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.     

Heavy metal pollution in surface water and sediment: A preliminary assessment of an urban river in a developing country

The concentration and chemical fractionation of globally alarming six heavy metals (Cr, Ni, Cu, As, Cd and Pb) were measured in surface water and sediment of an urban river in Bangladesh. The decreasing trend of metals were observed in water as Cr > Cu > As > Ni > Pb > Cd and in sediment as Cr > Ni > Cu > Pb > As > Cd. The level of studied metals exceeded the safe limits of drinking water, indicated that water from this river is not safe for drinking and/or cooking purposes. However, the investigated metals showed low mobility except for Cd and Pb which could pose a severe threat to the aquatic environment. Contamination factor (CF) and geoaccumulation index (I_geo) demonstrated that most of the sediment samples were moderately to heavily contaminated by Cr, As, Cd and Pb. The pollution load index (PLI) values were above one (>1) indicates progressive deterioration of the sediment quality. The extent of pollution by heavy metals in the river Korotoa implies that the condition is much frightening to the biota and inhabitants in the vicinity of the river as well.     

Comparing multiple correspondence and principal component analyses with biomechanical signals. Example with turning the steering wheel

The purpose of this article is to compare Principal Component Analysis (PCA) and a much less used method, i.e. MCA (Multiple Correspondence Analysis) with data being first changed into membership values to fuzzy space windows. For such a comparison, data from an experimental study about turning the steering wheel is used. In a didactic perspective, this article only considers one multidimensional signal with 5 components: 3 linked to the steering wheel angle and hand positions and 2 to hand effort variables. A discussion weighs out the pros and the cons of both methods with criteria such as the possibility to show complex relational phenomena, the analysis/computing time or the information loss inherent to the averaging stage (in the perspective to analyze several hundreds of large multidimensional signals).     

Electrophysiological evidence for the autoregulation of β-cell secretion by insulin

Electrophysiological studies of cultured rat pancreatic β-cells using intracellular microelectrodes show that exogenous insulin over the range of 0.1–10.0 μg/ml inhibits the electrical activity due to 27.8 mM glucose in a dose-related manner. This inhibitory effect is manifested by a mean increase of the membrane potential from about ?20 to ?30 mV and inhibition of the manner of cells impaled showing spike activity from 60 to less than 10%. The inhibitory influence of insulin is rapid occuring within 5 min for the highest level used. The results provide evidence for a negative feedback role of insulin in regulating its own release.     

Uncoupling of mitochondrial oxidative phosphorylation by thallium.

The mechanism of integration of λ$\text{bio}$ll, which is deleted of all the known λ recombination genes, was studied using $\text{bio}$ deleted hosts as recipients. The presence of $\text{rec}$BC DNase and $\text{exo}$I in the recipient cells affected the fate of λ$\text{bio}$ll DNA. In nine of ten $\text{imm}\text{λ}{}^{\mathrm{+}}$ transductants, insertion of the λ$\text{bio}$ll genome took place somewhere between J and N and the remaining one had abnormally permuted prophage λ. In this lysogen (#42), the sequence of prophage genes was similar to that of vegetative phage λ. The properties of lysogen #42 were compared with those of other lysogens.     

Village Drift and Riverine Settlement: Modeling Akimel O'odham Land Use

Regular unscheduled movements of rancherías within a confined area or settlement district result in the phenomenon described as "village drift," a process whereby a settlement may change its location gradually by several kilometers over a period of years. This article presents a model of village drift based on data acquired from recent archaeological and geomorphological field studies and archival research on the Akimel O'odham, the Gila River Pima of south-central Arizona. The model provides an excellent example of human ecodynamics---an emerging landscape perspective that emphasizes the coevolution of humans and their ecosystem---with implications for understanding prehistoric and historic settlement in desert riverine environments.     

Presence and development of populations of the introduced brown alga Sargassum muticum in the southwest Netherlands

Of the three Brachionus species used in aquaculture, Brachionus rubens, B. calycilorus and B. plicatilis, the latter is most widely used in raising marine fish and shrimp larvae due to its tolerance to the marine environment. In freshwater aquaculture the use of B. rubens and B. calycilorus is limited, probably because inert food products are readily available as feed for freshwater larvae.The rotifer Brachionus plicatilis is used in large numbers as the first food organism in intensive cultures of marine fish and shrimp larvae. An adequate supply of these rotifers relies on mass cultures. The reproductive rate of rotifers in these cultures depends on food quality and quantity, salinity, temperature and pH of the medium. Removal of waste products from culture tanks leads to higher and more efficient production of rotifers over extended periods of time. Rotifers have to be enriched with polyunsaturated fatty acids, which are essential for proper development and survival of marine fish and shrimp larvae.The future use of preserved rotifers and their resting eggs may help to overcome unforeseen failures of live cultures and may lead to more efficient use of these organisms in raising freshwater and marine fish and shrimp larvae.     

Effect of differential gastric evacuation and multispecies prey items on estimates of daily energy intake in juvenile chinook salmon

Synopsis The caloric density of stomach contents in juvenile chinook salmon,Oncorhynchus tshawytscha, was not affected by gastric evacuation, suggesting a constant caloric density of stomach contents during evacuation. Differences in the caloric density of prey consumed did affect caloric density of stomach contents over a 24-h period. Consumption of the amphipodCorophium sp. was associated with reduced caloric densities of stomach contents. During periods whenCorophium contributed more than 4% of the stomach contents, average caloric density declined from 5.56 to 5.33 kcal g^–1. Despite this difference, estimates of daily energy intake of juvenile chinook salmon were only 3%, greater when developed from the mean caloric density of stomach contents excludingCorophium.     

On subspecific taxa ofHypericum empetrifolium (Hypericaceae) from Crete

The morphology, altitudinal distribution and phytocoenology ofHypericum empetrifolium Willd., var.oliganthum Rech. fil. and var.tortuosum Rech. fil. are reassessed and as a result, the taxa are treated at subspecific rank. Essential characters proved to be growth form, number of flowers, foliage and epidermal surface characters, shape of seeds and testa sculpturing.The different growth forms can be interpreted as adaptations to the local habitats.Hypericum empetrifolium Willd. subsp.empetrifolium is a low subshrub of various vegetation types known as phrygana whereasHypericum empetrifolium Willd. subsp.oliganthum (Rech. f.)Hagemann grows as a cushion-like dwarf shrub in chasmophyte associations rich in relic species.Hypericum empetrifolium Willd. subsp.tortuosum (Rech. f.)Hagemann is confined in the high mountain regions and grows as a true dwarf espalier shrub with low spreading shoots.Dedicated to Hofrat Univ.-Prof. DrK. H. Rechinger on the occasion of his 80th birthday.     

Effect of abscisic acid on the photosynthetic oxygen evolution in barley chloroplasts

In vivo effect of abscisic acid (ABA) on photosynthetic oxygen evolution was investigated in barley chloroplasts. The most important kinetic parameters of O₂-producing reactions were changed. The results show inhibition of the O₂-flash yields at ABA concentrations of 10 mol/l and 100 mol/l and an increase in the degree of damping of the oscillations. ABA has a marked effect on the distribution of the oxygenevolving centers in S₀ and S₁ states and on sum of the centers (S₀+S₁) estimated according to the Kok model. In addition, the amplitude and the shape of the initial oxygen burst under continuous illumination are also significantly altered. At a concentration of 100 mol/l, ABA strongly inhibits Hill reaction activity measured by DCPIP reduction. The results cannot be explained by the hypothesis of socalled stomata effect. On the other hand, no effects were observed on the investigated parameters in experiments involving ABA applied in vitro to isolated chloroplasts. It is hypothesized that ABA disrupts the granal chloroplasts structure and raises the degree of participation of the cooperative mechanism of O₂-evolution connected with the functioning of PS II centers in the stroma situated thylakoids.Abbreviations DCPIP 2,6-Dichlorophenolindophenol - DCMU 3-(3,4-dichlorophenil)-1,1-dimethylurea - HEPES N-2-Hydroxyethylpiperazine-N-2-ethane sulfonic acid - PSII photosystem II - RubisCO Ribulose-1,5-bis-phosphate carboxylase-oxygenase