Regulation of HDACi−Triggered Autophagy by the Tumor Suppressor Protein p53

Cancer is a complex genetic and epigenetic-based disease that has developed a multitude of mechanisms in evading cell death. Deregulation of apoptosis and autophagy are commonly encountered during the development of human tumors. Histone deacetylase inhibitors (HDACi) have been employed to reverse epigenetically deregulated gene expression caused by aberrant post-translational protein modifications. These interfere with histone acetyltransferase- and deacetylase-mediated acetylation of histone and non-histone proteins, and thereby exert a wide array of HDACi-stimulated cytotoxic effects. Key determinants of HDACi lethality that interfere with cellular growth in a multitude of tumor cells are apoptosis and autophagy. Currently, the factors that determine the mode of HDACi-elicited cell death are mostly unclear however. Experimental evidence of the last decade convincingly reports that the frequently mutated tumor suppressor protein p53 can act either as an activator or as an inhibitor of autophagy depending on its subcellular localization, and linked to its mode of action. Consistently, we recently described p53 as a regulatory switch that governs if histone deacetylase inhibitor-administered uterine sarcoma cells undergo autophagy or apoptosis. By highlighting this novel finding, we summarize in this chapter the role of p53-mediated signaling during the activation of the autophagic pathway in tumor cells in response to HDACi

Headwaters are critical reservoirs of microbial diversity for fluvial networks

Streams and rivers form conspicuous networks on the Earth and are among nature's most effective integrators. Their dendritic structure reaches into the terrestrial landscape and accumulates water and sediment en route from abundant headwater streams to a single river mouth. The prevailing view over the last decades has been that biological diversity also accumulates downstream. Here, we show that this pattern does not hold for fluvial biofilms, which are the dominant mode of microbial life in streams and rivers and which fulfil critical ecosystem functions therein. Using 454 pyrosequencing on benthic biofilms from 114 streams, we found that microbial diversity decreased from headwaters downstream and especially at confluences. We suggest that the local environment and biotic interactions may modify the influence of metacommunity connectivity on local biofilm biodiversity throughout the network. In addition, there was a high degree of variability in species composition among headwater streams that could not be explained by geographical distance between catchments. This suggests that the dendritic nature of fluvial networks constrains the distributional patterns of microbial diversity similar to that of animals. Our observations highlight the contributions that headwaters make in the maintenance of microbial biodiversity in fluvial networks

Functional characterization of rare RAB12 variants and their role in musician’s and other dystonias

Mutations in RAB (member of the Ras superfamily) genes are increasingly recognized as cause of a variety of disorders including neurological conditions. While musician’s dystonia (MD) and writer’s dystonia (WD) are task-specific movement disorders, other dystonias persistently affect postures as in cervical dystonia. Little is known about the underlying etiology. Next-generation sequencing revealed a rare missense variant (c.586A>G; p.Ile196Val) in RAB12 in two of three MD/WD families. Next, we tested 916 additional dystonia patients; 512 Parkinson’s disease patients; and 461 healthy controls for RAB12 variants and identified 10 additional carriers of rare missense changes among dystonia patients (1.1%) but only one carrier in non-dystonic individuals (0.1%; p = 0.005). The detected variants among index patients comprised p.Ile196Val (n = 6); p.Ala174Thr (n = 3); p.Gly13Asp; p.Ala148Thr; and p.Arg181Gln in patients with MD; cervical dystonia; or WD. Two relatives of MD patients with WD also carried p.Ile196Val. The two variants identified in MD patients (p.Ile196Val; p.Gly13Asp) were characterized on endogenous levels in patient-derived fibroblasts and in two RAB12-overexpressing cell models. The ability to hydrolyze guanosine triphosphate (GTP), so called GTPase activity, was increased in mutants compared to wildtype. Furthermore, subcellular distribution of RAB12 in mutants was altered in fibroblasts. Soluble Transferrin receptor 1 levels were reduced in the blood of all three tested p.Ile196Val carriers. In conclusion, we demonstrate an enrichment of missense changes among dystonia patients. Functional characterization revealed altered enzyme activity and lysosomal distribution in mutants suggesting a contribution of RAB12 variants to MD and other dystonias

Pemodelan Daya Pengadukan Selama Proses Dehidrasi Osmotik Irisan Mangga dalam Larutan Gula

This study discusses mathematical model of agitation power due to the change of sugar solution concentration during the process of mango slices osmotic dehydration. The sugar solution agitation was performed in several levels of rotational speed to correlate the power number with the Reynolds number. Then, the obtained model was used to calculate the power consumption for various temperature and initial rotational speed of shaft. The results showed that the correlation can be used for various conditions of shaft rotational speed and solution concentration. Osmotic dehydration for 8 hours at conditions of 30-50OC with rotational speed of 143-525 rpm results in solution dilution from 61OBx to 50.5-52.5OBx. Temperature of 30OC with initial shaft rotational speed of 500 rpm results in power consumption ten times higher than that of 50OC and 148 rpm. Moreover, power consumption reduction up to 80% of initial energy consumption due to the dilution of the sugar solution during the osmotic dehydration process was obtained

Alimentación nocturna bajo iluminación artificial de la Gaviota Capucho-Café (Larus Maculipennis) en el muelle de Puerto Madryn (Chubut, Argentina)

Se describe la alimentación nocturna en un ambiente marino de la Gaviota Capucho Café (Larus maculipennis) en noviembre de 2009. Las gaviotas se congregaron durante la noche en el extremo de un muelle de 800 m de extensión en Puerto Madryn (Chubut, Argentina). Las aguas alrededor del extremo del muelle estaban iluminadas por potentes luces que atraían a muchas presas pequeñas a la superficie. Varios cientos de gaviotas, presumiblemente individuos reproductivos provenientes de una colonia cercana, se alimentaron diariamente en este sitio usando diferentes técnicas de alimentación y capturando presas de diferentes especies y tallas. Las presas potenciales fueron capturadas para su identificación a través de muestreos verticales con una red de plancton. Las presas que seguramente capturaron las gaviotas eran Isopoda de tamaño relativamente grande (Idothea sp.), Polychaeta (Platynereis sp.) y larvas de peces (Patagonotothen sp.), así como crustáceos de menor tamaño, mayormente Amphipoda (Phoxocephalidae) y Mysidacea. Las presas pequeñas fueron capturadas mientras las gaviotas nadaban, mediante el picoteo en superficie, mientras que las más grandes fueron capturadas sobrevolando bajo sobre la superficie y a través de zambullidas superficiales. Durante el día, solo unas pocas gaviotas se aventuraron dentro de la bahía, indicando que tomaron ventaja de la oportunidad de alimentación nocturna facilitada por la iluminación artificial. La clara ganancia a corto plazo de la explotación de esta novedosa oportunidad de alimentación podría ser compensada por posibles amenazas tales como una mayor vulnerabilidad a los predadores o la contaminación por derrame de hidrocarburos de los barcos amarrados junto al muelle.This paper describes nocturnal, marine feeding behaviour in the Brown-hooded Gull (Larus maculipennis) in November 2009. The gulls assembled at night at the end of a long pier, running 800 m offshore into the Golfo Nuevo, at Puerto Madryn, Chubut Province, Argentina. Powerful lights predictably lighted the water around the end of the pier and attracted many small prey animals to the surface. Several hundreds of gulls, presumed to be local breeders, came every night to feed on this bounty, using various feeding techniques and taking several prey species and sizes. Potential prey items were caught to be identified by vertical plankton hauls. The gulls most likely took relatively large Isopoda (Idothea sp.), Polychaeta (Platynereis sp.) and fish larvae (Patagonotothen sp.) as well as smaller crustaceans, mostly Amphipoda (Phoxocephalidae) and Mysidacea. The gulls caught small prey items while swimming, by rapid surface pecking, while they hunted the larger prey species by flying low over the water and performing shallow, vertical plunge-dives. During daylight, only few gulls ventured from land into the bay, indicating that they took advantage of the nocturnal feeding opportunity, facilitated by artificial lighting. The clear short-term gain of exploiting this novel foraging opportunity may be offset by potential threats such as increased vulnerability to predators or contamination by oil spills from ships moored along the pier.Fil: Leopold, Mardik F.. Institute for Marine Resources and Ecosystem Studies; Países BajosFil: Philippart, Catharina J.M.. Royal Netherlands Institute for Sea Research; Países BajosFil: Yorio, Pablo Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina. Wildlife Conservation Society; Estados Unido

Funnels in Energy Landscapes

Local minima and the saddle points separating them in the energy landscape are known to dominate the dynamics of biopolymer folding. Here we introduce a notion of a "folding funnel" that is concisely defined in terms of energy minima and saddle points, while at the same time conforming to a notion of a "folding funnel" as it is discussed in the protein folding literature.Comment: 6 pages, 3 figures, submitted to European Conference on Complex Systems 200

Ideally embedded space-times

Due to the growing interest in embeddings of space-time in higher-dimensional spaces we consider a specific type of embedding. After proving an inequality between intrinsically defined curvature invariants and the squared mean curvature, we extend the notion of ideal embeddings from Riemannian geometry to the indefinite case. Ideal embeddings are such that the embedded manifold receives the least amount of tension from the surrounding space. Then it is shown that the de Sitter spaces, a Robertson-Walker space-time and some anisotropic perfect fluid metrics can be ideally embedded in a five-dimensional pseudo-Euclidean space.Comment: layout changed and typos corrected; uses revtex

Excitation of Small Quantum Systems by High-Frequency Fields

The excitation by a high frequency field of multi--level quantum systems with a slowly varying density of states is investigated. A general approach to study such systems is presented. The Floquet eigenstates are characterized on several energy scales. On a small scale, sharp universal quasi--resonances are found, whose shape is independent of the field parameters and the details of the system. On a larger scale an effective tight--binding equation is constructed for the amplitudes of these quasi--resonances. This equation is non--universal; two classes of examples are discussed in detail.Comment: 4 pages, revtex, no figure