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Natural products (NPs) are fantastic sources of inspiration for novel pharmaceuticals, oftentimes showing unique bioactivity against interesting targets. Specifically, NPs containing furan moieties show activity against a variety of diseases including fungal infections, and cancers. However, it is challenging to discover and isolate these small molecules from cell supernatant. The work described herein showcases the development of a molecular probe that can covalently modify furan moieties via a [4 + 2] Diels–Alder cycloaddition, making them easily identifiable on liquid chromatography–mass spectrometry (LC–MS). The molecular probe, which undergoes this reaction with a variety of furans, was designed with both a UV-tag and a mass tag to enable easy identification. The probe has been tested with a variety of purified furans, including natural products, methylenomycin furan (MMF) hormones, and MMF derivatives. Moreover, the molecular probe has been tested in crude supernatants of various Streptomyces strains and enables identification of MMFs.

BackgroundEnd stage renal disease (ESRD) is associated with elevated fibrinogen levels and fibrinolysis inhibition. However, there is a paucity of data on how renal transplantation impacts coagulation. we hypothesize that renal transplantation recipients with good functioning grafts will have improved fibrinolytic activity following surgery.MethodsKidney recipients were analyzed pre-operatively and on post-operative day 1(POD1) using three different TEG assays with and without two concentration of tissue-plasminogen activator (t-PA). TEG indices and percent reduction in creatinine from pre-op to POD1 were measured, with >50% defining "good" graft function. Follow up was done at 6, 12, and 24 months.ResultsPercent lysis(LY30) on POD1 the t-PA TEG was significantly correlated to change creatinine from pre-op to POD-1(p = 0.006). A LY30 ≥ 23% was associated with good early graft function, and lower creatinine at 24-months(p = 0.028) compared to recipients with low POD1 LY30.ConclusionsPost-operative tPA-TEG LY30 is associated with favorable early and late outcomes in kidney transplant.

Colonization by vegetation governs variability in carbon accumulation rates in salt marshes, suggesting that accelerating sea level rise will enhance their carbon sequestration through landward expansion, according to carbon analysis and dating of cores from seven marshes in North Carolina

Ebola virus (EBOV) infection often results in fatal illness in humans, yet little is known about how EBOV usurps host pathways during infection. To address this, we used affinity tag-purification mass spectrometry (AP-MS) to generate an EBOV-host protein-protein interaction (PPI) map. We uncovered 194 high-confidence EBOV-human PPIs, including one between the viral transcription regulator VP30 and the host ubiquitin ligase RBBP6. Domain mapping identified a 23 amino acid region within RBBP6 that binds to VP30. A crystal structure of the VP30-RBBP6 peptide complex revealed that RBBP6 mimics the viral nucleoprotein (NP) binding to the same interface of VP30. Knockdown of endogenous RBBP6 stimulated viral transcription and increased EBOV replication, whereas overexpression of either RBBP6 or the peptide strongly inhibited both. These results demonstrate the therapeutic potential of biologics that target this interface and identify additional PPIs that may be leveraged for novel therapeutic strategies.

Land cover and use around the margins of estuaries has shifted since 1950 at many sites in North America due to development pressures from higher population densities. Small coastal watersheds are ubiquitous along estuarine margins and most of this coastal land-cover change occurred in these tidal creek watersheds. A change in land cover could modify the contribution of sediments from tidal creek watersheds to downstream areas and affect estuarine habitats that rely on sediments to persist or are adversely impacted by sediment loading. The resilience of wetlands to accelerating relative sea-level rise depends, in part, on the supply of lithogenic sediment to support accretion and maintain elevation; however, subtidal habitats such as oyster reefs and seagrass beds are stressed under conditions of high turbidity and sedimentation. Here we compare sediment accumulation rates before and after 1950 using 210Pb in 12 tidal creeks across two distinct regions in North Carolina, one region of low relief tidal-creek watersheds where land cover change since 1959 was dominated by fluctuations in forest, silviculture, and agriculture, and another region of relatively high relief tidal-creek watersheds where land-use change was dominated by increasing suburban development. At eight of the creeks, mass accumulation rates (g cm-2 y-1) measured at the outlet of the creeks increased contemporaneously with the largest shift in land cover, within the resolution of the land-cover data set (~5-years). All but two creek sites experienced a doubling or more in sediment accumulation rates (cm yr-1) after 1950 and most sites experienced sediment accumulation rates that exceeded the rate of local relative sea-level rise, suggesting that there is an excess of sediment being delivered to these tidal creeks and that they may slowly be infilling. After 1950, land cover within one creek watershed changed little, as did mass accumulation rates at the coring location, and another creek coring site did not record an increase in mass accumulation rates at the creek outlet despite a massive increase in development in the watershed that included the construction of retention ponds. These abundant tidal-creek watersheds have little relief, area, and flow, but they are impacted by changes in land cover more, in terms of percent area, than their larger riverine counterparts, and down-stream areas are highly connected to their associated watersheds. This work expands the scientific understanding of connectivity between lower coastal plain watersheds and estuaries and provides important information for coastal zone managers seeking to balance development pressures and environmental protections.

We report the results of drone lidar survey at a high-elevation archaeological site in the Chachapoyas region of Peruvian Amazonia. Unlike traditional airborne remote sensing, drone lidar produces very high-density measurements at a wide range of scan angles by operating at low altitudes and slow flight speeds. These measurements can resolve near vertical surfaces and novel dimensions of variability in architectural datasets. We show in a case study at Kuelap that the number of detected structures almost exactly matches the number reported from previous ground level surveys, and we use these data to quantify the relative circularity and size frequency distribution of architectural structures. We demonstrate variability in domestic architecture that was obscured in previous models produced using low-resolution remote sensing. Spatial analysis of these attributes produces new hypotheses about the site's construction history and social organization. [ABSTRACT FROM AUTHOR]

Trauma patients with hypersensitivity to tissue plasminogen activator mediated fibrinolysis quantified by tissue plasminogen activator thromboelastography are at increased risk of massive transfusion. The tissue plasminogen activator thromboelastography assay has been tested in trauma patients using native thromboelastography with no exogenous activator. We hypothesize that adding an activator will expedite the time to results. Healthy whole blood was assayed with and without exogenous plasmin, which acts to deplete inhibitors of fibrinolysis, mimicking trauma blood. Samples were assessed using native, kaolin, and rapid thromboelastography with and without tissue plasminogen activator. The tissue plasminogen activator thromboelastography indices of time to maximum amplitude and lysis at 30 minutes were contrasted between healthy blood with and without plasmin using the three different activators. The activators were then used with a tissue plasminogen activator thromboelastography in 100 trauma patients to assess performance in predicting massive transfusion. In healthy blood, regardless of activator, lysis at 30 minutes did not increase with plasmin alone, but did increase with tissue plasminogen activator (P =. 012). Adding tissue plasminogen activator and plasmin increased lysis at 30 minutes (P =. 036). Time to maximum amplitude was reduced with tissue plasminogen activator and plasmin compared with tissue plasminogen activator alone (P =. 012). Activated thromboelastographies had increased lysis at 30 minutes (P =. 002), but no difference in time to maximum amplitude compared with native thromboelastographies. In trauma patients, native tissue plasminogen activator thromboelastography had greater performance in predicting massive transfusion than activated tissue plasminogen activator thromboelastographies with no difference in time to maximum amplitude. Adding an activator to tissue plasminogen activator thromboelastography does not expedite time to maximum amplitude in healthy blood depleted of fibrinolysis inhibitors. Activated tissue plasminogen activator thromboelastographies are inferior to native tissue plasminogen activator thromboelastography for predicting massive transfusion and do not reduce the time to results. [ABSTRACT FROM AUTHOR]