Amyloidosis is a protein conformational disorder with the distinctive feature of extracellular accumulation of amyloid fibrils that come from different proteins. In the ligamentum flavum of the lumbar spine, amyloid deposits were frequently found in elderly patients with lumbar spinal canal stenosis and were at least partially formed by wild-type transthyretin. However, how amyloid deposits in the ligamentum flavum affect lumbar spinal canal stenosis has remained unclear. In this study, we analyzed clinical, pathologic, and radiologic findings of patients with lumbar spinal canal stenosis who had amyloid deposits in the ligamentum flavum. We studied 95 ligamentum flavum specimens obtained from 56 patients with lumbar spinal canal stenosis and 21 ligamentum flavum specimens obtained from 19 patients with lumbar disk herniation. We evaluated histopathologic findings and clinicoradiologic manifestations, such as thickness of the ligamentum flavum and lumbar spinal segmental instability. We found that all 95 ligamentum flavum specimens resected from patients with lumbar spinal canal stenosis had amyloid deposits, which we classified into two types, transthyretin-positive and transthyretinnegative, and that transthyretin amyloid formation in the ligamentum flavum of patients with lumbar spinal canal stenosis was an age-associated phenomenon. The amount of amyloid in the ligamentum flavum was related to clinical manifestations of lumbar spinal canal stenosis, such as thickness of the ligamentum flavum and lumbar spinal segmental instability, in the patients with lumbar spinal canal stenosis with transthyretin-positive amyloid deposits. To our knowledge, this report is the first to show clinicopathologic correlations in transthyretin amyloid deposits of the ligamentum flavum. In conclusion, transthyretin amyloid deposits in the ligamentum flavum may be related to the pathogenesis of lumbar spinal canal stenosis in elderly patients.

Phase transitions of solid-state materials can be controlled optically by electronic excitation. In semiconductors, the semiconductor-to-metal transition occurs upon excitation of approximately 10 % of the valence electrons.[1] This bandgap collapse occurs nonthermally, faster than the thermal-energy transfer from electrons to atoms when ultrashort pulses are utilized. In dielectrics, a metallic plasma state can be created at the focus of a typical tightly focused 100 nJ/200 fs pulse, creating a ∼ 10 14 W cm -2 intensity within a volume of subwavelength cross section. Such a pulse ionizes the focal volume almost instantaneously within one or few optical cycles by multiphoton absorption and launches a shock wave with subsequent fast (< 100 ns) thermal quenching. Transitions leading to different materials phases [2][3][4] with altered chemical properties [5,6] are expected to be formed.Here, we demonstrate control over the crystallinity and chemical reactivity of sapphire (Al 2 O 3 ) using femtosecondpulse exposure. Crystalline-to-amorphous and amorphous-topolycrystalline transitions were induced inside a sapphire sample using single-and multi-pulse irradiation, respectively. Wet etching of the amorphized sapphire in an aqueous solution of hydrofluoric acid showed extremely high selectivity (> 10 4 , calculated as the ratio of the channel's lengthening to its widening) relative to that of the crystalline and polycrystalline phases. This method allowed us to fabricate a 3D network of channels without apparent constraints on their length. The processing of sapphire, the most chemically inert and the hardest oxide, opens new opportunities in different industries; for example, sapphire substrates can be patterned for the growth of defect-free GaN in high-luminosity light-emitting diodes (LEDs) and laser diodes (LDs).The femtosecond pulses used in our experiments possess a peak power of tens of killowatts, which is much lower than the threshold for self-focusing (several megawatts), allowing the unique conditions of energy delivery to the focal volume to be exploited by keeping the nonlinear effects of light propagation negligible. The benchmark feature size for 3D nanostructures, usually set at 100 nm, can be surpassed by using tightly focused femtosecond pulses. [7] In crystalline dielectrics and glasses, the dielectric breakdown, a full ionization of the focal volume, causes extensive crack formation when pulses longer than 1 ps are utilized.[8] However, we show that in the case of femtosecond pulses, the photomodified region can be elastically sustained without crack formation inside the crystalline phase as long as it is confined within small sub-micrometer dimensions. Figure 1 shows a typical transmission electron microscopy (TEM) image of the cross section of the photomodified region made by a single femtosecond pulse inside sapphire. The di- COMMUNICATIONS

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarticular synovitis of the diarthrodial joints. Several proinflammatory cytokines derived from both infiltrating inflammatory cells and activated resident cells within the RA joint play a fundamental role in the processes that cause inflammation. However, anticytokine treatment is beneficial but not curative, the effects are only partial, and nonresponses are common. Therefore, an effort has been made to identify other key regulators of inflammation in articular structures to develop new therapies to suppress synovial inflammation and joint destruction in RA. Adipose tissue-derived angiopoietin-like protein 2 (Angptl2) activates an inflammatory cascade in endothelial cells and induces chemotaxis of monocytes/macrophages in obesity, resulting in initiation and propagation of inflammation within adipose tissues and obesity-related metabolic diseases. Angptl2 mRNA and protein are abundantly expressed in hyperplastic rheumatoid synovium of RA patients, especially in fibroblast-like and macrophage-like synoviocytes, but not in B and T lymphocytes. Angptl2 concentration in joints of RA patients was also significantly increased in comparison with patients with osteoarthritis, which in comparison with RA represents a significantly lower inflammatory grade form of arthritis. Notably, Angptl2 promoted increased chemotactic activities of CD14+CD16- monocytes from synovial fluid of RA patients. Therefore, Angptl2 acts as an important rheumatoid synovium-derived inflammatory mediator in RA pathogenesis.

No abstract

Our results indicate that Chop plays a direct role in chondrocyte apoptosis and that Chop-mediated apoptosis contributes to the progression of cartilage degeneration in mice.