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IL-6, among an increasing number of other recently identified myokines, thus remains an important topic in myokine research.

It appears in muscle tissue and in the circulation during exercise at levels up to one hundred times basal rates, as noted, and is seen as having a beneficial impact on health and bodily functioning when elevated in response to physical exercise.

CD is the common signal transducer for several cytokines including leukemia inhibitory factor LIF , ciliary neurotropic factor , oncostatin M , IL and cardiotrophin-1 , and is almost ubiquitously expressed in most tissues.

In contrast, the expression of CD is restricted to certain tissues. As IL-6 interacts with its receptor, it triggers the gp and IL-6R proteins to form a complex, thus activating the receptor.

These complexes bring together the intracellular regions of gp to initiate a signal transduction cascade through certain transcription factors , Janus kinases JAKs and Signal Transducers and Activators of Transcription STATs.

IL-6 is probably the best-studied of the cytokines that use gp , also known as IL-6 signal transducer IL6ST , in their signalling complexes.

In addition to the membrane-bound receptor, a soluble form of IL-6R sIL-6R has been purified from human serum and urine. Many neuronal cells are unresponsive to stimulation by IL-6 alone, but differentiation and survival of neuronal cells can be mediated through the action of sIL-6R.

Interleukin-6 has been shown to interact with interleukin-6 receptor , [22] [23] [24] and glycoprotein There is considerable functional overlap and interaction between Substance P SP , the natural ligand for the neurokinin type 1 receptor NK1R, a mediator of immunomodulatory activity and IL Hence, there is an interest in developing anti-IL-6 agents as therapy against many of these diseases.

Anti-IL-6 therapy was initially developed for treatment of autoimmune diseases , but due to the role of IL-6 in chronic inflammation, IL-6 blockade was also evaluated for cancer treatment.

High IL-6 levels are associated with the development of encephalitis in children and immunodeficient mouse models infected with Enterovirus 71 ; this highly contagious virus normally causes a milder illness called Hand, foot, and mouth disease but can cause life-threatening encephalitis in some cases.

EV71 patients with a certain gene polymorphism in IL-6 also appear to be more susceptible to developing encephalitis. IL-6 has been shown to lead to several neurological diseases through its impact on epigenetic modification within the brain.

The induction of epigenetic modification by IL-6 has been proposed as a mechanism in the pathology of schizophrenia through the hypermethylation and repression of the GAD67 promoter.

The epigenetic effects IL-6 have also been implicated in the pathology of depression. Depression is marked by altered connectivity, in particular between the anterior cingulate cortex and several other limbic areas, such as the hippocampus.

Additional preclinical and clinical data, suggest that Substance P [SP] and IL-6 may act in concert to promote major depression.

SP, a hybrid neurotransmitter-cytokine, is co-transmitted with BDNF through paleo-spinothalamic circuitry from the periphery with collaterals into key areas of the limbic system.

SP and IL6 both relax tight junctions of the blood brain barrier, such that effects seen in fMRI experiments with these molecules may be a bidirectional mix of neuronal, glial, capillary, synaptic, paracrine, or endocrine-like effects.

The IL-6 antibody sirukumab is now undergoing clinical trials against major depressive disorder. Obesity is a known risk factor in the development of severe asthma.

Recent data suggests that the inflammation associated with obesity, potentially mediated by the cytokine IL6, plays a role in causing poor lung function and increased risk for developing asthma exacerbations.

From Wikipedia, the free encyclopedia. IL6 Gene location Human Chr. Chromosome 7 human [1]. Exercise and Sport Sciences Reviews.

Journal of Applied Physiology. Compr Physiol 3 3: The Journal of Physiology. Claus Brandt and Bente K. Journal of Biomedicine and Biotechnology. Volume , Article ID , 6 pages.

Muscle as an endocrine organ: Focus on muscle-derived interleukin The Journal of Biological Chemistry. The interleukin-6 receptor can serve as an alpha-receptor for CTNF".

Expert Opinion on Investigational Drugs. Polski Merkuriusz Lekarski in Polish. Current Opinion in Rheumatology. Expert Opinion on Therapeutic Targets.

Annals of the Rheumatic Diseases. International Journal of Molecular Sciences. International Journal of Oncology.

International Journal of Cancer. The Journal of Neuroscience. Archives of General Psychiatry. Biochimica et Biophysica Acta.

Brain, Behavior, and Immunity. Business Korea reported that the issues were connected to the triple-layer cell NAND storage of the affected models.

Triple-layer cells can store three bits of data per cell of flash, and are cheaper than dual-layer cell solutions, but at the cost of performance.

It was reported that Apple had planned to switch the affected model lines back to multi-layer cell flash, and address the performance issues on existing devices in a future iOS update.

It was reported that the optical image stabilization systems on some iPhone 6 Plus models were faulty, failing to properly stabilize when the phone is being held perfectly still, leading to blurry photos and "wavy"-looking videos.

On August 21, , Apple instituted a repair program for iPhone 6 Plus models released between September and January , citing that faulty rear cameras on affected models may produce blurry pictures.

Some iPhone 6 and iPhone 6 Plus models have an issue in which the front-facing camera is somehow "shifted", or out of place. Apple stated that they would replace most affected iPhone 6 models with this issue, free of charge.

Despite numerous complaints regarding this issue, it does not seem to actually affect the camera itself. It is said that the camera is not what has shifted, but a piece of protective foam around the camera module itself that has gone out of place.

If the iPhone 6 home button is repaired or modified by a third party, the device will fail security checks related to Touch ID as the components have not been "re-validated" for security reasons—a process which can only be performed by an authorized Apple outlet.

Failing these checks disables all features related to Touch ID. Such effects have sometimes happened as a result of damage as well.

It was reported these same hardware integrity checks would trigger an unrecoverable loop into "Recovery Mode" if iOS is updated or restored, with attempts to restore the device via iTunes software resulting in an "error 53" message.

Beyond the explanation that this is related to hardware integrity errors regarding Touch ID components, Apple provided no official explanation of what specifically triggers error 53 or how it can be fixed without replacing the entire device.

On February 18, , Apple released an iOS 9. Touchscreen control components on iPhone 6 logic boards have insufficient support, including a lack of underfill—which strengthens and stabilizes integrated circuits , and a lack of rigid metal shielding on the logic board unlike previous iPhone models; the touchscreen controller is instead shielded by a flexible "sticker".

Normal use of the device can cause the logic board to flex internally, which strains the touchscreen IC connectors and leads to a degradation or outright loss of touchscreen functionality.

A symptom that has been associated with this type of failure is a flickering grey bar near the top of the display. As such, the larger iPhone 6 Plus is more susceptible to the flaw, but it has also been reported on a small percentage of iPhone 6 models.

Initially, Apple did not officially acknowledge this issue. The issue was widely discussed on Apple's support forum—where posts discussing the issue have been subject to censorship.

Apple Stores are not equipped with the tools needed to perform the logic board repair, which had led to affected users sending their devices to unofficial, third-party repair services.

An Apple Store employee interviewed by Apple Insider reported that six months after they first started noticing the problem, Apple had issued guidance instructing them to tell affected users that this was a hardware issue which could not be repaired, and that their iPhone had to be replaced.

However, some in-stock units have also been afflicted with this issue out of the box, leading to an employee stating that they were "tired of pulling service stock out of the box, and seeing the exact same problem that the customer has on the replacement".

On August 30, , a group of three iPhone 6 owners sued Apple Inc. On November 17, , Apple officially acknowledged the issue and announced a paid repair program for affected iPhone 6 Plus models, stating that "some iPhone 6 Plus devices may exhibit display flickering or Multi-Touch issues after being dropped multiple times on a hard surface and then incurring further stress on the device".

From Wikipedia, the free encyclopedia. September 19, [4]. September 26, [4]. October 17, [5] [6].

October 23, [6]. October 24, [6]. October 30, [6]. October 31, [6]. Apple Newsroom Archive [76]. Retrieved December 6, Retrieved September 9, Retrieved September 11, Retrieved September 18, Retrieved October 2, Retrieved October 14, Retrieved July 27, Retrieved August 4, Retrieved September 16, Retrieved September 12, Retrieved August 22, Retrieved August 24, Retrieved January 10, Retrieved August 3, Retrieved September 23, Retrieved March 1, Retrieved September 10, Retrieved September 15, Retrieved June 7, Retrieved September 24, Retrieved October 19, Retrieved September 25, An open letter to Tim Cook".

Retrieved September 29, Retrieved October 3, Retrieved October 4, Retrieved November 15, Retrieved February 5, Retrieved February 18, Retrieved August 31, The gray flickering is an epidemic".

Apple faces class-action lawsuit". Retrieved December 13, Retrieved September 26, Retrieved September 28, Apple hardware since

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