Immunosuppression by Mutated Calreticulin Released from Malignant Cells

1. Download : Download high-res image (218KB)
2. Download : Download full-size image

     

Go with the flow: tidal import and export of larvae from semi-enclosed bays

There is a growing body of evidence that suggests the effective functioning of marine reserves is dependent on the dispersal and recruitment of larvae. Enhanced production inside reserves is predicted to lead to a net larval export and increased settlement and recruitment outside reserve boundaries. However, larval retention in bays is also well documented. Since bays are increasingly being used as reserve areas, planktonic larvae of benthic marine invertebrates were sampled from two semi-enclosed marine reserves during flood and ebb tides to determine whether these bays are acting as net exporters of larvae. Neither reserve was a net importer or exporter of species richness, larval abundance or diversity, although one reserve showed a small export of species richness during the hours of darkness. Both reserves balanced the net import of some species with a net export of others, which was generally related to adult or larval abundance, although exceptions were found in one reserve. Significant effects of light were found, with the net import or export of some species occurring exclusively during either the hours of daylight or darkness. An increased understanding of larval sink-source dynamics in bays is essential for ensuring their effective use as marine reserves to meet specific conservation needs. Guest editors: J. Davenport, G. Burnell, T. Cross, M. Emmerson, R. McAllen, R. Ramsay & E. Rogan Challenges to Marine Ecosystems     

Narrow-leaved lupine seeds as a dietary protein source for fattening rabbits: a comparison with white lupine seeds

Lupine seeds have the potential to be an alternative to imported dietary proteins. In rabbits, it has been indicated that White lupine seed (WLS) is a suitable protein source. Other lupine species, for example, narrow-leaved lupine seed (NLS), have not yet been tested in rabbit diets. Two experiments were carried out to evaluate the effect of the dietary inclusion of NLS on growth performance, sanitary risk index (SRI), coefficients of total tract apparent digestibility (CTTAD) and nitrogen output in fattening rabbits. Narrow-leaved lupine was compared with WLS as a main protein source. For Experiment I, a total of 198 Hyplus rabbits (37 days of age) were allocated into two groups (99 rabbits per group), fed the WLS I diet (120 g/kg of WLS cv. Amiga) or the NLS I diet (150 g/kg of NLS cv. Probor), and used for performance and carcass trait evaluations. In addition, the CTTAD of the diets and the nitrogen output were determined in 10 Hyplus rabbits per treatment (37 days of age). For Experiment II, a total of 180 Hyplus rabbits (32 days of age) were allocated into two groups (90 rabbits per group), fed the WLS II diet (120 g/kg of WLS cv. Amiga) or the NLS II diet (130 g/kg of NLS cv. Primadona), and used for performance and carcass trait evaluations. In addition, the CTTAD of the diets was determined in 10 Hyplus rabbits per treatment (32 days of age). Regardless of the treatment, the dietary inclusion of NLS had a negative effect on growth of the rabbits. The nitrogen excretion and coefficients of nitrogen retention of rabbits were not affected by the treatments. In Experiment I, SRI (37 to 80 days of age) was higher in rabbits fed the NLS I diet than in those fed the WLS I diet (38.4% v. 23.2%, respectively; P = 0.031). Similarly, in Experiment II (32 to 74 days of age), SRI was higher in rabbits fed the NLS II diet than in rabbits fed the WLS II diet (37.8% v. 23.3%, respectively; P = 0.052). In conclusion, regardless of the variety, the dietary inclusion of NLS had no negative effect on the nitrogen output or dressing-out percentage of rabbits when compared to those of rabbits fed the WLS diets. With respect to the SRI and performance, however, NLS did not provide a satisfactory outcome.     

The effects of capture, net retention and preservation upon lengths of larval and juvenile bass, Dicentrarchus labrax (L.)

Relationships between live and preserved lengths of larval and juvenile bass, Dicentrarchus labrax , subjected to simulated capture, net retention and preservation were investigated. Bass larvae and juveniles shrank during the period of net retention following death. Preserved lengths of larvae, but not of juveniles, decreased significantly when increased periods of net retention preceded preservation. The time which larvae or juveniles remained in 4% formaldehyde in distilled water buffered with 3gl⁻¹ sodium acetate trihydrate or in 70% ethanol in distilled water neutralized with 1gl⁻¹ calcium carbonate powder, had no significant effect upon preserved length. Appropriate data were pooled to calculate transformation factors for estimating live from preserved length. Shrinkage phenomena, and their effects, are discussed. It is suggested that larval bass captured and preserved during standard ichthyoplankton surveys are unsuitable for determination of live length.     

Identification and in silico prediction of metabolites of tebufenozide derivatives by major human cytochrome P450 isoforms

Cytochrome P450 (CYP) enzymes constitute a superfamily of heme-containing monooxygenases. CYPs are involved in the metabolism of many chemicals such as drugs and agrochemicals. Therefore, examining the metabolic reactions by each CYP isoform is important to elucidate their substrate recognition mechanisms. The clarification of these mechanisms may be useful not only for the development of new drugs and agrochemicals, but also for risk assessment of chemicals. In our previous study, we identified the metabolites of tebufenozide, an insect growth regulator, formed by two human CYP isoforms: CYP3A4 and CYP2C19. The accessibility of each site of tebufenozide to the reaction center of CYP enzymes and the susceptibility of each hydrogen atom for metabolism by CYP enzymes were evaluated by a docking simulation and hydrogen atom abstraction energy estimation at the density functional theory level, respectively. In this study, the same in silico prediction method was applied to the metabolites of tebufenozide derivatives by major human CYPs (CYP1A2, 2C9, 2C19, 2D6, and 3A4). In addition, the production rate of the metabolites by CYP3A4 was quantitively analyzed by frequency based on docking simulation and hydrogen atom abstraction energy using the classical QSAR approach. Then, the obtained QSAR model was applied to predict the sites of metabolism and the metabolite production order by each CYP isoform.     

Mass Spectrometry–Driven Discovery of Neuropeptides Mediating Nictation Behavior of Nematodes

Neuropeptides regulate animal physiology and behavior, making them widely studied targets of functional genetics research. While the field often relies on differential -omics approaches to build hypotheses, no such method exists for neuropeptidomics. It would nonetheless be valuable for studying behaviors suspected to be regulated by neuropeptides, especially when little information is otherwise available. This includes nictation, a phoretic strategy of Caenorhabditis elegans dauers that parallels host-finding strategies of infective juveniles of many pathogenic nematodes. We here developed a targeted peptidomics method for the model organism C. elegans and show that 161 quantified neuropeptides are more abundant in its dauer stage compared with L3 juveniles. Many of these have orthologs in the commercially relevant pathogenic nematode Steinernema carpocapsae, in whose infective juveniles, we identified 126 neuropeptides in total. Through further behavioral genetics experiments, we identify flp-7 and flp-11 as novel regulators of nictation. Our work advances knowledge on the genetics of nictation behavior and adds comparative neuropeptidomics as a tool to functional genetics workflows.     

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.