Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.     

Stress integrated tests and cytological analyses reveal Brassica villosa subsp. drepanensis seed quality decrease upon long-term storage

Under stress integrated germination test (SIGT), seeds undergo osmo-saline stresses, which enable to detect differences in vigour of long-term stored seeds with high germination percentage (G%). The quality of Brassica villosa subsp. drepanensis seeds stored in a genebank (at ? 20°C for 16 years) was compared with seeds at harvest by standard germination tests (GT), SIGT and cytogenetic analysis. No differences were detected in G% and mean germination time under GT. Conversely, SIGT performed with NaCl ? 0.9 MPa osmotic potential did not influence G% at harvest but reduced that of stored seeds, SIGT at ? 1.4 MPa reduced G% of both. Cytogenetic analysis showed reduction of mitotic index, appearance of chromosomal aberrations and smaller nucleoli in stored seeds compared with harvest seeds germinated in water. SIGT at ? 0.9 MPa had no effect on mitotic index, but increased chromosome aberrations and nucleoli number. SIGT at ? 1.4 MPa inhibited G% of harvest and stored seeds, reduced mitoses in harvest and completely prevented it in stored seeds. The results indicate that GT does not faithfully reflect the quality of stored seeds, with misinterpretation of their vigour, whereas SIGT and cytogenetical parameters are sensitive, reliable and inexpensive methods for early prediction of genetic erosion in germplasm banks.     

Scale sensitivity of synthetic long‐term vegetation time series derived through overlay of short‐term field records

Questions: Is change in cover of dominant species driving the velocity of succession or is it species turnover (1)? Is the length of the time‐step chosen in sampling affecting our recognition of the long‐term rate of change (2)1 Location: 74 permanent plots located in the Swiss National Park, SE Switzerland, ca. 1900 m a.s.l. Methods: We superimpose several time‐series from permanent plots to one single series solely based on compositional dissimilarity. As shown earlier (Wildi & Schütz 2000) this results in a synthetic series covering about 400 to 650 yr length. Continuous power transformation of cover‐percentage scores is used to test if the dominance or the presence‐absence of species is governing secondary succession from pasture to forest. The effect of time step length is tested by sub‐samples of the time series. Results: Altering the weight of presence‐absence versus dominance of species affects the emerging time frame, while altering time step length is uncritical. Where species turnover is fast, different performance scales yield similar results. When cover change in dominant species prevails, the solutions vary considerably. Ordinations reveal that the synthetic time series seek for shortest paths of the temporal pattern whereas in the real system longer lasting alternatives exist. Conclusions: Superimposing time series differs from the classical space‐for‐time substitution approach. It is a computation‐based method to investigate temporal patterns of hundreds of years fitting between direct monitoring (usually limited to decades) and the analysis of proxy‐data (for time spans of thousands of years and more).     

Use of time in a decision‐making process by a parasitoid

1. Time perception is seldom studied in invertebrates, with the limited experimental evidence being insufficient to provide a comprehensive pattern of the capacity of invertebrates to measure time and use it in decision‐making processes. 2. In this study, it was hypothesized that insect parasitoids have evolved the capacity to measure time precisely and to use it to optimize foraging decisions related to host exploitation. To examine time perception in females of the gregarious egg parasitoid Trichogramma euproctidis, the present study used their ability to adjust their investment (number of eggs laid) in a host to the initial transit duration (interval between the first contact with the host and the following contact with the substrate). Females utilize this method to assess host egg size, as a large egg necessarily requires more time to evaluate than a small host. In this study, the initial transit duration for a given sized egg was artificially extended by suspending it. 3. For similar sized hosts, female T. euproctidis significantly increased both oviposition duration and progeny allocation following a longer initial transit duration. 4. These results demonstrate the intrinsic capacity of this parasitoid to measure time and to adjust their progeny investment accordingly. This is believed to be one of the few demonstrations of a retrospective measure of time in an invertebrate.     

Mechanisms of madness: evolutionary psychiatry without evolutionary psychology

Delusions are currently characterised as false beliefs produced by incorrect inference about external reality (DSM IV). This inferential conception has proved hard to link to explanations pitched at the level of neurobiology and neuroanatomy. This paper provides that link via a neurocomputational theory, based on evolutionary considerations, of the role of the prefrontal cortex in regulating offline cognition. When pathologically neuromodulated the prefrontal cortex produces hypersalient experiences which monopolise offline cognition. The result is characteristic psychotic experiences and patterns of thought. This bottom-up account uses neural network theory to integrate recent theories of the role of dopamine in delusion with the insights of inferential accounts. It also provides a general model for evolutionary psychiatry which avoids theoretical problems imported from evolutionary psychology.     

Orchid seed sensitivity to nitrate reflects habitat preferences and soil nitrate content

• Orchids are distributed around the world, however, the factors shaping their specific distribution and habitat preferences are largely unknown. Moreover, many orchids are at risk of becoming threatened as landscapes change, sometimes declining without apparent reason. One important factor affecting plant distribution is nutrient levels in the environment. Nitrates can inhibit not only orchid growth and persistence, but also seed germination.
• We used in vitro axenic cultures to exactly determine the germination sensitivity of seven orchid species to nitrates and correlated this with soil properties of the natural sites and with the species’ habitat preferences.
• We found high variation in response to nitrate between species. Orchids from oligotrophic habitats were highly sensitive, while orchids from more eutrophic habitats were almost insensitive. Sensitivity to nitrate was also associated with soil parameters that indicated a higher nitrification rate.
• Our results indicate that nitrate can affect orchid distribution via direct inhibition of seed germination. Nitrate levels in soils are increasing rapidly due to intensification of agricultural processes and concurrent soil pollution, and we propose this increase could cause a decline in some orchid species.

     

DIA-Based Proteomics Identifies IDH2 as a Targetable Regulator of Acquired Drug Resistance in Chronic Myeloid Leukemia

Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR.     

Time of day effect on balance performance,functional capacities and risk of fall in women with rheumatoid arthritis

ABSTRACT

Objective: This study explored the time of day effect of balance performance, functional capacities and risk of fall in three different times in patients with rheumatoid arthritis (RA) and the association between these variations and those of RA symptoms.

Methods: A “discontinual” protocol, composed of three test sessions, carried out at 6 am, 2 pm and 10 pm was set up, in order to investigate the time of day effect of balance performance, functional capacities, risk of fall, stiffness, range of motion, swollen and painful joints in women with RA.

Results: Time Up and Go Test (TUGT), Functional Reach Test (FRT) and tinetti test scores were significantly higher (p < .01) at 6 am and at 10 pm compared to 2 pm. Stiffness, range of motion, swollen and painful joints values were significantly higher (p < .01) at 6 am and at 10 pm compared to 2 pm. A significant difference was observed on the stiffness, range of motion and swollen joints values between 6 am and 10 pm that were higher at 6 am (p < .05).

Using Pearson’s coefficient, correlations were found between RA symptom values; and TUGT, FRT and Tinetti test scores.

Conclusion: Results showed a time of day effect of balance performance, functional capacities and risk of falls in women with RA. This variation indicates an alteration of performance at 6 am and 10 pm. Fluctuations of stiffness, limited range of motion, swollen and painful joints noted are concomitant to those of balance performance, functional capacities, and risk of fall.

Abbreviations: RA: rheumatoid arthritis; H&O questionnaire: Horne and Ostberg questionnaire; PSQI: Pittsburgh sleep quality index; HAQ: health assessment questionnaire; SF-36: the short form-36; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; TUGT: Time Up and Go Test; FRT: Functional Reach Test