Increased Adenine Nucleotide Degradation in Skeletal Muscle Atrophy

Adenine nucleotides (AdNs: ATP, ADP, AMP) are essential biological compounds that facilitate many necessary cellular processes by providing chemical energy, mediating intracellular signaling, and regulating protein metabolism and solubilization. A dramatic reduction in total AdNs is observed in atrophic skeletal muscle across numerous disease states and conditions, such as cancer, diabetes, chronic kidney disease, heart failure, COPD, sepsis, muscular dystrophy, denervation, disuse, and sarcopenia. The reduced AdNs in atrophic skeletal muscle are accompanied by increased expression/activities of AdN degrading enzymes and the accumulation of degradation products (IMP, hypoxanthine, xanthine, uric acid), suggesting that the lower AdN content is largely the result of increased nucleotide degradation. Furthermore, this characteristic decrease of AdNs suggests that increased nucleotide degradation contributes to the general pathophysiology of skeletal muscle atrophy. In view of the numerous energetic, and non-energetic, roles of AdNs in skeletal muscle, investigations into the physiological consequences of AdN degradation may provide valuable insight into the mechanisms of muscle atrophy

Time to Leave Uchronia: Queer Eco-Temporalities for a Livable World

My dissertation is a Feminist contribution to Environmental Political Theory focused on temporality. My research investigates the tension between the urgent need to act fast in a fast-changing world, and the necessity for time to pause and think through such radical and rapid changes. As it signals our nearing the planet’s limits, the emergence of the “anthropocene” crisis challenges growth-driven “progress.” I begin this dissertation with a survey of Environmental Thought that helps situate my contribution to the ongoing debates in this field, underscoring that as ecosophers pose the question of the nonhuman, in so doing they also are confronted with problems related to temporality. Then, building on the concept of “utopia,” I critique a temporality that assumes infinite growth on a planet with finite resources, while constantly postponing its promises of abundance to an impossible future. The concept I propose is “uchronia”: growth-driven progress is a timeless (ou-chronos), dangerously idealized (eu-chronos) temporality, just like “utopia” refers to both a “nowhere” place and an “ideal” place (ou- and eu-topos). I draw from Nietzsche’s concept of eternal return to problematize teleologies of progress: the eternal return prompts us to live our lives as though we were prepared to re-live them eternally. In contrast with uchronia, alternative, queer eco-temporalities – I call these “anti-uchronia,” “heterochronia,” and “synchrony” – build upon and radicalize sustainability. However, not all “eco-temporalities” – alternatives to the hegemonic, in-crisis temporalities – constitute themselves as non-linear or radical – i.e not all of them are queer: I have also coined the concept of “counter-uchronia” to describe certain understandings of “sustainable growth,” justifications of geoengineering and carbon markets creation, as well as primitivist (often virilist) environmentalist discourses which respectively advocate the “return” to a golden past of harmony with (often feminized) “Nature,” or technofixes and green capitalism to amend and resume growth-driven progress’ uchronian course. To advance this conceptual framework, I offer close readings of environmental science fiction stories, activist manifestos, graffiti art, performing arts including contemporary dance and circus, as well as the Intergovernmental Panel on Climate Change scientific reports

Impact of Tumor-Derived CCL2 on Macrophage Effector Function

Monocyte chemoattractant protein-1 (MCP-1, CCL2) is produced by many different types of cells. In the current investigation, the effect of tumor-derived CCL2 on macrophages was evaluated to determine the extent to which this chemokine influenced the innate immune response to cancer. To do this, we used the 4T1 murine mammary carcinoma cell line that constitutively expresses CCL2 and generated 4T1 expressing an antisense CCL2 transcript. The antisense-CCL2-expressing 4T1 produced no detectable CCL2. Macrophages from female BALB/c mice were exposed to supernatants from these tumor cells. The results showed that tumor-derived CCL2 was capable of modulating cytokine gene expression but not protein production in resting, activated, and tumor-associated macrophages. In addition, tumor-derived CCL2 did not affect phagocytic activity, nitric oxide production, or cytolytic activity of the macrophages. Overall, these data suggest that tumor-derived CCL2 does not directly influence macrophage-mediated antitumor activity

Beyond Worst-Case Analysis for Joins with Minesweeper

We describe a new algorithm, Minesweeper, that is able to satisfy stronger runtime guarantees than previous join algorithms (colloquially, `beyond worst-case guarantees') for data in indexed search trees. Our first contribution is developing a framework to measure this stronger notion of complexity, which we call {\it certificate complexity}, that extends notions of Barbay et al. and Demaine et al.; a certificate is a set of propositional formulae that certifies that the output is correct. This notion captures a natural class of join algorithms. In addition, the certificate allows us to define a strictly stronger notion of runtime complexity than traditional worst-case guarantees. Our second contribution is to develop a dichotomy theorem for the certificate-based notion of complexity. Roughly, we show that Minesweeper evaluates $\beta$-acyclic queries in time linear in the certificate plus the output size, while for any $\beta$-cyclic query there is some instance that takes superlinear time in the certificate (and for which the output is no larger than the certificate size). We also extend our certificate-complexity analysis to queries with bounded treewidth and the triangle query.Comment: [This is the full version of our PODS'2014 paper.

Accurate Ritz wavelengths of parity-forbidden [Fe II], [Ti II] and [Cr II] infrared lines of astrophysical interest

With new astronomical infrared spectrographs the demands of accurate atomic data in the infrared have increased. In this region there is a large amount of parity-forbidden lines, which are of importance in diagnostics of low-density astrophysical plasmas. We present improved, experimentally determined, energy levels for the lowest even LS terms of Fe II, Ti II and Cr II, along with accurate Ritz wavelengths for parity-forbidden transitions between and within these terms. Spectra of Fe II, Ti II and Cr II have been produced in a hollow cathode discharge lamp and acquired using high-resolution Fourier Transform (FT) spectrometry. The energy levels have been determined by using observed allowed ultraviolet transitions connecting the even terms with upper odd terms. Ritz wavelengths of parity-forbidden lines have then been determined. Energy levels of the four lowest Fe II terms (a$^{6}$D, a$^{4}$F, a$^{4}$D and a$^{4}$P) have been determined, resulting in 97 different parity-forbidden transitions with wavelengths between 0.74 and 87 micron. For Ti II the energy levels of the two lowest terms (a$^{4}$F and b$^{4}$F) have been determined, resulting in 24 different parity-forbidden transitions with wavelengths between 8.9 and 130 micron. Also for Cr II the energy levels of the two lowest terms (a$^{6}$S and a$^{6}$D) have been determined, in this case resulting in 12 different parity-forbidden transitions with wavelengths between 0.80 and 140 micron.Comment: Accepted for publication in A&A, 13 pages, 6 figures, 9 table

Answering Conjunctive Queries under Updates

We consider the task of enumerating and counting answers to $k$-ary conjunctive queries against relational databases that may be updated by inserting or deleting tuples. We exhibit a new notion of q-hierarchical conjunctive queries and show that these can be maintained efficiently in the following sense. During a linear time preprocessing phase, we can build a data structure that enables constant delay enumeration of the query results; and when the database is updated, we can update the data structure and restart the enumeration phase within constant time. For the special case of self-join free conjunctive queries we obtain a dichotomy: if a query is not q-hierarchical, then query enumeration with sublinear$^\ast$ delay and sublinear update time (and arbitrary preprocessing time) is impossible. For answering Boolean conjunctive queries and for the more general problem of counting the number of solutions of k-ary queries we obtain complete dichotomies: if the query's homomorphic core is q-hierarchical, then size of the the query result can be computed in linear time and maintained with constant update time. Otherwise, the size of the query result cannot be maintained with sublinear update time. All our lower bounds rely on the OMv-conjecture, a conjecture on the hardness of online matrix-vector multiplication that has recently emerged in the field of fine-grained complexity to characterise the hardness of dynamic problems. The lower bound for the counting problem additionally relies on the orthogonal vectors conjecture, which in turn is implied by the strong exponential time hypothesis. $^\ast)$ By sublinear we mean $O(n^{1-\varepsilon})$ for some $\varepsilon>0$, where $n$ is the size of the active domain of the current database

Antioxidant and Hepatoprotective Effects of Silibinin in a Rat Model of Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease related to the metabolic syndrome, obesity and diabetes. The rising prevalence of NASH and the lack of efficient treatments have led to the exploration of different therapeutic approaches. Milk thistle (Silibum marianum) is a medicinal plant used for its hepatoprotective properties in chronic liver disease since the 4th century BC. We explored the therapeutic effect of silibinin, the plant's most biologically active extract, in an experimental rat NASH model. A control group was fed a standard liquid diet for 12 weeks. The other groups were fed a high-fat liquid diet for 12 weeks without (NASH) or with simultaneous daily supplement with silibinin–phosphatidylcholine complex (Silibinin 200 mg kg−1) for the last 5 weeks. NASH rats developed all key hallmarks of the pathology. Treatment with silibinin improved liver steatosis and inflammation and decreased NASH-induced lipid peroxidation, plasma insulin and TNF-α. Silibinin also decreased O2∙− release and returned the relative liver weight as well as GSH back to normal. Our results suggest that milk thistle's extract, silibinin, possesses antioxidant, hypoinsulinemic and hepatoprotective properties that act against NASH-induced liver damage. This medicinal herb thus shows promising therapeutic potential for the treatment of NASH

A continuous non-linear shadowing model of columnar growth

We propose the first continuous model with long range screening (shadowing) that described columnar growth in one space dimension, as observed in plasma sputter deposition. It is based on a new continuous partial derivative equation with non-linear diffusion and where the shadowing effects apply on all the different processes.Comment: Fast Track Communicatio

NCX 1000 Alone or in Combination with Vitamin E Reverses Experimental Nonalcoholic Steatohepatitis in the Rat Similarly to UDCA

We explored the therapeutic effect of NCX 1000, a derivative of ursodeoxycholic acid (UDCA) with nitric oxide (NO) donating properties, alone or in combination with vitamin E, in an experimental model of NASH in the rat. Methods. A control group was fed a standard liquid diet (Control), and the NASH groups were fed a high-fat liquid diet for 12 weeks without (NASH) or with simultaneous daily gavage with either NCX 1000 at 15 or 30 mg/kg (N15 and N30, resp.), or N15 plus vitamin E 100 mg/kg (N15  + VitE) for the last 6 weeks; UDCA 17.2 mg/kg was used as a reference. Results. NASH rats developed all key features of the disease. Treatments with N30 improved liver histology, decreased lipid peroxidation, and completely suppressed increases in LDH release, plasma insulin, and TNF-α. It also decreased O2∙− release and returned liver weight and glutathione back to normal. All effects were similar to the reference treatment, UDCA. The N15 treatment was less efficient than the N30 group, but became comparable to the latter when combined to vitamin E. Conclusion. Our study demonstrates that NCX 1000 has potent cytoprotective, antioxidant, and hypoinsulinemic properties that can be enhanced by combination with vitamin E