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In September 2023 members of the cell adhesion and cell migration research community came together to share their latest research and consider how our work might be translated for clinical practice. Alongside invited speakers, selected speakers and poster presentations, the meeting also included a round table discussion of how we might overcome the challenges associated with research translation. This meeting report seeks to highlight the key outcomes of that discussion and spark interest in the cell adhesions and cell migration research community to cross the perceived valley of death and translate our work into therapeutic benefit.

In this study, we addressed the functional significance of co-operative DNA binding of the cytokine-driven transcription factor STAT1 (signal transducer and activator of transcription 1) in an experimental murine model of acute myocardial infarction (MI). STAT1 knock-in mice expressing a phenylalanine-to-alanine substitution at position 77 in the STAT1 amino-terminal domain were examined for the early clinical effects produced by ligation of the left anterior descending coronary artery (LAD), an established model for MI. The F77A mutation has been previously reported to disrupt amino-terminal interactions between adjacent STAT1 dimers resulting in impaired tetramerization and defective co-operative binding on DNA, while leaving other protein functions unaffected. Our results demonstrate that a loss of STAT1 tetramer stabilization improves survival of adult male mice and ameliorates left ventricular dysfunction in female mice, as determined echocardiographically by an increased ejection fraction and a reduced left intra-ventricular diameter. We found that the ratio of STAT3 to STAT1 protein level was higher in the infarcted tissue in knock-in mice as compared to wild-type (WT) mice, which was accompanied by an enhanced infiltration of immune cells in the infarcted area, as determined by histology. Additionally, RNA sequencing of the infarcted tissue 24 h after LAD ligation revealed an upregulation of inflammatory genes in the knock-in mice, as compared to their WT littermates. Concomitantly, genes involved in oxidative phosphorylation and other metabolic pathways showed a significantly more pronounced downregulation in the infarcted tissue from STAT1F77A/F77A mice than in WT animals. Based on these results, we propose that dysfunctional STAT1 signalling owing to a lack of oligomerisation results in a compensatory increase in STAT3 expression and promotes early infiltration of immune cells in the infarcted area, which has beneficial effects on left ventricular remodelling in early MI following LAD ligation.

Aim of study: To evaluate corn grain micronization for calves fed a grower diet. Area of study: Padinska Skela – Belgrade, Serbia. Material and methods: Thirty weaned Holstein dairy calves (65–74 days of age) were randomly assigned to one of two treatments with growers containing micronized (MCG) or untreated corn grain (UCG). The experimental period lasted for 60 days. Main results: The values of total tract apparent digestibility of dry matter (DM), organic matter (OM), crude protein (CP), and nonfiber carbohydrates (NFC) were higher for calves fed MCG versus those within the UCG treatment by 3.9% (p

Coronavirus disease 2019 (COVID-19) is a viral respiratory infection caused by the severe acute respiratory syndrome virus (SARS-CoV-2). Vaccines that protect against SARS-CoV-2 infection have been widely employed to reduce the incidence of symptomatic and severe disease. However, adenovirus-based SARS-CoV-2 vaccines can cause a rare, thrombotic disorder termed vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT often develops in the first 5 to 30 days following vaccination and is characterized by thrombocytopenia and thrombosis in unusual locations (e.g., cerebral venous sinus thrombosis). The diagnosis is confirmed by testing for anti-PF4 antibodies, as these antibodies are capable of platelet activation without any cofactor. It can be clinically challenging to differentiate VITT from a similar disorder called heparin-induced thrombocytopenia (HIT), since heparin is commonly used in hospitalized patients. VITT and HIT have similar pathobiology and clinical manifestations but important differences in testing including the need for PF4-enhanced functional assays and the poor reliability of rapid immunoassays for the detection of anti-platelet factor 4 (PF4) antibodies. In this review we summarize the epidemiology of VITT; highlight similarities and differences between HIT and VITT; and provide an update on the clinical diagnosis of VITT.

Abstract Aims Endothelial activation and inflammatory cell infiltration have important roles in the development of cardiac fibrosis induced by renin–angiotensin system activation. NADPH oxidases (Nox proteins) are expressed in endothelial cells (ECs) and alter their function. Previous studies indicated that Nox2 in ECs contributes to angiotensin II (AngII)‐induced cardiac fibrosis. However, the effects of EC Nox4 on cardiac fibrosis are unknown. Methods and results Transgenic (TG) mice overexpressing endothelial‐restricted Nox4 were studied alongside wild‐type (WT) littermates as controls. At baseline, Nox4 TG mice had significantly enlarged hearts compared with WT, with elongated cardiomyocytes (increased by 18.5%, P 0.05), but there were no differences in cardiac hypertrophy or contractile function between the two groups. TG hearts displayed significantly decreased inflammatory cell infiltration with reduced levels of vascular cell adhesion molecule 1 in both the vasculature and myocardium compared with WT after AngII treatment. TG microvascular ECs stimulated with AngII in vitro supported significantly less leukocyte adhesion than WT ECs. Conclusions A chronic increase in endothelial Nox4 stimulates physiological cardiac hypertrophy and protects against AngII‐induced cardiac fibrosis by inhibiting EC activation and the recruitment of inflammatory cells.

Vascular endothelial cell (EC) dysfunction contributes to the occurrence of diabetic complications. Here the authors report that in diabetic conditions, upregulation of the RNA binding protein QKI-7 in ECs due to the imbalance of RNA splicing factors CUG-BP and hnRNPM contributes to EC dysfunction, and that in vivo QKI-7 silencing improves blood flow recovery in diabetic mice with limb ischemia.

Despite the key role of heterotrophic bacterioplankton in the biogeochemistry of tropical coastal waters, their dynamics have been poorly investigated in relation to the different dissolved organic matter (DOM) pools usually available. In this study we conducted four seasonal incubations of unfiltered and predator-free seawater (Community and Filtered treatment, respectively) at three Red Sea coastal sites characterized by different dominant DOM sources: Seagrass, Mangrove, and Phytoplankton. Bacterial abundance, growth and physiological status were assessed by flow cytometry and community composition by 16S rRNA gene amplicons. The Seagrass site showed the highest initial abundances (6.93 ± 0.30 × 105 cells mL–1), coincident with maximum DOC concentrations (>100 μmol C L–1), while growth rates peaked at the Mangrove site (1.11 ± 0.09 d–1) and were consistently higher in the Filtered treatment. The ratio between the Filtered and Community maximum bacterial abundance (a proxy for top-down control by protistan grazers) showed minimum values at the Seagrass site (1.05 ± 0.05) and maximum at the Phytoplankton site (1.24 ± 0.30), suggesting protistan grazing was higher in open waters, especially in the first half of the year. Since the Mangrove and Seagrass sites shared a similar bacterial diversity, the unexpected lack of bacterial response to predators removal at the latter site should be explained by differences in DOM characteristics. Nitrogen-rich DOM and fluorescent protein-like components were significantly associated with enhanced specific growth rates along the inshore-offshore gradient. Our study confirms the hypotheses that top–down factors control bacterial standing stocks while specific growth rates are bottom-up controlled in representative Red Sea shallow, oligotrophic ecosystems.

Nox2 is a ROS-generating enzyme, deficiency of which increases suppression by Tregs in vitro and in an in vivo model of cardiac remodeling. As Tregs have emerged as a candidate therapy in autoimmunity and transplantation, we hypothesized that Nox2 deficiency in Tregs in recipient mice may improve outcomes in a heart transplant model. We generated a potentially novel B6129 mouse model with Treg-targeted Nox2 deletion (Nox2fl/flFoxP3Cre+ mice) and transplanted with hearts from CB6F1 donors. As compared with those of littermate controls, Nox2fl/flFoxP3Cre+ mice had lower plasma levels of alloantibodies and troponin-I, reduced levels of IFN-γ in heart allograft homogenates, and diminished cardiomyocyte necrosis and allograft fibrosis. Single-cell analyses of allografts revealed higher absolute numbers of Tregs and lower CD8+ T cell infiltration in Nox2-deficient recipients compared with Nox2-replete mice. Mechanistically, in addition to a greater suppression of CD8+CD25– T effector cell proliferation and IFN-γ production, Nox2-deficient Tregs expressed higher levels of CCR4 and CCR8, driving cell migration to allografts; this was associated with increased expression of miR-214-3p. These data indicate that Nox2 deletion in Tregs enhances their suppressive ability and migration to heart allografts. Therefore, Nox2 inhibition in Tregs may be a useful approach to improve their therapeutic efficacy.

Background: The aim of this study was to compare the rates of vaccination against COVID-19 infection in psychiatric outpatients and the general population, as well as rates of infected patients. In addition, the level and type of anxiety due to the pandemic were observed in patients with psychotic, anxiety, and depressive disorders. Materials and Methods: In the present study, 171 patients with pre-existing mental disorders completed the questionnaire about the doses and types of vaccination against COVID-19. During 2021–2023, patients with different mental disorders, aged from 18 to 80, were included. All patients filled in a self-reported questionnaire including general information (age, sex, marriage, education, working status, comorbid conditions) as well as questions about mental health, receiving vaccination, and the course of COVID-19 infection if it was present. All patients gave informed consent for the interview. Results: Patients with pre-existing mental disorders were more likely to be vaccinated against COVID-19 compared with the general population. The Sinopharm vaccine was most frequently applied. In the observed patients, 46.8% were infected, but just 7% had a medium or serious form of infection and were not vaccinated. Conclusions: In our study, the percentage of vaccinated psychiatric patients was greater than that in the general population, except in psychotic patients, who were mostly limited by fear. Such results can be explained by the high percentage of somatic comorbidities in this population and perhaps insufficient information about the positive effects of vaccination. [ABSTRACT FROM AUTHOR]

Sectorization of a water distribution network (WDN) into district meter areas (DMAs) is considered a key strategy for an efficient management of WDNs. Typically, it involves a two-stage procedure: a clustering stage, in which the division of the WDN into clusters is performed, and a dividing stage, which involves the placement of valves and flow meters on the cluster's boundary pipes to define the DMAs. While recently published methods attempt to enhance both the clustering and dividing stages, they fail to provide decision-making flexibility. They also neglect to consider the presence of existing valves in the WDN, which can significantly affect the evaluated implementation cost, often considered the primary decision-driving factor. This paper presents improvements to the previously introduced DeNSE method for sectorization of WDNs, aiming to address these deficiencies. The methodology consists of a clustering stage, based on the network uniformity index, and a dividing stage, in which the originally used heuristic procedure is replaced with Genetic Algorithm (GA) optimization, minimizing implementation cost. Consideration of existing valves in WDN and criteria for water supply security are also included in the dividing stage to offer a better estimate of implementation costs and post-sectorized operational efficiency of the WDN. Finally, GIS visualization is implemented, and a hydraulic model of the sectorized WDN (EPANET file) is generated, providing practitioners with valuable insights and decision-making flexibility. The methodology is tested on a part of the Amsterdam WDN in the Netherlands, serving as a pilot for methodology evaluation. A range of feasible sectorization solutions is generated and compared based on implementation cost and three performance indicators (PIs). The paper provides an in-depth discussion on the selection of preferable sectorization solution. The reported results demonstrate the method's efficiency in optimizing sectorization solutions with minimum implementation cost whilst preserving the WDN operational efficiency and meeting the local design criteria. [ABSTRACT FROM AUTHOR]

Diagnosing heparin-induced thrombocytopenia (HIT) requires functional assays measuring platelet activation as they are highly specific and sensitive. A useful functional test for diagnosing HIT is the serotonin release assay (SRA), but this assay is technically demanding and requires a radioactive marker. We describe an alternate functional HIT assay, the platelet viability assay (PVA), that overcomes the need for a radioactive marker by using a viability dye endpoint to measure platelet activation. We compared the performance characteristics of the PVA to the SRA. Serum samples from 76 patients with suspected HIT were tested in both the PVA and the SRA. The PVA uses calcein-AM as a marker of platelet viability, with decreases in fluorescence and cell size as surrogate markers for platelet activation. A significant linear correlation (Spearman correlation, r = −0.78, P

The choice of revegetating via direct seeding or planting nursery-grown seedlings influences the potential stresses suffered by seedlings such as herbivory and drought. The outcome of the balance between both revegetation methods may ultimately depend on how species identity and traits such as seed and seedling size interact with environmental conditions. To test this, we will conduct a continental-scale experiment consisting of one mini-experiment replicated by multiple participants across Europe. Each participant will establish a site with seeded and planted individuals of one or more native, locally growing oak (Quercus) species; the selection of this genus aims to favour continental-scale participation and to allow testing the response of a widely distributed genus of broad ecological and economic relevance. At each site, participants will follow the present protocol for seed collection, seeding in the field, nursery cultivation, outplanting, protection against herbivores, site maintenance, and measurement of seedling performance and environmental variables. Each measurement on each species at each site will produce one effect size; the data will be analysed through mixed-effects meta-analysis. With this approach we will assess the main effect of revegetation method, species, plant functional traits, and the potential effect of site-specific effect moderators. Overall, we will provide a continental-scale estimate on the seeding vs. planting dilemma and analyse to what extent the differences in environmental conditions across sites, seed size, functional traits, and the phylogenetic relatedness of species can account for the differences in the effect of revegetation method on seedling performance across study sites and species.

The mechanisms of platelet underproduction in immune thrombocytopenia (ITP) remain unknown. While the number of megakaryocytes is normal or increased in ITP bone marrow, further studies of megakaryocyte integrity are needed. Megakaryocytes are responsible for the production of platelets in the bone marrow, and they are possible targets of immune-mediated injury in ITP. Since the biological process of megakaryocyte apoptosis impacts platelet production, we investigated megakaryocyte DNA fragmentation as a marker of apoptosis from ITP bone marrow biopsies. Archived bone marrow biopsy specimens from ITP patients, bone marrow specimens from controls with normal platelet counts, and bone marrow specimens from thrombocytopenic controls with myelodysplastic syndrome (MDS) were evaluated. Sections were stained with anti-CD61 for megakaryocyte enumeration, and terminal deoxynucleotidyl transferase dUTP nick-end labeling was used as an apoptotic indicator. In ITP patients, megakaryocyte apoptosis was reduced compared to nonthrombocytopenic controls. Megakaryocyte apoptosis was similarly reduced in thrombocytopenic patients with MDS. These results suggest a link between megakaryocyte apoptosis and platelet production.