Sediment mass‐balance analysis provides key constraints on stratigraphic architecture and its controls. We use the data‐rich Middle Jurassic Brent Delta sediment routing system in the proto‐Viking ...Graben, Northern North Sea, to estimate sediment budgets and mass‐balance between source areas and depositional sinks. Published studies are synthesised to provide an age‐constrained sequence stratigraphic framework, consisting of four previously defined genetic sequences (J22, J24, J26, J32). Genetic sequence J32 (3.9 Myr) records transverse progradation of basin‐margin deltas, sourced from the Shetland Platform to the west and Norwegian Landmass to the east. Genetic sequences J24 (1.1 Myr) and J26 (0.9 Myr) record the rapid progradation and subsequent aggradation of the Brent Delta along the basin axis, sourced from the uplifted Mid‐North Sea High to the south, and the western and eastern source regions. Genetic sequence J32 (2.2 Myr) records the retreat of the Brent Delta. Sediment budgets for the four genetic sequences are estimated using palaeogeographical reconstructions, isopach maps, and sedimentological analysis of core and well‐log data. The estimated net‐depositional sediment budget for the mapped Brent Delta system is 2.0–2.8 Mt/year. Temporal variations in net‐depositional sediment budget were driven by changes in tectonic boundary conditions, such as the onset of uplift before the deposition of genetic sequence J24. Over the same time period, the Shetland Platform, Norwegian Landmass and Mid‐North Sea High source regions are estimated to have supplied 2.3–5.6, 5.0–14.1, and 2.8–9.4 Mt/year of sediment, respectively, using the BQART sediment load model and independent geometrical reconstruction of eroded volumes, which are constrained by isostatic uplift estimates based on the geochemistry of syn‐depositional volcanic rocks. The net‐depositional sediment budget in the sink is an order‐of‐magnitude smaller than the total sediment budget supplied by the source regions (13.9–23 Mt/year). This discrepancy suggests that along‐shore transport by wave‐generated currents into the coeval Faroe‐Shetland Basin and/or down‐dip transport by gravity flows into the coeval western Møre Basin played a key role in redistributing sediments away from the Brent Delta system.
Middle Jurassic palaeogeographical reconstruction of the North Sea (left), illustrating interpreted dispersal of excess sediment supplied by the Brent Delta sediment routing system; this excess sediment is inferred from sediment budgets predicted from source regions by the empirical BQART model, which are oneorder of magnitude greater than mapped sediment budget in the Brent Delta depositional sink (right).
Osteoporosis is a highly prevalent condition, characterized by compromised bone strength and fragility fractures and with an important associated socio-economic burden. Bisphosphonates are well ...established as the first line treatment for osteoporosis. However, while randomized control trials have in general demonstrated reasonable anti-fracture efficacy at the spine, they have shown moderate reduction in fracture incidence for non-vertebral sites. Furthermore, oral bisphosphonates are commonly associated with adverse gastrointestinal effects and both oral and parenteral bisphosphonates have been linked with osteonecrosis of the jaw and atypical femoral fracture, two rare but debilitating side effects. In addition, bisphosphonates are not recommended in patients with GFR <35 ml/min/1.73 m
2
. Hence, there is a clear requirement for newer agents, which are able to reduce fracture risk further, whilst overcoming the limitations of bisphosphonates. Over the past 20 years, knowledge and a deeper understanding of the various signalling pathways involved in bone remodelling has increased, enabling identification of additional targets for therapy. This review focuses on these newer therapies and includes anti-resorptive agents such as raloxifene and other selective oestrogen receptor modulators, the monoclonal antibody denosumab (which inhibits the RANKL pathway), odanacatib, a cathepsin K inhibitor and the anabolic agents, PTH analogue; PTH (1–34) and anti-sclerostin antibodies (activator of the Wnt pathway). Strontium ranelate will not be reviewed as recent reports highlight concerns surrounding its cardiovascular safety and together with an apparent increased risk of thrombosis, its future use remains uncertain. Some of these agents such as raloxifene, denosumab and teriparatide are already in clinical use whilst others are at varying stages of development. This review will provide an overview of the mechanisms of action of these therapeutic agents on the skeleton and assess their efficacy in osteoporosis and fracture prevention.
•Male and female rats exhibit similar neuroinflammatory responses to stress.•Stress-induced neuroimmune changes may occur through distinct sex-specific mechanisms.•Microglia are a likely cellular ...source of priming in male but not female rats.•Prior stress enhances peripheral immune signals in female rats only.•It is critical to investigate mechanisms underlying biological phenomena in both sexes.
Exposure to stressors can enhance neuroinflammatory responses, and both stress and neuroinflammation are predisposing factors in the development of psychiatric disorders. Females suffer disproportionately more from several psychiatric disorders, yet stress-induced changes in neuroinflammation have primarily been studied in males. Here we tested whether exposure to inescapable tail shock sensitizes or ‘primes’ neuroinflammatory responses in male and female rats. At 24 h post-stress, male and female rats exposed to a peripheral immune challenge enhanced neuroinflammatory responses and exacerbated anxiety- and depressive-like behaviors. These changes are likely glucocorticoid dependent, as administering exogenous CORT, caused a similar primed inflammatory response in the hippocampus of male and female rats. Further, stress disinhibited anti-inflammatory signaling mechanisms (such as CD200R) in the hippocampus of male and female rats. In males, microglia are considered the likely cellular source mediating neuroinflammatory priming; stress increased cytokine expression in ex vivo male microglia. Conversely, microglia isolated from stressed or CORT treated females did not exhibit elevated cytokine responses. Microglia isolated from both stressed male and female rats reduced phagocytic activity; however, suggesting that microglia from both sexes experience stress-induced functional impairments. Finally, an immune challenge following either stress or CORT in females, but not males, increased peripheral inflammation (serum IL-1β). These novel data suggest that although males and females both enhance stress-induced neuroinflammatory and behavioral responses to an immune challenge, this priming may occur through distinct, sex-specific mechanisms.
This paper presents the measured sensitivity of CSIRO's first Mk. II phased array feed (PAF) on an ASKAP antenna. The Mk. II achieves a minimum system-temperature-over-efficiency T sys /η of 78 K at ...1.23 GHz and is 95 K or better from 835 MHz to 1.8 GHz. This PAF was designed for the Australian SKA Pathfinder telescope to demonstrate fast astronomical surveys with a wide field of view for the Square Kilometre Array (SKA).
Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function ...applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC-vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder.
The effects of chitin (1→4)-2-acetamido-2-deoxy-
β-
d-glucan and its partially deacetylated derivatives, chitosans, on the proliferation of human dermal fibroblasts and keratinocytes were examined in ...vitro. Chitosans with relatively high degrees of deacetylation strongly stimulated fibroblast proliferation while samples with lower levels of deacetylation showed less activity. Fraction, CL313A, a shorter chain length, 89% deacetylated chitosan chloride was further evaluated using cultures of fibroblasts derived from a range of human donors. Some fibroblast cultures produced a positive mitogenic response to CL313A treatment with proliferation rates being increased by approximately 50% over the control level at an initial concentration of 50
μg/ml, whilst others showed no stimulation of proliferation or even a slight inhibition (<10%). The stimulatory effect on fibroblast proliferation required the presence of serum in the culture medium suggesting that the chitosan may be interacting with growth factors present in the serum and potentiating their effect. In contrast to the stimulatory effects on fibroblasts, fraction CL313A inhibited human keratinocyte mitogenesis with up to 40% inhibition of proliferation being observed at 50
μg/ml. In general highly deacetylated chitosans were more active than those with a lower degree of deacetylation. These data demonstrate that highly deacetylated chitosans can modulate human skin cell mitogenesis in vitro. Analysis of their effects on cells in culture may be useful as a screen for their potential activity in vivo as wound healing agents, although in the case of fibroblasts it is important to select appropriate strains of cells for use in the screen.
This article, the third in the series, presents kinetic and photochemical data evaluated by the IUPAC Subcommittee on Gas Kinetic Data Evaluation for Atmospheric Chemistry. It covers the gas phase ...and photochemical reactions of inorganic halogen species, which were last published in J. Phys. Chem. Ref. Data, in 2000 (Atkinson et al., 2000), were updated on the IUPAC website in 2003 and are updated again in the present evaluation. The article consists of a summary sheet, containing the recommended kinetic parameters for the evaluated reactions, and five appendices containing the data sheets, which provide information upon which the recommendations were made.
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