Tracing the dominant sources of sediment flowing towards Lake Victoria using geochemical tracers and a Bayesian mixing model

PurposeLake Victoria has been increasingly silting over the past decades, impacting water quality and loss of biodiversity. Sediment control strategies require information on the relative and absolute contributions of sediment from different sources. However, to date, there is no continuous monitoring of sediment flux or water quality in any of the tributaries, prohibiting an assessment of the scale of the problem. The aim of this study was to trace the dominant sources of riverine sediment using geochemical fingerprinting, thereby generating a knowledge base for improving land management and reducing sediment yields in Simiyu River catchment, one of the main contributing rivers to Lake Victoria.Materials and methodsGeochemical tracer concentrations were analyzed in transported sediment from the main river and two tributaries (riverbed sediments) and from soils in five dominant land use types (agricultural land, bush land, forest land, channel banks, and main river banks). Dominant sources to the Simiyu main river sediment were attributed using the Bayesian MixSIAR model.Results and discussionThe mixing model outputs showed that the Simiyu tributary was the dominant source of sediment to the Simiyu main river with 63.2%, while the Duma tributary accounted for 36.8%. Cultivated land was shown to be the main land use source of riverine sediment, accounting for 80.0% and 86.4% in Simiyu and Duma sub-tributaries, respectively, followed by channel banks with 9.0% in both sub-tributaries. Direct unmixing of the Simiyu main river sediment to the land use sources yielded 64.7% contribution of cultivated land and 26.5% of channel banks.ConclusionThe demonstrated application of sediment source tracing provides an important pathway for quantifying the dominant sources of sediment in the rivers flowing towards Lake Victoria. Eroded soil from agricultural areas is the biggest contributor to transported sediment in the Simiyu River. This information is vital for the design of catchment wide management plans that should focus on reducing soil erosion and sediment delivery from farming areas to the river networks, ultimately supporting both food security and water quality in the Lake Victoria Basin

Two Antagonistic MALT1 Auto-Cleavage Mechanisms Reveal a Role for TRAF6 to Unleash MALT1 Activation.

The paracaspase MALT1 has arginine-directed proteolytic activity triggered by engagement of immune receptors. Recruitment of MALT1 into activation complexes is required for MALT1 proteolytic function. Here, co-expression of MALT1 in HEK293 cells, either with activated CARD11 and BCL10 or with TRAF6, was used to explore the mechanism of MALT1 activation at the molecular level. This work identified a prominent self-cleavage site of MALT1 isoform A (MALT1A) at R781 (R770 in MALT1B) and revealed that TRAF6 can activate MALT1 independently of the CBM. Intramolecular cleavage at R781/R770 removes a C-terminal TRAF6-binding site in both MALT1 isoforms, leaving MALT1B devoid of the two key interaction sites with TRAF6. A previously identified auto-proteolysis site of MALT1 at R149 leads to deletion of the death-domain, thereby abolishing interaction with BCL10. By using MALT1 isoforms and cleaved fragments thereof, as well as TRAF6 WT and mutant forms, this work shows that TRAF6 induces N-terminal auto-proteolytic cleavage of MALT1 at R149 and accelerates MALT1 protein turnover. The MALT1 fragment generated by N-terminal self-cleavage at R149 was labile and displayed enhanced signaling properties that required an intact K644 residue, previously shown to be a site for mono-ubiquitination of MALT1. Conversely, C-terminal self-cleavage at R781/R770 hampered the ability for self-cleavage at R149 and stabilized MALT1 by hindering interaction with TRAF6. C-terminal self-cleavage had limited impact on MALT1A but severely reduced MALT1B proteolytic and signaling functions. It also abrogated NF-κB activation by N-terminally cleaved MALT1A. Altogether, this study provides further insights into mechanisms that regulate the scaffolding and activation cycle of MALT1. It also emphasizes the reduced functional capacity of MALT1B as compared to MALT1A

Crystal structure of the anthrax lethal factor

Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax(1-3). It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways(4-6). Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62772/1/414229a0.pd

Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation

In mammals, ∼100 deubiquitinases act on ∼20,000 intracellular ubiquitination sites. Deubiquitinases are commonly regarded as constitutively active, with limited regulatory and targeting capacity. The BRCA1-A and BRISC complexes serve in DNA double-strand break repair and immune signaling and contain the lysine-63 linkage-specific BRCC36 subunit that is functionalized by scaffold subunits ABRAXAS and ABRO1, respectively. The molecular basis underlying BRCA1-A and BRISC function is currently unknown. Here we show that in the BRCA1-A complex structure, ABRAXAS integrates the DNA repair protein RAP80 and provides a high-affinity binding site that sequesters the tumor suppressor BRCA1 away from the break site. In the BRISC structure, ABRO1 binds SHMT2α, a metabolic enzyme enabling cancer growth in hypoxic environments, which we find prevents BRCC36 from binding and cleaving ubiquitin chains. Our work explains modularity in the BRCC36 DUB family, with different adaptor subunits conferring diversified targeting and regulatory functions.ISSN:1097-2765ISSN:1097-416

Health costs in anthroposophic therapy users: a two-year prospective cohort study

BACKGROUND: Anthroposophic therapies (counselling, special medication, art, eurythmy movement, and rhythmical massage) aim to stimulate long-term self-healing processes, which theoretically could lead to a reduction of healthcare use. In a prospective two-year cohort study, anthroposophic therapies were followed by a reduction of chronic disease symptoms and improvement of quality of life. The purpose of this analysis was to describe health costs in users of anthroposophic therapies. METHODS: 717 consecutive outpatients from 134 medical practices in Germany, starting anthroposophic therapies for chronic diseases, participated in a prospective cohort study. We analysed direct health costs (anthroposophic therapies, physician and dentist consultations, psychotherapy, medication, physiotherapy, ergotherapy, hospital treatment, rehabilitation) and indirect costs (sick leave compensation) in the pre-study year and the first two study years. Costs were calculated from resource utilisation, documented by patient self-reporting. Data were collected from January 1999 to April 2003. RESULTS: Total health costs in the first study year (bootstrap mean 3,297 Euro; 95% confidence interval 95%-CI 3,157 Euro to 3,923 Euro) did not differ significantly from the pre-study year (3,186 Euro; 95%-CI 3,037 Euro to 3,711 Euro), whereas in the second year, costs (2,771 Euro; 95%-CI 2,647 Euro to 3,256 Euro) were significantly reduced by 416 Euro (95%-CI 264 Euro to 960 Euro) compared to the pre-study year. In each period hospitalisation and sick-leave together amounted to more than half of the total health costs. Anthroposophic therapies and medication amounted to 3%, 15%, and 8% of total health costs in the pre-study year, first year, and second study year, respectively. The cost reduction in the second year was largely accounted for by a decrease of inpatient hospitalisation, leading to a hospital cost reduction of 519 Euro (95%-CI 377 Euro to 904 Euro) compared to the pre-study year. CONCLUSION: In patients starting anthroposophic therapies for chronic disease, total health costs did not increase in the first year, and were reduced in the second year. This reduction was largely explained by a decrease of inpatient hospitalisation. Within the limits of a pre-post design, study findings suggest that anthroposophic therapies are not associated with a relevant increase in total health costs