Chiroptical Properties and Absolute Configuration of Chiral, Open Chain Di- and Tri-substituted Allenes: a Polarizability Approach

A second order treatment of the optical activity of chiral diand tri-substituted open chain allenes, by means of the polarizability model of DeVoe, makes it possible to establish a simple relationship between optical rotatory power and absolute configuration of these compounds

Expression of LGR-5, MSI-1 and DCAMKL-1, putative stem cell markers, in the early phases of 1,2-dimethylhydrazine-induced rat colon carcinogenesis: correlation with nuclear β-catenin.

BACKGROUND: Colon cancer stem cells may drive carcinogenesis and account for chemotherapeutic failure. Although many markers for these cells have been proposed, there is no complete agreement regarding them, nor has their presence in the early phases of carcinogenesis been characterized in depth. METHODS: The expression of the putative markers LGR-5 (leucine-rich-repeat-containing G-protein-coupled receptor 5), MSI-1 (Musashi-1) and DCAMKL-1 (doublecortin and calcium/calmodulin-dependent protein kinase-like-1) was studied in normal colon mucosa (NM), in the precancerous lesions Mucin Depleted Foci (MDF) and in macroscopic tumours (adenomas) of 1,2-dimethylhydrazine-treated rats. Co-localization between these markers and nuclear β-catenin (NBC), an attributed feature of cancer stem cells, was also determined. Moreover, since PGE(2) could increase NBC, we tested whether short-term treatment with celecoxib, a COX-2 inhibitor (2 weeks, 250 ppm in the diet) could reduce the expression of these markers. RESULTS: LGR-5 expression in NM was low (Labelling Index (LI): 0.22±0.03 (means±SE)) with positive cells located mainly at the base of the crypts. Compared to NM, LGR-5 was overexpressed in MDF and tumours (LI: 4.7±2.0 and 2.9±1.0 in MDF and tumours, respectively, P<0.01 compared to NM). DCAMKL-1 positive cells, distributed along the length of normal crypts, were reduced in MDF and tumours. Nuclear expression of MSI-1, located mainly at the base of normal crypts, was not observed in MDF or tumours. In both MDF and tumours, few cells co-expressed LGR-5 and NBC (LI: 1.0±0.3 and 0.4±0.2 in MDF and tumours, respectively). Notwithstanding the lower expression of DCAMKL-1 in tumours, the percentage of cells co-expressing DCAMKL-1 and NBC was higher than in NM (LI: 0.5±0.1 and 0.04±0.02 in tumours and NM, respectively). MSI-1 and NBC co-localization was not observed. Celecoxib did not reduce cells co-expressing LGR-5 and NBC. CONCLUSIONS: Based on its prevalent localization at the base of normal crypts, as expected for stem cells, and on the overexpression in precancerous lesions and tumours, we support LGR-5, but not MSI-1 or DCAMKL-1, as putative neoplastic stem cell marker. In both MDF and tumours, we identified LGR-5-positive cells co-expressing NBC which could be a subpopulation with the highest stem cell features

Venice as a paradigm of coastal flooding under multiple compound drivers

Full comprehension of the dynamics of hazardous sea levels is indispensable for assessing and managing coastal flood risk, especially under a changing climate. The 12 November 2019 devastating flood in the historical city of Venice (Italy) stimulated new investigations of the coastal flooding problem from different perspectives and timescales. Here Venice is used as a paradigm for coastal flood risk, due to the complexity of its flood dynamics facing those of many other locations worldwide. Spectral decomposition was applied to the long-term 1872-2019 sea-level time series in order to investigate the relative importance of different drivers of coastal flooding and their temporal changes. Moreover, a multivariate analysis via copulas provided statistical models indispensable for correctly understanding and reproducing the interactions between the variables at play. While storm surges are the main drivers of the most extreme events, tides and long-term forcings associated with planetary atmospheric waves and seasonal to inter-annual oscillations are predominant in determining recurrent nuisance flooding. The non-stationary analysis revealed a positive trend in the intensity of the non-tidal contribution to extreme sea levels in the last three decades, which, along with relative sea-level rise, contributed to an increase in the frequency of floods in Venice

Imaging and Laboratory Biomarkers in Cardiovascular Disease

Imaging and laboratory biomarkers are an essential support to modern practice of medicine, allowing a better identification, severity titration, staging and follow-up of atherosclerosis and heart failure disease. This review provides an overview of imaging, biochemical and genetic biomarkers used in clinical practice and for research purposes in order to evaluate the 4 different aspect of patient vulnerability to cardiovascular disease: arterial; blood; myocardial; metabolic vulnerability. Yet, no single perfect biomarker exists and there is wide room for optimization and integration between clinical evaluation and biomarker evaluation. In general, a targeted approach tailored on the individual patient should be preferred to a carpet diagnostic bombing, which will lead to an exorbitant multiplier of costs, risks and inappropriate testing

Mucin Depleted Foci, Colonic Preneoplastic Lesions Lacking Muc2, Show Up-Regulation of Tlr2 but Not Bacterial Infiltration

Mucin depleted foci (MDF) are precancerous lesions of the colon in carcinogen-treated rodents and humans at high risk. Since MDF show signs of inflammation we hypothesized that the defective mucous production would expose them to the risk of being penetrated by intestinal bacteria, which can be sensed by Toll-like receptors (Tlrs) and activate inflammatory pathways. To verify this hypothesis we tested the expression of 84 genes coding for Tlrs and associated pathways using RT-qPCR in MDF (n = 7) from 1,2-dimethylhydrazine (DMH)-treated rats. Among the 84 tested genes, 26 were differentially expressed in MDF with 5 genes significantly up-regulated and 21 down-regulated when compared to the normal mucosa. Tlr2, as well as other downstream genes (Map4k4, Hspd1, Irak1, Ube2n), was significantly up-regulated. Among the genes regulating the NFkB pathway, only Map4k4 was significantly up-regulated, while 19 genes were not varied and 6 were down-regulated. Tlr2 protein was weakly expressed both in normal mucosa and MDF. To determine whether inflammation observed in MDF could be caused by bacteria contacting or infiltrating crypts, we performed fluorescence in situ hybridization (FISH) experiments with a rRNA universal bacterial probe. None of the 21 MDF tested, showed bacteria inside the crypts, while among the colonic tumors (n = 15), only one had very few bacteria on the surface and on the surrounding normal mucosa. In conclusion, the up-regulation of Tlr2 in MDF, suggests a link between this receptor and carcinogenesis, possibly related to a defective barrier function of these lesions. The data of FISH experiments do not support the hypothesis that inflammation in MDF and tumors is stimulated by bacterial infiltration

Human deciduous teeth from the Middle Stone Age layers of Sibudu Cave (South Africa)

Abstract: In the African Pleistocene, the fossil evidence for early Homo sapiens populations is still relatively limited. Here we present two additional specimens (two deciduous teeth) recovered from the Middle Stone Age (MSA) deposits of Sibudu Cave (KwaZulu‐Natal, South Africa). We describe their morphology and metrics, using three‐dimensional models of the teeth obtained from high‐resolution micro‐CT images. The first specimen is a Ldm1 (HUM. TO 1) recovered in the BS5 layer dated 77.3 ± 2.7 ka, and associated with stone tools assigned to the “pre‐Still Bay” assemblage. The other specimen is a Rdi1 (HUM. TO 2) coming from the Pinkish Grey Sand (PGS) layer, dated 64.7±2.3 ka, and associated with a Howieson’s Poort industry. Both teeth are well preserved, with minor post mortem cracks not affecting the overall morphology, and they comprise the intact, worn crown and the remnants of the roots, naturally resorbed. A large carious lesion occupies most of the distal face and part of the occlusal surface in the Ldm1; also a chip of enamel is missing from the disto‐buccal corner. In the Rdi1 average enamel thickness and relative enamel thickness values have been measured. For both teeth, we compared mesiodistal (MD) and bucco‐lingual (BL) diameters with those of other Late Pleistocene deciduous teeth and extant Homo sapiens. The analysis has shown that the teeth are comparable in size with the other MSA specimens described in the literature

Antialactone: A New γ-Lactone from Antiaris africana, and its Absolute Configuration Determined from TDDFT CD Calculations

Four compounds were isolated from the stem bark of Antiaris africana. One of them, a γ-lactone named antialactone (1a), is reported for the first time as a natural product. The structures were determined by comprehensive analyses of their 1D and 2D NMR spectra and EI MS data. The absolute configuration of antialactone acetate (1b) was established by TDDFT CD calculations and comparison with measured CD spectra. The remaining three known compounds were identified, by comparing their spectroscopic data with those reported in the literature, as lichenxanthone, β-sitosterol, and betulinic acid

Potential role of low kV ex vivo micro-CT for 3D morphometry of paraffin embedded coronary vessels before histology

Purpose: Micro CT is an established tool for non destructive 3D inspection of small specimens. Aim of the study was to demonstrate that despite its limitations in differentiation of soft materials, micro CT can reliably display coronary vessel structure and surrounding tissues after paraffin embedding. Data were obtained from coronary specimens of pig, physical phantoms and numerical simulations. Preliminary images with dual-energy techniques are also shown. Methods: A micro CT scanner built by our group was used for the experiments. The x-ray tube was set up in the range of 20-50 kV; the voxel size was set to 21 &#956;m. A phantom composed of formalin fixed fat and myocardium of rat, dehydrated and paraffin embedded, was used to measure the contrast of different tissues with respect to background. Similar acquisitions were simulated numerically. Real samples of pig excised coronary arteries were processed in the same way and acquired with the same settings; resulting images were compared to those obtained by histology. Results: In phantom, the myocardium contrast vs. paraffin varied from 40% at 20 kV to 29% at 50 kV. The fat contrast vs. background was 2% at 20 kV, whereas it was indistinguishable from the background at 50 kV; all the contrasts in phantom appeared lower than those expected from simulations, probably because of tissue shrinkage. In the samples from pig (see Figure), the vessel wall contrast was 25% greater than the myocardium contrast; the pericardium and a balloon induced stenosis were clearly distinguished. All micro CT scans were shorter than 1 hour. Conclusion: Micro CT is a useful complementary tool for the 3D morphometry of coronary vessels after paraffin embedding, and it can help for the preliminary identification of features of interest for subsequent histological analysis

Maternal and Sex Dependency of Insulin Resistance: Longitudinal PET and Echocardiography Study from the Healthy Fetus to the Adult Minipig

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