Molecular Sensing by Nanoporous Crystalline Polymers

Chemical sensors are generally based on the integration of suitable sensitive layers and transducing mechanisms. Although inorganic porous materials can be effective, there is significant interest in the use of polymeric materials because of their easy fabrication process, lower costs and mechanical flexibility. However, porous polymeric absorbents are generally amorphous and hence present poor molecular selectivity and undesired changes of mechanical properties as a consequence of large analyte uptake. In this contribution the structure, properties and some possible applications of sensing polymeric films based on nanoporous crystalline phases, which exhibit all identical nanopores, will be reviewed. The main advantages of crystalline nanoporous polymeric materials with respect to their amorphous counterparts are, besides a higher selectivity, the ability to maintain their physical state as well as geometry, even after large guest uptake (up to 10–15 wt%), and the possibility to control guest diffusivity by controlling the orientation of the host polymeric crystalline phase. The final section of the review also describes the ability of suitable polymeric films to act as chirality sensors, i.e., to sense and memorize the presence of non-racemic volatile organic compounds

Stroke by inducing HDAC9-dependent deacetylation of HIF-1 and Sp1, promotes TfR1 transcription and GPX4 reduction, thus determining ferroptotic neuronal death

: Background: The inhibition of histone deacetylase 9 (HDAC9) represents a promising druggable target for stroke intervention. Indeed, HDAC9 is overexpressed in neurons after brain ischemia where exerts a neurodetrimental role. However, mechanisms of HDAC9-dependent neuronal cell death are not yet well established. Methods: Brain ischemia was obtained in vitro by primary cortical neurons exposed to glucose deprivation plus reoxygenation (OGD/Rx) and in vivo by transient middle cerebral artery occlusion. Western blot and quantitative real-time polymerase chain reaction were used to evaluate transcript and protein levels. Chromatin immunoprecipitation was used to evaluate the binding of transcription factors to the promoter of target genes. Cell viability was measured by MTT and LDH assays. Ferroptosis was evaluated by iron overload and 4-hydroxynonenal (4-HNE) release. Results: Our results showed that HDAC9 binds to hypoxia-inducible factor 1 (HIF-1) and specificity protein 1 (Sp1), two transcription activators of transferrin 1 receptor (TfR1) and glutathione peroxidase 4 (GPX4) genes, respectively, in neuronal cells exposed to OGD/Rx. Consequently, HDAC9 induced: (1) an increase in protein level of HIF-1 by deacetylation and deubiquitination, thus promoting the transcription of the pro-ferroptotic TfR1 gene; and (2) a reduction in Sp1 protein levels by deacetylation and ubiquitination, thus resulting in a down-regulation of the anti-ferroptotic GPX4 gene. Supporting these results, the silencing of HDAC9 partially prevented either HIF-1 increase and Sp1 reduction after OGD/Rx. Interestingly, silencing of the neurodetrimental factors, HDAC9, HIF-1, or TfR1 or the overexpression of the prosurvival factors Sp1 or GPX4 significantly reduced a well-known marker of ferroptosis 4-HNE after OGD/Rx. More important, in vivo, intracerebroventricular injection of siHDAC9 reduced 4-HNE levels after stroke by preventing: (1) HIF-1 and TfR1 increase and thus the augmented intracellular iron overload; and (2) a reduction of Sp1 and its target gene GPX4. Conclusions: Collectively, results obtained suggest that HDAC9 mediates post-traslational modifications of HIF-1 and Sp1 that, in turn, increases TfR1 and decreases GPX4 expression, thus promoting neuronal ferroptosis in in vitro and in vivo models of stroke

Molecular simulation of carbon dioxide sorption in nanoporous crystalline phase of sydiotactic polystyrene

Nanoporous crystalline δe-form of syndiotactic polystyrene (sPS) is characterized by the rather peculiar behavior of being able to absorb considerable amounts of low molecular weight penetrants, in contrast to the general behavior reported for the crystalline phase of polymers that is impervious to penetrants. In particular, the δe nanoporous crystalline form of sPS displays a sorption capacity of penetrants that is several times higher than the one of the amorphous phase of sPS. In this paper, sorption thermodynamics of carbon dioxide in the δe nanoporous crystalline form of semicrystalline sPS is analyzed by means of Grand Canonical Monte Carlo (GCMC) molecular simulation methods, evaluating sorption isotherms as well as isosteric heats of sorption based on a semi-empirical molecular force-field. In fact, in the last years, this technique has been successfully used to investigate sorption properties of periodic crystals of a wide range of materials, including zeolites and polymers, supplying reliable estimates and representing a valid support to the experimental activity. While computational techniques allow direct determination of sorption properties of purely crystalline systems, experimental characterization of sorption in a semicrystalline polymer, as is the case of sPS under investigation, does not give a straight estimation of sorption capacity of the crystalline phase since sorption measurement incorporates other contributions related to the amorphous phase and interphases, as well as to possible defects of the crystalline phase. However, in the case of sPS at the investigated gas pressures, contribution of the amorphous and non-crystalline phases to carbon dioxide sorption can be neglected, and it has been possible to directly compare simulation predictions with experimental results, showing that GCMC computations supply excellent estimates for sorption isotherms and isosteric heats of sorption

Emerging Role of DREAM in Healthy Brain and Neurological Diseases

: The downstream regulatory element antagonist modulator (DREAM) is a multifunctional Ca2+-sensitive protein exerting a dual mechanism of action to regulate several Ca2+-dependent processes. Upon sumoylation, DREAM enters in nucleus where it downregulates the expression of several genes provided with a consensus sequence named dream regulatory element (DRE). On the other hand, DREAM could also directly modulate the activity or the localization of several cytosolic and plasma membrane proteins. In this review, we summarize recent advances in the knowledge of DREAM dysregulation and DREAM-dependent epigenetic remodeling as a central mechanism in the progression of several diseases affecting central nervous system, including stroke, Alzheimer's and Huntington's diseases, amyotrophic lateral sclerosis, and neuropathic pain. Interestingly, DREAM seems to exert a common detrimental role in these diseases by inhibiting the transcription of several neuroprotective genes, including the sodium/calcium exchanger isoform 3 (NCX3), brain-derived neurotrophic factor (BDNF), pro-dynorphin, and c-fos. These findings lead to the concept that DREAM might represent a pharmacological target to ameliorate symptoms and reduce neurodegenerative processes in several pathological conditions affecting central nervous system

Fluorescence Correlation Spectroscopy in Semiadhesive Wall Proximity

With examination of diffusion in heterogeneous media through fluorescence correlation spectroscopy, the temporal correlation of the intensity signal shows a long correlation tail and the characteristic diffusion time results are no longer easy to determine. Excluded volume and sticking effects have been proposed to justify such deviations from the standard behavior since all contribute and lead to anomalous diffusion mechanisms . Usually, the anomalous coefficient embodies all the effects of environmental heterogeneity providing too general explanations for the exotic diffusion recorded. Here, we investigated whether the reason of anomalies could be related to a lack of an adequate interpretative model for heterogeneous systems and how the presence of obstacles on the detection volume length scale could affect fluorescence correlation spectroscopy experiments. We report an original modeling of the autocorrelation function where fluorophores experience reflection or adsorption at a wall placed at distances comparable with the detection volume size. We successfully discriminate between steric and adhesion effects through the analysis of long time correlations and evaluate the adhesion strength through the evaluation of probability of being adsorbed and persistence time at the wall on reference data. The proposed model can be readily adopted to gain a better understanding of intracellular and nanoconfined diffusion opening the way for a more rational analysis of the diffusion mechanism in heterogeneous systems and further developing biological and biomedical applications

New anti-nodal monoclonal antibodies targeting the nodal pre-helix loop involved in cripto-1 binding

Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the Cripto-1-mediated signalling. To achieve this, antibodies were raised against hNodal(44-67) and mAbs generated by the hybridoma technology. We have selected one mAb, named 3D1, which strongly associates with full-length rhNodal (KD 1.4 nM) and recognizes the endogenous protein in a panel of human melanoma cell lines by western blot and FACS analyses. 3D1 inhibits the Nodal-Cripto-1 binding and blocks Smad2/3 phosphorylation. Data suggest that inhibition of the Nodal-Cripto-1 axis is a valid therapeutic approach against melanoma and 3D1 is a promising and interesting agent for blocking Nodal-Cripto mediated tumor development. These findings increase the interest for Nodal as both a diagnostic and prognostic marker and as a potential new target for therapeutic intervention

Erprobung von Elektrofahrzeugen der neuesten Generation auf der Insel Ruegen und Energieversorgung fuer Elektrofahrzeuge durch Solarenergie und Stromtankstellen. Anhang Abschlussbericht

This final report (2 volumes) describes the project contents and the results of the works in the frame of a research project subsidised by the Federal Ministry for Education, Science, Research and Technology as well as by the Ministry of Finance of Mecklenburg Vorpommern. Based on the areas of responsibility of the Deutsche Automobilgesellschaft mbH, Zirkow the results of the project on Ruegen are presented in 13 chapters. They provide an overview of the total project. The operational results, such as driving performance, readiness for use and reliability of the components of all electric-powered vehicles have been evaluated. (orig./AKF)Der vorliegende Abschlussbericht (2 Baende) stellt den Projektinhalt und die Ergebnisse der Arbeiten fuer ein vom Bundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie (BMBF) sowie dem Wirtschaftsministerium Mecklenburg Vorpommern gefoerdertes Vorhaben dar. In 13 Kapiteln werden die Ergebnisse des Ruegenprojektes aus den Aufgabenbereichen der DAUG ausgefuehrt, die zur Uebersicht des Gesamtprojektes dienen. Im Besonderen werden hierbei die Betriebsergebnisse, wie z.B. Fahrleistungen, Einsatzbereitschaft und Zuverlaessigkeit der Komponenten fuer alle Elektrofahrzeuge ausgewertet. (orig./AKF)SIGLEAvailable from TIB Hannover: F97B442+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany); Wirtschaftsministerium des Landes Mecklenburg-Vorpommern, Schwerin (Germany)DEGerman