SHARPENING

Role of CX3CR1/CX3CL1 axis in primary and secondary involvement of the nervous
system by cancer
Federica Marchesi a, Marco Locatelli b, Graziella Solinas a, Marco Erreni a,
Paola Allavena a, Alberto Mantovani a,c,⁎


CX3CL1 or Fractalkine is a peculiar chemokine that can exist either in a soluble form, like all the other chemokines, and as a cell membrane molecule.

CX3CL1 is one of the most expressed chemokines in the central nervous system, where it regulates the communication between neurons, glia and microglia. 

 Fig. 1. CX3CR1 in primary tumors of the nervous system and metastasis. Different tumors expressing CX3CR1 are represented, together with the organs or tissues which are the site of secondary localization. 

Fig. 2. Perineural invasion in pancreatic adenocarcinoma. 
(A) Histological section of pancreatic cancer (T) invading the perineural space (N, circled section).
Immunoreactivity with an anti-CX3CR1 depicts pancreatic tumor cells (magnification 40×).
(B) Schematic representation of some of the molecular mechanisms involved in perineural invasion. 
A nerve inside the pancreas developing a tumor is represented. 
Tumor cells adhere to neural cells, infiltrating the perineural space. 
Molecules involved in this interaction include the chemokine Fractalkine/Neurotactin (CX3CL1) expressed by neurons and its receptor CX3CR1 on tumor cells. 
Neurotropins secreted by neural and tumor cells sustain growth and survival of both intratumoral nerves and cancer cells.

INFECTIOUS AGENT

Presence of neutralizing antibodies to HSV were found in the serum of previously infected adults. Only individuals with neutralizing antibodies developed recurrent lesions. Remarkably, measles and rubella antibodies are associated with protection from subsequent episodes of the disease.

National Herpes Hotline 
(919) 361-8488

National Herpes Resource Center 
herpesnet@ashastd.org

 

One significant advance of our understanding of herpes infection was the detection of antigenic differences between HSV types. Already in 1968, antigenic and biologic differences between HSV-1 and HSV-2 were found by Nahmias and Dowdle. The observation was that HSV-1 was more frequently associated with nongenital infection whereas HSV-2 was associated with genital disease.

Infection of epithelial cells in the mucosal surface gives rise to productive replication, resulting in the production of progeny virions, which can spread to infect additional epithelial cells. Virus enters innervating sensory neurons, and nucleocapsids are transported to the neuronal cell body. The viral DNA is released into the neuronal nucleus and circularizes. Circular viral DNA persists in the neuronal cell nucleus, and the latency-associated transcript is expressed. b | Upon reactivation, viral lytic gene expression is initiated, and newly formed capsids are transported to the axonal termini. Infectious virus is released from the axon and infects epithelial cells, resulting in recurrent infection and virus shedding.
 

Oj, I suddenly was attacked by John Blund. Will ferociously continue tomorrow.

God natt, noapte buna, spakujna nocin and good night herpes wherever you are.

RESEARCH

Book tip of the day:
How Pathogenic Viruses work   - found on shelf in the office


Review Macrophages and cytokines in the early defence against herpes simplex virus - S. Ellermann-Eriksen:

HSV-1 and HSV-2 are old viruses, with a history of evolution shared with humans.
Thus, it is generally well-adapted viruses (thus), infecting many of us without doing much harm,
and with the capacity of hiding in our neurons for life. No harm.

Normally, the primary HSV infection is asymptomatic, and a crucial element (HSV infection or asymptomatic HSV infection?) in the early restriction of virus replication (asymptomatic infection crucial to restriction of virus replication by immune system - macrophages, cytokines, NK cells, nitric oxide?) and thus (thus?) avoidance of symptoms (avoidance - aha) from the infection is the concerted action of different arms of the innate immune response.

HSV infection is asymptomatic normally. Innate immune system arranges actions to make herpes infection asymptomatic, which benefits both host and virus. Virus and host - we live in forced symbiosis. Moderate is better (lagom är bäst)? There are multiple heros in the united universe, which exists.

Virus infection or innate immune system. I am confused. I need to think more.

PROGRESSIVE HERPES

Facts about Herpes you might not know:

• viral DNA  - at least 152 kbp
• capsid
• 162 capsomeres
• tegument - layer of proteins
• envelope
• glycosylated and non-glycosylated proteins, lipids and polyamines 

DNA

HSV-1 AND HSV-2  DNA contains covalently linked  components designated

• L  = LONG
• S =  SHORT

Each component is composed of unique sequences, U (L) and U (S).      

                 

Current studies show that these DNA encode at least 84 different polypeptides mapped in different regions.  

How does HSV infect a cell?

HSV attaches to the cell surface receptors, fuse its envelope to the plasma membrane and allow the de-enveloped capsid to be transported to the nuclear pores.
The DNA is released into the nucleus at the pore.
      

Scheme of infection compared in different viruses.

The key events in viral replication that occur in the nucleus include:

• transcription
• DNA synthesis
• capsid assembly
• DNA packaging
• envelopment

HSV envelopment and release

NO POPULATION

This is the last post I make about Flow Jo analysis, don't want to infect the blog with this too...

But what really is up with this program, why, why , why do you eat hours of my time like this!!

I am calling Flow Jo company as we speak! It is enough, I mean that's the least you can do Jo, to save the work I put into your space!

KNOW

Things you didn't know about fraktalkine (CX3CR1) but wish you did:

• Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice    --->  What?!?

• Association of Common Polymorphisms in the Fractalkine Receptor (CX3CR1) With Obesity.    

                 --> I am so off the sweets!

• CX3CR1/CX3CL1 axis negatively controls glioma cell invasion and is modulated by transforming growth factor-beta1.           -->  Oopsii!
• 
  

  The monocyte chemokine receptor CX3CR1 does not play a significant role in the pathogenesis of experimental autoimmune uveoretinitis (EAU).  --->    EAU in rats, mice, guinea pigs and monkeys is a prototypic T-cell mediated autoimmune disease that targets the neural retina and related tissues.

   

HERREGUD

Herpes did it again, it managed to infect even this blog!

(Herpes har ju lyckats igen, den har tom infekterat den här bloggen!)

Will buy some Acyclovir tomorrow to treat it with..

(Får köpa lite Acyclovir och smörja in den imorgon...)

I thought I saw some blisters on the layout!

(Jag tyckte väl att jag såg lite blåsor på layouten!)

DEATH

This is a fundamental problem for us, and no rational argument will help.

ITCHY

Does it show on the picutres exactly how itchy it is?
I mean the virus.
Always infection, impossible to cure and only treatable.
Viral breathing and thinking in every soul.
The smallest particle with the smallest genome outclevers everyone
and everything.
This is what they call evolution.
We are only messengers of the future which is ahead.
And soon very soon we will be replaced by semi-humans.
Finally.
Right now I would just like to be virus, so I can feel what it's
like to be successful, if only for a day, and because soon
we will all be dead.
And then it's too late to transform.
Or?

FEAUTY

The most beautiful picture of today.

FRAKTALKINE

A new class of membrane-bound chemokine with a CX₃C motif
J. Fernando Bazan^*, Kevin B. Bacon^†, Gary Hardiman^*, Wei Wang^†, Ken Soo^†, Devora Rossi^†, David R. Greaves^‡, Albert Zlotnik^† & Thomas J. Schall^†
Departments of^* Molecular Biology and ^† Immunology, DNAX Research Institute, 901 California Avenue, Palo Alto, California 94304, USA
^‡ Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK 




Chemokines direct the trafficking of white blood cells in immune surveillance, playing a key role in inflammatory and infectious diseases such as AIDS^1–5. 

All chemokines studied so far are secreted proteins of relative molecular mass 7K–15K and fall into three families that are defined by a cysteine signature motif: 

CXC, CC and C (refs 3, 6, 7), where C is a cysteine and X any amino-acid residue.

We report here the identification and characterization of a fourth human chemokine type, derived from non-haemopoietic cells and bearing a new CX₃C fingerprint. 


Unlike other chemokine types, the polypeptide chain of the human CX₃C chemokine is predicted to be part of a 373-aminoacid protein that carries the chemokine domain on top of an extended mucin-like stalk.

This molecule can exist in two forms: either membrane-anchored or as a shed 95K glycoprotein. The soluble CX₃C chemokine has potent chemoattractant activity for T cells and monocytes, and the cell-surface-bound protein, which is induced on activated primary endothelial cells, promotes strong adhesion of those leukocytes. 

The structure, biochemical features, tissue distribution and chromosomal localization of CX₃C chemokine all indicate that it represents a unique class of chemokine that may constitute part of the molecular control of leukocyte traffic at the endothelium.

MY RESEARCH ROAD

Sly Fox by Nas: Rap Music is Art

I will become the first rapper of herpes.
But not like that.
I will sing about HSV-2 specific CD8+ T cells,
chemokines and latency,
and how herpes lead the way to the brain,
and make us schizo.
Who knows maybe if you treat schizofrenic
people with Acyclovir they might recover.

Well, it's worth to think about.
I told you there must be a way to make herpes look good.


Again, thank you Mayowa for Sly!

GO SCHIZO WITH HERPES

I guess it is somewhat confusing to scroll down my post.
How can I fix this?

I am thinking of starting blog nr 2. My photoblog.
Or is variety good? Is it good to write a post title named
HERPES SIMPLEX VIRUS and then show pictures of sea?

I don't know. It seems luring to direct this blog into herpes.

Neatly organized posts about herpes molecules 1-50,000 swimming
through 1 billion nervous system synapses during a time
period of average 70 yrs. In millions of people.
I will try to fit it into one blog.

People suffering from the infection and/or schizofrenia
can comment my posts to get support.

How many blogs are there actually which are truly herpes-
specific?

How many herpes blogs combine infection with photography?

Finally how many herpes blogs combine latency with music,
dancing and fishing?


I think none: there is a need of more all-in-one herpes blogs.

I will start rapping about herpes as well.

Herpes is my middle name

On the third place of Google search of Fraktalkine. Not bad blogging.

Soon it will be on PubMed I hope.

Here are some more of fraktalkine then.

The CX3CL1 - Ligand for fraktalkine.

Fraktalkine search gave me also German 

Wikipedia hit of Structures of chemokines. Nice.

Now my lunch is over. Back to work.

This mouse mat from Dubai cost only 100,000 Dirham.

The cup is from Starbucks. And I use it for tea, embarrasing.

But who drinks that much coffee actually?

My dissertation coming up soon

The stairs in the conference hall where I will have
my dissertation in 2011.

One of the tables in the audience.

It will be written on the table:
Latent Lucia, Holy Olga and Katarina the Great came and
conquered.

We like

Söndag

Idag blir det trip till Saltholmen för fortsatt fiske.
Men först några ord om herpes.


The species has yielded at least one herpesvirus and frequently several diverse herpesviruses.
The number of herpesviruses in nature is exceeding the 130 herpesviruses identified to date.
In humans there are nine herpesviruses which have been isolated (maybe I will discover the tenth - oh if only I could!): HSV-2, HSV-2 (my HS's), HCMV, VZV and EBV and HHV-6a, HHV-6B, HHV-7 and HHV-8.
Others include for example: Cercopithecine herpesvirus 5 (African Green monkey cytomegalovirus), Cercopithecine herpesvirus 8 (Rhesus monkey cytomegalovirus), Cercopithecine herpesvirus10 (Rhesus leukocyte-associated HV strain 1), Cercopithecine herpesvirus 14 (African green monkey EBV-like HV).
Ateline herpesvirus 1 (Spider monkey HV), Cebine herpesvirus 1 (Capuchin HV (AL-5) ), Pongine herpesvirus 1 (Chimpanzee HV; pan HV), Pongine herpesvirus 2 (Orangutan HV), Pongine herpesvirus 3 (Gorilla HV).
Saimiriine herpesvirus 2 (Squirrel monkey HV, HV saimiri), Bovine herpesvirus 2 (Bovine mammillitis), Bubaline herpesvirus 5 (Water buffalo herpesvirus), Cervid herpesvirus 1 (Red deer HV), Canid herpesvirus 1 (Canine HV), Erinaceid herpesvirus (European hedgehog HV).
Murid herpesvirus 1 (Mouse cytomegalovirus), Murid herpevirus 2 (Rat cytomegalovirus), Murid herpesvirus 3 (Mouse thymic HV), Gruid herpesvirus 1 (Crane HV).
Angiullid herpesvirus 1 (Japanese eel HV), Cyprinid herpesvirus 1 (Carp pox HV), Cyprinid herpesvirus 2 (Hematopoietic necrosis HV of goldfish), Ictalurid herpesvirus 1 (Channel catfish), Acipenserid herpesvirus 1 (White sturgeon herpesvirus 1).

Ostreid herpesvirus 1 (Pacific oyster herpesvirus), oh no, not the oysters too!
OsHV-1 have established a separate lineage about a billion years ago, and the fish viruses about 400 million years ago. I am still young. Herpes is derived from the Greek word meaning 'creep'.

Ok, guess no fishing today...  Why did I read about herpes?? It is better to be ignorant.
How is the pathology of the oysters I wonder? Blisters?

Prior to death, no gross physiological signs are detectable. The main histological changes consist of enlarged and abnormally shaped nuclei and abnormal chromatin patterns throughout the connective tissues (Renault et al., 1994b, 1995). 

Green monkey. Retrieved from my Barbados blog:

Barbados Flying Fish

The Flying Fish is the National Icon of the island of Barbados

Flying Fish, common to tropical seas, are found in the warm waters surrounding the island of Barbados. 

Does it fly?
Just like birds, they break the water’s surface, and fly distances of up to 100 yards at about 30 miles per hour.
Some wing their way into fishermen’s boats. Flying Fish do not actually fly the same way as birds, because birds vibrate their wings during flight. This fish gets its power and speed from its tail fin, which it moves from side to side with powerful strokes. 
It is much easier to move through the air than it is through the water, (there is less resistance in air), and the Flying Fish launch themselves from the water like rockets.
 

Other descriptions state the fish glide through the air, rather than fly.
However Flying Fish do have wings, and once air born, they spread their  wings, and appear to be "flying".

However you want to describe the flight of the Flying Fish, the silvery-blue fish can be seen in mass out in the waters off the coast of Barbados.

Flying Fish can easily be identified by their huge flying fins and lopsided tails. They have forked tails, and the lower part of the tail is much longer and larger than the upper - thus giving a lopsided appearance.
Flying Fish take flight to escape predators such as swordfish, tunas, and other larger fish, but they cannot escape the nets of the Barbadian fishermen.

The National Dish of Barbados is Cou-Cou and Flying Fish.
Bajans love steamed Flying Fish in gravy with Cou-Cou. Cou-cou is made out of corn meal and okra.  

 We like our Flying Fish battered and FRIED!

The taste of Flying Fish is quite delicate, and it does not have a "fishy" taste.
It's really good when seasoned with fresh lime, battered and fried. 

So I guess no fly-fishing either.

Glad I went into biology lesson today. This  was the whole purpose I started my biology carrier.
Time for Saltholmen now.

Dagens Herpes

Because Robots Don't Get Herpes!