Deformations of symplectic foliations

We develop the deformation theory of symplectic foliations, i.e. regular foliations equipped with a leafwise symplectic form. The main result of this paper is that each symplectic foliation has an attached $L_\infty$-algebra controlling its deformation problem. Indeed, viewing symplectic foliations as regular Poisson structures, we establish a one-to-one correspondence between the small deformations of a given symplectic foliation and the Maurer-Cartan elements of the associated $L_\infty$-algebra. Using this, we show that infinitesimal deformations of symplectic foliations can be obstructed. Further, we relate symplectic foliations with foliations on one side and with (arbitrary) Poisson structures on the other, showing that obstructed infinitesimal deformations of the former may give rise to unobstructed infinitesimal deformations of the latter

Artery-vein specification in the zebrafish trunk is pre-patterned by heterogeneous Notch activity and balanced by flow-mediated fine tuning

How developing vascular networks acquire the right balance of arteries, veins and lymphatic vessels to efficiently supply and drain tissues is poorly understood. In zebrafish embryos, the robust and regular 50:50 global balance of intersegmental veins and arteries that form along the trunk, prompts the intriguing question how the organism keeps "count". Previous studies suggest that the ultimate fate of an intersegmental vessel (ISV) is determined by the identity of the approaching secondary sprout emerging from the posterior cardinal vein (PCV). Here, we show that the formation of a balanced trunk vasculature involves an early heterogeneity in endothelial cell (EC) behavior and Notch signaling activity in the seemingly identical primary ISVs that is independent of secondary sprouting and flow. We show that Notch signaling mediates the local patterning of ISVs, and an adaptive flow-mediated mechanism subsequently fine-tunes the global balance of arteries and veins along the trunk. We propose that this dual mechanism provides the adaptability required to establish a balanced network of arteries, veins and lymphatic vessels

Broncho-alveolar lavage fluid recovery correlates with airway neutrophilia in lung transplant patients

SummaryBroncho-alveolar lavage (BAL) is important to assess airway inflammation. There is debate about the volume instilled, but the variation of BAL fluid recovery (BFR) has received little attention. We investigated the association between BFR and rejection/infection status after lung transplantation (LTx).We combined clinical findings, FEV1, transbronchial biopsies and BAL analysis (BFR, interleukin-8 (IL8), cell counts, microbiology) of 115 samples/LTx patients. The patients were divided into 4 groups: stable (subdivided in colonized and non-colonized), acute rejection (AR), Bronchiolitis Obliterans Syndrome (BOS) and infection.BFR was significantly lower in AR, BOS and infection, and correlated with the severity of AR and BOS. A 10ml decrease of BFR was associated with a FEV1 decrease of 4.4% and a %neutrophils and IL8 increase of 9.6% and 9.7pg/ml, respectively. Colonized stable patients had no significant differences in airway inflammation, FEV1 and BFR compared to the non-colonized stable patients.We conclude that a low BFR is an indicator of lung rejection or infection. BFR variation is related to airway obstruction and neutrophilic inflammation, which can cause an increased compliance of the airway wall, making it more collapsible. Airway colonization in stable patients had no effect on airway inflammatory parameters, BFR and FEV1

Functional agro-biodiversity: an evaluation of current approaches and outcomes

The European Union’s ‘Green Deal’ proposes an ambitious roadmap towards climate neutrality by 2050 and the adoption of a circular economy. Functional AgroBiodiversity (FAB) measures, which balance food production with minimised impacts on nature, are a promising way to achieve this on farmland. Here, we undertake a rapid evidence assessment to highlight Functional Agro-Biodiversity (FAB) management measures which help to realise biodiversity, climate neutrality, efficiency in use of natural resources and the circular economy. We report evidence on the effectiveness of 10 common FAB measures employed in Europe following a resurgence of interest and increased availability of data on their impact. The review found that the outcomes of implementing FAB measures were largely positive, with a number of mixed effects. There are evidence gaps, e.g., the impact of FAB measures on yield, the magnitude and timescale of impacts, the effect of landscape context. We signpost the most relevant and well-documented FAB measures, providing a reference for land managers and practitioners to select FAB measures to achieve specific ecological and agricultural outcomes. It is also important to note that a combination of measures implemented in a strategic way can enhance the output success

What's the effect of the implementation of general practitioner cooperatives on caseload? Prospective intervention study on primary and secondary care

<p>Abstract</p> <p>Background</p> <p>Out-of-hours care in the primary care setting is rapidly changing and evolving towards general practitioner 'cooperatives' (GPC). GPCs already exist in the Netherlands, the United Kingdom and Scandinavia, all countries with strong general practice, including gatekeepers' role. This intervention study reports the use and caseload of out-of-hours care before and after implementation of a GPC in a well subscribed region in a country with an open access health care system and no gatekeepers' role for general practice.</p> <p>Methods</p> <p>We used a prospective before/after interventional study design. The intervention was the implementation of a GPC.</p> <p>Results</p> <p>One year after the implementation of a GPC, the number of patient contacts in the intervention region significantly increased at the GPC (OR: 1.645; 95% CI: 1.439-1.880), while there were no significant changes in patient contacts at the Emergency Department (ED) or in other regions where a simultaneous registration was performed. Although home visits decreased in all general practitioner registrations, the difference was more pronounced in the intervention region (intervention region: OR: 0.515; 95% CI: 0.411-0.646, other regions: OR: 0.743; 95% CI: 0.608-0.908). At the ED we observed a decrease in the number of trauma cases (OR: 0.789; 95% CI: 0.648-0.960) and of patients who came to hospital by ambulance (OR: 0.687; 95% CI: 0.565-0.836).</p> <p>Conclusions</p> <p>One year after its implementation more people seek help at the GPC, while the number of contacts at the ED remains the same. The most prominent changes in caseload are found in the trauma cases. Establishing a GPC in an open health care system, might redirect some patients with particular medical problems to primary care. This could lead to a lowering of costs or a more cost-effective out of hours care, but further research should focus on effective usage to divert patient flows and on quality and outcome of care.</p

Zebrafish prox1b Mutants Develop a Lymphatic Vasculature, and prox1b Does Not Specifically Mark Lymphatic Endothelial Cells

Background: The expression of the Prospero homeodomain transcription factor (Prox1) in a subset of cardinal venous cells specifies the lymphatic lineage in mice. Prox1 is also indispensible for the maintenance of lymphatic cell fate, and is therefore considered a master control gene for lymphangiogenesis in mammals. In zebrafish, there are two prox1 paralogues, the previously described prox1 (also known as prox1a) and the newly identified prox1b. Principal Findings: To investigate the role of the prox1b gene in zebrafish lymphangiogenesis, we knocked-down prox1b and found that depletion of prox1b mRNA did not cause lymphatic defects. We also generated two different prox1b mutant alleles, and maternal-zygotic homozygous mutant embryos were viable and did not show any lymphatic defects. Furthermore, the expression of prox1b was not restricted to lymphatic vessels during zebrafish development. Conclusion: We conclude that Prox1b activity is not essential for embryonic lymphatic development in zebrafish

Single-cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma

Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-time in vivo monitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs—features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets

Blood flow drives lumen formation by inverse membrane blebbing during angiogenesis in vivo

How vascular tubes build, maintain and adapt continuously perfused lumens to meet local metabolic needs remains poorly understood. Recent studies showed that blood flow itself plays a critical role in the remodelling of vascular networks, and suggested it is also required for the lumenization of new vascular connections. However, it is still unknown how haemodynamic forces contribute to the formation of new vascular lumens during blood vessel morphogenesis. Here we report that blood flow drives lumen expansion during sprouting angiogenesis in vivo by inducing spherical deformations of the apical membrane of endothelial cells, in a process that we have termed inverse blebbing. We show that endothelial cells react to these membrane intrusions by local and transient recruitment and contraction of actomyosin, and that this mechanism is required for single, unidirectional lumen expansion in angiogenic sprouts. Our work identifies inverse membrane blebbing as a cellular response to high external pressure. We show that in the case of blood vessels such membrane dynamics can drive local cell shape changes required for global tissue morphogenesis, shedding light on a pressure-driven mechanism of lumen formation in vertebrates