Azetidinones as Zinc‐Binding Groups to Design Selective HDAC8 Inhibitors

2‐Azetidinones, commonly known as β‐lactams, are well‐known heterocyclic compounds. Herein we described the synthesis and biological evaluation of a series of novel β‐lactams. In vitro inhibition assays against HDAC isoforms showed an interesting isoform‐selectivity of these compounds towards HDAC6 and HDAC8. The isoform selectivity changed in response to modification of the azetidinone‐ring nitrogen atom substituent. The presence of an N‐thiomethyl group is a prerequisite for the activity of these compounds in the micromolar range towards HDAC8.     

Preparation and physical properties of LLDPE grafted with novel nonionic surfactants

Copolymers of linear low‐density polyethylene (LLDPE) grafted with two novel nonionic surfactants, acrylic glycerol monostearate ester (AGMS) and acrylic polyoxyethylenesorbitan monooleate ester (ATWEEN80), containing hydrophilic and hydrophobic groups and 1‐olefin double bond were prepared by using a plasticorder at 190°C. To evaluate the grafting degree, two different approaches based on ¹H‐NMR data were proposed, and FTIR calibration was showed to validate these methods. The rheological response of the molten polymers, determined under dynamic shear flow at small‐amplitude oscillations, indicated that crosslinking formation of the chains could be decreased with increasing the monomer concentration. Their thermal behavior was studied by DSC and polarization microscope (PLM): The crystallization temperature (T_C) of grafted LLDPE shifted to higher temperature compared with neat LLDPE because the grafted chains acted as nucleating agents. Water and glycerol were used to calculate the surface free energy of grafted LLDPE films. The results indicated that the novel polyoxyethylene surfactant ATWEEN80 could greatly improve the hydrophilicity of LLDPE and the surface free energy varied from 33 mN/m of neat LLDPE to 106 mN/m of the grafted LLDPE film. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Morphology and rheological behavior of maltene–polymer blends. I. Effect of partial hydrogenation of poly(styrene‐block‐butadiene‐block‐styrene‐block)‐type copolymers

Because of the importance of the maltene–polymer interaction for the better performance of polymer‐modified asphalts, this article reports the effects of the molecular characteristics of two commercial poly(styrene‐block‐butadiene‐block‐styrene‐block) (SBS) polymers and their partially hydrogenated derivatives [poly{styrene‐block[(butadiene)_1?x–(ethylene‐co‐butylene)_x]‐block‐styrene‐block} (SBEBS)] on the morphology and rheological behavior of maltene–polymer blends (MPBs) with polymer concentrations of 3 and 10% (w/w). Each SBEBS and its parent SBS had the same molecular weight and polystyrene block size, but they differed from each other in the composition of the elastomeric block, which exhibited the semicrystalline characteristics of SBEBS. Maltenes were obtained from Ac‐20 asphalt (Pemex, Salamanca, Mexico), and the blends were prepared by a hot‐mixing procedure. Fluorescence microscopy images indicated that all the blends were heterogeneous, with polymer‐rich and maltene‐rich phases. The rheological behavior of the blends was determined from oscillatory shear flow data. An analysis of the storage modulus, loss modulus, complex modulus, and phase angle as a function of the oscillatory frequency at various temperatures allowed us to conclude that the maltenes behaved as pseudohomogeneous viscoelastic materials that could dissipate stress without presenting structural changes; moreover, all the MPBs were more viscoelastic than the neat maltenes, and this depended on both the characteristics and amount of the polymer. The MPBs prepared with SBEBS were more viscoelastic and possessed higher elasticity than those prepared with SBS. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Presence and distribution of FMRFamide-like immunoreactivity in the cyprid of the barnacle Balanus amphitrite (Cirripedia, Crustacea)

The presence and distribution of FMRFamide-like peptides (FLPs) in the cyprid larvae of the barnacle Balanus amphitrite were investigated using immunohistochemical methods. Barnacles are considered to be one of the most important constituents of animal fouling communities, and the cyprid stage is specialized for settlement and metamorphosis in to the sessile adult condition. FLPs immunoreactive (IR) neuronal cell bodies were detected in both the central and the peripheral nervous system. One bilateral group of neurons somata was immunodetected in the brain, and IR nerve fibers were observed in the neuropil area and optic lobes. Intense immunostaining was also observed in the frontal filament complex: frontal filament tracts leaving the optic lobes and projecting towards the compound eyes, swollen nerve endings in the frontal filament vesicles, and thin nerve endings in the external frontal filament. Thin IR nerve fibers were also present in the cement glands. Two pairs of neuronal cell bodies were immunodetected in the posterior ganglion; some of their axons appear to project to the cirri. FLPs IR neuronal cell bodies were also localized in the wall of the dilated midgut and in the narrow hindgut; their processes surround the gut wall and allow gut neurons to synapse with one another. Our data demonstrated the presence of FLPs IR substances in the barnacle cyprid. We hypothesize that these peptides act as integrators in the central nervous system, perform neuromuscular functions for thoracic limbs, trigger intestinal movements and, at the level of the frontal filament, play a neurosecretory role.     

Use of ATR-FTIR spectroscopy coupled with chemometrics for the authentication of avocado oil in ternary mixtures with sunflower and soybean oils

Avocado oil is a high-value and nutraceutical oil whose authentication is very important since the addition of low-cost oils could lower its beneficial properties. Mid-FTIR spectroscopy combined with chemometrics was used to detect and quantify adulteration of avocado oil with sunflower and soybean oils in a ternary mixture. Thirty-seven laboratory-prepared adulterated samples and 20 pure avocado oil samples were evaluated. The adulterated oil amount ranged from 2% to 50% (w/w) in avocado oil. A soft independent modelling class analogy (SIMCA) model was developed to discriminate between pure and adulterated samples. The model showed recognition and rejection rate of 100% and proper classification in external validation. A partial least square (PLS) algorithm was used to estimate the percentage of adulteration. The PLS model showed values of R² > 0.9961, standard errors of calibration (SEC) in the range of 0.3963–0.7881, standard errors of prediction (SEP estimated) between 0.6483 and 0.9707, and good prediction performances in external validation. The results showed that mid-FTIR spectroscopy could be an accurate and reliable technique for qualitative and quantitative analysis of avocado oil in ternary mixtures.     

AMPK Phosphorylation Is Controlled by Glucose Transport Rate in a PKA-Independent Manner

To achieve growth, microbial organisms must cope with stresses and adapt to the environment, exploiting the available nutrients with the highest efficiency. In Saccharomyces cerevisiae, Ras/PKA and Snf1/AMPK pathways regulate cellular metabolism according to the supply of glucose, alternatively supporting fermentation or mitochondrial respiration. Many reports have highlighted crosstalk between these two pathways, even without providing a comprehensive mechanism of regulation. Here, we show that glucose-dependent inactivation of Snf1/AMPK is independent from the Ras/PKA pathway. Decoupling glucose uptake rate from glucose concentration, we highlight a strong coordination between glycolytic metabolism and Snf1/AMPK, with an inverse correlation between Snf1/AMPK phosphorylation state and glucose uptake rate, regardless of glucose concentration in the medium. Despite fructose-1,6-bisphosphate (F1,6BP) being proposed as a glycolytic flux sensor, we demonstrate that glucose-6-phosphate (G6P), and not F1,6BP, is involved in the control of Snf1/AMPK phosphorylation state. Altogether, this study supports a model by which Snf1/AMPK senses glucose flux independently from PKA activity, and thanks to conversion of glucose into G6P.     

New Insights into Cancer Targeted Therapy: Nodal and Cripto-1 as Attractive Candidates

The transforming growth factor beta (TGF-β) signaling is fundamental for correct embryonic development. However, alterations of this pathway have been correlated with oncogenesis, tumor progression and sustaining of cancer stem cells (CSCs). Cripto-1 (CR-1) and Nodal are two embryonic proteins involved in TGF-β signaling. Their expression is almost undetectable in terminally differentiated cells, but they are often re-expressed in tumor cells, especially in CSCs. Moreover, cancer cells that show high levels of CR-1 and/or Nodal display more aggressive phenotypes in vitro, while in vivo their expression correlates with a worse prognosis in several human cancers. The ability to target CSCs still represents an unmet medical need for the complete eradication of certain types of tumors. Given the prognostic role and the selective expression of CR-1 and Nodal on cancer cells, they represent archetypes for targeted therapy. The aim of this review is to clarify the role of CR-1 and Nodal in cancer stem populations and to summarize the current therapeutic strategy to target CSCs using monoclonal antibodies (mAbs) or other molecular tools to interfere with these two proteins.     

Atrazine Inhalation Causes Neuroinflammation,Apoptosis and Accelerating Brain Aging

Background: exposure to environmental contaminants has been linked to an increased risk of neurological diseases and poor outcomes. Chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Several studies have demonstrated that ATR has the potential to be harmful to the brain’s neuronal circuits. Until today nobody has explored the effect of ATR inhalation on young and aged mice. Methods: young and aged mice were subject to 25 mg of ATR in a vehicle made with saline and 10% of Dimethyl sulfoxide (DMSO) every day for 28 days. At the end of experiment different behavioral test were made and brain was collected. Results: exposure to ATR induced the same response in terms of behavioral alterations and motor and memory impairment in mice but in aged group was more marked. Additionally, in both young and aged mice ATR inhalations induced oxidative stress with impairment in physiological antioxidant response, lipid peroxidation, nuclear factor kappa-light-chain-enhancer of activated B cells (nf-κb) pathways activation with consequences of pro-inflammatory cytokines release and apoptosis. However, the older group was shown to be more sensitive to ATR inhalation. Conclusions: our results showed that aged mice were more susceptible compared to young mice to air pollutants exposure, put in place a minor physiologically response was seen when exposed to it.