TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc

Abstract: The central region of the intervertebral disc (IVD) is rich in proteoglycans, leading to a hyperosmotic environment, which fluctuates with daily loading. The cells of the nucleus pulposus (NP cells) have adapted to this environment via the function of tonicity enhancer binding protein (TonEBP), and NP cells have been shown to express several water channels known as aquaporins (AQP). We have previously shown that AQP1 and 5 decrease during IVD degeneration. Here, the regulation of AQP1 and 5 by hyperosmotic conditions and the role of TonEBP in this regulation was investigated. AQP1 and 5 gene expression was upregulated by hyperosmotic conditions mimicking the osmolality of the healthy IVD, which was abrogated by TonEBP knockdown. Furthermore, AQP1 and 5 immunopositivity was significantly reduced in TonEBPΔ/Δ E17.5 mice when compared with wildtype controls, indicating in vivo expression of AQP1 and 5 is controlled at least in part by TonEBP. This hyperosmotic regulation of AQP1 and 5 could help to explain the decreased AQP1 and 5 expression during degeneration, when the osmolality of the NP decreases. Together this data suggests that TonEBP-regulated osmo-adaptation may be disrupted during IVD degeneration when the expression of both AQPs is reduced

Ultraslow spreading and volcanism at the eastern end of Gakkel Ridge, Arctic Ocean

Ultraslow spreading ridges are poorly understood plate boundaries consisting of magmatic and amagmatic segments that expose mostly mantle peridotite and only traces of basalt and gabbro. The slowest part of the global spreading system is represented by the eastern Gakkel Ridge in the Central Arctic Ocean, where crustal accretion is characterized by extreme focusing of melt to discrete magmatic centers. Close to its eastern tip lies the unusual 5,310 m deep Gakkel Rift Deep (GRD) with limited sediment infill, which is in strong contrast to the broader sediment-filled rift valleys to the east and west. Here, we report an 40Ar/39Ar age of 3.65±0.01 Ma for a pillow basalt from a seamount located on the rim the GRD confirming ultraslow spreading rates of ~7 mm/yr close to the Laptev Sea as suggested from aeromagnetic data. Its geochemistry points to an alkaline lava, attributed to partial melting of a source that underwent prior geochemical enrichment. We note that the GRD extracts compositionally similar melts as the sparsely magmatic zone further west but at much slower spreading velocities of only ~6-7 mm/yr, indicating the widespread occurrence of similarly fertile mantle in the High Arctic. This enriched source differs from sub-continental lithospheric mantle that influences magmatism along the Western Volcanic Zone (Goldstein et al. 2008) and is similar to metasomatized mantle - shown to influence melt genesis along the Eastern Volcanic Zone

Evidence for a Moist to Wet Source Transition Throughout the Oman‐UAE Ophiolite, and Implications for the Geodynamic History

The Oman‐United Arab Emirates (UAE) ophiolite represents the largest and best‐preserved fragment of obducted oceanic lithosphere in the world. However, debate continues regarding its geodynamic history. This debate is in part a consequence of the lateral variability in the later stage magmatic units, with arc signatures considered to be well developed in the north of the ophiolite but less so in the south. In this study, we investigate later stage intrusions in the central and southern part of the ophiolite. These intrusions vary from wehrlite to gabbro and tonalite and crosscut all levels of the main ophiolite sequence from the mantle peridotites up to the sheeted dike complex. They are characterized by the presence of magmatic amphibole, low TiO2 (<1 wt%), document an enrichment in Th, Sr, and Ba, depletion of Y and Dy, and decreasing Dy/Yb and Dy/Dy* with increased fractionation. These data record hydrous fractionation with a significant role for amphibole, which is comparable to many arc‐type magmas. The relative Nb and light rare earth element ((La/Yb)nchon < 1) depletion and coupled Nd and Hf isotope variations indicate the same (but depleted) Indian mid‐ocean ridge basalts‐type mantle source as the main ophiolite sequence. More radiogenic Pb isotope compositions of plagioclase imply the addition of a fluid component likely derived from sediments or altered oceanic crust. These intrusions occur across larger areas than previously reported, implying the entire ophiolite formed in a setting characterized by arc‐type magmas, such as a suprasubduction zone setting

A multi-scale modelling framework to guide management of plant invasions in a transboundary context

Background Attention has recently been drawn to the issue of transboundary invasions, where species introduced and naturalized in one country cross international borders and become problematic in neighbouring countries. Robust modelling frameworks, able to identify the environmental drivers of invasion and forecast the current and future potential distribution of invasive species, are needed to study and manage invasions. Limitations due to the lack of species distribution and environmental data, or assumptions of modelling tools, often constrain the reliability of model predictions. Methods We present a multiscale spatial modelling framework for transboundary invasions, incorporating robust modelling frameworks (Multimodel Inference and Ensemble Modelling) to overcome some of the limitations. The framework is illustrated using Hakea sericea Schrad. (Proteaceae), a shrub or small tree native to Australia and invasive in several regions of the world, including the Iberian Peninsula. Two study scales were considered: regional scale (western Iberia, including mainland Portugal and Galicia) and local scale (northwest Portugal). At the regional scale, the relative importance of environmental predictors sets was evaluated and ranked to determine the main general drivers for the species distribution, while the importance of each environmental predictor was assessed at the local scale. The potential distribution of H. sericea was spatially projected for both scale areas. Results Model projections for western Iberia suggest that a large area is environmentally suitable in both Portugal and Spain. Climate and landscape composition sets were the most important determinants of this regional distribution of the species. Conversely, a geological predictor (schist lithology) was more important in explaining its local-scale distribution. Conclusions After being introduced to Portugal, H. sericea has become a transboundary invader by expanding in parts of Galicia (Spain). The fact that a larger area is predicted as environmentally suitable in Spain raises concerns regarding its potential continued expansion. This highlights the importance of transboundary cooperation in the early management of invasions. By reliably identifying drivers and providing spatial projections of invasion at multiple scales, this framework provides insights for the study and management of biological invasions, including the assessment of transboundary invasion risk.This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors - COMPETE and by National Funds through FCT - Foundation for Science and Technology under the project PTDC/AAGMAA/4539/2012 / FCOMP-01-0124-FEDER-027863 (IND_CHANGE). J. Vicente is supported by POPH/FSE funds and by National Funds through FCT - Foundation for Science and Technology through Post-doctoral grant SFRH/BPD/84044/2012. D.M. Richardson acknowledges support from the DST-NRF Centre of Excellence for Invasion Biology and the National Research Foundation (grant 85417).info:eu-repo/semantics/publishedVersio

The presence of extracellular matrix degrading metalloproteinases during fetal development of the intervertebral disc

Matrix metalloproteinases (MMPs) regulate connective tissue architecture and cell migration through extracellular matrix (ECM) degradation and are associated with both physiological and pathological processes. Although they are known to play a role in skeletal development, little is known about the role of MMPs in intervertebral disc (IVD) development. Sixteen fetal human lumbar spine segments, obtained at autopsy, were compared with five normal, non-fetal L4–L5 IVDs. Intensity and/or localization of immunohistochemical staining for MMP-1, -2, -3 and -14 were evaluated by three independent observers. MMP-2 production and activation was quantified by gelatin zymography. MMP-1 and -14 were abundantly present in the nucleus pulposus (NP) and notochordal (NC) cells of the fetal IVDs. In non-fetal IVDs, MMP-1 and -14 staining was significantly less intense (p = 0.001 and p < 0.001, respectively). MMP-3 was found in almost the entire IVD with no significant difference from non-fetal IVDs. MMP-2 staining in the NC and NP cells of the fetal IVD was moderate, but weak in the non-fetal IVD. Gelatin zymography showed a negative correlation of age with MMP-2 activity (p < 0.001). MMP-14 immunostaining correlated positively with MMP-2 activity (p = 0.001). For the first time, the presence of MMP-1, -2, -3 and -14 in the fetal human IVD is shown and the high levels of MMP-1, -2 and -14 suggest a role in the development of the IVD. In particular, the gradual decrease in MMP-2 activation during gestation pinpoints this enzyme as key player in fetal development, possibly through activation by MMP-1 and -14

Magmatic processes in developing oceanic crust revealed in a cumulate xenolith collected at the East Pacific Rise, 9°50′N

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 7 (2006): Q12O04, doi:10.1029/2006GC001316.The petrology and geochemistry of a xenolith, a fragment of a melt-bearing cumulate, within a recently erupted mid-ocean ridge (MOR) lava flow provide information on petrogenetic processes occurring within the newly forming oceanic crust beneath the northern East Pacific Rise (NEPR). The xenolith reveals important petrologic information about MOR magmatic systems concerning (1) melt distribution in a crystal-dominated mush; (2) melt-crystal reactions within the mush; (3) the chemistry of melts that have contributed to the cumulate lithology; and (4) the chemistry of axial melts that enter the axial magma system. The xenolith was enclosed within a moderately primitive, normal mid-ocean ridge basalt (NMORB) erupted in 1991 within the neovolcanic zone of the NEPR, at approximately 9°50′N. The sample is a matrix-dominated, cumulate olivine anorthosite, composed of anorthite (An94-90) and bytownite (An89-70), intergranular olivine (Fo86±0.3), minor sulfide and spinel, and intergranular glass. Marginal corrosion of plagioclase, and possibly olivine, and internal remelting of plagioclase indicate syntexis. It is surmised that the pore volume was eviscerated several times with moderately primitive basaltic melts and reduced by intergranular crystallization of forsteritic olivine. The presence of anorthite as a cumulate phase in the xenolith and the observation of anorthite xenocrysts in NMORB lavas, and as a cumulate phase in ophiolite gabbros, indicate that Ca-rich melts that are not a part of the NMORB lineage play an important role in the construction of the oceanic crust.The Mineral Resources Program, USGS, provided support to W.I.R. for this research. Field and laboratory research was supported by NSF grants OCE-9402360, 9403773, and 0138088 to M.R.P. and NSF grants OCE-9819261 and OCE-0525863 to D.J.F

Volcanic–plutonic connection and associated Au‐Cu mineralization of the Tulasu ore district, Western Tianshan, NW China: Implications for mineralization potential in Palaeozoic arc terranes

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record Constructing the plutonic–volcanic connections in volcanic arc setting is essential for understanding a variety of magmatic processes from continental crust differentiation to formation of magmatic-hydrothermal ore deposits. Based on the combination of zircon U–Pb geochronology and Hf isotope and whole-rock geochemistry and Sr-Nd isotopes, we evaluated the potential connections between volcanic and plutonic rocks from the Tulasu Basin, the largest epithermal gold ore district in the Chinese Western Tianshan. The peak of volcanism coincides well with the major plutonism,representing an important magma event at ~347–367 Ma. These contemporaneous volcanic and plutonic rocks show broadly similar arc-related geochemical signatures and zircon in-situ Hf (εHf[t] =−1.0–14.3) and whole-rock Nd (εNd[t] =−4.2–4.6) isotopic compositions, indicative of formation from parental magmas derived from a common depleted mantle source metasomatized by slab-derived melts, despite diverse consequent processes (fractional crystallization, crustal contamination, and magma mixing/mingling) during their differentiation in a subduction-related setting. Volcanic rocks from the Axi caldera in the centre of the Tulasu district are geochemically less evolved than the coeval porphyritic granite, which indicates that the intrusive rocks might originate from residual melts left behind by extraction of erupted magmas. In contrast, the porphyry Cu mineralized Kexiaxi pluton, which occurs in the margin of the Tulasu district, is compositionally indistinguishable from the coeval volcanic suites. This implies that the Kexiaxi pluton represents the intrusive equivalent of a common magma reservoir feeding the volcanic eruptions, and magma fluxes may have controlled their differentiation. We thus suggest that the depleted mantle derived calc-alkaline magma, modified during slab-related melt metasomatism, crustal contamination, and magma mixing may have played an important role in copper enrichment at Kexiaxi. Finally, the relatively water-rich and fertile nature of arc magma of the Tulasu district indicates high exploration potential for significant porphyry Cu-Au deposits. The existing alteration-immobile fertility proxy (V/Sc) for intrusive rocks may also be useful to assess the fertility of cogenetic volcanic rocks, in turn with implications for unexposed porphyry Cu deposits at depths.European Commissio

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

Cell-based regenerative medicine therapies have been proposed for repairing the degenerated intervertebral disc (a major cause of back pain). However, for this approach to be successful, it is essential to characterise the phenotype of its native cells to guarantee that implanted cells differentiate and maintain the correct phenotype to ensure appropriate cell and tissue function. While recent studies have increased our knowledge of the human nucleus pulposus (NP) cell phenotype, their ontogeny is still unclear. The expression of notochordal markers by a subpopulation of adult NP cells suggests that, contrary to previous reports, notochord-derived cells are retained in the adult NP, possibly coexisting with a second population of cells originating from the annulus fibrosus or endplate. It is not known, however, how these two cell populations interact and their specific role(s) in disc homeostasis and disease. In particular, notochordal cells are proposed to display both anabolic and protective roles; therefore, they may be the ideal cells to repair the degenerate disc. Thus, understanding the ontogeny of the adult NP cells is paramount, as it will inform the medical and scientific communities as to the ideal phenotype to implant into the degenerate disc and the specific pathways involved in stem cell differentiation towards such a phenotype. © 2014 The Author(s)

Radiographic assessment of the femorotibial joint of the CCLT rabbit experimental model of osteoarthritis

<p>Abstract</p> <p>Background</p> <p>The purposes of the study were to determine the relevance and validity of in vivo non-invasive radiographic assessment of the CCLT (Cranial Cruciate Ligament Transection) rabbit model of osteoarthritis (OA) and to estimate the pertinence, reliability and reproducibility of a radiographic OA (ROA) grading scale and associated radiographic atlas.</p> <p>Methods</p> <p>In vivo non-invasive extended non weight-bearing radiography of the rabbit femorotibial joint was standardized. Two hundred and fifty radiographs from control and CCLT rabbits up to five months after surgery were reviewed by three readers. They subsequently constructed an original semi-quantitative grading scale as well as an illustrative atlas of individual ROA feature for the medial compartment. To measure agreements, five readers independently scored the same radiographic sample using this atlas and three of them performed a second reading. To evaluate the pertinence of the ROA grading scale, ROA results were compared with gross examination in forty operated and ten control rabbits.</p> <p>Results</p> <p>Radiographic osteophytes of medial femoral condyles and medial tibial condyles were scored on a four point scale and dichotomously for osteophytes of medial fabella. Medial joint space width was scored as normal, reduced or absent. Each ROA features was well correlated with gross examination (p < 0.001). ICCs of each ROA features demonstrated excellent agreement between readers and within reading. Global ROA score gave the highest ICCs value for between (ICC 0.93; CI 0.90-0.96) and within (ICC ranged from 0.94 to 0.96) observer agreements. Among all individual ROA features, medial joint space width scoring gave the highest overall reliability and reproducibility and was correlated with both meniscal and cartilage macroscopic lesions (r_s= 0.68 and r_s= 0.58, p < 0.001 respectively). Radiographic osteophytes of the medial femoral condyle gave the lowest agreements while being well correlated with the macroscopic osteophytes (r_s= 0.64, p < 0.001).</p> <p>Conclusion</p> <p>Non-invasive in vivo radiography of the rabbit femorotibial joint is feasible, relevant and allows a reproducible grading of experimentally induced OA lesion. The radiographic grading scale and atlas presented could be used as a template for in vivo non invasive grading of ROA in preclinical studies and could allow future comparisons between studies.</p

Towards an end-to-end analysis and prediction system for weather, climate, and marine applications in the Red Sea

Author Posting. © American Meteorological Society, 2021. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society 102(1), (2021): E99-E122, https://doi.org/10.1175/BAMS-D-19-0005.1.The Red Sea, home to the second-longest coral reef system in the world, is a vital resource for the Kingdom of Saudi Arabia. The Red Sea provides 90% of the Kingdom’s potable water by desalinization, supporting tourism, shipping, aquaculture, and fishing industries, which together contribute about 10%–20% of the country’s GDP. All these activities, and those elsewhere in the Red Sea region, critically depend on oceanic and atmospheric conditions. At a time of mega-development projects along the Red Sea coast, and global warming, authorities are working on optimizing the harnessing of environmental resources, including renewable energy and rainwater harvesting. All these require high-resolution weather and climate information. Toward this end, we have undertaken a multipronged research and development activity in which we are developing an integrated data-driven regional coupled modeling system. The telescopically nested components include 5-km- to 600-m-resolution atmospheric models to address weather and climate challenges, 4-km- to 50-m-resolution ocean models with regional and coastal configurations to simulate and predict the general and mesoscale circulation, 4-km- to 100-m-resolution ecosystem models to simulate the biogeochemistry, and 1-km- to 50-m-resolution wave models. In addition, a complementary probabilistic transport modeling system predicts dispersion of contaminant plumes, oil spill, and marine ecosystem connectivity. Advanced ensemble data assimilation capabilities have also been implemented for accurate forecasting. Resulting achievements include significant advancement in our understanding of the regional circulation and its connection to the global climate, development, and validation of long-term Red Sea regional atmospheric–oceanic–wave reanalyses and forecasting capacities. These products are being extensively used by academia, government, and industry in various weather and marine studies and operations, environmental policies, renewable energy applications, impact assessment, flood forecasting, and more.The development of the Red Sea modeling system is being supported by the Virtual Red Sea Initiative and the Competitive Research Grants (CRG) program from the Office of Sponsored Research at KAUST, Saudi Aramco Company through the Saudi ARAMCO Marine Environmental Center at KAUST, and by funds from KAEC, NEOM, and RSP through Beacon Development Company at KAUST