ARHGEF18/p114RhoGEF Coordinates PKA/CREB Signaling and Actomyosin Remodeling to Promote Trophoblast Cell-Cell Fusion During Placenta Morphogenesis

Coordination of cell-cell adhesion, actomyosin dynamics and gene expression is crucial for morphogenetic processes underlying tissue and organ development. Rho GTPases are main regulators of the cytoskeleton and adhesion. They are activated by guanine nucleotide exchange factors in a spatially and temporally controlled manner. However, the roles of these Rho GTPase activators during complex developmental processes are still poorly understood. ARHGEF18/p114RhoGEF is a tight junction-associated RhoA activator that forms complexes with myosin II, and regulates actomyosin contractility. Here we show that p114RhoGEF/ARHGEF18 is required for mouse syncytiotrophoblast differentiation and placenta development. In vitro and in vivo experiments identify that p114RhoGEF controls expression of AKAP12, a protein regulating protein kinase A (PKA) signaling, and is required for PKA-induced actomyosin remodeling, cAMP-responsive element binding protein (CREB)-driven gene expression of proteins required for trophoblast differentiation, and, hence, trophoblast cell-cell fusion. Our data thus indicate that p114RhoGEF links actomyosin dynamics and cell-cell junctions to PKA/CREB signaling, gene expression and cell-cell fusion

Correlates of self-reported exposure to advertising of tobacco products and electronic cigarettes across 28 European Union member states.

BACKGROUND: Despite advertising bans in most European Union (EU) member states, outlets for promotion of tobacco products and especially e-cigarettes still exist. This study aimed to assess the correlates of self-reported exposure to tobacco products and e-cigarettee advertising in the EU. METHODS: We analysed data from wave 82.4 of the Eurobarometer survey (November-December 2014), collected through interviews in 28 EU member states (n=27 801 aged ≥15 years) and data on bans of tobacco advertising extracted from the Tobacco Control Scale (TCS, 2013). We used multilevel logistic regression to assess sociodemographic correlates of self-reported exposure to any tobacco and e-cigarette advertisements. RESULTS: 40% and 41.5% of the respondents reported having seen any e-cigarette and tobacco product advertisement respectively within the past year. Current smokers, males, younger respondents, those with financial difficulties, people who had tried e-cigarettes and daily internet users were more likely to report having seen an e-cigarette and a tobacco product advertisement. Respondents in countries with more comprehensive advertising bans were less likely to self-report exposure to any tobacco advertisements (OR 0.87; 95% CI 0.79 to 0.96 for one-unit increase in TCS advertising score), but not e-cigarette advertisements (OR 1.08; 95% CI 0.95 to 1.22). CONCLUSION: Ten years after ratification of the Framework Convention for Tobacco Control, self-reported exposure to tobacco and e-cigarette advertising in the EU is higher in e-cigarette and tobacco users, as well as those with internet access. The implementation of the Tobacco Products Directive may result in significant changes in e-cigarette advertising, therefore improved monitoring of advertising exposure is required in the coming years

MEMS Piezoelectric Energy Harvester Powered Wireless Sensor Module Driven by Noisy Base Excitation

Despite recent advances in MEMS vibration energy harvesting and ultra-low power wireless sensors, designing a wireless sensor system entirely powered by a single MEMS device under noisy base excitation has remained a challenge. This paper presents a wireless sensor system co-integrated with a single MEMS piezoelectric vibration energy harvester chip excited by band-limited large amplitude noisy vibration characteristic of an automotive application. The use of soft stoppers in the MEMS package enables the harvesters to operate at an excitation level of 10 g(rms). A custom thick AlN (Aluminum Nitride) piezoelectric process is employed to fabricate the MEMS harvesters with a single MEMS chip generating 179 μW rectified power under these excitation conditions. A low-power wireless sensor module and a receiver module were also designed and demonstrated in this work. Experiments show that the wireless sensor module can be powered solely by the MEMS energy harvester commencing from the cold state. Successful wireless data transmission and receival of sensor data packets are recorded under representative conditions

On the perturbative S-matrix of generalized sine-Gordon models

Motivated by its relation to the Pohlmeyer reduction of AdS_5 x S^5 superstring theory we continue the investigation of the generalized sine-Gordon model defined by SO(N+1)/SO(N) gauged WZW theory with an integrable potential. Extending our previous work (arXiv:0912.2958) we compute the one-loop two-particle S-matrix for the elementary massive excitations. In the N = 2 case corresponding to the complex sine-Gordon theory it agrees with the charge-one sector of the quantum soliton S-matrix proposed in hep-th/9410140. In the case of N > 2 when the gauge group SO(N) is non-abelian we find a curious anomaly in the Yang-Baxter equation which we interpret as a gauge artifact related to the fact that the scattered particles are not singlets under the residual global subgroup of the gauge group

Mapping community pharmacy services in Brazil: a scoping review

The delivery of clinical pharmacy services has been growing in Brazilian community pharmacies, and it is necessary to have a comprehensive understanding of the topic. This scoping review aimed to provide an overview of Brazilian studies about clinical pharmacy services in community pharmacies. Original research articles, with no restriction of time, study design, or patients health condition, were included. Searches were conducted in PubMed, Scopus, Web of Science, Scielo, and Lilacs. Two reviewers conducted the screening, full-text reading, and data extraction independently. ROB and ROBINS-I were used for the assessment of quality. Charts and tables were built to summarise the data. Seventy-two articles were included. A diversity of study designs, number of participants, terms used, and outcomes was found. São Paulo and Sergipe States had the highest number of studies (n=10). Pharmacists interventions were not fully reported in 65% of studies, and most studies presented an unclear risk of bias. Studies were very diverse, impairing the comparisons between the results and hindering their reproducibility. This review suggests using guidelines and checklists for better structuration of pharmacists interventions as well as reporting results and measuring fidelity in future research. (c) 2022, Faculdade de Ciencias Farmaceuticas (Biblioteca). All rights reserved

Herpesvirus skin disease in free-living common frogs Rana temporaria in Great Britain

Infectious disease is a significant driver of global amphibian declines, yet despite this, relatively little is known about the range of pathogens that affect free-living amphibians. Recent detection of the tentatively named Ranid herpesvirus 3 (RHV3), associated with skin disease in free-living common frogs Rana temporaria in Switzerland, helps to address this paucity in knowledge, but the geographic distribution and epidemiology of the pathogen remains unclear. Syndromic surveillance for ranid herpesvirus skin disease was undertaken throughout Great Britain (GB), January 2014 to December 2016. Reports of common frogs with macroscopic skin lesions with a characteristic grey appearance were solicited from members of the public. Post-mortem examination was conducted on one affected frog found dead in 2015 at a site in England. In addition, archived samples from an incident involving common frogs in England in 1997 with similar macroscopic lesions were further investigated. Transmission electron microscopy identified herpes-like virions in skin lesions from both the 1997 and 2015 incidents. RHV3, or RHV3-like virus, was detected in skin lesions from the 2015 case by PCR and sequencing. Our findings indicate that herpesvirus skin disease is endemic in common frogs in GB, with widespread distribution at apparently low prevalence. Further research into the role of host immunity, virus latency and the significance of infection to host survival is required to better understand the epidemiology and impact of cutaneous herpesvirus infections in amphibian populations

Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.We acknowledge the Wellcome Trust for supporting this work. H.B was supported by a Wellcome Trust clinical PhD fellowship. We acknowledge the Research Foundation Flanders (FWO) (FWO-G.A093.11 and FWO-G.0924.15 to T.V.; the travel grant V.4.140.10.N.00 to T.V.; N.V.d.A., E.F.G. and K.T. are Ph.D. students supported by FWO 1.1.H.28.12, FWO G.0924.15 and FWO 1126016N, respectively) and KU Leuven SymBioSys (PFV/10/016 to T.V.; P.K. is a PhD. student supported with PFV/10/016).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1116

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function

Depleted circulatory complement-lysis inhibitor (CLI) in childhood cerebral malaria returns to normal with convalescence

BACKGROUND: Cerebral malaria (CM), is a life-threatening childhood malaria syndrome with high mortality. CM is associated with impaired consciousness and neurological damage. It is not fully understood, as yet, why some children develop CM. Presented here is an observation from longitudinal studies on CM in a paediatric cohort of children from a large, densely-populated and malaria holoendemic, sub-Saharan, West African metropolis. METHODS: Plasma samples were collected from a cohort of children with CM, severe malarial anaemia (SMA), uncomplicated malaria (UM), non-malaria positive healthy community controls (CC), and coma and anemic patients without malaria, as disease controls (DC). Proteomic two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry were used in a discovery cohort to identify plasma proteins that might be discriminatory among these clinical groups. The circulatory levels of identified proteins of interest were quantified by ELISA in a prospective validation cohort. RESULTS: The proteome analysis revealed differential abundance of circulatory complement-lysis inhibitor (CLI), also known as Clusterin (CLU). CLI circulatory level was low at hospital admission in all children presenting with CM and recovered to normal level during convalescence (p < 0.0001). At acute onset, circulatory level of CLI in the CM group significantly discriminates CM from the UM, SMA, DC and CC groups. CONCLUSIONS: The CLI circulatory level is low in all patients in the CM group at admission, but recovers through convalescence. The level of CLI at acute onset may be a specific discriminatory marker of CM. This work suggests that CLI may play a role in the pathophysiology of CM and may be useful in the diagnosis and follow-up of children presenting with CM