p53 Loss in Breast Cancer Leads to Myc Activation,Increased Cell Plasticity,and Expression of a Mitotic Signature with Prognostic Value

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Direct enantioselective vinylogous Mannich‐type reactions of acyclic enals: New experimental insights into the E/Z‐dilemma

The direct heterofunctionalization of acyclic α,β‐unsaturated aldehydes with N‐acylquinolinium ions contemplating the formation of two stereocentres is studied using dienamine catalysis. This work gives some new experimental insights on the remote stereocontrol in dienamine catalysis using unbiased aliphatic systems and large electrophiles, pointing to a (Z)‐preference of the reactive configuration of the second double bond.     

Organocatalytic alkylation of carbohydrate‐containing aldehydes with dihydroquinoline N,O‐acetals: Absolute configuration of 1,2‐dihydroquinolines

The direct catalytic α‐amidoalkylation of dihydroquinolines with aldehydes bearing oxygen functionalities at different positions in a Mannich‐type reaction has been studied. β‐Alkoxy‐aldehyde 1d gave high enantioselectivity, albeit with an inherently poor diastereoselectivity, while the use of α‐alkoxy aldehydes 1c was detrimental also to enantioselectivity. Mannich‐type reactions have been studied for the first time using new chiral carbohydrate‐derived aldehydes 1a,b showing a reactivity markedly influenced by the presence of water. The chiral glycidic backbone showed a slight but significant influence on the overall stereochemical outcome only when present in α‐position of the aldehyde. The absolute stereochemistry of the products was studied by electronic circular dichroism (ECD) spectra and compared with theoretical calculations. ECD analysis easily provides the absolute configuration of 1,2‐dihydroquinoline derivatives such as quinoline‐1(2H)‐carboxylates.     

Towards novel S-DABOC inhibitors: synthesis, biological investigation, and molecular modeling studies

A small family of S-DABO cytosine analogs (S-DABOCs) has been synthesized and biologically evaluated as HIV-1 inhibitor both on wild type (wt) and drug-resistant mutants leading to the identification of an interesting compound (5d). Molecular modeling studies have been finally performed in order to rationalize the results.     

Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis

Little is known about the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms and the presence of insulin resistance and the early evolution of atherosclerosis in nondiabetic subjects with cardiovascular disease (CAD) and stent implantation. The present study was performed in an attempt to better understand whether metabolic, endothelial, and angiographic findings characteristic of subjects with cardiovascular disease and in-stent restenosis are related to NOS3 variants. This is a case-control study performed from 2002 to 2006. All subjects admitted to the study were recruited in the Nord-Centre of Italy, most from Milan and its surrounding towns. Measures of glucose tolerance, insulin sensitivity, markers of endothelial dysfunction, forearm vasodilation, and adipokine levels were determined and associated to the frequency of two single-nucleotide polymorphisms of NOS3, i.e., Glu298Asp (rs1799983, G/T) and rs753482 (intron 18 A/C). A total of 747 subjects, not known to have diabetes, were evaluated: 333 subjects had asymptomatic CAD, 106 subjects had unstable angina and were evaluated for in-stent restenosis 6 mo after stent placement, and 308 were control subjects. The presence of TT and CC minor alleles was significantly greater in case groups compared with control subjects. At phenotypic level, subjects with the polymorphisms were characterized by hyperinsulinemia and reduced reactive hyperemia, whereas increased leptin and decreased adiponectin levels were present in subjects with restenosis in the presence of reduced minimal lumen diameter and length of stenosis almost doubled. Hyperinsulinemia, endothelial dysfunction, and a more atherogenic profile seem to be peculiar features of subjects with asymptomatic CAD and restenosis carrying NOS3 gene variants.     

Paleoenvironmental changes during sapropel 19 (i-cycle 90) deposition: Evidences from geochemical,mineralogical and micropaleontological proxies in the mid-Pleistocene Montalbano Jonico land section (southern Italy)

An integrated micropaleontological, geochemical and mineralogical study has been performed across the mid-Pleistocene sapropel 19 (i-cycle 90) from the Montalbano Jonico land section (southern Italy), to reconstruct the paleoenvironmental conditions at time of its formation. The sapropel interval is characterized by two oxygen depletion phases (phase A and C) interrupted by a temporary re-oxygenation interval (phase B). The beginning and the end of sapropel deposition are dated at 957 ± 0.81 kyr and 950 ±0.86 kyr respectively. The duration of the interruption is estimated to 0.350 ± 0.32 kyr. The multiproxy approach highlights that deposition of sapropel 19 reflects a period of enhanced freshwater runoff induced by a wetter climate. As a consequence of a more efficient fluvial erosion, a higher terrigenous input, mostly ascribable to a southern Apennines source, and an increased turbidity of surface waters accompanied most of sapropel deposition. Biotic and abiotic proxies document that different paleoenvironmental conditions occur through phases A–C. The beginning of phase A is characterized by warm on-land paleoclimate as well as warm and oligotrophic surface water conditions. During the upper part of phase A temperature starts decreasing and surface waters appear more productive. This change probably represents the prelude to cooler and drier conditions characterizing phase B, which displays a river supply reduction and an eolian input increase (Sahara dust). During phase C the restored depleted oxygen environment at the bottom sediments is clearly coupled with the re-establishment of humid conditions and increased river supply. At the same time, enhanced mixing of water column, a cooler paleoclimate, and increased productivity of surface waters are recorded, the latter likely favored by the enhanced mixing of water column and also increased delivery of land-derived nutrients. The end of phase C is marked by a restored “normal” run-off. Enhanced productivity in surface waters and low oxygen conditions at the bottom sediments persist slightly above phase C. The overall results suggest that the onset of sapropel deposition is related to water stratification that caused low oxygen exchanges with the sea-bottom. Although enhanced productivity characterizes most of the sapropel deposition it was not the primary factor triggering sapropel deposition.     

Direct identification in food samples of Listeria spp. and Listeria monocytogenes by molecular methods

A new molecular approach for the detection and identification of Listeria spp. and Listeria monocytogenes in food is presented here. The method is based on the PCR amplification of a fragment of the iap gene from the five species belonging to the genus and on the analysis of the PCR products obtained by denaturing gradient gel electrophoresis (DGGE). The protocol was first optimized by using strains from international collections. Based on the differences present in the sequences amplified, it was possible to obtain species-specific DGGE migration that allowed fast and easy identification of L. monocytogenes, L. innocua, L. welshimeri, L. seeligeri, and L. ivanovii. Moreover, for L. monocytogenes serotypes, partial differentiation was possible. The optimized protocol was used for identification of Listeria strains traditionally isolated from food and for direct detection and identification of Listeria members in food after an overnight enrichment. Identification of 48 food isolates and direct detection of Listeria spp. in 73 food samples show the potential of the method that can be used as a fast screening test to investigate the presence of Listeria spp. and L. monocytogenes in food.