Schneidersaunders7148

This study was aimed at identifying and quantifying mixing proportions in surface waters downstream of historical Cu-W-F skarn mine tailings at Yxsjöberg, Sweden, using 18O, 2H, and 87Sr/86Sr isotopes. In addition, a simple mathematical model was developed to evaluate the consistency of the mixing calculations. Hydrochemical and isotopic data from 2 groundwater wells, 6 surface water and 2 rainwater sampling sites, spanning 6 sampling campaigns between May and October were used. Three mixed surface waters downstream of the tailings were identified, namely C7, C11 and C14. C7 was directly influenced by groundwater from the tailings whereas C11 was also subsequently influenced by C7. C14 on the other hand, had contributions from C11. Sequential mixing calculations indicated that the contribution of the groundwater to C7 ranges from 1 to 17%. The subsequent contribution of C7 to C11 varied from 49 to 91% whereas C14 had contributions of C11 ranging between 16 and 56%. A strong agreement between the model data (MD) and measured raw data (RD) for C11 and C14 indicated the accuracy of the mixing calculations. Variations between the MD and RD at C7, however, was mainly due to sorption and reductive processes underneath the tailings, which tend to attenuate the amount of dissolved ions reaching the surface waters, resulting in a low ionic contribution of the tailings groundwater to the surface water. The low ionic contribution of the groundwater to C7 suggested that although the tailings impoundment is of environmental concern, its impact on the downstream surface waters is small. The results of this study suggest that mixing calculations in surface waters involving a closed system such as groundwater (as an end-member) must be treated with caution. It is recommended that the interpretation of such mixing results must be coupled with detailed knowledge of the potential hydrogeochemical processes along its flow paths. Trypanosomatids are a monophyletic group of parasitic flagellated protists belonging to the order Kinetoplastida. Their cytoskeleton is primarily made up of microtubules in which no actin microfilaments have been detected. Although all these parasites contain actin, it is widely thought that their actin cytoskeleton is reduced when compared to most eukaryotic organisms. However, there is increasing evidence that it is more complex than previously thought. As in other eukaryotic organisms, trypanosomatids encode for a conventional actin that is expected to form microfilament-like structures, and for members of three conserved actin-related proteins probably involved in microfilament nucleation (ARP2, ARP3) and in gene expression regulation (ARP6). 10074-G5 clinical trial In addition to these canonical proteins, also encode for an expanded set of actins and actin-like proteins that seem to be restricted to kinetoplastids. Analysis of their amino acid sequences demonstrated that, although very diverse in primary sequence when compared onfusum (an early branching trypanosomatid) and in Bodo saltans (a closely related free-living organism belonging to the trypanosomatid sister order of Bodonida) suggesting they were all present in their common ancestor. Secondary losses of these genes may have occurred during speciation within the trypanosomatids, with salivarian trypanosomes having lost many of them and stercorarian trypanosomes retaining most. Conserved amongst all eukaryotes is a family of mitochondrial carrier proteins (SLC25A) responsible for the import of various solutes across the inner mitochondrial membrane. We previously reported that the human parasite Trypanosoma brucei possesses 26 SLC25A proteins (TbMCPs) amongst which two, TbMCP11 and TbMCP8, were predicted to function as phosphate importers. The transport of inorganic phosphate into the mitochondrion is a prerequisite to drive ATP synthesis by substrate level and oxidative phosphorylation and thus crucial for cell viability. In this paper we describe the functional characterization of TbMCP11. In procyclic form T. brucei, the RNAi of TbMCP11 blocked ATP synthesis on mitochondrial substrates, caused a drop of the mitochondrial oxygen consumption and drastically reduced cell viability. The functional complementation in yeast and mitochondrial swelling experiments suggested a role for TbMCP11 as inorganic phosphate carrier. Interestingly, procyclic form T. brucei cells in which TbMCP11 was depleted displayed an inability to either replicate or divide the kinetoplast DNA, which resulted in a severe cytokinesis defect. The article is an 'In Memoriam' article honouring the memory of Sir Michael Berridge. Long-term treatment with 3-nitropropionic acid (3-NPA), a toxin derived from plants and fungi, may reproduce symptoms and biochemical characteristics of Huntington's disease (HD). Our study evaluated the effects of 3-NPA on the physiological and behavioral responses in zebrafish larvae and adults. Larvae exposed to 0.1, 0.2, or 0.5 mM 3-NPA exhibited an increase in heart rate at 2- and 5-days post-fertilization (dpf). There was a decrease in the ocular distance at 5 dpf with 0.05 mM 3-NPA treatment. However, 3-NPA did not alter larval locomotor parameters. Adult zebrafish received 3-NPA intraperitoneal injections (a total of seven injections at doses 10, 20, or 60 mg/kg every 96 h) and showed a decrease in weight loss, locomotion and aggressive behavior. No changes were observed in anxiety-like behavior and social interaction between 3-NPA-exposed animals and control groups. However, 3-NPA-treated animals (at 60 mg/kg) demonstrated impaired long-term aversive memory. Overall, 3-NPA exposure induced morphological and heart rate alterations in zebrafish larvae. Additionally, our study showed behavioral changes in zebrafish that were submitted to long-term 3-NPA treatment, which could be related to HD symptoms. Acute liver failure (ALF) is a life-threatening illness that occurs in the absence of pre-existing liver disease. When symptoms seriously progress under continuous supportive medical care, liver transplantation becomes the only therapeutic strategy. However, the available sources of organs for liver transplantation differ worldwide. In regions in which organs from cadaveric donors are more common, deceased donor liver transplantation (DDLT) is performed in this urgent situation. Conversely, in countries where cadaveric donors are scarce, living donor liver transplantation (LDLT) is the only choice. Special considerations must be made for urgent LDLT for ALF, including the expedited evaluation of living donors, technical issues, and the limitations of ABO blood type combinations between recipients and donor candidates. In this review, we highlight the role of LDLT for ALF and the considerations that distinguish it from DDLT. LDLT is well-established as a life-saving procedure for ALF patients and there is often no alternative to LDLT, especially in countries where DDLT is not feasible. However, from a global perspective, an increase in the deceased donor pool might be an urgent and important necessity. Dynamic preservation strategies are a promising option to improve graft quality before transplantation, and to extend preservation time for either logistic or treatment reasons. In contrast to normothermic oxygenated perfusion, which intends to mimic physiological conditions in the human body, with subsequent clinical application for up to 24 hrs, hypothermic perfusion is mainly used for a relatively short period with protection of mitochondria and subsequent reduction of oxidative injury upon implantation. The results from two randomized controlled trials, where recruitment has finished are expected this year. Both ex situ perfusion techniques are increasingly applied in clinical transplantation including recent reports on viability assessment, which could open the door for an increased liver utilization in the future. Eight previously undescribed diterpenoids, euphoroyleans A-H, including two cembranes, three ingenanes, two ent-atisanes, and one ent-kaurane, along with 22 known analogues were isolated from the whole plants of Euphorbia royleana. The structures of euphoroyleans A-H, including the absolute configurations, were elucidated by extensive spectroscopic analyses, chemical transformation, and single crystal X-ray diffractions. All the isolates were screened for their chemoreversal abilities on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) cancer cell line HepG2/DOX, and eight compounds exhibited significant activities. Among them, ingol-3,7,12-triacetate-8-benzoate, the most active MDR modulator with no obvious cytotoxicity, could enhance the efficacy of anticancer drug DOX to ca. 105 folds at 10 μM, being stronger than the positive drug verapamil. Mechanistic study revealed that ingol-3,7,12-triacetate-8-benzoate could inhibit the transport activity of P-gp rather than its expression, and the possible recognition mechanism between compounds and P-gp was predicted by molecular docking. Metallothioneins (MTs) are low molecular weight, cysteine-rich, metal-binding proteins that are important for essential metal homeostasis, protection against oxidative stress, and buffering against toxic heavy metals. In this work the gene encoding an MT type 2 from Avicennia marina (Forssk.) Vierh. (AmMT2) was cloned into pET41a and transformed into the Escherichia coli strain Rosetta (DE3). Following the induction with isopropyl β-D-1-thiogalactopyranoside, AmMT2 was expressed as glutathione-S-transferase (GST)-tagged fusion protein. The accumulation of Zn2+, Cu2+, Fe2+, Ni2+ and Cd2+ for strain R-AmMT2 was 4, 8, 5.4, 2 and 1.6 fold of control strain suggesting the role of AmMT2 in accumulation of metals. Particularly the strain R-AmMT2 was able to accumulate 30.7 mg per g dry weight. The cells expressing AmMT2 was more tolerant to hydrogen peroxide and had higher catalase (CAT) activity. To understand the mechanistic action of AmMT2 hydrogen peroxide tolerance, the activity of CAT in the E. coli protein extract was assayed after addition of pure Fe2+/GST-AmMT complex and Apo/GST-AmMT2 in vitro. Whereas, the activity of CAT did not change by the addition of Apo/GST-AmMT2, the activity of CAT significantly increased after addition of Fe2+/GST-AmMT2. These results show that AmMT2 activates CAT through Fe2+ transfer which subsequently causes the oxidative stress tolerance. The current study aims to evaluate whether peripheral blood miR-324-5p could be used to differentiate patients with metabolic disorders and healthy controls. Our data showed that miR-324-5p levels were elevated in the peripheral blood of patients with hyperglycemia or hyperlipidemia. In addition, the expression of miR-324-5p was enhanced in the peripheral blood and liver of db/db mice. Further study indicated that overexpression of miR-324-5p reduced the activation of the AKT/GSK pathway and increased lipid accumulation, while the inhibition of miR-324-5p activated the AKT/GSK pathway and decreased lipid accumulation. A dual luciferase assay revealed that Rho-associated coiled-coil containing protein kinase 1 (ROCK1) was a target gene of miR-324-5p. In addition, silencing ROCK1 deteriorated lipid and glucose metabolism. More importantly, knockdown of ROCK1 reversed the miR-324-5p inhibitor-induced improvement of glucose and lipid metabolism. In summary, miR-324-5p plays a regulatory role in glucose and lipid metabolism by targeting ROCK1, which is involved in metabolic disorders.