Search

The islands of Pitcairn, Henderson, Ducie, and Oeno (commonly known as Pitcairn) make up a single territory, the last remaining British Overseas Territory in the Pacific Ocean. During the period [...]

Maintenance of connective tissue integrity is fundamental to sustain function, requiring protein turnover to repair damaged tissue. However, connective tissue proteome dynamics remain largely undefined, as do differences in turnover rates of individual proteins in the collagen and glycoprotein phases of connective tissue extracellular matrix (ECM). Here, we investigate proteome dynamics in the collagen and glycoprotein phases of connective tissues by exploiting the spatially distinct fascicular (collagen-rich) and interfascicular (glycoprotein-rich) ECM phases of tendon. Using isotope labelling, mass spectrometry and bioinformatics, we calculate turnover rates of individual proteins within rat Achilles tendon and its ECM phases. Our results demonstrate complex proteome dynamics in tendon, with ~1000 fold differences in protein turnover rates, and overall faster protein turnover within the glycoprotein-rich interfascicular matrix compared to the collagen-rich fascicular matrix. These data provide insights into the complexity of proteome dynamics in tendon, likely required to maintain tissue homeostasis.

Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor whose dysfunction is linked to developmental dysplasia of the hip, osteoporosis and osteoarthritis. Our work addresses the critical question of how these skeletal pathologies emerge. Here, we show the abundant expression of LRP1 in skeletal progenitor cells at mouse embryonic stage E10.5 and onwards, especially in the perichondrium, the stem cell layer surrounding developing limbs essential for bone formation. Lrp1 deficiency in these stem cells causes joint fusion, malformation of cartilage/bone template and markedly delayed or lack of primary ossification. These abnormalities, which resemble phenotypes associated with Wnt signalling pathways, result in severe and persistent skeletal defects including a severe deficit in hip joint and patella, and markedly deformed and low-density long bones leading to dwarfism and impaired mobility. Mechanistically, we show that LRP1 regulates core non-canonical Wnt/planar cell polarity (PCP) components that may explain the malformation of long bones. LRP1 directly binds to Wnt5a, facilitates its cell-association and endocytic degradation and recycling. In the developing limbs, LRP1 partially colocalises with Wnt5a and its deficiency alters abundance and distribution of Wnt5a and Vangl2. Finally, using Xenopus as a model system, we show the regulatory role for LRP1 in Wnt/PCP signalling. We propose that in skeletal progenitors, LRP1 plays a critical role in formation and maturity of multiple bones and joints by regulating Wnt signalling, providing novel insights into the fundamental processes of morphogenesis and the emergence of skeletal pathologies. [ABSTRACT FROM AUTHOR]

Reviews of American Samoa, Hawai'i, Samoa, Tokelau, Tonga, Tuvalu, and Wallis and Futuna are not included in this issue. COOK ISLANDS This review covers the two-year period from July 2016 [...]

We present the first complete far-infrared spectrum (43-197 μm) of M82, the brightest infrared galaxy in the sky, taken with the Long Wavelength Spectrometer of the Infrared Space Observatory (ISO). We detected seven fine structure emission lines, [O I] 63 and 145 μm, [O III] 52 and 88 μm , [N II] 122 μm, [N III] 57 μm, and [C II] 158 μm, and fitted their ratios to a combination starburst and photodissociation region (PDR) model. The best fit is obtained with H II regions with n = 250 cm-3, an ionization parameter of 10-3.5, and PDRs with n = 103.3 cm-3 and a far-ultraviolet flux of G0 = 102.8. We applied both continuous and instantaneous starburst models, with our best fit being a 3-5 Myr old instantaneous burst model with a 100 M⊙ cutoff. We also detected the ground-state rotational line of OH in absorption at 119.4 μm. No excited level OH transitions are apparent, indicating that the OH is almost entirely in its ground state with a column density ∼4 × 1014 cm-2. The spectral energy distribution over the long-wavelength spectrometer wavelength range is well fitted with a 48 K dust temperature and an optical depth, τDust ∝ λ-1.