Perfluoropolyether-based organic-inorganic hybrid coatings

Perfluoropolyether-based organic-inorganic hybrids were prepared by sol-gel process and applied as functional coatings onto glass substrates. Contact angle analysis and X-ray photoemission spectroscopy were carried out in order to characterize the surface of the prepared coatings. A strong hydrophobic and lipophobic character was observed for all tested compositions. The wettability behaviour was found to be dependent on both the coating technique and the reaction time of the sol-gel reaction. A strong surface segregation of perfluoropolyether segments was noted for all the prepared samples as evidenced by XPS analysis. On the basis of the obtained results, these materials could be used as functional coatings to prepare water and oil repellent glasses or other substrates.     

Effects of crosslink density and length on the number of intramolecular crosslinks (defects) introduced into a rubbery network

Estimates are presented for the effects of the crosslink density, or the molecular weight of polymer chains between crosslinks, and the length of crosslinks, or crosslinking agents, upon the expected ratio of internal or intramolecular (possibly elastically ineffective) to external or intermolecular (elastically effective) crosslinks introduced in rubber networks crosslinked in both the dry and dissolved states. Model calculations are performed on cis-1,4-polyisoprene with the following results: (i) in rubber networks formed by crosslinking in the dry state, the number of possibly inactive, intramolecular crosslinks introduced is negligibly small; and (ii) the relative number of intramolecular crosslinks introduced may become appreciable for those networks formed by lightly crosslinking low molecular weight rubber molecules in solutions, where the volume fraction of rubber present is small, using initiators that produce short crosslinks.     

Infrared thermovision technique for the assessment of thermal transmittance value of opaque building elements on site

Due to new regulations in the field of energy saving, international standards concerning energy requirements of buildings have been developed. In this field, during the design phase, one of the most important parameters to be considered is the value of heat losses coefficient through the envelope. Anyway, very often a great difference is experienced between predicted performance of building elements as calculated using the methods prescribed in technical standards, and the one considering as-build conditions, particularly in the field of building renovation where the envelope thermal transmittance value must be measured on site. Till now, the only method accepted by international standards is the heat flowmeter (HFM) that presents some restriction and some uncertainty in the results. In this study a faster and less invasive method is proposed, the infrared thermovision technique (ITT) whose full potentiality has never been investigated yet, in order to acquire quantitative data of real thermal transmittances of the building envelope in a quasi-steady state condition. The theoretic background is presented together with the application in three case studies. The results indicate that, following a specific methodology, it is possible to record significant data useful to perform a proper assessment of energy performance of existing buildings.     

DNA Binding Mode Analysis of a Core-Extended Naphthalene Diimide as a Conformation-Sensitive Fluorescent Probe of G-Quadruplex Structures

G-quadruplex existence was proved in cells by using both antibodies and small molecule fluorescent probes. However, the G-quadruplex probes designed thus far are structure- but not conformation-specific. Recently, a core-extended naphthalene diimide (c_ex-NDI) was designed and found to provide fluorescent signals of markedly different intensities when bound to G-quadruplexes of different conformations or duplexes. Aiming at evaluating how the fluorescence behaviour of this compound is associated with specific binding modes to the different DNA targets, c_ex-NDI was here studied in its interaction with hybrid G-quadruplex, parallel G-quadruplex, and B-DNA duplex models by biophysical techniques, molecular docking, and biological assays. c_ex-NDI showed different binding modes associated with different amounts of stacking interactions with the three DNA targets. The preferential binding sites were the groove, outer quartet, or intercalative site of the hybrid G-quadruplex, parallel G-quadruplex, and B-DNA duplex, respectively. Interestingly, our data show that the fluorescence intensity of DNA-bound c_ex-NDI correlates with the amount of stacking interactions formed by the ligand with each DNA target, thus providing the rationale behind the conformation-sensitive properties of c_ex-NDI and supporting its use as a fluorescent probe of G-quadruplex structures. Notably, biological assays proved that c_ex-NDI mainly localizes in the G-quadruplex-rich nuclei of cancer cells.     

The Interplay between PARP Inhibitors and Immunotherapy in Ovarian Cancer: The Rationale behind a New Combination Therapy

Ovarian cancer (OC) has a high impact on morbidity and mortality in the female population. Survival is modest after platinum progression. Therefore, the search for new therapeutic strategies is of utmost importance. BRCA mutations and HR-deficiency occur in around 50% of OC, leading to increased response and survival after Poly (ADP-ribose) polymerase inhibitors (PARPis) administration. PARPis represent a breakthrough for OC therapy, with three different agents approved. On the contrary, immune checkpoint inhibitors (ICIs), another breakthrough therapy for many solid tumors, led to modest results in OC, without clinical approvals and even withdrawal of clinical trials. Therefore, combinations aiming to overcome resistance mechanisms have become of great interest. Recently, PARPis have been evidenced to modulate tumor microenvironment at the molecular and cellular level, potentially enhancing ICIs responsiveness. This represents the rationale for the combined administration of PARPis and ICIs. Our review ought to summarize the preclinical and translational features that support the contemporary administration of these two drug classes, the clinical trials conducted so far, and future directions with ongoing studies.     

Fine Mapping and Candidate Gene Analysis of Pm36, a Wild Emmer-Derived Powdery Mildew Resistance Locus in Durum Wheat

Powdery mildew (PM) is an economically important foliar disease of cultivated cereals worldwide. The cultivation of disease-resistant varieties is considered the most efficient, sustainable and economical strategy for disease management. The objectives of the current study were to fine map the chromosomal region harboring the wild emmer PM resistance locus Pm36 and to identify candidate genes by exploiting the improved tetraploid wheat genomic resources. A set of backcross inbred lines (BILs) of durum wheat were genotyped with the SNP 25K chip array and comparison of the PM-resistant and susceptible lines defined a 1.5 cM region (physical interval of 1.08 Mb) harboring Pm36. The genetic map constructed with F_2:3 progenies derived by crossing the PM resistant line 5BIL-42 and the durum parent Latino, restricted to 0.3 cM the genetic distance between Pm36 and the SNP marker IWB22904 (physical distance 0.515 Mb). The distribution of the marker interval including Pm36 in a tetraploid wheat collection indicated that the positive allele was largely present in the domesticated and wild emmer Triticum turgidum spp. dicoccum and ssp. dicoccoides. Ten high-confidence protein coding genes were identified in the Pm36 region of the emmer, durum and bread wheat reference genomes, while three added genes showed no homologous in the emmer genome. The tightly linked markers can be used for marker-assisted selection in wheat breeding programs, and as starting point for the Pm36 map-based cloning.     

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer’s Disease from Other Neurological Disorders

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn alone. Regression analyses showed an association of higher Ng concentrations with MMSE < 24, pathological Aβ 42/40 ratios, pTau, tTau and the ApoEε4 genotype. Aβ 42/Ng was associated with MMSE < 24, an AD-related FDG-PET pattern, the ApoEε4 genotype, pathological Aβ 42 levels and Aβ 42/40 ratios, pTau, and tTau. Moreover, APO-Eε4 carriers showed higher Ng concentrations than non-carriers. Our results support the idea that the Aβ 42/Ng ratio is a reliable index of synaptic dysfunction/degeneration able to discriminate AD from other neurological conditions.