The transcription factor GATA6 is essential for branching morphogenesis and epithelial cell differentiation during fetal pulmonary development

Recent loss-of-function studies in mice show that the transcription factor GATA6 is important for visceral endoderm differentiation. It is also expressed in early bronchial epithelium and the observation that this tissue does not receive any contribution from Gata6 double mutant embryonic stem (ES) cells in chimeric mice suggests that GATA6 may play a crucial role in lung development. The aim of this study was to determine the role of GATA6 in fetal pulmonary development. We show that Gata6 mRNA is expressed predominantly in the developing pulmonary endoderm and epithelium, but at E15.5 also in the pulmonary mesenchyme. Blocking or depleting GATA6 function results in diminished branching morphogenesis both in vitro and in vivo. TTF1 expression is unaltered in chimeric lungs whereas SPC and CC10 expression are attenuated in abnormally branched areas of chimeric lungs. Chimeras generated in a ROSA26 background show that endodermal cells in these abnormally branched areas are derived from Gata6 mutant ES cells, implicating that the defect is intrinsic to the endoderm. Taken together, these data demonstrate that GATA6 is not essential for endoderm specification, but is required for normal branching morphogenesis and late epithelial cell differentiation

Consumption of nitrate-rich beetroot juice with or without vitamin C supplementation increases the excretion of urinary nitrate, nitrate, and N-nitroso compounds in humans

Consumption of nitrate-rich beetroot juice (BRJ) by athletes induces a number of beneficial physiological health effects, which are linked to the formation of nitric oxide (NO) from nitrate. However, following a secondary pathway, NO may also lead to the formation of N-nitroso compounds (NOCs), which are known to be carcinogenic in 39 animal species. The extent of the formation of NOCs is modulated by various other dietary factors, such as vitamin C. The present study investigates the endogenous formation of NOCs after BRJ intake and the impact of vitamin C on urinary NOC excretion. In a randomized, controlled trial, 29 healthy recreationally active volunteers ingested BRJ with or without additional vitamin C supplements for one week. A significant increase of urinary apparent total N-nitroso Compounds (ATNC) was found after one dose (5 to 47 nmol/mmol: p < 0.0001) and a further increase was found after seven consecutive doses of BRJ (104 nmol/mmol: p < 0.0001). Vitamin C supplementation inhibited ATNC increase after one dose (16 compared to 72 nmol/mmol, p < 0.01), but not after seven daily doses. This is the first study that shows that BRJ supplementation leads to an increase in formation of potentially carcinogenic NOCs. In order to protect athlete’s health, it is therefore important to be cautious with chronic use of BRJ to enhance sports performances

Resource requirements for the implementation of a global H2-powered aviation

In this paper, the resource requirements for the implementation of global H2-powered aviation are investigated to answer one of the main questions asked by many stakeholders in the aviation industry: Are there any resource limitations for the implementation of H2-powered aviation on a global scale? For this, the raw material, renewable energy and water demands for the deployment and operational phase are investigated on a global and regional perspective. It is found that the iridium demand for a global hydrogen economy could be critical as it would exceed not only the current annual production by a factor of 11 but also the current reserves about 1.7 times. The H2-powered aviation alone is not the main driver of iridium demand but could increase the limitations. With reduced specific raw material demands of further optimized electrolysis technologies and increased annual raw material production, the limitations especially for the iridium demand could be overcome. Renewable energy capacities and water availability are sufficient for demands from H2-powered aircraft on a global perspective. Nevertheless, the limited availability of renewable energy sources in some regions and regional water constraints may necessitate hydrogen import for certain airports. While water desalination is likely to overcome water constraints in regions close to the sea, for airports located in regions with detrimental availability of renewable energy sources the import of hydrogen is the only way to ensure a hydrogen supply for H2-powered aviation

Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin

An innovative postnatal risk assessment and corresponding care pathways in Preventive Child Healthcare

Aims This study aims to evaluate the effectiveness of an innovative postnatal risk assessment (the postnatal Rotterdam Reproductive Risk Reduction checklist: R4U) and corresponding care pathways in Preventive Child Healthcare (PCHC), along with PCHC professional satisfaction. Design Four PCHC organizations located in three municipalities with a higher adverse perinatal outcome than the national average were selected for participation. The study concerns a historically controlled study design. Methods The study enrolled participants from September 2016 until December 2017. The historical cohort existed of children born in previous years from 2008 until 2016. The outcome measure was defined as catch-up growth: more than 0.67 standard deviation score weight for height increase in the first 6 months of life. PCHC professional opinion was assessed with a digital survey. Results After the inclusion period, 1,953 children were included in the intervention cohort and 7,436 children in the historical cohort. Catch-up growth was significantly less common in the intervention cohort; 14.9% versus 19.5% in the historical cohort (p < 0.001). A regression sensitivity analysis, using matching, showed an odds ratio of 0.957 (95% CI 0.938-0.976) for the intervention cohort. In the survey, 74 PCHC physicians and nurses participated; most of them were neutral concerning the benefits of the postnatal R4U. Conclusion This study shows that the implementation of a novel postnatal risk assessment including in PCHC is feasible and effective. Final efforts to ensure a widespread implementation should be taken. Impact PCHC offers a unique opportunity to recognize and address risk factors for growth and development in children and to implement care pathways. Effective and widely implemented risk assessments in antenatal and PCHC are scarce. To our knowledge, this kind of evidence-based postnatal risk assessment has not been implemented in PCHC before and seizes the opportunity to prevent catch-up growth and its long-term effects

Innovative postnatal risk assessment in preventive child health Care:A study protocol

AIM: To introduce the rationale and design of a postnatal risk assessment study, which will be embedded in Preventive Child Health Care. This study will evaluate: (a) the predictive value of an innovative postnatal risk assessment, meant to assess the risk of growth and developmental problems in young children; and (b) its effectiveness in combination with tailored care pathways. DESIGN: This study concerns a historically controlled study design and is designed as part of the Healthy Pregnancy 4 All-2 program. We hypothesize that child growth and developmental problems will be reduced in the intervention cohort due to the postnatal risk assessment and corresponding care pathways. METHODS: The study was approved in August 2016. Children and their parents, visiting well-baby clinics during regular visits, will participate in the intervention (N = 2,650). Additional data of a historical control group (N = 2,650) in the same neighbourhoods will be collected. The intervention, consisting of the risk assessment and its corresponding care pathways, will be executed in the period between birth and 2 months of (corrected) age. The predictive value of the risk assessment and its effectiveness in combination with its corresponding care pathways will be assessed by Preventive Child Health Care nurses and physicians in four Preventive Child Health Care organisations in three municipalities with adverse perinatal outcomes. A total risk score above a predefined threshold, which is based on a weighted risk score, determines structured multidisciplinary consultation. DISCUSSION: The successful implementation of this innovative postnatal risk assessment including corresponding care pathways has potential for further integration of risk assessment and a family-centred approach in the work process of Preventive Child Health Care nurses and physicians. IMPACT: This study introduces a systematic approach in postnatal health care which may improve growth and developmental outcomes of children and even future generations

Correction:Reducing growth and developmental problems in children: Development of an innovative postnatal risk assessment

[This corrects the article DOI: 10.1371/journal.pone.0217261.]

Numerical investigation of the in-plane seismic performance of unstrengthened and TRM-strengthened rammed earth walls

The large availability of raw earth around the World led to its extensive use as a building material through history. Thus, earthen materials integrate several historical monuments, but their main use was to build living and working environments for billions of people. On the other hand, past earthquakes revealed their inadequate seismic behavior, which is a matter of concern as a significant percentage of earthen buildings are located in regions with medium to high seismic hazard. Nevertheless, their seismic behavior and the development of efficient strengthening solutions are topics that are not yet sufficiently investigated in the literature. In this context, this study investigates numerically the in-plane seismic behavior of a rammed earth component by means of advanced nonlinear finite element modeling, which included performing nonlinear static (pushover) and nonlinear dynamic analyses. Moreover, the strengthening effectiveness of a low-cost textile-reinforced mortar on such component was also evaluated. The strengthening was observed to increase the load and displacement capacities, to preserve the integrity for higher lateral load levels and to postpone failure without adding significant mass to the system. Furthermore, the pushover analysis was shown to predict reliably the capacities of the models with respect to the incremental dynamic analysis.This work was financed by FEDER funds through the Competitively Factors Operational Programme (COMPETE) and by national funds through the Foundation for Science and Technology (FCT) within the scope of projects POCI-01-0145-FEDER-016737 (PTDC/ECM-EST/2777/2014) and POCI-01-0145-FEDER-007633. The support from grant SFRH/BPD/97082/2013 is also acknowledged

Transient receptor potential canonical 4 and 5 proteins as targets in cancer therapeutics

Novel approaches towards cancer therapy are urgently needed. One approach might be to target ion channels mediating Ca²+ entry because of the critical roles played by Ca²+ in many cell types, including cancer cells. There are several types of these ion channels, but here we address those formed by assembly of transient receptor potential canonical (TRPC) proteins, particularly those which involve two closely related members of the family: TRPC4 and TRPC5. We focus on these proteins because recent studies point to roles in important aspects of cancer: drug resistance, transmission of drug resistance through extracellular vesicles, tumour vascularisation, and evoked cancer cell death by the TRPC4/5 channel activator (−)-englerin A. We conclude that further research is both justified and necessary before these proteins can be considered as strong targets for anti-cancer cell drug discovery programmes. It is nevertheless already apparent that inhibitors of the channels would be unlikely to cause significant adverse effects, but, rather, have other effects which may be beneficial in the context of cancer and chemotherapy, potentially including suppression of innate fear, visceral pain and pathological cardiac remodelling

Völkisch und sozial? : Neonazistische Agitation gegen die neue EU-Freizügigkeit für Arbeitnehmerinnen

Wnt/β-catenin signalling pathway is crucial for the formation of many tissues and organs during development. In recent years, this pathway has also been found to regulate the biology of stem cells in the intestine and probably in other organs in adult life. Abnormal activation of Wnt/β-catenin signalling, which controls the expression of a high number of genes, is critical for the initiation and progression of most colorectal cancers. In line with this, the gene expression signature induced by activation of the Wnt/β-catenin pathway defines the intestinal stem cells present at the bottom of the crypts and also colon cancer stem cells. This supports the importance of inhibitors of the Wnt/β-catenin pathway as potential agents in colorectal cancer therapy. However, the complexity, wide activity in the organism modulating the biology of several cell types, and characteristics of this pathway have delayed the identification of suitable targets and so, the development of such inhibitors that are only now reaching the clinic.Peer reviewe