Effect Of Zinc Cations On The Kinetics Of Supramolecular Assembly And The Chirality Of Porphyrin J-Aggregates

Dilute aqueous solutions of anionic meso-4-sulfonatophenyl-porphyrin (TPPS) extract zinc(ii) ions from glass or quartz surfaces at room temperature and efficiently form the corresponding metal complex (ZnTPPS). The partial or complete formation of ZnTPPS has been probed by UV/Vis spectroscopy and both static and time-resolved fluorescence. The source of zinc(ii) ions has been clearly identified through inductively coupled plasma optical emission spectrometry. The presence of increasing amounts of ZnTPPS slows down the rate of TPPS J-aggregate formation in acid solution. This influences the nucleation step and has a profound impact on the onset of chirality in these species. This evidence indicates the important role of this adventitious metal ion in the interpretation of various spectroscopic and kinetic data for the self-assembly of the TPPS porphyrin and provides some insights into controversial findings on their chirality. The use of this metal derivative as the starting compound for in situ formation of monomeric TPPS is suggested

Mechanism For Copper(II)-Mediated Disaggregation Of A Porphyrin J-Aggregate

J-aggregates of anionic meso-tetrakis(4-sulfonatophenyl)porphyrin form at intermediate pH (2.3–3.1) in the presence of NiSO₄ or ZnSO₄ (ionic strength, I.S. = 3.2 M). These aggregates convert to monomeric porphyrin units via metallation with copper(II) ions. The kinetics for the disassembly process, as monitored by UV/vis spectroscopy, exhibits zeroth-order behavior. The observed zeroth-order rate constants show a two-term dependence on copper(II) ion concentrations: linear and second order. Also observed is an inverse dependence on hydrogen ion concentration. Activation parameters have been determined for the disassembly process leading to ΔH^≠ = (+163 ± 15) kJ·mol⁻¹ and ΔS^≠ = (+136 ± 11) J·K⁻¹. A mechanism is proposed in which copper(II) cation is in pre-equilibrium with a reactive site at the rim of the J-aggregate. An intermediate copper species is thus formed that eventually leads to the final metallated porphyrin either through an assisted attack of a second metal ion or through a direct insertion of the metal cation into the macrocycle core

Spreading factors of a globally invading coastal copepod

The Mediterranean Sea is one of the areas most affected by alien invasions, which are continuously increasing also due to intense human activities and environmental changes that favor the introduction of species previously unable to colonize the basin. This is the case of the copepods of the genus Pseudodiaptomus, first described in the Indian Ocean and considered one of the most resistant to unfavorable conditions but never recorded in the Mediterranean until 2011 though present in adjacent seas. Pseudodiaptomus marinus, in particular, is common in shallow marine-brackish waters and is one of the species often found in ballast waters and in aquaculture plants. Native of Japan, it has started spreading since 1950s and its populations have established in several harbours, eutrophic inlets and lagoons along the coasts of the Pacific and Indian Oceans. In the last few years, P. marinus has been increasingly reported in European Seas (Mediterranean Sea and North Sea). In this paper, we review the invasion history of this species with a special emphasis on its records in the Mediterranean Sea, and its occurrence and establishment in Sicilian waters. We also compare the biological traits and population dynamics of P. marinus with those of other representative of the genus and discuss about the possible mechanisms of introduction in new environments. Aim of our work is to understand the reasons of successful invasion of P. marinus and the environmental and biological factors that may lead to its further biogeographic expansion

"Pseudodiaptomus Marinus" Sato, 1913, a New Invasive Copepod in Lake Faro (Sicily): Observations on the Swimming Behaviour and the Sex-Dependent Responses to Food

Background: The calanoid copepod Pseudodiaptomus marinus Sato, 1913 is an estuarine-coastal species, living in shallow eutrophic inshore waters. It is native of the Indo-Pacific region, but in the last 50 years, it has successfully colonized new areas worldwide. P. marinus, first recorded in Lake Faro (Messina, Italy) in October 2008, is now a stable component of the zooplankton assemblage of the lake. By means of video recordings, for the first time, the swimming behaviour of males and non-ovigerous and ovigerous females of P. marinus has been studied. The individuals were filmed in the presence and absence of food to evaluate how the presence of prey might affect the swimming behaviour. Results: The swimming motion showed marked sex-dependent features and responses to the presence of food. Mechanisms through which behaviour might influence the outcome of a new colonization were analysed. The behaviour of P. marinus was then compared with that of the congeneric Pseudodiaptomus annandalei showing the typical behaviour displayed by the representatives of the genus Pseudodiaptomus of living in proximity of the bottom. Conclusions: Environmental and hydrological conditions in Lake Faro have likely provided the newly introduced P. marinus a suitable environment for settling, although normally the presence of an anoxic deep layer would be detrimental for a demersal species. In this case, the plasticity in the behaviour of P. marinus enhanced its capacity for colonising new environments. Switching from demersal to pelagic habitat or being fully planktonic allowed it to express its large individual variability in motion strategies and thus to successfully colonize the lake

Reelin expression in human prostate cancer: a marker of tumor aggressiveness based on correlation with grade.

Reelin is a glycoprotein that plays a critical role in the regulation of neuronal migration during brain development and, since reelin has a role in the control of cell migration, it might represents an important factor in cancer pathology. In this study, 66 surgical specimens of prostate cancer were analyzed for reelin expression by immunohistochemical method. The reelin expression was correlated with Gleason score and individual Gleason patterns. Reelin expression was found in 39% prostate cancers. Stromal tissues, normal epithelial cells and prostate intraepithelial neoplasia (PIN) of any grade around and distant from cancer were always negative for reelin. Reelin was found in malignant prostatic epithelial glands of 50% cases Gleason score 10, 52% Gleason score 9, 56% Gleason score 8, 18% Gleason score 7, while no sample of prostate cancers with Gleason score 6 showed reelin expression (P=0,005). As reelin staining is frequently found in high Gleason score prostate cancers, we explored whether reelin expression is influenced by single Gleason patterns

Intracellular fate and impact on gene expression of doxorubicin/cyclodextrin-graphene nanomaterials at sub-toxic concentration

The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString® technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field

Sex-Based Dimorphism of Anticancer Immune Response and Molecular Mechanisms of Immune Evasion

PURPOSE: We previously demonstrated that sex influences response to immune checkpoint inhibitors. In this article, we investigate sex-based differences in the molecular mechanisms of anticancer immune response and immune evasion in patients with NSCLC. EXPERIMENTAL DESIGN: We analyzed (i) transcriptome data of 2,575 early-stage NSCLCs from seven different datasets; (ii) 327 tumor samples extensively characterized at the molecular level from the TRACERx lung study; (iii) two independent cohorts of 329 and 391 patients, respectively, with advanced NSCLC treated with anti–PD-1/anti–PD-L1 drugs. RESULTS: As compared with men, the tumor microenvironment (TME) of women was significantly enriched for a number of innate and adaptive immune cell types, including specific T-cell subpopulations. NSCLCs of men and women exploited different mechanisms of immune evasion. The TME of females was characterized by significantly greater T-cell dysfunction status, higher expression of inhibitory immune checkpoint molecules, and higher abundance of immune-suppressive cells, including cancer-associated fibroblasts, MDSCs, and regulatory T cells. In contrast, the TME of males was significantly enriched for a T-cell–excluded phenotype. We reported data supporting impaired neoantigens presentation to immune system in tumors of men, as molecular mechanism explaining the findings observed. Finally, in line with our results, we showed significant sex-based differences in the association between TMB and outcome of patients with advanced NSCLC treated with anti–PD-1/PD-L1 drugs. CONCLUSIONS: We demonstrated meaningful sex-based differences of anticancer immune response and immune evasion mechanisms, that may be exploited to improve immunotherapy efficacy for both women and men. TRANSLATIONAL RELEVANCE: It is well known that sex (i.e., the biological differences between men and women) and gender (i.e., behavioral differences associated with being male or female) are variables that affect immune responses to both foreign and selfantigens. Such sex- and gender-based dimorphism of immune system function, in turn reflects complex interactions between genes, hormones, the environment, and commensal microbiome composition. In our previous works, we showed that patients' sex is significantly associated with effectiveness of immune checkpoint inhibitors (ICIs) in patients with several solid tumors, including NSCLC. Here, we identified meaningful differences in molecular mechanisms that drive anticancer immune response as well as in immune evasion mechanisms exploited by NSCLCs arising in men and women. Importantly, we showed that all the findings reported, were not related to other variables potentially associated with sex such as patients' age, stage of disease, tumor histotype, and smoking status. The findings reported in this our work explain our previous clinical observations and can open this area to different immunotherapy strategies in males and females with NSCLC to further improve prognosis of both

Rhetoric and reality: Critical perspective on education in a 3D virtual world

The emergence of any new educational technology is often accompanied by inflated expectations about its potential for transforming pedagogical practice and improving student learning outcomes. A critique of the rhetoric accompanying the evolution of 3D virtual world education reveals a similar pattern, with the initial hype based more on rhetoric than research demonstrating the extent to which rhetoric matches reality. Addressed are the perceived gaps in the literature through a critique of the rhetoric evident throughout the evolution of the application of virtual worlds in education and the reality based on the reported experiences of experts in the field of educational technology, who are all members of the Australian and New Zealand Virtual Worlds Working Group. The experiences reported highlight a range of effective virtual world collaborative and communicative teaching experiences conducted in members’ institutions. Perspectives vary from those whose reality is the actuation of the initial rhetoric in the early years of virtual world education, to those whose reality is fraught with challenges that belie the rhetoric. Although there are concerns over institutional resistance, restrictions, and outdated processes on the one-hand, and excitement over the rapid emergence of innovation on the other, the prevailing reality seems to be that virtual world education is both persistent and sustainable. Explored are critical perspectives on the rhetoric and reality on the educational uptake and use of virtual worlds in higher education, providing an overview of the current and future directions for learning in virtual worlds

Rhetoric and reality: Critical perspective on education in a 3D virtual world

The emergence of any new educational technology is often accompanied by inflated expectations about its potential for transforming pedagogical practice and improving student learning outcomes. A critique of the rhetoric accompanying the evolution of 3D virtual world education reveals a similar pattern, with the initial hype based more on rhetoric than research demonstrating the extent to which rhetoric matches reality. Addressed are the perceived gaps in the literature through a critique of the rhetoric evident throughout the evolution of the application of virtual worlds in education and the reality based on the reported experiences of experts in the field of educational technology, who are all members of the Australian and New Zealand Virtual Worlds Working Group. The experiences reported highlight a range of effective virtual world collaborative and communicative teaching experiences conducted in members’ institutions. Perspectives vary from those whose reality is the actuation of the initial rhetoric in the early years of virtual world education, to those whose reality is fraught with challenges that belie the rhetoric. Although there are concerns over institutional resistance, restrictions, and outdated processes on the one-hand, and excitement over the rapid emergence of innovation on the other, the prevailing reality seems to be that virtual world education is both persistent and sustainable. Explored are critical perspectives on the rhetoric and reality on the educational uptake and use of virtual worlds in higher education, providing an overview of the current and future directions for learning in virtual worlds

Establishment of Motor Neuron-V3 Interneuron Progenitor Domain Boundary in Ventral Spinal Cord Requires Groucho-Mediated Transcriptional Corepression

Background: Dorsoventral patterning of the developing spinal cord is important for the correct generation of spinal neuronal types. This process relies in part on cross-repressive interactions between specific transcription factors whose expression is regulated by Sonic hedgehog. Groucho/transducin-like Enhancer of split (TLE) proteins are transcriptional corepressors suggested to be recruited by at least certain Sonic hedgehog-controlled transcription factors to mediate the formation of spatially distinct progenitor domains within the ventral spinal cord. The aim of this study was to characterize the involvement of TLE in mechanisms regulating the establishment of the boundary between the most ventral spinal cord progenitor domains, termed pMN and p3. Because the pMN domain gives rise to somatic motor neurons while the p3 domain generates V3 interneurons, we also examined the involvement of TLE in the acquisition of these neuronal fates. Methodology and Principal Findings: A combination of in vivo loss- and gain-of-function studies in the developing chick spinal cord was performed to characterize the role of TLE in ventral progenitor domain formation. It is shown here that TLE overexpression causes increased numbers of p3 progenitors and promotes the V3 interneuron fate while suppressing the motor neuron fate. Conversely, dominant-inhibition of TLE increases the numbers of pMN progenitors and postmitotic motor neurons. Conclusion: Based on these results, we propose that TLE is important to promote the formation of the p3 domain an