Competitive aminal formation during the synthesis of a highly soluble, isopropyl-decorated imine porous organic cage.

The synthesis of a new porous organic cage decorated with isopropyl moieties (CC21) was achieved from the reaction of triformylbenzene and an isopropyl functionalised diamine. Unlike structurally analogous porous organic cages, its synthesis proved challenging due to competitive aminal formation, rationalised using control experiments and computational modelling. The use of an additional amine was found to increase conversion to the desired cage

The Role of Bile in the Regulation of Exocrine Pancreatic Secretion

As early as 1926 Mellanby (1) was able to show that introduction of bile into the duodenum of anesthetized cats produces a copious flow of pancreatic juice. In conscious dogs, Ivy & Lueth (2) reported, bile is only a weak stimulant of pancreatic secretion. Diversion of bile from the duodenum, however, did not influence pancreatic volume secretion stimulated by a meal (3,4). Moreover, Thomas & Crider (5) observed that bile not only failed to stimulate the secretion of pancreatic juice but also abolished the pancreatic response to intraduodenally administered peptone or soap

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

The Silences Framework: A Method for researching sensitive themes and marginalized health perspectives (English version)

Objective: To describe the experience of applying of The Silences Framework to underpin health research investigating Tuberculosis/HIV/AIDS coinfection . Method: The Silences Framework originally developed following a study exploring the decisions and silences surrounding black Caribbean men living in England, discussing the themes 'sexual health' and 'ethnicity'. Following this study a conceptual a theory for research on sensitive issues and health care of marginalized populations was developed called 'Screaming Silences' which forms the foundation of The Silences Framework. Screaming Silences define research areas and experiences that are poorly studied, little understood or silenced. Results: The Silences Framework supports researchers in revealing "silences" in the subjects they study - as such results may reflect how beliefs, values, and experiences of some groups influence their health. This framework provides the application of four complementary stages: working the silences, hearing silences, voicing silences and working with the silences. The analysis occurs cyclically and can be repeated as long as the silences inherent in a study are not revealed. Conclusion: this article presents The Silences Framework and the application of the notion of "sounds of silence", mapping an antiessentialist theoretical framework for its use in sensitive research in health and nursing areas, being a reference for other researchers in studies involving marginalized populations. KEYWORDS: Inequalities in health. Methods. Nursing. Coinfection. Research. Tuberculosis. Acquired immunodeficiency syndrome

Enhanced AGAMOUS expression in the centre of the Arabidopsis flower causes ectopic expression over its outer expression boundaries

Spatial regulation of C-function genes controlling reproductive organ identity in the centre of the flower can be achieved by adjusting the level of their expression within the genuine central expression domain in Antirrhinum and Petunia. Loss of this control in mutants is revealed by enhanced C-gene expression in the centre and by lateral expansion of the C-domain. In order to test whether the level of central C-gene expression and hence the principle of ‘regulation by tuning’ also applies to spatial regulation of the C-function gene AGAMOUS (AG) in Arabidopsis, we generated transgenic plants with enhanced central AG expression by using stem cell-specific CLAVATA3 (CLV3) regulatory sequences to drive transcription of the AG cDNA. The youngest terminal flowers on inflorescences of CLV3::AG plants displayed homeotic features in their outer whorls indicating ectopic AG expression. Dependence of the homeotic feature on the age of the plant is attributed to the known overall weakening of repressive mechanisms controlling AG. Monitoring AG with an AG-I::GUS reporter construct suggests ectopic AG expression in CLV3::AG flowers when AG in the inflorescence is still repressed, although in terminating inflorescence meristems, AG expression expands to all tissues. Supported by genetic tests, we conclude that upon enhanced central AG expression, the C-domain laterally expands necessitating tuning of the expression level of C-function genes in the wild type. The tuning mechanism in C-gene regulation in Arabidopsis is discussed as a late security switch that ensures wild-type C-domain control when other repressive mechanism starts to fade and fail

Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

Current opportunities to catalyze research in nutrition and cancer prevention – an interdisciplinary perspective

Cancer Research UK and Ludwig Cancer Research convened an inaugural international Cancer Prevention and Nutrition Conference in London on December 3–4, 2018. Much of the discussion focused on the need for systematic, interdisciplinary approaches to better understand the relationships of nutrition, exercise, obesity and metabolic dysfunction with cancer development. Scientists at the meeting underscored the importance of studying the temporal natural history of exposures that may cumulatively impact cancer risk later in life. A robust dialogue identified obesity as a major risk for cancer, and the food environment, especially high energy and low nutrient processed foods, as strong and prevalent risk factors for obesity. Further engagement highlighted challenges in the post-diagnostic setting, where similar opportunities to understand the complex interplay of nutrition, physical activity, and weight will inform better health outcomes. Going forward, holistic research approaches, encompassing insights from multiple disciplines and perspectives, will catalyze progress urgently needed to prevent cancer and improve public health

Analysis of IL12B Gene Variants in Inflammatory Bowel Disease

IL12B encodes the p40 subunit of IL-12, which is also part of IL-23. Recent genome-wide association studies identified IL12B and IL23R as susceptibility genes for inflammatory bowel disease (IBD). However, the phenotypic effects and potential gene-gene interactions of IL12B variants are largely unknow

Assessing Implicit Odor Localization in Humans Using a Cross-Modal Spatial Cueing Paradigm

Navigation based on chemosensory information is one of the most important skills in the animal kingdom. Studies on odor localization suggest that humans have lost this ability. However, the experimental approaches used so far were limited to explicit judgements, which might ignore a residual ability for directional smelling on an implicit level without conscious appraisal.A novel cueing paradigm was developed in order to determine whether an implicit ability for directional smelling exists. Participants performed a visual two-alternative forced choice task in which the target was preceded either by a side-congruent or a side-incongruent olfactory spatial cue. An explicit odor localization task was implemented in a second experiment.No effect of cue congruency on mean reaction times could be found. However, a time by condition interaction emerged, with significantly slower responses to congruently compared to incongruently cued targets at the beginning of the experiment. This cueing effect gradually disappeared throughout the course of the experiment. In addition, participants performed at chance level in the explicit odor localization task, thus confirming the results of previous research.The implicit cueing task suggests the existence of spatial information processing in the olfactory system. Response slowing after a side-congruent olfactory cue is interpreted as a cross-modal attentional interference effect. In addition, habituation might have led to a gradual disappearance of the cueing effect. It is concluded that under immobile conditions with passive monorhinal stimulation, humans are unable to explicitly determine the location of a pure odorant. Implicitly, however, odor localization seems to exert an influence on human behaviour. To our knowledge, these data are the first to show implicit effects of odor localization on overt human behaviour and thus support the hypothesis of residual directional smelling in humans

Heritability of chronic venous disease

Varicose veins without skin changes have a prevalence of approximately 20% in Northern and Western Europe whereas advanced chronic venous insufficiency affects about 3% of the population. Genetic risk factors are thought to play an important role in the aetiology of both these chronic venous diseases (CVD). We evaluated the relative genetic and environmental impact upon CVD risk by estimating the heritability of the disease in 4,033 nuclear families, comprising 16,434 individuals from all over Germany. Upon clinical examination, patients were classified according to the CEAP guidelines as either C2 (simple varicose veins), C3 (oedema), C4 (skin changes without ulceration), C5 (healed ulceration), or C6 (active ulcers). The narrow-sense heritability (h2) of CVD equals 17.3% (standard error 2.5%, likelihood ratio test P = 1.4 × 10−13). The proportion of disease risk attributable to age (at ascertainment) and sex, the two main risk factors for CVD, was estimated as 10.7% (Kullback–Leibler deviance R2). The heritability of CVD is high, thereby suggesting a notable genetic component in the aetiology of the disease. Systematic population-based searches for CVD susceptibility genes are therefore warranted