Ambrein: a minor, but common constituent of mammalian faeces?

For nearly 200 years, the only natural source of the alcohol ambrein has been coproliths produced in about 1% of sperm whales and in related jetsam. However, the finding of ambrein in adipocere/faeces of human corpses, led us to hypothesise that ambrein might occur in the faeces of other mammals. Herein, we used a recently developed gas chromatography-mass spectrometry method, with suitable derivatisation of the hindered hydroxy group of ambrein, to screen a number of extracts of mammalian faeces. Minor proportions of ambrein were detected in digested human sewage sludge and in the dung of elephant, domestic cattle, giraffe and buffalo. Whether ambrein formation in the terrestrial species is associated with coprolith formation, is unknown, but solid deposits known as enteroliths and fecaliths occur in humans and some domestic animals

Tracking Holocene palaeostratification and productivity changes in the Western Irish Sea: A multi-proxy record

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The Western Irish Sea preserves an exceptionally thick (ca. 40 m) Holocene succession that is ideally suited to understanding the pattern of palaeostratification and water mass productivity changes in the region, and their relationship with sea level, sedimentation, and biota. Additionally, the presence of shallow-buried methane provides an opportunity to explore its potential impact on the local pattern of Holocene marine environmental change. Multi-proxy investigation of a cored borehole succession through the Holocene interval tracks changes from mixed to seasonally stratified conditions. In the earliest Holocene (11.2–10 ka), high productivity, mixed water conditions prevailed, with abundant and diverse foraminifera and dominant heterotrophic dinoflagellate cysts. Productivity was probably driven by high nutrient fluxes related to high rates of sedimentation (>1600 cm/kyr), in turn influenced by relatively low sea level and restricted sediment accommodation space across shelf areas to the east of the borehole site (eastern Irish Sea Basin). With rising sea level in the later part of the Early Holocene, the region evolved into a relatively lower productivity mixed water mass system, with significant changes in ecology revealed by dinoflagellate cysts and foraminifera. In the latest Early Holocene and earliest Mid Holocene (ca. 8.4–8.2 ka) a return to higher productivity is signalled by dinoflagellate cyst data; a result of seasonal stratification becoming established, evidenced by sharply increased summer sea surface temperature estimates (typically 16–17 °C) that contrast with an opposite (more positive) trend in δ18O values for benthic foraminifera. Reductions in turbulent mixing associated with stratification might have exacerbated the palaeoecological impact of shallow-buried methane associated with the borehole site, potentially evidenced by a significant change in dominant benthic foraminifera and strong, localised excursions in the benthic δ13C/δ18O record

Controls on amorphous organic matter type and sulphurization in a Mississippian black shale

Paleoredox proxies (Fe speciation, trace element and δ34Spy) integrated with sedimentological and palynological observations link the distribution and type of particulate organic matter (OM) preserved to hydrocarbon source rock potential. In the Mississippian Bowland Shale Formation (Lancashire, UK), particulate OM is dominated by “heterogeneous” amorphous OM (AOM), primarily “sharp-edged, pellet-like” (AOMpel) and “heterogeneous, granular” (AOMgr) types. AOMpel is abundant in muds deposited under anoxic and moderately to highly sulphidic conditions and most likely represents the fecal minipellets of zooplankton and/or pellets of macro-zooplankters. We recognize two intervals, “A” and “B,” which exhibit Sorg/TOC > 0.04, suggesting a bulk Type II-S kerogen composition. The Interval A palynofacies is typified by pyritized AOMpel (AOMpyr) particles that contain high-relief organic spheres surrounding individual pyrite framboids, within each AOMpyr particle. These textures are interpreted as sulphurized OM local to pyrite framboids (Sorg-PF). Sorg-PF is rarely observed in Interval B, and absent in all other samples. Redox oscillation between ferruginous and euxinic conditions during early diagenesis of Interval A likely promoted S cycling in microenvironments surrounding pyrite framboids, which generated reactive S species and reactive OM required for sulphurization. Early diagenetic redox oscillation processes were apparently triggered by relative sea level fall, associated with an increased supply of FeHR from adjacent shelves into the basin. Interval B represents deposition during the late stages of basin infill and transition from anoxic to (sub)oxic bottom waters, where AOMpel is replaced by AOMgr as the dominant type of AOM. A large particle diameter at the limit of the mesh size (500 μm), sheet-like, fragmented character, and presence of candidate organic sheaths suggests AOMgr at least partially represent fragments of benthic microbial mats, probably as sulphide-oxidizers. A ternary plot of AOMpel + AOMpyr versus AOMgr versus spores + phytoclasts links the observed palynofacies to bottom and pore water redox conditions, water column productivity and proximity to fluvial (deltaic) supply of spores and phytoclasts. These variables were moderated by changing basin accommodation, driven primarily by eustatic sea level fluctuation. A sequence-stratigraphic control on AOM type and sulphurization is important for understanding the link between source rock heterogeneity and the timing of hydrocarbon generation and expulsion from this source rock

DNA topoisomerases participate in fragility of the oncogene RET

Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting

Age-related difference in susceptibility of ApcMin/+ mice towards the chemopreventive efficacy of dietary aspirin and curcumin

The nonsteroidal anti-inflammatory drug aspirin and the spice curcumin retard adenoma formation when administered long-term to ApcMin/+ mice, a model of human familial adenomatous polyposis coli. Both agents interfere with cyclooxygenase activity. When aspirin is administered to ApcMin/+ mice only postweaning, but not before, it is inefficacious, while curcumin given postweaning is active. Here the hypothesis was tested that dietary aspirin (0.05%) or curcumin (0.2%) prevent or delay adenoma formation in offsprings when administered to ApcMin/+ mothers and up to the end of weaning, but not afterwards. Whereas curcumin was without effect when administered in this way, aspirin reduced numbers of intestinal adenomas by 21%. When aspirin given up to the end of weaning was combined with curcumin administered from the end of weaning for the rest of the animals' lifetime, intestinal adenoma numbers were reduced by 38%. The combination was not superior to intervention postweaning with curcumin alone. These results show that aspirin exerts chemopreventive activity in the ApcMin/+ mouse during tumour initiation/early promotion, while curcumin is efficacious when given at a later stage of carcinogenic progression. Thus, the results suggest that in this mouse model aspirin and curcumin act during different ‘windows’ of neoplastic development

Dietary Blue Pigments Derived from Genipin, Attenuate Inflammation by Inhibiting LPS-Induced iNOS and COX-2 Expression via the NF-κB Inactivation

The edible blue pigments produced by gardenia fruits have been used as value-added colorants for foods in East Asia for 20 years. However, the biological activity of the blue pigments derived from genipin has not been reported.The anti-inflammatory effect of blue pigments was studied in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage in vitro. The secretions of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) were inhibited in concentration-dependent manner by blue pigments. Real-time reverse-transcription polymerase chain reaction (Real-time RT-PCR) analyses demonstrated that the mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α) was inhibited, moreover, ELISA results showed that the productions of IL-6 and TNF-α were inhibited. Cell-based ELISA revealed the COX-2 protein expression was inhibited. The proteome profiler array showed that 12 cytokines and chemokines involved in the inflammatory process were down-regulated by blue pigments. Blue pigments inhibited the nuclear transcription factor kappa-B (NF-κB) activation induced by LPS, and this was associated with decreasing the DNA-binding activity of p65 and p50. Furthermore, blue pigments suppressed the degradation of inhibitor of κB (IκB) α, Inhibitor of NF-κB Kinase (IKK) α, IKK-β, and phosphorylation of IκB-α. The anti-inflammatory effect of blue pigments in vivo was studied in carrageenan-induced paw edema and LPS-injecting ICR mice. Finally, blue pigments significantly inhibited paw swelling and reduced plasma TNF-α and IL-6 production in vivo.These results suggest that the anti-inflammatory properties of blue pigments might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1β, and TNF-α expression through the down-regulation of NF-κB activation, which will provide strong scientific evidence for the edible blue pigments to be developed as a new health-enhancing nutritional food for the prevention and treatment of inflammatory diseases