Language has a fundamentally social function. Processes of human interaction along with domain-general cognitive processes shape the structure and knowledge of language. Recent research in the cognitive sciences has demonstrated that patterns of use strongly affect how language is acquired, is used, and changes. These processes are not independent of one another but are facets of the same complex adaptive system (CAS). Language as a CAS involves the following key features: The system consists of multiple agents (the speakers in the speech community) interacting with one another.

Objectives-To evaluate synovial membrane hypertrophy, tenosynovitis, and erosion development of the 2nd to 5th metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints by magnetic resonance imaging in a group of patients with rheumatoid arthritis (RA) or suspected RA followed up for one year. Additionally, to compare the results with radiography, bone scintigraphy, and clinical findings. Patients and methods-Fifty five patients were examined at baseline, of whom 34 were followed up for one year. Twenty one patients already fulfilled the American College of Rheumatology (ACR) criteria for RA at baseline, five fulfilled the criteria only after one year's follow up, whereas eight maintained the original diagnosis of early unclassified polyarthritis. The following MRI variables were assessed at baseline and one year: synovial membrane hypertrophy score, number of erosions, and tenosynovitis score. Results-MRI detected progression of erosions earlier and more often than did radiography of the same joints; at baseline the MRI to radiography ratio was 28:4. Erosions were exclusively found in patients with RA at baseline or fulfilling the ACR criteria at one year. At one year follow up, scores of MR synovial membrane hypertrophy, tenosynovitis, and scintigraphic tracer accumulation had not changed significantly from baseline; in contrast, swollen and tender joint counts had declined significantly (p<0.05). Conclusions-MRI detected more erosions than radiography. MR synovial membrane hypertrophy and scintigraphy scores did not parallel the changes seen over time in clinically assessed swollen and tender joint counts. Although joint disease activity may be assessed as quiescent by conventional clinical methods, a more detailed evaluation by MRI may show that a pathological condition is still present within the synovium.

N-myristoyltransferase (NMT) attaches the fatty acid myristate to the N-terminal glycine of proteins to sort them into soluble and membrane-bound fractions. Function of the energy-sensing AMP-activated protein kinase (AMPK) is myristoylation-dependent. In rheumatoid arthritis (RA), pathogenic T cells shift glucose away from ATP production towards synthetic and proliferative programs, promoting proliferation, cytokine production, and tissue invasion. We found that RA T cells have a defect in NMT1 function, which prevented AMPK activation and enabled unopposed mTORC1 signaling. Lack of the myristate lipid tail disrupted the lysosomal translocation and activation of AMPK. Instead, myristoylation-incompetent RA T cells hyperactivated the mTORC1 pathway and differentiated into pro-inflammatory T H 1 and T H 17 T helper cells. In vivo, NMT1 loss caused robust synovial tissue inflammation, whereas forced NMT1 overexpression rescued AMPK activation and suppressed synovitis. Thus, NMT1 has tissue-protective functions by facilitating lysosomal recruitment of AMPK and dampening of mTORC1 signaling.

Highlights d The DNA repair nuclease MRE11A is located in mitochondria d Mitochondrial MRE11A protects mtDNA from oxidation and cytoplasmic leakage d MRE11A low T cells fail to produce ATP and undergo caspase-1-dependent pyroptosis d MRE11A loss of function results in tissue inflammation

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