Lignin nanoparticles as sustainable photoprotective carriers for sunscreen filters

Sunscreen filters may be degraded after prolonged UV exposure with loss of their shielding property and generation of harmful radical species. They are contained in cosmetic formulations in high concentrations, so the improvement of photostability is of relevance for safety concerns. We report here that lignin nanoparticles are sustainable carriers and photostabilizers of two common UV chemical filters, namely, avobenzone and octyl methoxycinnamate. These compounds have been encapsulated by nanoprecipitation into kraft lignin nanoparticles using eco-certified dimethyl isosorbide as a primary solvent and deionized water as an antisolvent. After the encapsulation, both compounds significantly prolonged the half-life stability against UV irradiation. The stabilizing properties of lignin nanoparticles were further improved by coencapsulation of avobenzone and octyl methoxycinnamate with hydroxytyrosol, a natural phenol with antioxidant activity recovered from olive oil wastes and characterized by skin regenerative properties

Relating process languages for security and communication correctness (extended abstract)

Process calculi are expressive specification languages for concurrency. They have been very successful in two research strands: (a) the analysis of security protocols and (b) the enforcement of correct message-passing programs. Despite their shared foundations, languages and reasoning techniques for (a) and (b) have been separately developed. Here we connect two representative calculi from (a) and (b): we encode a (high-level) π-calculus for multiparty sessions into a (low-level) applied π-calculus for security protocols. We establish the correctness of our encoding, and we show how it enables the integrated analysis of security properties and communication correctness by re-using existing tools

Age-Related Reference Intervals of the Main Biochemical and Hematological Parameters in C57BL/6J, 129SV/EV and C3H/HeJ Mouse Strains

BACKGROUND: Although the mouse is the animal model most widely used to study the pathogenesis and treatment of human diseases, reference values for biochemical parameters are scanty or lacking for the most frequently used strains. We therefore evaluated these parameters in the C57BL/6J, 129SV/EV and C3H/HeJ mice. METHODOLOGY/PRINCIPAL FINDINGS: We measured by dry chemistry 26 analytes relative to electrolyte balance, lipoprotein metabolism, and muscle/heart, liver, kidney and pancreas functions, and by automated blood counter 5 hematological parameters in 30 animals (15 male and 15 female) of each mouse strain at three age ranges: 1-2 months, 3-8 months and 9-12 months. Whole blood was collected from the retro-orbital sinus. We used quality control procedures to investigate analytical imprecision and inaccuracy. Reference values were calculated by non parametric methods (median and 2.5(th) and 97.5(th) percentiles). The Mann-Whitney and Kruskal-Wallis tests were used for between-group comparisons. Median levels of GLU, LDH, Chol and BUN were higher, and LPS, AST, ALP and CHE were lower in males than in females (p range: 0.05-0.001). Inter-strain differences were observed for: (1) GLU, t-Bil, K+, Ca++, PO(4)- (p<0.05) and for TAG, Chol, AST, Fe++ (p<0.001) in 4-8 month-old animals; (2) for CK, Crea, Mg++, Na++, K+, Cl- (p<0.05) and BUN (p<0.001) in 2- and in 10-12 month-old mice; and (3) for WBC, RBC, HGB, HCT and PLT (p<0.05) during the 1 year life span. CONCLUSION/SIGNIFICANCE: Our results indicate that metabolic variations in C57BL/6J, 129SV/EV and C3H/HeJ mice after therapeutic intervention should be evaluated against gender- and age-dependent reference intervals

Grotta del Cavallo (Apulia-Southern Italy). The Uluzzian in the mirror

The Uluzzian techno-complex is commonly considered to be a \u201ctransitional industry\u201d mostly on the basis of some inferred characteristics such as a chiefly flake-based production, a small amount of Upper Palaeolithic-like tools and a combination of Middle and Upper Palaeolithic elements both in the toolkit and in the technical systems. Following its discovery, the Uluzzian was identified as the Italian counterpart of the French Ch\ue2telperronian and attributed to Neandertals. However, a study issued in 2011 has established the modern character of the two deciduous teeth found in 1964 in the Uluzzian deposit of Grotta del Cavallo, fostering renewed interests to the Uluzzian culture, which real nature is almost unknown to the international scientific community. Here we provide preliminary results of the study on the lithic assemblage from the earliest Uluzzian layer and on backed pieces from the whole Uluzzian sequence of Grotta del Cavallo (Apulia, Italy), the type site of the Uluzzian. Moreover, besides a thorough review on the stratigraphy of Grotta del Cavallo (Supplementary Materials), we provide updated information on the human remains by presenting two unpublished teeth from the reworked deposit of the same cave. We conclude that the early Uluzzians demonstrate original technological behavior and innovations devoid of any features deriving or directly linked with the late Mousterian of Southern Italy. Therefore, the novelty nature of the Uluzzian techno-complex (with respect to the preceding Mousterian) complies with the recent reassessment of the two deciduous teeth from Grotta del Cavallo in suggesting an earliest migration of modern humans in southern Europe around 45,000 years ago

Congenital Heart Block Maternal Sera Autoantibodies Target an Extracellular Epitope on the α1G T-Type Calcium Channel in Human Fetal Hearts

Background:Congenital heart block (CHB) is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV) block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB.Methodology/Principal Findings:We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene) in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation). Using human fetal hearts (20-22 wks gestation), our immunoprecipitation (IP), Western blot analysis and immunofluorescence (IF) staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I). Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved) of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN) cells.Conclusions/Significance:Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets. © 2013 Strandberg et al

Stimulation of homology-directed gene targeting at an endogenous human locus by a nicking endonuclease

Homologous recombination (HR) is a highly accurate mechanism of DNA repair that can be exploited for homology-directed gene targeting. Since in most cell types HR occurs very infrequently (∼10−6 to 10−8), its practical application has been largely restricted to specific experimental systems that allow selection of the few cells that become genetically modified. HR-mediated gene targeting has nonetheless revolutionized genetics by greatly facilitating the analysis of mammalian gene function. Recent studies showed that generation of double-strand DNA breaks at specific loci by designed endonucleases greatly increases the rate of homology-directed gene repair. These findings opened new perspectives for HR-based genome editing in higher eukaryotes. Here, we demonstrate by using donor DNA templates together with the adeno-associated virus (AAV) Rep78 and Rep68 proteins that sequence- and strand-specific cleavage at a native, predefined, human locus can also greatly enhance homology-directed gene targeting. Our findings argue for the development of other strategies besides direct induction of double-strand chromosomal breaks to achieve efficient and heritable targeted genetic modification of cells and organisms. Finally, harnessing the cellular HR pathway through Rep-mediated nicking expands the range of strategies that make use of AAV elements to bring about stable genetic modification of human cells

Selection-Independent Generation of Gene Knockout Mouse Embryonic Stem Cells Using Zinc-Finger Nucleases

Gene knockout in murine embryonic stem cells (ESCs) has been an invaluable tool to study gene function in vitro or to generate animal models with altered phenotypes. Gene targeting using standard techniques, however, is rather inefficient and typically does not exceed frequencies of 10−6. In consequence, the usage of complex positive/negative selection strategies to isolate targeted clones has been necessary. Here, we present a rapid single-step approach to generate a gene knockout in mouse ESCs using engineered zinc-finger nucleases (ZFNs). Upon transient expression of ZFNs, the target gene is cleaved by the designer nucleases and then repaired by non-homologous end-joining, an error-prone DNA repair process that introduces insertions/deletions at the break site and therefore leads to functional null mutations. To explore and quantify the potential of ZFNs to generate a gene knockout in pluripotent stem cells, we generated a mouse ESC line containing an X-chromosomally integrated EGFP marker gene. Applying optimized conditions, the EGFP locus was disrupted in up to 8% of ESCs after transfection of the ZFN expression vectors, thus obviating the need of selection markers to identify targeted cells, which may impede or complicate downstream applications. Both activity and ZFN-associated cytotoxicity was dependent on vector dose and the architecture of the nuclease domain. Importantly, teratoma formation assays of selected ESC clones confirmed that ZFN-treated ESCs maintained pluripotency. In conclusion, the described ZFN-based approach represents a fast strategy for generating gene knockouts in ESCs in a selection-independent fashion that should be easily transferrable to other pluripotent stem cells

The origin and legacy of the Etruscans through a 2000-year archeogenomic time transect

The origin, development, and legacy of the enigmatic Etruscan civilization from the central region of the Italian peninsula known as Etruria have been debated for centuries. Here we report a genomic time transect of 82 individuals spanning almost two millennia (800 BCE to 1000 CE) across Etruria and southern Italy. During the Iron Age, we detect a component of Indo-European–associated steppe ancestry and the lack of recent Anatolian-related admixture among the putative non–Indo-European–speaking Etruscans. Despite comprising diverse individuals of central European, northern African, and Near Eastern ancestry, the local gene pool is largely maintained across the first millennium BCE. This drastically changes during the Roman Imperial period where we report an abrupt population-wide shift to ~50% admixture with eastern Mediterranean ancestry. Last, we identify northern European components appearing in central Italy during the Early Middle Ages, which thus formed the genetic landscape of present-day Italian populations

Evolution of innovation policy in Emilia-Romagna and Valencia: Similar reality, similar results?

This is an author's accepted manuscript of an article published in: “European Planning Studies"; Volume 22, Issue 11, 2014; copyright Taylor & Francis; available online at: http://dx.doi.org/10.1080/09654313.2013.831398[EN] This paper examines the evolution of regional innovation policy in Emilia-Romagna and Valencia, two regions with similar economic features that implemented close innovation policies in the 1970s and 1980s. We investigate whether their similarities have led to parallel targets, policy tools and governance developments. We show that innovation policy in both regions suffered from the effects of privatization, budget constraints and changes to manufacturing during the 1990s and we highlight the consequences. Although Emilia-Romagna experienced deeper changes to its innovation policy, privatizations and/or the replacement of public funds promoted commercial approaches and induced market failures in both regions. The worst effects of these policies were the implementation of less-risky innovation projects, the shift towards extraregional projects and markets, and the favouring of large firms.López Estornell, M.; Barberá Tomás, JD.; Garcia Reche, A.; Mas Verdú, F. (2013). Evolution of innovation policy in Emilia-Romagna and Valencia: Similar reality, similar results?. European Planning Studies. 22(11):2287-2304. doi:10.1080/09654313.2013.831398S22872304221