Exceptionally Strong Effect of Small Structural Variations in Functionalized 3,4-Phenylenedioxythiophenes on the Surface Nanostructure and Parahydrophobic Properties of Their Electropolymerized Films

Electropolymerization of electron-rich aromatics/heteroaromatics to form conducting polymers is an easy and powerful technique to form surfaces of different nanostructures and hydrophobicity/wettability. Understanding the factors governing the growth of the polymer nanostructures and controlling the surface morphology are the big challenges for the surface and materials science. In this paper, we report the design and synthesis of a series of 3,4-phenylenedioxythiophenes (PheDOTs) substituted at the benzene ring with 2-naphthylmethyl-, 1-naphthylmethyl-, and 9-anthracenylmethyl-groups (2Na-PheDOT, 1Na-PheDOT, and 9Ant-PheDOT). They have been electropolymerized in either potentiostatic or potentiodynamic conditions to form the polymer surfaces of different morphologies. Even small changes in the structure of PheDOT monomers by varying the side groups (2-/1-naphthyl-or 9-anthracenyl-) result in the formation of very different polymer surface nanostructures: From monodirectionally growing (one-dimensional) vertically aligned nanotubes for 2Na-PheDOT to ribbonlike nanostructures (two-dimensional) for 1Na-PheDOT, and a mixture of these two structures for 9Ant-PheDOT. Moreover, the surfaces of the p[2Na-PheDOT] polymer, electrodeposited from the monomer 2Na-PheDOT and the dimer (2Na-PheDOT)2 (which have different solubilities and the reactivities on electropolymerization, but formally lead to the polymer of the same chemical structure), show very different nanostructures. In contrast to 2Na-PheDOT, which forms vertically aligned nanotubes of the polymer on the surface, the polymerization of (2Na-PheDOT)2 leads to spherical particles [three-dimensional (3D)] when Bu4NClO4 is used as an electrolyte and a membrane structure with spherical holes (3D) in the case of more hydrophobic Bu4NPF6. The importance of water for gas bubble formation (O2 and H2) during electropolymerization and creation of the surface nanostructures has been demonstrated and discussed. The formation of these different nanostructures is accompanied by different wettability of the surface, from hydrophilic (with an apparent water droplet contact angle of θw ∼40-70°) to highly hydrophobic (θw up to 129-134°). The sticky, parahydrophobic surface formed from 1Na-PheDOT showed high adhesion to water, with no water droplets moving after inclination of the surface to 90° (rose-petal effect). Copyright © 2019 American Chemical Society.Government Council on Grants, Russian FederationThe authors thank the Center Commun de Microscopie Appliquée (CCMA, Univ. Nice Sophia Antipolis) for the realization of the SEM images. E.L.K. thanks the Russia President Ph.D. Scholarship for studying abroad to visit Bangor University and also thanks Act 211 Government of the Russian Federation for financial support (contract No. 02.A03.21.0006). I.S. thanks the Erasmus+ student mobility program for supporting her internship at Bangor University. I.F.P. thanks SIFE-NPU for generous startup funding

Rapid systematic review of clinical trials on pharmacological therapies for rare gynecological cancers

The purpose of this study is to systematically review clinical trials on pharmacological therapies for rare gynecological cancers and analyze their characteristics. The PRISMA guidelines for systematic reviews were followed and two databases were searched (WHO´s International Clinical Trials Registry Platform and clinicaltrials.gov). The Jadad score was used to assess the methodological quality of completed clinical trials. A total of 212 records, covering trials from 1993 to 2022, were included in the final review. More than half were phase II trials (110; 51.89%) and the status of recruiting was mainly completed (80; 37.74%). There were 26 (12.26%) terminated or withdrawn clinical trials. Just 42.45% of the trials were specific only for rare types of gynecological cancers. The most common type of investigated therapy was chemotherapy (89; 41.98%), followed by targeted therapy (64; 30.19%) and a combination of therapies (23.11%). However, in the last five years there was an increase in trials investigating targeted therapies such as immunotherapy, overgrowth-related and angiogenesis-related therapies. All completed trials except one, had a Jadad score 0-2, indicating low-quality. Thirty-six (45.00%) completed clinical trials had neither posted results, nor publications. Higher quality clinical trials with better reporting of results are needed for rare gynecological cancers.peer-reviewe

Social difference, cultural arbitrary and identity : an analysis of a new national curriculum document in a non-secular environment

This article focuses on the idea of the Curriculum as a 'selection from the cultures of society' and as a site of contestation for legitimacy and identity affirmation. The purpose is to shed some light on the nature of curricular reform being advocated in a specific context - Malta. Throughout the past four years, there has been a revamping of the National Minimum Curriculum (NMC) document in Malta, established in 1988. The 'old' National Minimum Curriculum was subject to criticism focusing on a variety of issues (echoing criticisms levelled at similar National Curricula elsewhere), including issues concerning difference and identity. The first part of the article deals briefly with the issues concerning difference raised in this criticism, focusing on the issues of class, race/ethnicity, gender and disability. The second part focuses on the long and gradual build up towards the development of the new National Curriculum document. The process centres around two documents, the preliminary Tomorrow's Schoolsdocument and the draft NMC document. The issues of equity and the affirmation of social difference, as well as the move towards de-streaming, are discussed. It is argued that this process of reform benefited from the criticism of the earlier NMC document. The process of reform involved an attempt at widespread participation by various stakeholders - parents, teachers, students, unions, women's organisations, disabled person's organisations etc. The final section focuses on the final new NMC document. In this section, the authors explore the compromises, which have been made in reaction to the draft document, indicating the interests at play. Whose cultural arbitrary is reflected in the final document? The article concludes with a discussion centring around lessons to be drawn from a process of curricular reform, involving issues related to identity and difference, carried out in a country characterised by a non-secular environment.peer-reviewe

Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

<p>Abstract</p> <p>Background</p> <p>MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility.</p> <p>Methods</p> <p>We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (<it>MSH3</it>, <it>MSH4</it>, <it>MSH6</it>, <it>MLH1</it>, <it>MLH3</it>, <it>PMS1 </it>and <it>MUTYH</it>).</p> <p>Results</p> <p>Using unconditional logistic regression we found that <it>MLH3 </it>(L844P, G>A) polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) (p = 0.03) and OR = 0.62 (0.41-0.94) (p = 0.03), respectively.</p> <p>Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: <it>MSH3 </it>Ala1045Thr/<it>MSH6 </it>Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83), p = 0.01] associated with a decreased risk; and <it>MSH4 </it>Ala97Thr/<it>MLH3 </it>Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49), p = 0.01], GG/AA [OR = 2.11 (1.12-3,98), p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15), p = 0.02] all associated with an increased risk for breast cancer.</p> <p>Conclusion</p> <p>It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.</p

MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography.

MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MALTIR) forms filaments in vitro and induces formation of crystalline higher-order assemblies of the MyD88 TIR domain (MyD88TIR). These crystals are too small for conventional X-ray crystallography, but are ideally suited to structure determination by microcrystal electron diffraction (MicroED) and serial femtosecond crystallography (SFX). Here, we present MicroED and SFX structures of the MyD88TIR assembly, which reveal a two-stranded higher-order assembly arrangement of TIR domains analogous to that seen previously for MALTIR. We demonstrate via mutagenesis that the MyD88TIR assembly interfaces are critical for TLR4 signaling in vivo, and we show that MAL promotes unidirectional assembly of MyD88TIR. Collectively, our studies provide structural and mechanistic insight into TLR signal transduction and allow a direct comparison of the MicroED and SFX techniques

New records of rare species in the Mediterranean Sea (October 2021)

This Collective Article presents information about 27 taxa belonging to five Phyla (one Ochrophyta, one Cnidaria, three Arthropoda, two Mollusca and twenty Chordata) and extending from the Western Mediterranean Sea to the Levantine Sea and theBlack Sea (Sea of Marmara). The new records were reported from 11 countries as follows: Algeria: occurrence of the Africanstriped grunt Parapristipoma octolineatum; Spain: new records of eight uncommon fish species (Gadella maraldi, Hypleurochilusbananensis, Lobotes surinamensis, Parapristipoma octolineatum, Selene dorsalis, Sphoeroides marmoratus, Tetragonuruscuvieri, and Trachyrincus scabrus) from the Spanish Mediterranean; Italy: new record of the football octopus Ocythoe tuberculatafrom the Southern Tyrrhenian Sea; a rare sighting of a juvenile phase of a moray eel of the genus Gymnothorax, tentativelyidentified as Gymnothorax cf. unicolor in the Ligurian Sea; first record of adult Facciola’s sorcerer Facciolella oxyrhynchus inthe Adriatic Sea; occurrence of the tope shark Galeorhinus galeus in the Northern Adriatic Sea; Libya: first confirmed recordof the pen shell Pinna rudis; first documented record of the palaemonid shrimp Brachycarpus biunguiculatus; first record of thefish Sudis hyalina; Malta: new records of Grant’s rockling, Gaidropsarus granti; multiple concomitant reports of the rare hydromedusanspecies Aequorea forskalea; Croatia: a record of the skipjack tuna Katsuwonus pelamis in the Southern Adriatic Sea;Albania: new record of the bigeye thresher shark Alopias superciliosus; Greece: confirmation of the rare brown alga Sargassumflavifolium occurrence in the Eastern Mediterranean Sea; first record of the scaleless dragonfish Bathophilus nigerrimus; Turkey:first occurrence of the calanoid copepod Pteriacartia josephinae in the Aegean Sea; first documented record of the Cremona’s seaslug Placida cremoniana for the easternmost Mediterranean Sea; new record of the yellow-headed goby Gobius xanthocephalusin the Sea of Marmara; Cyprus: first record of the Liechtenstein’s goby Corcyrogobius liechtensteini; an individual of the Yellowfintuna Thunnus albacares captured with handline by an artisanal fisher; Lebanon: an individual of the Black marlin Istiompaxindica captured in a gill ne

MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography.

MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MALTIR) forms filaments in vitro and induces formation of crystalline higher-order assemblies of the MyD88 TIR domain (MyD88TIR). These crystals are too small for conventional X-ray crystallography, but are ideally suited to structure determination by microcrystal electron diffraction (MicroED) and serial femtosecond crystallography (SFX). Here, we present MicroED and SFX structures of the MyD88TIR assembly, which reveal a two-stranded higher-order assembly arrangement of TIR domains analogous to that seen previously for MALTIR. We demonstrate via mutagenesis that the MyD88TIR assembly interfaces are critical for TLR4 signaling in vivo, and we show that MAL promotes unidirectional assembly of MyD88TIR. Collectively, our studies provide structural and mechanistic insight into TLR signal transduction and allow a direct comparison of the MicroED and SFX techniques

Megahertz pulse trains enable multi-hit serial femtosecond crystallography experiments at X-ray free electron lasers

The European X-ray Free Electron Laser (XFEL) and Linac Coherent Light Source (LCLS) II are extremely intense sources of X-rays capable of generating Serial Femtosecond Crystallography (SFX) data at megahertz (MHz) repetition rates. Previous work has shown that it is possible to use consecutive X-ray pulses to collect diffraction patterns from individual crystals. Here, we exploit the MHz pulse structure of the European XFEL to obtain two complete datasets from the same lysozyme crystal, first hit and the second hit, before it exits the beam. The two datasets, separated by <1 µs, yield up to 2.1 Å resolution structures. Comparisons between the two structures reveal no indications of radiation damage or significant changes within the active site, consistent with the calculated dose estimates. This demonstrates MHz SFX can be used as a tool for tracking sub-microsecond structural changes in individual single crystals, a technique we refer to as multi-hit SFX