Cognitive processing of spatial relations in Euclidean diagrams

The cognitive processing of spatial relations in Euclidean diagrams is central to the diagram-based geometric practice of Euclid's Elements. In this study, we investigate this processing through two dichotomies among spatial relations—metric vs topological and exact vs co-exact—introduced by Manders in his seminal epistemological analysis of Euclid's geometric practice. To this end, we carried out a two-part experiment where participants were asked to judge spatial relations in Euclidean diagrams in a visual half field task design. In the first part, we tested whether the processing of metric vs topological relations yielded the same hemispheric specialization as the processing of coordinate vs categorical relations. In the second part, we investigated the specific performance patterns for the processing of five pairs of exact/co-exact relations, where stimuli for the co-exact relations were divided into three categories depending on their distance from the exact case. Regarding the processing of metric vs topological relations, hemispheric differences were found for only a few of the stimuli used, which may indicate that other processing mechanisms might be at play. Regarding the processing of exact vs co-exact relations, results show that the level of agreement among participants in judging co-exact relations decreases with the distance from the exact case, and this for the five pairs of exact/co-exact relations tested. The philosophical implications of these empirical findings for the epistemological analysis of Euclid's diagram-based geometric practice are spelled out and discussed

Sources of Dietary Protein in Relation to Blood Pressure in a General Dutch Population

Background - Little is known about the relation of different dietary protein types with blood pressure (BP). We examined whether intake of total, plant, animal, dairy, meat, and grain protein was related to BP in a cross sectional cohort of 20,820 Dutch adults, aged 20–65 y and not using antihypertensive medication. Design - Mean BP levels were calculated in quintiles of energy-adjusted protein with adjustment for age, sex, BMI, education, smoking, and intake of energy, alcohol, and other nutrients including protein from other sources. In addition, mean BP difference after substitution of 3 en% carbohydrates or MUFA with protein was calculated. Results - Total protein and animal protein were not associated with BP (ptrend = 0.62 and 0.71 respectively), both at the expense of carbohydrates and MUFA. Systolic BP was 1.8 mmHg lower (ptrend36 g/d) than in the lowest

Gene expression profiling reveals a conserved microglia signature in larval zebrafish

International audienceMicroglia are the resident macrophages of the brain. Over the past decade, our understanding of the function of these cells has significantly improved. Microglia do not only play important roles in the healthy brain but are involved in almost every brain pathology. Gene expression profiling allowed to distinguish microglia from other macro-phages and revealed that the full microglia signature can only be observed in vivo. Thus, animal models are irreplaceable to understand the function of these cells. One of the popular models to study microglia is the zebrafish larva. Due to their optical transparency and genetic accessibility, zebrafish larvae have been employed to understand a variety of microglia functions in the living brain. Here, we performed RNA sequencing of larval zebrafish microglia at different developmental time points: 3, 5, and 7 days post fertilization (dpf). Our analysis reveals that larval zebrafish microglia rapidly acquire the core microglia signature and many typical microglia genes are expressed from 3 dpf onwards. The majority of changes in gene expression happened between 3 and 5 dpf, suggesting that differentiation mainly takes place during these days. Furthermore, we compared the larval microglia transcriptome to published data sets of adult zebrafish microglia, mouse microglia, and human microglia. Larval microglia shared a significant number of expressed genes with their adult counterparts in zebrafish as well as with mouse and human microglia. In conclusion, our results show that larval zebrafish microglia mature rapidly and express the core microglia gene signature that seems to be conserved across species. K E Y W O R D S brain, evolution, microglia, RNA sequencing, transcriptome, zebrafis

Colony-Stimulating Factor 1 Receptor (CSF1R) Regulates Microglia Density and Distribution, but Not Microglia Differentiation In Vivo

Microglia are brain-resident macrophages with trophic and phagocytic functions. Dominant loss-of-function mutations in a key microglia regulator, colony-stimulating factor 1 receptor (CSF1R), cause adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a progressive white matter disorder. Because it remains unclear precisely how CSF1R mutations affect microglia, we generated an allelic series of csf1r mutants in zebrafish to identify csf1r-dependent microglia changes. We found that csf1r mutations led to aberrant microglia density and distribution and regional loss of microglia. The remaining microglia still had a microglia-specific gene expression signature, indicating that they had differentiated normally. Strikingly, we also observed lower microglia numbers and widespread microglia depletion in postmortem brain tissue of ALSP patients. Both in zebrafish and in human disease, local microglia loss also presented in regions without obvious pathology. Together, this implies that CSF1R mainly regulates microglia density and that early loss of microglia may contribute to ALSP pathogenesis. Oosterhof et al. show that colony-stimulating factor 1 receptor (CSF1R) primarily regulates microglia density and not their normal differentiation. In addition, they find widespread depletion of microglia in CSF1R-haploinsufficient zebrafish and leukodystrophy patients, also in the absence of pathology, indicating that microglia depletion may contribute to loss of white matter

Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations

The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent. We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation. We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls. B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles. Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls. Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis. The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL. Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP

<i>ATP5PO </i>levels regulate enteric nervous system development in zebrafish, linking Hirschsprung disease to Down Syndrome

Hirschsprung disease (HSCR) is a complex genetic disorder characterized by the absence of enteric nervous system (ENS) in the distal region of the intestine. Down Syndrome (DS) patients have a &gt;50-fold higher risk of developing HSCR than the general population, suggesting that overexpression of human chromosome 21 (Hsa21) genes contribute to HSCR etiology. However, identification of responsible genes remains challenging. Here, we describe a genetic screening of potential candidate genes located on Hsa21, using the zebrafish. Candidate genes were located in the DS-HSCR susceptibility region, expressed in the human intestine, were known potential biomarkers for DS prenatal diagnosis, and were present in the zebrafish genome. With this approach, four genes were selected: RCAN1, ITSN1, ATP5PO and SUMO3. However, only overexpression of ATP5PO, coding for a component of the mitochondrial ATPase, led to significant reduction of ENS cells. Paradoxically, in vitro studies showed that overexpression of ATP5PO led to a reduction of ATP5PO protein levels. Impaired neuronal differentiation and reduced mitochondrial ATP production, were also detected in vitro, after overexpression of ATP5PO in a neuroblastoma cell line. Finally, epistasis was observed between ATP5PO and ret, the most important HSCR gene. Taken together, our results identify ATP5PO as the gene responsible for the increased risk of HSCR in DS patients in particular if RET variants are also present, and show that a balanced expression of ATP5PO is required for normal ENS development.</p

Επισκόπηση ζιζανίων σε αμπελώνες Επαρχίας Λεμεσού

Από τα πιο σημαντικά, αν όχι το πιο σημαντικό πρόβλημα στη γεωργία σήμερα αποτελεί η παρουσία των ζιζανίων στις καλλιέργειες. Η εμφάνιση τους σε γεωργικές καλλιέργειες τα καθιστά ένα από τα πιο δυσεπίλυτα προβλήματα για τους παραγωγούς σήμερα. Η παρουσία τους οδηγεί σε άνισο ανταγωνισμό με τα καλλιεργούμενα φυτά σε θρεπτικά στοιχεία, φως, χώρο και νερό. Σ όλες τις χώρες τα ζιζάνια αποτελούν βασικό πρόβλημα στη γεωργία, έτσι και στη μικρή αλλά γεωργική Κύπρο, τα ζιζάνια δεν μπορούσαν να μην προκαλούν σοβαρές ζημιές. Σκοπός της παρούσας μελέτης ήταν η επιτόπια επισκόπηση καθώς και η καταγραφή σε αντιπροσωπευτικά εδαφοδείγματα από κάθε περιοχή των ζιζανίων σε αμπελώνες της επαρχίας Λεμεσού, σε πεδινές και ημιορεινές περιοχές. Πραγματοποιήθηκε επιτόπια επισκόπηση σε 4 διαφορετικές περιοχές ( δύο πεδινές και δύο ημιορεινές) σε δύο ή τρεις διαφορετικές εποχές. Από κάθε περιοχή, πάρθηκαν τυχαία δείγματα εδάφους, από 4-5 αγρούς της κάθε περιοχής, βάθους 0-30 οπι, σε 5 σημεία σε κάθε αγρό, σε απόσταση περίπου 100 πι μεταξύ τους. Τα μικτά δείγματα από κάθε αγρό μεταφέρθηκαν στο εργαστήριο, τοποθετήθηκαν σε φυτοδοχεία (30 χ 5 οπι) όπου έγινε βλάστηση και καταγραφή ζιζανίων για τρεις διαδοχικές περιόδους, διάρκειας ενός μήνα η κάθε μια. Μεταξύ των καταγραφών μεσολαβούσε διάστημα 15 ημερών και αναμόχλευση του εδάφους. Στην επιτόπια επισκόπηση των ζιζανίων στους πιο πάνω αμπελώνες καταγράφηκαν συνολικά 24 διαφορετικά είδη ζιζανίων από τα οποία τα 20 ήταν πλατύφυλλα και τα 4 αγρωστώδη. Στα εδαφοδείγματα στο εργαστήριο παρατηρήθηκαν συνολικά 22 είδη ζιζανίων εκ των οποίων τα 20 ήταν πλατύφυλλα και τα 2 αγρωστώδη. Τα ζιζάνια με τη μεγαλύτερη συχνότητα από τα πλατύφυλλα ήταν το πορφυρό λάμιο, η στελλάρια και η τσουκνίδα με συχνότητα 3/4 (αριθμός χωριών με παρουσία του ζιζανίου). Από τα αγρωστώδη τα ζιζάνια με την μεγαλύτερη συχνότητα ήταν η ήρα 4/4

Dual-Labeling Strategies for Nuclear and Fluorescence Molecular Imaging: A Review and Analysis

Molecular imaging is used for the detection of biochemical processes through the development of target-specific contrast agents. Separately, modalities such as nuclear and near-infrared fluorescence (NIRF) imaging have been shown to non-invasively monitor disease. More recently, merging of these modalities has shown promise owing to their comparable detection sensitivity and benefited from the development of dual-labeled imaging agents. Dual-labeled agents hold promise for whole-body and intraoperative imaging and could bridge the gap between surgical planning and image-guided resection with a single, molecularly targeted agent. In this review, we summarized the literature for dual-labeled antibodies and peptides that have been developed and have highlighted key considerations for incorporating NIRF dyes into nuclear labeling strategies. We also summarized our findings on several commercially available NIRF dyes and offer perspectives for developing a toolkit to select the optimal NIRF dye and radiometal combination for multimodality imaging

Enantioselective Catalysis of the Aza-Cope Rearrangement by a Chiral Supramolecular Assembly

The chiral supramolecular catalyst Ga{sub 4}L{sub 6} [L = 1,5-bis(2,3-dihydroxybenzoylamino)naphthalene] is a molecular tetrahedron that catalyzes the 3-aza-Cope rearrangement of allyl enammonium cations. This catalysis is accomplished by preorganizing the substrate in a reactive conformation within the host. This work demonstrates that through the use of enantiopure assembly, its chiral cavity is capable of catalyzing the 3-aza-Cope rearrangement enantioselectively, with yields of 21-74% and enantiomeric excesses from 6 to 64% at 50 C. At lower temperatures, the enantioselectivity improved, reaching 78% ee at 5 C. This is the highest enantioselectivity to date induced by the chiral cavity of a supramolecular assembly