1,487 research outputs found

    Research notes: Cross pollination studies of soybeans using a genetic male sterile system

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    Information regarding cross pollinating insects in soybeans has been mainly restricted to honeybees. Erickson (1975) reported that attractiveness of soybeans to honey bees appeared to be heritable. Jaycox (1970) reported on the ecological relationships between honey bees and soybeans

    Polyphony in Architecture

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    Based on interviews with a number of architects and managers from a wide range of organizations, we characterize how architecture is perceived in practice. We identify three groups of organizations that differ with respect to their level of architectural thinking and the alignment of business and IT on architectural issues. Analysis of the interviews further indicates that these three groups differ in the architecture aspects and critical success factors they emphasize. Our results provide a starting point for assessing architecture maturity and alignment within organizations, and can be used to help harmonize different architectural tunes played within organizations

    Identification of Nuclear Factor IV/Ku autoantigen in a human 2D-gel protein database Modification of the large subunit depends on cellular proliferation

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    AbstractNuclear Factor IV (NFIV)is a heterodimeric DNA-binding protein from HeLa cells, recognizing molecular ends and is identical to the autoantigenic target Ku. We have identified the two NFIV/Ku subunits, by comigration, in the 2D-gel database of transformed human amnion cell (AMA) proteins. We observed that the large subunit or NFIV/Ku consists of at least 3 charge variants that correspond to SSP IEFs 5705 (81.2 kDa, pI 5.74), 6707 (81.2 kDa, pI 5.67) and 6706 (81.9 kDa, pI 5.60) in the AMA catalogue. The relative amounts of the 2 major variants (IEFs 5705 and 6707) was dependent on the state of cell proliferation. Inhibition of DNA-synthesis by hydroxyurea also changed the relative levels of the variants, whereas aphidicolin or a thymidine block had no effect. These results suggest a possible role for NFIV/Ku in DNA replication

    Allogeneic NK cells induce the <i>in vitro</i> activation of monocyte-derived and conventional type-2 dendritic cells and trigger an inflammatory response under cancer-associated conditions

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    Natural killer (NK) cells are innate lymphocytes capable to recognize and kill virus-infected and cancer cells. In the past years, the use of allogeneic NK cells as anti-cancer therapy gained interest due to their ability to induce graft-versus-cancer responses without causing graft-versus-host disease and multiple protocols have been developed to produce high numbers of activated NK cells. While the ability of these cells to mediate tumor kill has been extensively studied, less is known about their capacity to influence the activity of other immune cells that may contribute to a concerted anti-tumor response in the tumor microenvironment (TME). In this study, we analyzed how an allogeneic off-the-shelf cord blood stem cell-derived NK-cell product influenced the activation of dendritic cells (DC). Crosstalk between NK cells and healthy donor monocyte-derived DC (MoDC) resulted in the release of IFNγ and TNF, MoDC activation, and the release of the T-cell-recruiting chemokines CXCL9 and CXCL10. Moreover, in the presence of prostaglandin-E2, NK cell/MoDC crosstalk antagonized the detrimental effect of IL-10 on MoDC maturation leading to higher expression of multiple (co-)stimulatory markers. The NK cells also induced activation of conventional DC2 (cDC2) and CD8 + T cells, and the release of TNF, GM-CSF, and CXCL9/10 in peripheral blood mononuclear cells of patients with metastatic colorectal cancer. The activated phenotype of MoDC/cDC2 and the increased release of pro-inflammatory cytokines and T-cell-recruiting chemokines resulting from NK cell/DC crosstalk should contribute to a more inflamed TME and may thus enhance the efficacy of T-cell-based therapies.</p

    Anomalous crossover between thermal and shot noise in macroscopic diffusive conductors

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    We predict the existence of an anomalous crossover between thermal and shot noise in macroscopic diffusive conductors. We first show that, besides thermal noise, these systems may also exhibit shot noise due to fluctuations of the total number of carriers in the system. Then we show that at increasing currents the crossover between the two noise behaviors is anomalous, in the sense that the low frequency current spectral density displays a region with a superlinear dependence on the current up to a cubic law. The anomaly is due to the non-trivial coupling in the presence of the long range Coulomb interaction among the three time scales relevant to the phenomenon, namely, diffusion, transit and dielectric relaxation time.Comment: 4 pages, 2 figure

    Development of a multiplexed activity-based protein profiling assay to evaluate activity of endocannabinoid hydrolase inhibitors

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    Endocannabinoids, an important class of signaling lipids involved in health and disease, are predominantly synthesized and metabolized by enzymes of the serine hydrolase superfamily. Activity-based protein profiling (ABPP) using fluorescent probes, such as fluorophosphonate (FP)-TAMRA and β-lactone-based MB064, enables drug discovery activities for serine hydrolases. FP TAMRA and MB064 have distinct, albeit partially overlapping, target profiles, but cannot be used in conjunction due to overlapping excitation/emission spectra. We therefore synthesized a novel FP-probe with a green BODIPY as fluorescent tag and studied its labeling profile in mouse proteomes. Surprisingly, we found that the reporter tag plays an important role in the binding potency and selectivity of the probe. A multiplexed ABPP-assay was developed in which a probe cocktail of FP-BODIPY and MB064 visualized most endocannabinoid serine hydrolases in mouse brain proteomes in a single experiment. The multiplexed ABPP-assay was employed to profile endocannabinoid hydrolase inhibitor activity and selectivity in mouse brain

    Blood and brain biochemistry and behaviour in NTBC and dietary treated tyrosinemia type 1 mice

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    Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in the tyrosine degradation pathway. Neurocognitive deficiencies have been described in TT1 patients, that have, among others, been related to changes in plasma large neutral amino acids (LNAA) that could result in changes in brain LNAA and neurotransmitter concentrations. Therefore, this project aimed to investigate plasma and brain LNAA, brain neurotransmitter concentrations and behavior in C57 Bl/6 fumarylacetoacetate hydrolase deficient (FAH-/-) mice treated with 2-(2-nitro-4-trifluoromethylbenoyl)-1,3-cyclohexanedione (NTBC) and/or diet and wild-type mice. Plasma and brain tyrosine concentrations were clearly increased in all NTBC treated animals, even with diet (p <0.001). Plasma and brain phenylalanine concentrations tended to be lower in all FAH-/- mice. Other brain LNAA, were often slightly lower in NTBC treated FAH-/- mice. Brain neurotransmitter concentrations were usually within a normal range, although serotonin was negatively correlated with brain tyrosine concentrations (p <0.001). No clear behavioral differences between the different groups of mice could be found. To conclude, this is the first study measuring plasma and brain biochemistry in FAH-/- mice. Clear changes in plasma and brain LNAA have been shown. Further research should be done to relate the biochemical changes to neurocognitive impairments in TT1 patients

    Sex, BMI and age differences in metabolic syndrome:The Dutch Lifelines Cohort Study

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    Introduction: To evaluate the prevalence of metabolic syndrome (MetS) and its individual components within sex-, body mass index (BMI)- and age combined clusters. In addition, we used the age-adjusted blood pressure thresholds to demonstrate the effect on the prevalence of MetS and elevated blood pressure. Subjects and methods: Cross-sectional data from 74,531 Western European participants, aged 18–79 years, were used from the Dutch Lifelines Cohort Study. MetS was defined according to the revised NCEP-ATPIII. Age-adjusted blood pressure thresholds were defined as recommended by the eight reports of the Joint National Committee (≥140/90 mmHg for those aged <60 years, and ≥150/90 mmHg for those aged ≥60 years). Results: 19.2% men and 12.1% women had MetS. MetS prevalence increased with BMI and age. Independent of BMI, abdominal obesity dominated MetS prevalence especially in women, while elevated blood pressure was already highly prevalent among young men. Applying age-adjusted blood pressure thresholds resulted in a 0.2–11.9% prevalence drop in MetS and 6.0–36.3% prevalence drop in elevated blood pressure, within the combined sex, BMI and age clusters. Conclusions: We observed a gender disparity with age and BMI for the prevalence of MetS and, especially, abdominal obesity and elevated blood pressure. The strict threshold level for elevated blood pressure in the revised NCEP-ATPIII, results in an overestimation of MetS prevalence
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