Antioxidative activity of Silibum marianum cultivated in Mongolia

Silibum marianum (Milk thistle) contains high amount of phenolic compounds with antioxidant properties. The aim of this work was to evaluate the antioxidant activity of  phenolic compounds included in Milk thistle. The  antioxidant properties of the leaves and seeds of milk thistle were examined by determining its ability to scavenge the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. The results obtained from DPPH assay confirm that Milk thistle extracts have high antioxidative activity.DOI: http://doi.dx.org/10.5564/mjc.v15i0.323 Mongolian Journal of Chemistry 15 (41), 2014, p53-5

A Survey on Approximation Mechanism Design without Money for Facility Games

In a facility game one or more facilities are placed in a metric space to serve a set of selfish agents whose addresses are their private information. In a classical facility game, each agent wants to be as close to a facility as possible, and the cost of an agent can be defined as the distance between her location and the closest facility. In an obnoxious facility game, each agent wants to be far away from all facilities, and her utility is the distance from her location to the facility set. The objective of each agent is to minimize her cost or maximize her utility. An agent may lie if, by doing so, more benefit can be obtained. We are interested in social choice mechanisms that do not utilize payments. The game designer aims at a mechanism that is strategy-proof, in the sense that any agent cannot benefit by misreporting her address, or, even better, group strategy-proof, in the sense that any coalition of agents cannot all benefit by lying. Meanwhile, it is desirable to have the mechanism to be approximately optimal with respect to a chosen objective function. Several models for such approximation mechanism design without money for facility games have been proposed. In this paper we briefly review these models and related results for both deterministic and randomized mechanisms, and meanwhile we present a general framework for approximation mechanism design without money for facility games

The fungus Neurospora crassa displays telomeric silencing mediated by multiple sirtuins and by methylation of histone H3 lysine 9

<p>Abstract</p> <p>Background</p> <p>Silencing of genes inserted near telomeres provides a model to investigate the function of heterochromatin. We initiated a study of telomeric silencing in <it>Neurospora crassa</it>, a fungus that sports DNA methylation, unlike most other organisms in which telomeric silencing has been characterized.</p> <p>Results</p> <p>The selectable marker, <it>hph</it>, was inserted at the subtelomere of Linkage Group VR in an <it>nst-1 </it>(n<it>eurospora </it>s<it>ir </it>t<it>wo</it>-1) mutant and was silenced when <it>nst-1 </it>function was restored. We show that NST-1 is an H4-specific histone deacetylase. A second marker, <it>bar</it>, tested at two other subtelomeres, was similarly sensitive to <it>nst-1 </it>function. Mutation of three additional SIR2 homologues, <it>nst-2</it>, <it>nst-3 </it>and <it>nst-5</it>, partially relieved silencing. Two genes showed stronger effects: <it>dim-5</it>, which encodes a histone H3 K9 methyltransferase and <it>hpo</it>, which encodes heterochromatin protein-1. Subtelomeres showed variable, but generally low, levels of DNA methylation. Elimination of DNA methylation caused partial derepression of one telomeric marker. Characterization of histone modifications at subtelomeric regions revealed H3 trimethyl-K9, H3 trimethyl-K27, and H4 trimethyl-K20 enrichment. These modifications were slightly reduced when telomeric silencing was compromised. In contrast, acetylation of histones H3 and H4 increased.</p> <p>Conclusion</p> <p>We demonstrate the presence of telomeric silencing in Neurospora and show a dependence on histone deacetylases and methylation of histone H3 lysine 9. Our studies also reveal silencing functions for DIM-5 and HP1 that appear independent of their role in <it>de novo </it>DNA methylation.</p

Effectiveness of offloading interventions to heal foot ulcers in persons with diabetes: a systematic review

Background Offloading interventions are commonly used in clinical practice to heal foot ulcers. The aim of this updated systematic review is to investigate the effectiveness of offloading interventions to heal diabetic foot ulcers. Methods We updated our previous systematic review search of PubMed, EMBASE, and Cochrane databases to also include original studies published between July 29, 2014 and August 13, 2018 relating to four offloading intervention categories in populations with diabetic foot ulcers: (a) offloading devices, (b) footwear, (c) other offloading techniques, and (d) surgical offloading techniques. Outcomes included ulcer healing, plantar pressure, ambulatory activity, adherence, adverse events, patient‐reported measures, and cost‐effectiveness. Included controlled studies were assessed for methodological quality and had key data extracted into evidence and risk of bias tables. Included non‐controlled studies were summarised on a narrative basis. Results We identified 41 studies from our updated search for a total of 165 included studies. Six included studies were meta‐analyses, 26 randomised controlled trials (RCTs), 13 other controlled studies, and 120 non‐controlled studies. Five meta‐analyses and 12 RCTs provided high‐quality evidence for non‐removable knee‐high offloading devices being more effective than removable offloading devices and therapeutic footwear for healing plantar forefoot and midfoot ulcers. Total contact casts (TCCs) and non‐removable knee‐high walkers were shown to be equally effective. Moderate‐quality evidence exists for removable knee‐high and ankle‐high offloading devices being equally effective in healing, but knee‐high devices have a larger effect on reducing plantar pressure and ambulatory activity. Low‐quality evidence exists for the use of felted foam and surgical offloading to promote healing of plantar forefoot and midfoot ulcers. Very limited evidence exists for the efficacy of any offloading intervention for healing plantar heel ulcers, non‐plantar ulcers, and neuropathic ulcers with infection or ischemia. Conclusion Strong evidence supports the use of non‐removable knee‐high offloading devices (either TCC or non‐removable walker) as the first‐choice offloading intervention for healing plantar neuropathic forefoot and midfoot ulcers. Removable offloading devices, either knee‐high or ankle‐high, are preferred as second choice over other offloading interventions. The evidence bases to support any other offloading intervention is still weak and more high‐quality controlled studies are needed in these areas

Parallel symbolic state-space exploration is difficult, but what is the alternative?

State-space exploration is an essential step in many modeling and analysis problems. Its goal is to find the states reachable from the initial state of a discrete-state model described. The state space can used to answer important questions, e.g., "Is there a dead state?" and "Can N become negative?", or as a starting point for sophisticated investigations expressed in temporal logic. Unfortunately, the state space is often so large that ordinary explicit data structures and sequential algorithms cannot cope, prompting the exploration of (1) parallel approaches using multiple processors, from simple workstation networks to shared-memory supercomputers, to satisfy large memory and runtime requirements and (2) symbolic approaches using decision diagrams to encode the large structured sets and relations manipulated during state-space generation. Both approaches have merits and limitations. Parallel explicit state-space generation is challenging, but almost linear speedup can be achieved; however, the analysis is ultimately limited by the memory and processors available. Symbolic methods are a heuristic that can efficiently encode many, but not all, functions over a structured and exponentially large domain; here the pitfalls are subtler: their performance varies widely depending on the class of decision diagram chosen, the state variable order, and obscure algorithmic parameters. As symbolic approaches are often much more efficient than explicit ones for many practical models, we argue for the need to parallelize symbolic state-space generation algorithms, so that we can realize the advantage of both approaches. This is a challenging endeavor, as the most efficient symbolic algorithm, Saturation, is inherently sequential. We conclude by discussing challenges, efforts, and promising directions toward this goal

Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease

BACKGROUND: Little is known about the roles of myeloid cell subsets in kidney injury and in the limited ability of the organ to repair itself. Characterizing these cells based only on surface markers using flow cytometry might not provide a full phenotypic picture. Defining these cells at the single-cell, transcriptomic level could reveal myeloid heterogeneity in the progression and regression of kidney disease. METHODS: Integrated droplet– and plate-based single-cell RNA sequencing were used in the murine, reversible, unilateral ureteric obstruction model to dissect the transcriptomic landscape at the single-cell level during renal injury and the resolution of fibrosis. Paired blood exchange tracked the fate of monocytes recruited to the injured kidney. RESULTS: A single-cell atlas of the kidney generated using transcriptomics revealed marked changes in the proportion and gene expression of renal cell types during injury and repair. Conventional flow cytometry markers would not have identified the 12 myeloid cell subsets. Monocytes recruited to the kidney early after injury rapidly adopt a proinflammatory, profibrotic phenotype that expresses Arg1, before transitioning to become Ccr2(+) macrophages that accumulate in late injury. Conversely, a novel Mmp12(+) macrophage subset acts during repair. CONCLUSIONS: Complementary technologies identified novel myeloid subtypes, based on transcriptomics in single cells, that represent therapeutic targets to inhibit progression or promote regression of kidney disease

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Neuroprotective Effect of Transplanted Human Embryonic Stem Cell-Derived Neural Precursors in an Animal Model of Multiple Sclerosis

BACKGROUND: Multiple sclerosis (MS) is an immune mediated demyelinating disease of the central nervous system (CNS). A potential new therapeutic approach for MS is cell transplantation which may promote remyelination and suppress the inflammatory process. METHODS: We transplanted human embryonic stem cells (hESC)-derived early multipotent neural precursors (NPs) into the brain ventricles of mice induced with experimental autoimmune encephalomyelitis (EAE), the animal model of MS. We studied the effect of the transplanted NPs on the functional and pathological manifestations of the disease. RESULTS: Transplanted hESC-derived NPs significantly reduced the clinical signs of EAE. Histological examination showed migration of the transplanted NPs to the host white matter, however, differentiation to mature oligodendrocytes and remyelination were negligible. Time course analysis of the evolution and progression of CNS inflammation and tissue injury showed an attenuation of the inflammatory process in transplanted animals, which was correlated with the reduction of both axonal damage and demyelination. Co-culture experiments showed that hESC-derived NPs inhibited the activation and proliferation of lymph node-derived T cells in response to nonspecific polyclonal stimuli. CONCLUSIONS: The therapeutic effect of transplantation was not related to graft or host remyelination but was mediated by an immunosuppressive neuroprotective mechanism. The attenuation of EAE by hESC-derived NPs, demonstrated here, may serve as the first step towards further developments of hESC for cell therapy in MS

Humanity or justice?

This paper reflects on a critique of cosmopolitanism mounted by Tom Campbell, who argues that cosmopolitans place undue stress on the issue of global justice. Campbell argues that aid for the impoverished needy in the third world, for example, should be given on the Principle of Humanity rather than on the Principle of Justice. This line of thought is also pursued by &lsquo;Liberal Nationalists&rsquo; like Yael Tamir and David Miller. Thomas Nagel makes a similar distinction and questions whether the ideal of justice can even be meaningfully applied on a global scale. The paper explores whether the distinction between the Principle of Humanity and the Principle of Justice might be a false dichotomy in that both principles could be involved in humanitarian assistance. It will suggest that both principles might be grounded in an ethics of caring and that the ethics of caring cannot be so sharply distinguished from the discourse of justice and of rights. As a result, the Principle of Humanity and the Principle of Justice cannot be so sharply distinguished either. It is because we care about others as human beings (Principle of Humanity) that we pursue justice for them (Principle of Justice) and the alleviation of their avoidable suffering