Combined population dynamics and entropy modelling supports patient stratification in chronic myeloid leukemia

Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patientderived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis

Handling and analysis of ices in cryostats and glove boxes in view of cometary samples

Comet nucleus sample return mission and other return missions from planets and satellites need equipment for handling and analysis of icy samples at low temperatures under vacuum or protective gas. Two methods are reported which were developed for analysis of small icy samples and which are modified for larger samples in cometary matter simulation experiments (KOSI). A conventional optical cryostat system was modified to allow for transport of samples at 5 K, ion beam irradiation, and measurement in an off-line optical spectrophotometer. The new system consists of a removable window plug containing nozzles for condensation of water and volatiles onto a cold finger. This plug can be removed in a vacuum system, changed against another plug (e.g., with other windows (IR, VIS, VUV) or other nozzles). While open, the samples can be treated under vacuum with cooling by manipulators (cut, removal, sample taking, irradiation with light, photons, or ions). After bringing the plug back, the samples can be moved to another site of analysis. For handling the 30 cm diameter mineral-ice samples from the KOSI experiments an 80x80x80 cm glove box made out of plexiglass was used. The samples were kept in a liquid nitrogen bath, which was filled from the outside. A stream a dry N2 and evaporating gas from the bath purified the glove box from impurity gases and, in particular, H2O, which otherwise would condense onto the samples

A novel IEF peptide fractionation method reveals a detailed profile of N-terminal Acetylation in chemotherapy-responsive and -resistant ovarian cancer cells

Although acetylation is regarded as a common protein modification, a detailed proteome wide profile of this posttranslational modification may reveal important biological insight regarding differential acetylation of individual proteins. Here we optimised a novel peptide IEF fractionation method for use prior to LC-MS/MS analysis in order to obtain a more in depth coverage of N-terminally acetylated proteins from complex samples. Application of the method to the analysis of the serous ovarian cancer cell line OVCAR-5 identified 341 N-terminally acetylated proteins, 23 of which are previously un-reported. The protein peptidyl-prolyl cis-trans isomerase A (PPIA) was detected in both the N-terminally acetylated and un-modified forms, and was further analysed by data independent acquisition in Carboplatin responsive parental OVCAR-5 cells and Carboplatin resistant OVCAR-5 cells. This revealed a higher ratio of un-acetylated to acetylated N-terminal PPIA in the parental compared to the Carboplatin resistant OVCAR-5 cells, and a 4.1-fold increase in PPIA abundance overall in the parental cells relative to Carboplatin-resistant OVCAR-5 cells (P = 0.015). In summary, the novel IEF peptide fractionation method presented here is robust, reproducible, and can be applied to the profiling of N-terminally acetylated proteins. All mass spectrometry data is available as a ProteomeXchange repository (PXD003547).Florian Weiland, Georgia Arentz, Manuela Klingler-Hoffmann, Peter McCarthy, Noor A. Lokman, Gurjeet Kaur, Martin K. Oehler, and Peter Hoffman

GPS TRACKING OF THE FORAGING MOVEMENTS OF OILBIRDS (STEATORNIS CARIPENSIS) FROM THE DUNSTON CAVE AT ASA WRIGHT NATURE CENTRE, TRINIDAD

The ranging behaviors of the Oilbird (Steatornis caripensis) in Trinidad are not well defined and are required to better outline fu- ture conservation management parameters for this species. Due to the nocturnal foraging behaviors of the Oilbird, past observations were restricted to colony site observations, video recordings, and limited electronic tracking over short periods. Utilizing newly developed small- scale Global Positioning System (GPS) data loggers, we were able to determine the flight and foraging behaviors of two oilbirds that roost at the Asa Wright Nature Centre for up to 270 days. The use of backpack style GPS tracking devices provided high site resolution and accuracy of the movements and a better understanding of the annual foraging behaviors of the oilbirds in the Asa Wright Nature Centre colony. The oilbirds’ home range was determined to be 3,564.6 km2, with an average trip distance from Dunston Cave of 7.33 km, excluding an interme- diary migration point in Venezuela. 48.5% of the foraging area consisted of locations within the Northern Range, while 27.7% of these trips remained within the Arima Valley, which is only partially protected from quarrying activities. This data document the previously unknown patterns of habitat use of the Oilbird and serves as a pilot study to determine the conservation importance of those habitats for the develop- ment of long-term conservation action plans for these iconic birds

Behavior of feral horses in response to culling and GnRH immunocontraception

AbstractWildlife management actions can alter fundamental behaviors of individuals and groups, which may directly impact their life history parameters in unforeseen ways. This is especially true for highly social animals because changes in one individual's behavior can cascade throughout its social network. When resources to support populations of social animals are limited and populations become locally overabundant, managers are faced with the daunting challenge of decreasing population size without disrupting core behavioral processes. Increasingly, managers are turning to fertility control technologies to supplement culling in efforts to suppress population growth, but little is quantitatively known about how either of these management tools affects behavior. Gonadotropin releasing hormone (GnRH) is a small neuropeptide that performs an obligatory role in mammalian reproduction and has been formulated into the immunocontraceptive GonaCon-B™. We investigated the influences of this vaccine on behavior of feral horses (Equus caballus) at Theodore Roosevelt National Park, North Dakota, USA, for a year preceding and a year following nonlethal culling and GnRH-vaccine treatment. We observed horses during the breeding season and found only minimal differences in time budget behaviors of free-ranging female feral horses treated with GnRH and those treated with saline. The differences observed were consistent with the metabolic demands of pregnancy and lactation. We observed similar social behaviors between treatment groups, reflecting limited reproductive behavior among control females due to high rates of pregnancy and suppressed reproductive behavior among treated females due to GnRH-inhibited ovarian activity. In the treatment year, band stallion age was the only supported factor influencing herding behavior (P<0.001), harem-tending behavior (P<0.001), and agonistic behavior (P=0.02). There was no difference between the mean body condition of control females (4.9 (95% CI=4.7–5.1)) and treated females (4.8 (95% CI=4.7–4.9)). Band fidelity among all females increased 25.7% in the year following vaccination and culling, despite the social perturbation associated with removal of conspecifics. Herding behavior by stallions decreased 50.7% following treatment and culling (P<0.001), while harem-tending behavior increased 195.0% (P<0.001). The amount of available forage influenced harem-tending, reproductive, and agonistic behavior in the year following culling and treatment (P<0.04). These changes reflected the expected nexus between a species with polygynous social structure and strong group fidelity and the large instantaneous change in population density and demography coincident with culling. Behavioral responses to such perturbation may be synergistic in reducing grazing pressure by decreasing energetically expensive competitive behaviors, but further investigation is needed to explicitly test this hypothesis

Correlated optical and structural analyses of individual GaAsP/GaP core–shell nanowires

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