Photomechanical and Photochromic Behavior of a Molecule Containing Multiple Photoactive Groups

Photomechanical and photochromic activities are reported for single crystals of a new multirespon-sive material, 2,4-di-tert-butyl-6-((E)-((4-((E)-phenyldiazenyl)phenyl)imino)methyl)phenol (Azim-1), with two photoactive groups that can undergo photoisomerization (azo and imine), and an ortho-hydroxy group that is capable of proton transfer. Upon irradiation with UV light, platy and needle-shaped crystals of Azim-1 rapidly bend towards the light source and return to their initial shape as soon as the irradiation is terminated. Upon prolonged exposure to UV light, the crystals change their color from yellow to red. The crystal structure of non-irradiated Azim-1 is reported, and the mecha-nisms of the photomechanical and photochromic responses are discussed

Firewalls: A necessary tool to enable social rights for undocumented migrants in social work

© 2020 The Authors. Published by SAGE. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1177/0020872820924454Firewalls are clear divisions between border policing and the provision of basic social rights. They have a dual character: to ensure that no information collected with the purpose of safeguarding basic social rights should be shared for immigration control purposes; and that migrants should not be subject to immigration control when being present at, or in the vicinity, of religious, private and public institutions upholding and providing social rights. This article suggests a normative argument for ‘firewalls’ in the context of social work and develops the concept theoretically as a principle practised and negotiated at different scales.Published onlin

Distinguishing mechanisms underlying EMT tristability

Abstract Background The Epithelial-Mesenchymal Transition (EMT) endows epithelial-looking cells with enhanced migratory ability during embryonic development and tissue repair. EMT can also be co-opted by cancer cells to acquire metastatic potential and drug-resistance. Recent research has argued that epithelial (E) cells can undergo either a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype that typically displays collective migration, or a complete EMT to adopt a mesenchymal (M) phenotype that shows individual migration. The core EMT regulatory network - miR-34/SNAIL/miR-200/ZEB1 - has been identified by various studies, but how this network regulates the transitions among the E, E/M, and M phenotypes remains controversial. Two major mathematical models – ternary chimera switch (TCS) and cascading bistable switches (CBS) - that both focus on the miR-34/SNAIL/miR-200/ZEB1 network, have been proposed to elucidate the EMT dynamics, but a detailed analysis of how well either or both of these two models can capture recent experimental observations about EMT dynamics remains to be done. Results Here, via an integrated experimental and theoretical approach, we first show that both these two models can be used to understand the two-step transition of EMT - E→E/M→M, the different responses of SNAIL and ZEB1 to exogenous TGF-β and the irreversibility of complete EMT. Next, we present new experimental results that tend to discriminate between these two models. We show that ZEB1 is present at intermediate levels in the hybrid E/M H1975 cells, and that in HMLE cells, overexpression of SNAIL is not sufficient to initiate EMT in the absence of ZEB1 and FOXC2. Conclusions These experimental results argue in favor of the TCS model proposing that miR-200/ZEB1 behaves as a three-way decision-making switch enabling transitions among the E, hybrid E/M and M phenotypes

Evaluation of an inter-professional workshop to develop a psychosocial assessment and child-centred communication training programme for paediatricians in training

BACKGROUND: The quality of psychosocial assessment of children in consultations varies widely. One reason for this difference is the variability in effective mental health and communication training at undergraduate and post-qualification levels. In recognition of this problem, the Royal College of Paediatrics and Child Health in the United Kingdom have developed the Child in Mind Project that aims to meet this deficit in medical training. This paper describes the evaluation of a workshop that explored the experiences and expectations of health care professionals in the development of a training programme for doctors. METHODS: The one-day inter-professional workshop was attended by 63 participants who were invited to complete evaluation forms before and immediately after the workshop. RESULTS: The results showed that the workshop was partially successful in providing an opportunity for an inter-professional group to exchange ideas and influence the development of a significant project. Exploring the content and process of the proposed training programme and the opportunity for participants to share experiences of effective practice were valued. Participants identified that the current culture within many health care settings would be an obstacle to successful implementation of a training programme. Working within existing training structures will be essential. Areas for improvement in the workshop included clearer statement of goals at the outset and a more suitable environment for the numbers of participants. CONCLUSIONS: The participants made a valuable contribution to the development of the training programme identifying specific challenges. Inter-professional collaborations are likely to result in more deliverable and relevant training programmes. Continued consultation with potential users of the programme – both trainers and trainees will be essential

Exacerbated fires in Mediterranean Europe due to anthropogenic warming projected with non-stationary climate-fire models

The observed trend towards warmer and drier conditions in southern Europe is projected to continue in the next decades, possibly leading to increased risk of large fires. However, an assessment of climate change impacts on fires at and above the 1.5 °C Paris target is still missing. Here, we estimate future summer burned area in Mediterranean Europe under 1.5, 2, and 3 °C global warming scenarios, accounting for possible modifications of climate-fire relationships under changed climatic conditions owing to productivity alterations. We found that such modifications could be beneficial, roughly halving the fire-intensifying signals. In any case, the burned area is robustly projected to increase. The higher the warming level is, the larger is the increase of burned area, ranging from ~40% to ~100% across the scenarios. Our results indicate that significant benefits would be obtained if warming were limited to well below 2 °C

The UPF3B gene, implicated in intellectual disability, autism, ADHD and childhood onset schizophrenia regulates neural progenitor cell behaviour and neuronal outgrowth

HMG Advance Access published July 2, 2013Loss-of-function mutations in UPF3B result in variable clinical presentations including intellectual disability (ID, syndromic and non-syndromic), autism, childhood onset schizophrenia and attention deficit hyperactivity disorder. UPF3B is a core member of the nonsense-mediatedmRNAdecay (NMD) pathway that functions to rapidly degrade transcripts with premature termination codons (PTCs). Traditionally identified in thousands of human diseases, PTCs were recently also found to be part of 'normal' genetic variation in human populations. Furthermore, many human transcripts have naturally occurring regulatory features compatible with 'endogenous'PTCsstrongly suggesting roles ofNMDbeyondPTCmRNAcontrol. In this study,weinvestigated the role of Upf3b andNMD in neural cells.Weprovide evidence that suggests Upf3b-dependentNMD(Upf3b-NMD) is regulated at multiple levels during development including regulation of expression and sub-cellular localization of Upf3b. Furthermore, complementary expression of Upf3b, Upf3a and Stau1 stratify the developing dorsal telencephalon, suggesting that alternativeNMD,andthe related Staufen1-mediatedmRNAdecay (SMD) pathways are differentially employed. A loss of Upf3b-NMD in neural progenitor cells (NPCs) resulted in the expansion of cell numbers at the expense of their differentiation. In primary hippocampal neurons, loss of Upf3b-NMD resulted in subtle neurite growth effects. Our data suggest that the cellular consequences of loss of Upf3b-NMD can be explained in-part by changes in expression of key NMD-feature containing transcripts, which are commonly deregulated also in patients with UPF3B mutations. Our research identifies novel pathological mechanisms of UPF3B mutations and at least partly explains the clinical phenotype of UPF3B patients.Lachlan A. Jolly, Claire C. Homan, Reuben Jacob, Simon Barry and Jozef Gec

Cellular Proteins in Influenza Virus Particles

Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensive proteomic analysis of purified influenza virus particles. In addition to the aforementioned nine virus-encoded proteins, we detected the presence of 36 host-encoded proteins. These include both cytoplasmic and membrane-bound proteins that can be grouped into several functional categories, such as cytoskeletal proteins, annexins, glycolytic enzymes, and tetraspanins. Interestingly, a significant number of these have also been reported to be present in virions of other virus families. Protease treatment of virions combined with immunoblot analysis was used to verify the presence of the cellular protein and also to determine whether it is located in the core of the influenza virus particle. Immunogold labeling confirmed the presence of membrane-bound host proteins on the influenza virus envelope. The identification of cellular constituents of influenza virions has important implications for understanding the interactions of influenza virus with its host and brings us a step closer to defining the cellular requirements for influenza virus replication. While not all of the host proteins are necessarily incorporated specifically, those that are and are found to have an essential role represent novel targets for antiviral drugs and for attenuation of viruses for vaccine purposes

Identification of constrained sequence elements across 239 primate genomes

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Two interpretations of human evolution: Essentialism and Darwinism

Despite intensive studies of a large number of fossils discovered during the 20th century there is no consensus as to the interpretation of the process of hominin evolution. Some authors see as many as six genera and some 17 species, while others argue for a single lineage from Plio/Pleistocene until today. Such diversity of interpretations of the same facts indicates lack of a uniform theoretical basis underlying studies of human evolution. Debates can be resolved using basic principles of scientific inquiry - parsimony and falsification of null hypotheses. Hypothesis testing is now possible with respect to the evolution of basic hominin characteristics such as brain size, body size and the size of the dentition that have sample sizes of a few hundred individual data points each. These characters display a continuous change with time. Analyses of variance do not falsify the null hypothesis of the existence of only one species at any time - variances around regression lines on time do not differ from the variance observed in the single species of Homo sapiens - distributions of residuals are normal. Thus, splitting of the hominin lineage into coeval species can only be based on descriptive characteristics that are liable to errors of subjective judgment.Maciej Henneber