Cross-regional prediction of long-term trajectory of stream water DOC response to climate change

There is no scientific consensus about how dissolved organic carbon (DOC) in surface waters is regulated. Here we combine recent literature data from 49 catchments with detailed stream and catchment process information from nine well established research catchments at mid- to high latitudes to examine the question of how climate controls stream water DOC. We show for the first time that mean annual temperature (MAT) in the range from −3° to +10° C has a strong control over the regional stream water DOC concentration in catchments, with highest concentrations in areas ranging between 0° and +3° C MAT. Although relatively large deviations from this model occur for individual streams, catchment topography appears to explain much of this divergence. These findings suggest that the long-term trajectory of stream water DOC response to climate change may be more predictable than previously thought

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Hillslope Hydrology

This course addresses basic questions of how watersheds function at the plot-hillslope-catchment scale, such as: 'Where does water go when it rains?', 'How long does it reside in the watershed?', and 'What pathway does it take to the stream channel?' Materials include a series of benchmark papers and other textual resources, and a series of video lectures and virtual field trips. Educational levels: Undergraduate lower division, Undergraduate upper division

Lysine-Specific Histone Demethylase 1 Inhibitors Control Breast Cancer Proliferation in ERα-Dependent and -Independent Manners

Lysine specific demethylase 1 (LSD1, also known as KDM1) is a histone modifying enzyme that regulates the expression of many genes important in cancer progression and proliferation. It is present in various transcriptional complexes including those containing the estrogen receptor (ER). Indeed, inhibition of LSD1 activity and or expression has been shown to attenuate estrogen signaling in breast cancer cells in vitro, implicating this protein in the pathogenesis of cancer. Herein we describe experiments that utilize small molecule inhibitors, phenylcyclopropylamines, along with small interfering RNA to probe the role of LSD1 in breast cancer proliferation and in estrogen-dependent gene transcription. Surprisingly, whereas we have confirmed that inhibition of LSD1 strongly inhibits proliferation of breast cancer cells, we have determined that the cytostatic actions of LSD1 inhibition are not impacted by ER status. These data suggest that LSD1 may be a useful therapeutic target in several types of breast cancer; most notably, inhibitors of LSD1 may have utility in the treatment of ER-negative cancers for which there are minimal therapeutic options

Analysis of hydrological seasonality across northern catchments using monthly precipitation–runoff polygon metrics

Seasonality is an important hydrological signature for catchment comparison. Here, the relevance of monthly precipitation–runoff polygons (defined as scatter points of 12 monthly average precipitation–runoff value pairs connected in the chronological monthly sequence) for characterizing seasonality patterns was investigated to describe the hydrological behaviour of 10 catchments spanning a climatic gradient across the northern temperate region. Specifically, the research objectives were to: (a) discuss the extent to which monthly precipitation–runoff polygons can be used to infer active hydrological processes in contrasting catchments; (b) test the ability of quantitative metrics describing the shape, orientation and surface area of monthly precipitation–runoff polygons to discriminate between different seasonality patterns; and (c) examine the value of precipitation–runoff polygons as a basis for catchment grouping and comparison. This study showed that some polygon metrics were as effective as monthly average runoff coefficients for illustrating differences between the 10 catchments. The use of precipitation–runoff polygons was especially helpful to look at the dynamics prevailing in specific months and better assess the coupling between precipitation and runoff and their relative degree of seasonality. This polygon methodology, linked with a range of quantitative metrics, could therefore provide a new simple tool for understanding and comparing seasonality among catchments

Lysine-Specific Histone Demethylase 1 Inhibitors Control Breast Cancer Proliferation in ERα-Dependent and -Independent Manners

Lysine specific demethylase 1 (LSD1, also known as KDM1) is a histone modifying enzyme that regulates the expression of many genes important in cancer progression and proliferation. It is present in various transcriptional complexes including those containing the estrogen receptor (ER). Indeed, inhibition of LSD1 activity and or expression has been shown to attenuate estrogen signaling in breast cancer cells <i>in vitro</i>, implicating this protein in the pathogenesis of cancer. Herein we describe experiments that utilize small molecule inhibitors, phenylcyclopropylamines, along with small interfering RNA to probe the role of LSD1 in breast cancer proliferation and in estrogen-dependent gene transcription. Surprisingly, whereas we have confirmed that inhibition of LSD1 strongly inhibits proliferation of breast cancer cells, we have determined that the cytostatic actions of LSD1 inhibition are not impacted by ER status. These data suggest that LSD1 may be a useful therapeutic target in several types of breast cancer; most notably, inhibitors of LSD1 may have utility in the treatment of ER-negative cancers for which there are minimal therapeutic options