULTS: Treatment of cultured neurons with IVIg reduced simulated ischemia-induced TLR2, TLR4, TLR8 and RAGE expressions, pro-apoptotic caspase-3 cleavage and phosphorylation of the cell death-associated kinases such as c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) as well as the p65 subunit of nuclear factor kappa B (NF-κB). These results were recapitulated in an in vivo model of stroke. IVIg treatment also upregulated the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) in cortical neurons under ischemic conditions. Finally, IVIg protected neurons against HMGB1-induced neuronal cell death by modulating TLR and RAGE expressions and signalling pathways.
CONCLUSIONS: Taken together, these results provide a rationale for the potential use of IVIg to target inappropriately activated components of the innate immune system following ischemic stroke.

PMID: 25886362 [PubMed - as supplied by publisher]



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peer review FGFR3 Cause the Most Common Genetic Form of Dwarfism, Achondroplasia

peer review FGFR3 Cause the Most Common Genetic Form of Dwarfism, Achondroplasia

peer review FGFR3 Cause the Most Common Genetic Form of Dwarfism, Achondroplasia
Mutations in the Transmembrane Domain of FGFR3 Cause the Most Common Genetic Form of Dwarfism, Achondroplasia
Rita Shiang,*t Leslie M. Thompson,“t Ya-Zhen Zhu,’ Deanna M. Church,’ Thomas J. Fielder,’ Maureen Bocian,* Sara T. Winokur,’ and John J. Wasmuth’*§ l Department of Biological Chemistry f Department of…

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Protein Structure Prediction: Methods and Protocols free ebook ,

Protein Structure Prediction: Methods and Protocols

<p>World-class investigators detail their most successful methods&mdash;and the theory behind them&mdash;for delineating the shape, form, and function of proteins. The protocols range from basic to advanced and include sequence alignment, the prediction of transmembrane protein structure, and the development of suitable folding potentials. There are also techniques for receptor site prediction, the identification of motifs and domains, the comparative modeling of proteins, the docking of peptides and ligands, and ab initio approaches to protein loop and side-chain prediction.&nbsp;</p>

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Ofatumumab for the treatment of chronic lymphocytic leukemia.

Ofatumumab for the treatment of chronic lymphocytic leukemia.

Expert Rev Hematol. 2015 Apr 16;:1-8

Authors: Grosicki S

Abstract
Ofatumumab is a humanized second-generation monoclonal antibody with the affinity to a transmembrane protein CD20. In in vitro studies, it exhibits higher efficacy towards chronic lymphocytic leukemia (CLL) cells compared to rituximab, and it can be explained by the fact that its epitope on the target CD20 protein is different as it includes a short as well as a long extracellular loop. Ofatumumab is especially effective in the lysis of CD20 low-expressing lymphocytes that are often observed in CLL. Currently, this agent is approved for the treatment of fludarabine- and alemtuzumab-refractory CLL. There are also promising preliminary results of the studies that indicate benefits of ofatumumab not only in patients with bulky/fludarabine-refractory CLL but also in treatment-naive patients with CLL with contraindications to fludarabine and in maintenance treatment.

PMID: 25882470 [PubMed - as supplied by publisher]



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