The Antimicrobial Activity of Peripheral Blood Neutrophils Is Altered in Patients with Primary Ciliary Dyskinesia

The airways of patients with primary ciliary dyskinesia (PCD) contain persistently elevated neutrophil numbers and CXCL8 levels. Despite their abundance, neutrophils fail to clear the airways from bacterial infections. We investigated whether neutrophil functions are altered in patients with PCD. Neutrophils from patients and healthy controls (HC) were isolated from peripheral blood and exposed to various bacterial stimuli or cytokines. Neutrophils from patients with PCD were less responsive to low levels of fMLF in three different chemotaxis assays (p < 0.05), but expression of the fMLF receptors was unaltered. PCD neutrophils showed normal phagocytic function and expression of adhesion molecules. However, PCD neutrophils produced less reactive oxygen species upon stimulation with bacterial products or cytokines compared to HC neutrophils (p < 0.05). Finally, the capacity to release DNA, as observed during neutrophil extracellular trap formation, seemed to be reduced in patients with PCD compared to HC (p = 0.066). These results suggest that peripheral blood neutrophils from patients with PCD, in contrast to those of patients with cystic fibrosis or COPD, do not show features of over-activation, neither on baseline nor after stimulation. If these findings extend to lung-resident neutrophils, the reduced neutrophil activity could possibly contribute to the recurrent respiratory infections in patients with PCD.     

Folivory Affects Composition of Nectar,Floral Odor and Modifies Pollinator Behavior

Herbivory induces changes in plants that influence the associated insect community. The present study addresses the potential trade-off between plant phytochemical responses to insect herbivory and interactions with pollinators. We used a multidisciplinary approach and have combined field and greenhouse experiments to investigate effects of herbivory in plant volatile emission, nectar production, and pollinator behavior, when Pieris brassicae caterpillars were allowed to feed only on the leaves of Brassica nigra plants. Interestingly, volatile emission by flowers changed upon feeding by herbivores on the leaves, whereas, remarkably, volatile emission by leaves did not significantly differ between infested and non-infested flowering plants. The frequency of flower visits by pollinators was generally not influenced by herbivory, but the duration of visits by honeybees and butterflies was negatively affected by herbivore damage to leaves. Shorter duration of pollinator visits could be beneficial for a plant, because it sustains pollen transfer between flowers while reducing nectar consumption per visit. Thus, no trade-off between herbivore-induced plant responses and pollination was evident. The effects of herbivore-induced plant responses on pollinator behavior underpin the importance of including ecological factors, such as herbivore infestation, in studies of the ecology of plant pollination.     

AI and Law: What about the future?

The introduction of results of AI and Law research in actual legal practice advances disturbingly slow. One of the problems is that most research can be classified as either theoretical or pragmatic, while combinations of these two are scarce. This interferes with the need for feedback as well as with the need of getting support, both financially and from actual legal practice. The conclusion of this paper is that an emphasis on research that generates operational and sophisticated systems is necessary in order to provide a future for AI and Law.     

Chocolate yield stress as measured by oscillatory rheology

Liquid chocolate exhibits a non-Newtonian flow behavior that is conventionally characterized by a yield stress and plastic viscosity. In general, yield stress is determined by shear rheology experiments and the data are plotted as viscosity as a function of shear stress or shear stress as a function of shear rate. For the shear stress-shear rate plot, a frequently used approach to estimate the yield stress is to fit the data to one of several established models, with the Casson model being the most popular. Even though ICA (former IOCCC) recommendation is not to use the Casson model, it is still frequently applied. With the Casson model, a good fit to the experimental data for the shear rate ranging from 5 s^{− 1} to 60 s^{− 1} is realized. However, this model is unable to resolve real differences between chocolate samples that manifest at shear rate values below 5 s^{− 1}. In this study, oscillatory rheology was applied and the stress at the end of the linear viscoelastic region (LVR) was taken as an estimate for the yield stress. This method was shown to be sensitive to fat content, emulsifier concentration and type of emulsifier. Furthermore, oscillatory rheology was found to be capable to capture differences in yield stress of chocolates that were not differentiated using the Casson model fitting approach.     

Mechanisms of Phenol Ozonation—Kinetics of Formation of Primary and Secondary Reaction Products

Organic acids are part of assimilable organic carbon (AOC) formed from natural organic matter (NOM) during ozonation for drinking water production. To elucidate the formation of organic acids, phenol as surrogate compound for NOM was ozonated while suppressing reactions of ^·OH radicals by addition of tert-butanol. Batch experiments show benzoquinone (40 and 18%), catechol (33 and 1%), cis,cis-muconic acid (6 and 3%), and hydroquinone (2 and 7%) to be the most abundant primary products at pH 7 and 3, respectively. The tertiary product oxalic acid was obtained in similar yields from phenol ozonation (0.8%) as during ozonation of lake water (1.6%). Together with other low molecular weight organic acids it was formed upon small ozone exposures, as was shown by time-dependent experiments in time ranges of 0.4–23 and 0.07–1.0 seconds for pH 3 and 7.25, respectively.     

Increased Angiogenesis and Lymphangiogenesis in Adenomyosis Visualized by Multiplex Immunohistochemistry

There is evidence for increased angiogenesis in the (ectopic) endometrium of adenomyosis patients under the influence of vascular endothelial growth factor (VEGF). VEGF stimulates both angiogenesis and lymph-angiogenesis. However, information on lymph vessels in the (ectopic) endometrium of adenomyosis patients is lacking. In this retrospective matched case-control study, multiplex immunohistochemistry was performed on thirty-eight paraffin embedded specimens from premenopausal women who had undergone a hysterectomy at the Amsterdam UMC between 2001 and 2018 to investigate the evidence for (lymph) angiogenesis in the (ectopic) endometrium or myometrium of patients with adenomyosis versus controls with unrelated pathologies. Baseline characteristics of both groups were comparable. In the proliferative phase, the blood and lymph vessel densities were, respectively, higher in the ectopic and eutopic endometrium of patients with adenomyosis than in the endometrium of controls. The relative number of blood vessels without α-smooth muscle actinin (α SMA) was higher in the eutopic and ectopic endometrium of adenomyosis patients versus controls. The level of VEGF staining intensity was highest in the myometrium but did not differ between patients with adenomyosis or controls. The results indicate increased angiogenesis and lymphangiogenesis in the (ectopic) endometrium affected by adenomyosis. The clinical relevance of our findings should be confirmed in prospective clinical studies.     

The Identification of Small Molecule Inhibitors That Reduce Invasion and Metastasis of Aggressive Cancers

Transformed epithelial cells can activate programs of epithelial plasticity and switch from a sessile, epithelial phenotype to a motile, mesenchymal phenotype. This process is linked to the acquisition of an invasive phenotype and the formation of distant metastases. The development of compounds that block the acquisition of an invasive phenotype or revert the invasive mesenchymal phenotype into a more differentiated epithelial phenotype represent a promising anticancer strategy. In a high-throughput assay based on E-cadherin (re)induction and the inhibition of tumor cell invasion, 44,475 low molecular weight (LMW) compounds were screened. The screening resulted in the identification of candidate compounds from the PROAM02 class. Selected LMW compounds activated E-cadherin promoter activity and inhibited cancer cell invasion in multiple metastatic human cancer cell lines. The intraperitoneal administration of selected LMW compounds reduced the tumor burden in human prostate and breast cancer in vivo mouse models. Moreover, selected LMW compounds decreased the intra-bone growth of xenografted human prostate cancer cells. This study describes the identification of the PROAM02 class of small molecules that can be exploited to reduce cancer cell invasion and metastases. Further clinical evaluation of selected candidate inhibitors is warranted to address their safety, bioavailability and antitumor efficacy in the management of patients with aggressive cancers.     

Traditional consumption of and rearing edible insects in Africa,Asia and Europe

ABSTRACT

The traditional consumption of edible insects is common in one third of the world's population, mostly in Latin America, Africa and Asia. There are over one thousand identified species of insects eaten in some stage of their life cycle; and they play important roles in ensuring food security. The most common way to collect insects are from the wild, which is seasonal with limited availability and has an increasing demand resulting in a disruption to the ecosystem. There is a growing interest shown in rearing insects for commercial purposes, and an industrial scale production will be required to ensure steady supplies. Industrial production will need to take into account the living environment of insects, the nutritional composition of their feed and the overall efficiency of the production system. We provide a short overview on the consumption of and rearing insects in Africa, Asia and Europe. For Africa, a snapshot is given for Nigeria, Ghana, Central African Republic, Kenya and Uganda, while the following countries are reported for Asia: China, Japan, Lao People's Democratic Republic, Thailand and Vietnam. In addition, a list of insect species with the highest potential for food and feed in the European Union is provided with some reference to The Netherlands and Finland. The review concludes that there is need to better understand the rearing and farming procedures that will yield high quality edible insects in Africa, Asia and Europe.     

Formation of assimilable organic carbon during oxidation of natural waters with ozone, chlorine dioxide, chlorine, permanganate, and ferrate

Five oxidants, ozone, chlorine dioxide, chlorine, permanganate, and ferrate were studied with regard to the formation of assimilable organic carbon (AOC) and oxalate in absence and presence of cyanobacteria in lake water matrices. Ozone and ferrate formed significant amounts of AOC, i.e. more than 100 μg/L AOC were formed with 4.6 mg/L ozone and ferrate in water with 3.8 mg/L dissolved organic carbon. In the same water samples chlorine dioxide, chlorine, and permanganate produced no or only limited AOC. When cyanobacterial cells (Aphanizomenon gracile) were added to the water, an AOC increase was detected with ozone, permanganate, and ferrate, probably due to cell lysis. This was confirmed by the increase of extracellular geosmin, a substance found in the selected cyanobacterial cells. AOC formation by chlorine and chlorine dioxide was not affected by the presence of the cells. The formation of oxalate upon oxidation was found to be a linear function of the oxidant consumption for all five oxidants. The following molar yields were measured in three different water matrices based on oxidant consumed: 2.4-4.4% for ozone, 1.0-2.8% for chlorine dioxide and chlorine, 1.1-1.2% for ferrate, and 11-16% for permanganate. Furthermore, oxalate was formed in similar concentrations as trihalomethanes during chlorination (yield ∼ 1% based on chlorine consumed). Oxalate formation kinetics and stoichiometry did not correspond to the AOC formation. Therefore, oxalate cannot be used as a surrogate for AOC formation during oxidative water treatment.     

Nonrigid point set matching of white matter tracts for diffusion tensor image analysis

Patient studies based on diffusion tensor images (DTI) require spatial correspondence between subjects. We propose to obtain the correspondence from white matter tracts, by introducing a new method for nonrigid matching of white matter fiber tracts in DTI. The method boils down to point set registration that involves simultaneously clustering and matching of the data points. The tracts are implicitly warped to a common frame of reference to avoid the potential bias toward one of the datasets. The algorithm gradually refines from global to local registration, which is implemented through deterministic annealing. Special care was taken to incorporate the spatial relation between fiber points and the uncertainty in principal diffusion orientation. As a result, the computed clusters are oriented along the fiber tracts and discriminate between adjacent but distinct fiber tracts. This is validated on synthetic and clinical data. The root-mean-squared distance with respect to expert-annotated landmarks is low (3 mm). In contrast to a state-of-the-art nonrigid registration technique, the proposed method is more robust to residual misalignments in terms of measured fractional anisotropy values.