Making community pharmacies psychologically informed environments (PIE):a feasibility study to improve engagement with people using drug services in Scotland

Funding: This work was funded by a research grant from Pharmacy Research UK: PRUK 2019-PA3-CM.Aim   This developmental study tested the feasibility of training pharmacy staff on the psychologically informed environments (PIE) approach to improve the delivery of care. Background: Community pharmacies provide key services to people who use drugs (PWUD) through needle exchange services, medication-assisted treatment and naloxone distribution. PWUD often have trauma backgrounds, and an approach that has been demonstrated to work well in the homeless sector is PIEs. Methods  Bespoke training was provided by clinical psychologists and assessed by questionnaire. Staff interviews explored changes made following PIE training to adapt the delivery of care. Changes in attitude of staff following training were assessed by questionnaire. Peer researchers interviewed patient/client on observed changes and experiences in participating pharmacies. Staff interviews were conducted six months after training to determine what changes, if any, staff had implemented. Normalisation process theory (NPT) provided a framework for assessing change. Findings Three pharmacies (16 staff) participated. Training evaluation was positive; all participants rated training structure and delivery as 'very good' or 'excellent'. There was no statistically significant change in attitudes. COVID-19 lockdowns restricted follow-up data collection. Staff interviews revealed training had encouraged staff to reflect on their practice and communication and consider potentially discriminatory practice. PIE informed communication skills were applied to manage COVID-19 changes. Staff across pharmacies noted mental health challenges for patients. Five patients were interviewed but COVID-19 delays in data collection meant changes in delivery of care were difficult to recall. However, they did reflect on interactions with pharmacy staff generally. Across staff and patient interviews, there was possible conflation of practice changes due to COVID-19 and the training. However, the study found that training pharmacy teams in PIE was feasible, well received, and further development is recommended. There was evidence of the four NPT domains to support change (coherence, cognitive participation, collective action and reflexive monitoring).Publisher PDFPeer reviewe

Candida albicans Hypha Formation and Mannan Masking of β-Glucan Inhibit Macrophage Phagosome Maturation

Received 28 August 2014 Accepted 28 October 2014 Published 2 December 2014 This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license. ACKNOWLEDGMENTS We thank Janet Willment, Aberdeen Fungal Group, University of Aberdeen, for kindly providing the soluble Dectin-1-Fc reporter. All microscopy was performed with the assistance of the University of Aberdeen Core Microscopy & Histology Facility, and we thank the IFCC for their assistance with flow cytometry. We thank the Wellcome Trust for funding (080088, 086827, 075470, 099215, 097377, and 101873). E.R.B. and A.J.P.B. are funded by the European Research Council (ERC-2009-AdG-249793), and J.L. is funded by a Medical Research Council Clinical Training Fellowship.Peer reviewedPublisher PD

Complement-Mediated Differential Immune Response of Human Macrophages to Sporothrix Species Through Interaction With Their Cell Wall Peptidorhamnomannans

Funding This work was supported by Fundação de Apoio à Pesquisa do Distrito Federal (FAP-DF)/CNPq, PRONEX grant ID: (FAP-DF, 0193.001.200/2016). VA is supported by the Centre Franco-Indien pour la Promotion de la Recherche Avancée (CEFIPRA) grant No. 5403-1 and ANR-DFG AfuINF grant. IG, VA, and CS were supported by the ANR-FUNHYDRO (ANR-16S-CE110020-01) grant. NG, GB and JW are supported by the Welcome Trust (102705, 097377, 101873, 215599 and 200208) and the Medical Research Council Centre for Medical Mycology (MR/N006364/2). Acknowledgments The authors acknowledge Dr. Lars Erwig, Dr. Jude Bain, and Dr. Kevin MacKenzie of University of Aberdeen for the scientific and technical support in the video microscopy experiments. LMLB was a research fellow of Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). We acknowledge Fundação Carlos Chagas Filho de Amparo a Pesquisa do estado do Rio de Janeiro (Faperj) and Pasteur-Roux-Cantarini postdoctoral fellowship for the research fellowships given to GWPN and SSWW, respectively.Peer reviewedPublisher PD

miR-515-5p controls cancer cell migration through MARK4 regulation

Here, we show that miR-515-5p inhibits cancer cell migration and metastasis. RNA-seq analyses of both oestrogen receptor receptor-positive and receptor-negative breast cancer cells overexpressing miR-515-5p reveal down-regulation of NRAS, FZD4, CDC42BPA, PIK3C2B and MARK4 mRNAs. We demonstrate that miR-515-5p inhibits MARK4 directly 3' UTR interaction and that MARK4 knock-down mimics the effect of miR-515-5p on breast and lung cancer cell migration. MARK4 overexpression rescues the inhibitory effects of miR-515-5p, suggesting miR-515-5p mediates this process through MARK4 down-regulation. Furthermore, miR-515-5p expression is reduced in metastases compared to primary tumours derived from both in vivo xenografts and samples from patients with breast cancer. Conversely, miR-515-5p overexpression prevents tumour cell dissemination in a mouse metastatic model. Moreover, high miR-515-5p and low MARK4 expression correlate with increased breast and lung cancer patients' survival, respectively. Taken together, these data demonstrate the importance of miR-515-5p/MARK4 regulation in cell migration and metastasis across two common cancers

Improved phylogenetic resolution within Siphonophora (Cnidaria) with implications for trait evolution

Siphonophores are a diverse group of hydrozoans (Cnidaria) that are found at most depths of the ocean - from the surface, like the familiar Portuguese man of war, to the deep sea. They play important roles in ocean ecosystems, and are among the most abundant gelatinous predators. A previous phylogenetic study based on two ribosomal RNA genes provided insight into the internal relationships between major siphonophore groups. There was, however, little support for many deep relationships within the clade Codonophora. Here, we present a new siphonophore phylogeny based on new transcriptome data from 29 siphonophore species analyzed in combination with 14 publicly available genomic and transcriptomic datasets. We use this new phylogeny to reconstruct several traits that are central to siphonophore biology, including sexual system (monoecy vs. dioecy), gain and loss of zooid types, life history traits, and habitat. The phylogenetic relationships in this study are largely consistent with the previous phylogeny, but we find strong support for new clades within Codonophora that were previously unresolved. These results have important implications for trait evolution within Siphonophora, including favoring the hypothesis that monoecy arose at least twice

Novel target identification & characterisation of key cell motility regulators in lung cancer metastasis

Lung cancer is the most common cancer killer worldwide. One of the major reasons for failing to cure this malignancy is the high rate of metastasis. Hence, understanding the mechanisms by which these cells metastasise is required to improve patients’ survival. Using the non-small cell lung cancer cell line A549 we optimised a 3D Invasion assay to enable a robotised high-throughput siRNA screen of large gene libraries. Despite thorough optimisation a pilot screen for the Phosphatome highlighted multiple issues with our set-up. Further optimisation work was conducted to improve the resolving power of the assay. However, as no clear explanation for the poor reproducibility could be uncovered, work began on a potential modulator of cell motility identified during a previous motility screen of the kinome. Microtubule affinity regulating kinases 4 (MARK4) is one of four members of the MARK family. A previously performed kinome siRNA screen for modulators of cell migration revealed that depletion of MARK4 reduced A549 cell migration. We validated this observation and additionally found that MARK4 silencing inhibited cell invasion through 3D collagen matrices. MARK4 depletion markedly changed cell structure, as exemplified by an increase tubulin network area. Follow-on experiments revealed an altered speed of microtubule polymerisation in MARK4-silenced cells. We observed that MARK4 downregulation promoted resistance to the chemotherapeutic agents Paciltaxel and Cisplatin, an effect potentially linked to a reduced proliferation in MARK4-silenced cells. MARK4 overexpression in NSCLC cells increased cell motility but did not impact the cell area or resistance to chemotherapy. A targeted siRNA cell motility screen of a selection of proposed MARK4 interacting proteins enabled us to connect MARK4 with Protein Phosphatase 2A and GSK3. Although further investigation is required into the signalling pathways upstream and downstream of MARK4, this work identified novel functions for this kinase and highlighted potential mechanisms underlying its effects.Open Acces

Managing the Oocyte Meiotic Arrest—Lessons from Frogs and Jellyfish

International audienceDuring oocyte development, meiosis arrests in prophase of the first division for a remarkably prolonged period firstly during oocyte growth, and then when awaiting the appropriate hormonal signals for egg release. This prophase arrest is finally unlocked when locally produced maturation initiation hormones (MIHs) trigger entry into M-phase. Here, we assess the current knowledge of the successive cellular and molecular mechanisms responsible for keeping meiotic progression on hold. We focus on two model organisms, the amphibian Xenopus laevis, and the hydrozoan jellyfish Clytia hemisphaerica. Conserved mechanisms govern the initial meiotic programme of the oocyte prior to oocyte growth and also, much later, the onset of mitotic divisions, via activation of two key kinase systems: Cdk1-Cyclin B/Gwl (MPF) for M-phase activation and Mos-MAPkinase to orchestrate polar body formation and cytostatic (CSF) arrest. In contrast, maintenance of the prophase state of the fully-grown oocyte is assured by highly specific mechanisms, reflecting enormous variation between species in MIHs, MIH receptors and their immediate downstream signalling response. Convergence of multiple signalling pathway components to promote MPF activation in some oocytes, including Xenopus, is likely a heritage of the complex evolutionary history of spawning regulation, but also helps ensure a robust and reliable mechanism for gamete production

Past, present and future of Clytia hemisphaerica as a laboratory jellyfish

The hydrozoan species Clytia hemisphaerica was selected in the mid 2000s to address the cellular and molecular basis of body axis specification in a cnidarian, providing a reliable daily source of gametes and building on a rich foundation of experimental embryology. The many practical advantages of this species include genetic uniformity of laboratory jellyfish, derived clonally from easily-propagated polyp colonies. Phylogenetic distance from other laboratory models adds value in providing an evolutionary perspective on many biological questions. Here we outline the current state of the art regarding available experimental approaches and in silico resources, and illustrate the contributions of Clytia to understanding embryo patterning mechanisms, oogenesis and regeneration. Looking forward, the recent establishment of transgenesis methods is now allowing gene function and imaging studies at adult stages, making Clytia particularly attractive for whole organism biology studies across fields and extending its scientific impact far beyond the original question of interest

Pairwise comparisons across species are problematic when analyzing functional genomic data

There is considerable interest in comparing functional genomic data across species. One goal of such work is to provide an integrated understanding of genome and phenotype evolution. Most comparative functional genomic studies have relied on multiple pairwise comparisons between species, an approach that does not incorporate information about the evolutionary relationships among species. The statistical problems that arise from not considering these relationships can lead pairwise approaches to the wrong conclusions and are a missed opportunity to learn about biology that can only be understood in an explicit phylogenetic context. Here, we examine two recently published studies that compare gene expression across species with pairwise methods, and find reason to question the original conclusions of both. One study interpreted pairwise comparisons of gene expression as support for the ortholog conjecture, the hypothesis that orthologs tend to have more similar attributes (expression in this case) than paralogs. The other study interpreted pairwise comparisons of embryonic gene expression across distantly related animals as evidence for a distinct evolutionary process that gave rise to phyla. In each study, distinct patterns of pairwise similarity among species were originally interpreted as evidence of particular evolutionary processes, but instead, we find that they reflect species relationships. These reanalyses concretely show the inadequacy of pairwise comparisons for analyzing functional genomic data across species. It will be critical to adopt phylogenetic comparative methods in future functional genomic work. Fortunately, phylogenetic comparative biology is also a rapidly advancing field with many methods that can be directly applied to functional genomic data

Rpl8 FASTA files for alignment

FASTA files used to derive the rpl8 alignmen