The effect of human activities on moisture content of soils and underlying permafrost from the McMurdo Sound region, Antarctica

Soils and the underlying permafrost from undisturbed sites and sites that had been disturbed by construction activities at Marble Point and Pram Point in the McMurdo Sound region were sampled from excavated pits and drill cores. Gravimetric moisture (ice) contents and particle size distribution were determined. Volumetric moisture contents were calculated from these results. At undisturbed sites soil moisture contents within the active layer (to c. 60 cm depth) were low and ranged from 0.5% by weight at the soil surface to 10% above the permafrost. The permafrost was generally completely saturated with ice, but sometimes contained considerable excess ice, with ice contents rising as high as 80% by volume. At disturbed sites, soil moisture contents within the active layer were similar to those of the undisturbed sites (generally <10% by weight) but within the permafrost, moisture contents were lower and less variable than in the undisturbed sites, rarely exceeding 20% by weight. The release of considerable quantities of water from the permafrost as a result of land disturbance during construction activities caused stream flows, soil shrinkage, land slumping and salinisation, resulting in significant permanent environmental damage. At Marble Point there has been no significant re-establishment of icy permafrost in the disturbed soils in the 30 years since land disturbance occurred

Heavy metal contamination in some soils of the McMurdo Sound region, Antarctica

Soil samples from eight sites at Marble Point and Pram Point, McMurdo Sound region, contaminated by human activities were examined for heavy metal content, using sequential extraction methods. The redistribution of lead, zinc and copper arising from point sources of these metals was demonstrated. The levels found are not considered to represent serious pollution but do indicate that human activities can change the chemistry of the Antarctic environment in localized areas

Effects of hydrocarbon spills on the temperature and moisture regimes of Cryosols in the Ross Sea region

Hydrocarbon spills have occurred on Antarctic soils where fuel oils are utilized, moved or stored. We investigated the effects of hydrocarbon spills on soil temperature and moisture regimes by comparing the properties of existing oil contaminated sites with those of nearby, uncontaminated, control sites at Scott Base, the old Marble Point camp, and Bull Pass in the Wright Valley. Hydrocarbon levels were elevated in fuel-contaminated samples. Climate stations were installed at all three locations in both contaminated and control sites. In summer at Scott Base and Marble Point the mean weekly maximum near surface (2 cm and 5 cm depth) soil temperatures were warmer (P<0.05), sometimes by more than 10°C, at the contaminated site than the control sites. At Bull Pass there were no statistically significant differences in near-surface soil temperatures between contaminated and control soils. At the Scott Base and Marble Point sites soil albedo was lower, and hydrophobicity was higher, in the contaminated soils than the controls. The higher temperatures at the Scott Base and Marble Point hydrocarbon contaminated sites are attributed to the decreased surface albedo due to soil surface darkening by hydrocarbons. There were no noteworthy differences in moisture retention between contaminated and control sites

Responsiveness of serum C‐reactive protein, interleukin‐17A, and interleukin‐17F levels to ustekinumab in psoriatic arthritis: lessons from two phase III, multicenter, double‐blind, placebo‐controlled trials

Objective: To evaluate the associations of C‐reactive protein (CRP) and circulating Th17‐associated cytokine levels with psoriatic arthritis (PsA) disease activity and therapeutic response to ustekinumab. Methods: Interleukin‐17A (IL‐17A), IL‐17F, IL‐23, and CRP concentrations were measured in serum samples collected as part of the 2 PSUMMIT phase III studies of ustekinumab in PsA (n = 927). In post hoc analyses, relationships of IL‐17A, IL‐17F, and CRP levels at baseline, week 4, and week 24 with baseline skin and joint disease activity and response to therapy were evaluated using generalized linear models and Pearson's product‐moment correlation tests. Results: Baseline serum levels of IL‐17A and IL‐17F were positively correlated with baseline skin disease scores (r = 0.39–0.62). IL‐23 levels were correlated with skin disease scores to a lesser extent (r = 0.26–0.31). No significant correlations were observed between these cytokine or CRP levels and baseline joint disease activity. There was no significant association of baseline levels of IL‐17A, IL‐17F, IL‐23, or CRP with therapeutic response to ustekinumab in either the skin or joints. Significant reductions from baseline in levels of IL‐17A, IL‐17F, and CRP were seen in patients treated with ustekinumab compared to those treated with placebo. Ustekinumab‐treated patients in whom 75% improvement in the Psoriasis Area and Severity Index score or 20% improvement according to the American College of Rheumatology criteria was achieved after 24 weeks of treatment had greater reductions in CRP level (geometric mean decreases of 51–58% versus 32–33%; P &lt; 0.05), but not IL‐17A or IL‐17F levels, than nonresponders. Conclusion: Baseline serum IL‐23/IL‐17 levels correlated with skin, but not joint, disease activity, suggesting tissue‐specific variation. However, neither baseline Th17‐associated cytokine levels nor CRP level were predictive of therapeutic response to ustekinumab in the skin or joints, despite rapid reductions in their levels following ustekinumab therapy

MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease

MicroRNA (miRNA) has the potential for cross-regulation and functional integration of discrete biological processes during complex physiological events. Utilizing the common human condition tendinopathy as a model system to explore the cross-regulation of immediate inflammation and matrix synthesis by miRNA we observed that elevated IL-33 expression is a characteristic of early tendinopathy. Using in vitro tenocyte cultures and in vivo models of tendon damage, we demonstrate that such IL-33 expression plays a pivotal role in the transition from type 1 to type 3 collagen (Col3) synthesis and thus early tendon remodelling. Both IL-33 effector function, via its decoy receptor sST2, and Col3 synthesis are regulated by miRNA29a. Downregulation of miRNA29a in human tenocytes is sufficient to induce an increase in Col3 expression. These data provide a molecular mechanism of miRNA-mediated integration of the early pathophysiologic events that facilitate tissue remodelling in human tendon after injury

Practical synthesis of pharmaceutically relevant molecules enriched in sp3 character

The expedient synthesis of compounds enriched in sp3 character is key goal in modern drug discovery. Herein, we report how a single pot Suzuki-Miyaura-hydrogenation can be used to furnish lead and fragment-like products in good to excellent yields. The approach has been successfully applied in formats amenable to parallel synthesis, in an asymmetric sense, and in the preparation of molecules with annotated biological activity

The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis

Summary: Expression of the initiator methionine tRNA (tRNAi Met) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi Met expression levels influence tumor progression. We have found that tRNAi Met expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi Met in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi Met contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi Met gene (2+tRNAi Met mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi Met mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi Met mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi Met significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi Metoverexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl- 3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi Met-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi Met mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi Met levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis

Integrin activation - the importance of a positive feedback

Integrins mediate cell adhesion and are essential receptors for the development and functioning of multicellular organisms. Integrin activation is known to require both ligand and talin binding and to correlate with cluster formation but the activation mechanism and precise roles of these processes are not yet resolved. Here mathematical modeling, with known experimental parameters, is used to show that the binding of a stabilizing factor, such as talin, is alone insufficient to enable ligand-dependent integrin activation for all observed conditions; an additional positive feedback is required.Comment: in press in Bulletin of Mathematical Biolog

Differential Neural Responses to Food Images in Women with Bulimia versus Anorexia Nervosa

BACKGROUND: Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. METHODS: We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). RESULTS: In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. CONCLUSIONS: Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating