Xenopatients 2.0: Reprogramming the epigenetic landscapes of patient-derived cancer genomes

In the science-fiction thriller film Minority Report, a specialized police department called “PreCrime” apprehends criminals identified in advance based on foreknowledge provided by 3 genetically altered humans called “PreCogs”. We propose that Yamanaka stem cell technology can be similarly used to (epi)genetically reprogram tumor cells obtained directly from cancer patients and create self-evolving personalized translational platforms to foresee the evolutionary trajectory of individual tumors. This strategy yields a large stem cell population and captures the cancer genome of an affected individual, i.e., the PreCog-induced pluripotent stem (iPS) cancer cells, which are immediately available for experimental manipulation, including pharmacological screening for personalized “stemotoxic” cancer drugs. The PreCog-iPS cancer cells will re-differentiate upon orthotopic injection into the corresponding target tissues of immunodeficient mice (i.e., the PreCrime-iPS mouse avatars), and this in vivo model will run through specific cancer stages to directly explore their biological properties for drug screening, diagnosis, and personalized treatment in individual patients. The PreCog/PreCrime-iPS approach can perform sets of comparisons to directly observe changes in the cancer-iPS cell line vs. a normal iPS cell line derived from the same human genetic background. Genome editing of PreCog-iPS cells could create translational platforms to directly investigate the link between genomic expression changes and cellular malignization that is largely free from genetic and epigenetic noise and provide proof-of-principle evidence for cutting-edge “chromosome therapies” aimed against cancer aneuploidy. We might infer the epigenetic marks that correct the tumorigenic nature of the reprogrammed cancer cell population and normalize the malignant phenotype in vivo. Genetically engineered models of conditionally reprogrammable mice to transiently express the Yamanaka stemness factors following the activation of phenotypic copies of specific cancer diseases might crucially evaluate a “reprogramming cure” for cancer. A new era of xenopatients 2.0 generated via nuclear reprogramming of the epigenetic landscapes of patient-derived cancer genomes might revolutionize the current personalized translational platforms in cancer research.     

Haematozoa in forest birds from southern Chile: Latitudinal gradients in prevalence and parasite lineage richness

Abstract The existence of latitudinal gradients in species richness and their abundance is known for many free living organisms but few cases have been reported for parasitic diseases. In addition, asymmetries between the Northern and Southern Hemispheres in several characteristics may affect the distribution and diversity of species at all ecological levels. In this respect, we study the distribution of several genera of blood parasites infecting birds along a latitudinal gradient that includes the world's southernmost forests ecosystems. Birds were mist‐netted and sampled for blood in localities across Chile ranging from 33°S to 55°S during the years 2003–06. Overall, 26 bird species were sampled and 27 parasite lineages were identified. The latter belonged to three genera: Plasmodium (8), Haemoproteus (8) and Leucocytozoon (11). We found a positive significant relationship between prevalence and latitude for Leucocytozoon lineages and a negative relationship for Haemoproteus, Plasmodium and mixed infections. However, we did not find a significant relationship between parasite diversity and latitude. We found 18 lineages infecting only one species of host, and 19 lineages appear in only one of the localities of sampling. This pattern implies that some parasite lineages may evolve in isolation in some species/localities. In addition, specificity at the host‐family level was only found for Haemoproteus lineages infecting birds in the family Emberizidae. Individuals of the long distance migrant bird white‐crested elaenia (Elaenia albiceps), were found infected by the same parasite lineages in localities separated by 20° of latitude. Infections by these lineages were detected in other sedentary birds including juveniles and nestlings of different bird species. Therefore, long distance migrants are able to distort the presence of latitudinal gradients of diseases due to the potential role of migrants in spreading infections. Geographical gradients in prevalence of avian haematozoa differ between parasite genera and hemispheres, probably in relation to the existence of appropriate vector–parasite–host interactions.     

Influence of land use on stream ecosystem function in a Mediterranean catchment

1. Due to the hierarchical organization of stream networks, land use changes occurring at larger spatial scales (i.e. the catchment) can affect physical, chemical and biological characteristics at lower spatial scales, ultimately altering stream structure and function. Anthropogenic effects on streams have primarily been documented using structural metrics such as water chemistry, channel alteration and algal biomass. Functional parameters, including metrics of nutrient retention and metabolism, are now being widely used as indicators of stream condition. 2. Within this hierarchical context, we used a multivariate approach to examine how structural and functional (i.e. nutrient retention and metabolism) attributes of streams are related to catchment variables, including land use. The study was done in 13 streams located within a single Mediterranean catchment, but draining sub‐catchments with contrasting land use. 3. At the catchment scale, results showed two contrasting land use gradients: (i) from forested‐ to urban‐dominated catchments and (ii) from low to moderate agricultural‐dominated catchments. Variation in structural and functional parameters was strongly related to these land use gradients. Specifically, NH₄⁺ demand (measured as the uptake velocity, V_f) decreased along the gradient from forested‐ to urban‐dominated catchments primarily in response to increases in stream nutrient concentrations [NH₄⁺, dissolved organic nitrogen (DON) and carbon (DOC)]. Both primary production and respiration increased along the gradient of agricultural development in response to increases in algal biomass (chlorophyll a). Soluble reactive phosphorus demand was not related to any of the land use gradients. 4. Our results illustrate the connections among factors operating at different spatial scales (i.e. from catchments to streams) and their distinct influence on stream ecosystem function. Managers should take into consideration these connections when designing stream management and restoration plans. Because ecologically successful stream management and restoration is expected to restore function as well as structure to streams, the use of appropriate measures of functional processes is required. Nutrient retention and metabolism parameters are good candidates to fill this gap.     

Time-resolved fluoroimmunoassay of potato virus M with monoclonal antibodies

Mouse monoclonal antibodies (MAbs) specific for potato virus M (PVM) were prepared and the properties of three of them were studied. MAb M4C1 is IgG2b, it binds with high affinity to PVM coat protein, to purified virus preparations and recognises PVM in infected potato leaves and tubers. MAb M6D5 is IgG2a and also reacts with PVM coat protein, purified PVM and with PVM in potato leaf and tuber extracts. In double-antibody sandwich ELISA (DAS ELISA) MAbs M4C1 and M6D5 reacted with all 17 PVM isolates tested. MAb M7 is IgG2b and recognises PVM only in indirect dot ELISA on nitrocellulose filters and viral coat protein on Western blots. MAbs against PVM were used as capture antibodies and europium-labelled MAbs as conjugates in time-resolved fluoroimmunoassay (EuTRFIA). The standard EuTRFIA curve of PVM detection is approximately linear over a range of PVM concentrations from 0.5 ng/ml to 1000 ng/ml. The lowest PVM concentration detectable in EuTRFIA was 0.5 ng/ml and correspondingly 6 ng/ml in DAS ELISA. The use of the europium chelate label allows PVM detection in potato leaf and tuber sap at dilutions greater than 10^--⁴ with very low background fluorescence. EuTRFIA with MAbs, with either one or two incubations is about 10–20 times more sensitive for PVM detection than is DAS ELISA. PVM and PVX, mixed with healthy potato tuber sap, were simultaneously tested in a single sample at concentrations lower than 10 ng/ml by double-label TRFIA using europium-labelled MAbs to PVM and samarium-labelled MAbs to PVX.     

Micromammal biostratigraphy of the Upper Miocene to lowest Pleistocene continental deposits of the Guadix basin,southern Spain

Minwer‐Barakat, R., García‐Alix, A., Suárez, E.M., Freudenthal, M. & Viseras, C. 2012 xx xx: Micromammal biostratigraphy of the Upper Miocene to lowest Pleistocene continental deposits of the Guadix basin, southern Spain. Lethaia, Vol. 45, pp. 594–614. Recent study of the small mammals (rodents and insectivores) from several fossil‐bearing sites situated in the central sector of the Guadix Basin (Southern Spain) has notably increased the knowledge of the mammal assemblages that existed in Southern Iberia from the latest Miocene to the earliest Pleistocene. On the basis of this new information, we propose a biozonation for the continental deposits of the Guadix Basin, which consists of six biozones ranging in age from the late Turolian (MN13) to the early Villanyian (MN17). These biozones, defined according to the rules of the International Stratigraphical Guide, include not only the mentioned recently discovered fossil sites, but also other, previously known, localities of the basin. Finally, we integrate the described biozones in the Neogene Mammal units and the European Land Mammal Ages, correlate them with several classical mammal sites from other Iberian basins and the rest of Europe, and establish an approximate numerical age for the lower and upper limits of each biozone. □Biostratigraphy, Guadix Basin, rodents, insectivores, Upper Miocene, Pliocene, Pleistocene.     

Enhancement of root hydraulic conductivity by methyl jasmonate and the role of calcium and abscisic acid in this process

The role of jasmonic acid in the induction of stomatal closure is well known. However, its role in regulating root hydraulic conductivity (L) has not yet been explored. The objectives of the present research were to evaluate how JA regulates L and how calcium and abscisic acid (ABA) could be involved in such regulation. We found that exogenous methyl jasmonate (MeJA) increased L of Phaseolus vulgaris, Solanum lycopersicum and Arabidopsis thaliana roots. Tomato plants defective in JA biosynthesis had lower values of L than wild‐type plants, and that L was restored by addition of MeJA. The increase of L by MeJA was accompanied by an increase of the phosphorylation state of the aquaporin PIP2. We observed that MeJA addition increased the concentration of cytosolic calcium and that calcium channel blockers inhibited the rise of L caused by MeJA. Treatment with fluoridone, an inhibitor of ABA biosynthesis, partially inhibited the increase of L caused by MeJA, and tomato plants defective in ABA biosynthesis increased their L after application of MeJA. It is concluded that JA enhances L and that this enhancement is linked to calcium and ABA dependent and independent signalling pathways.     

Oceanic Anoxic Event at the Cenomanian–Turonian boundary interval (OAE-2): ichnological approach from the Betic Cordillera, southern Spain

Ichnological analysis of dark sediments of the Oceanic Anoxic Event at the Cenomanian–Turonian boundary interval (OAE-2) from the Betic Cordillera, southern Spain, reveals the presence of ichnofabrics containing trace fossils Chondrites isp., Palaeophycus heberti , Planolites isp., Thalassinoides isp., Trichichnus linearis , Zoophycos isp., and other bioturbational structures. Analysis of the ichnofabrics and trace fossil diversity allowed the reconstruction of relative oxygenation. Before the OAE-2, oxygenation of sediments was generally good, but it was punctuated by short anoxic events. During the OAE-2i, several longer anoxic intervals were interrupted by shorter dysaerobic and oxic periods. After the OAE-2, oxygenation improved and almost all trace fossils known before OAE-2 reappeared, although oxygenation dropped a few times to anoxia. Generally, the short oxygenation changes reveal a periodicity, which may suggest a Milankovitch control.