Explore the vast range of titles available.

A 3-year time series of ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) measurements of NO2 and SO2 on the island Neuwerk has been analyzed for contributions from shipping emissions. The island is located in the German Bight, close to the main shipping lane (at a distance of 6–7 km) into the river Elbe towards the harbor of Hamburg. Measurements of individual ship plumes as well as of background pollution are possible from this location. A simple approach using the column amounts of the oxygen molecule dimer or collision complex, O4, for the determination of the horizontal light path length has been applied to retrieve path-averaged volume mixing ratios. An excellent agreement between mixing ratios determined from NO2 retrievals in the UV and visible parts of the spectrum has been found, showing the validity of the approach. Obtained mixing ratios of NO2 and SO2 are compared to co-located in situ measurements showing good correlation on average but also a systematic underestimation by the MAX-DOAS O4 scaling approach. Comparing data before and after the introduction of stricter fuel sulfur content limits (from 1 to 0.1 %) on 1 January 2015 in the North Sea Emission Control Area (ECA), a significant reduction in SO2 levels is observed. For situations with wind from the open North Sea, where ships are the only local source of air pollution, the average mixing ratio of SO2 decreased by a factor of 8, while for NO2 in the whole time series from 2013 to 2016, no significant change in emissions was observed. More than 2000 individual ship emission plumes have been identified in the data and analyzed for the emission ratio of SO2 to NO2, yielding an average ratio of 0.3 for the years 2013/2014 and decreasing significantly, presumably due to lower fuel sulfur content, in 2015/2016. By sorting measurements according to the prevailing wind direction and selecting two angular reference sectors representative for wind from the open North Sea and coast excluding data with mixed air mass origin, relative contributions of ships and land-based sources to air pollution levels in the German Bight have been estimated to be around 40 % : 60 % for NO2 as well as SO2 in 2013/2014, dropping to 14 % : 86 % for SO2 in 2015/2016.

The RIP kinases have emerged as essential mediators of cellular stress that integrate both extracellular stimuli emanating from various cell-surface receptors and signals coming from intracellular pattern recognition receptors. The molecular mechanisms regulating the ability of the RIP proteins to transduce the stress signals remain poorly understood, but seem to rely only partially on their kinase activities. Recent studies on RIP1 and RIP2 have highlighted the importance of ubiquitination as a key process regulating their capacity to activate downstream signaling pathways. In this study, we found that XIAP, cIAP1 and cIAP2 not only directly bind to RIP1 and RIP2 but also to RIP3 and RIP4. We show that cIAP1 and cIAP2 are direct E3 ubiquitin ligases for all four RIP proteins and that cIAP1 is capable of conjugating the RIPs with diverse types of ubiquitin chains, including linear chains. Consistently, we show that repressing cIAP1/2 levels affects the activation of NF-κB that is dependent on RIP1, -2, -3 and -4. Finally, we identified Lys51 and Lys145 of RIP4 as two critical residues for cIAP1-mediated ubiquitination and NF-κB activation.

This study provides evidence for a critical role of RIPK1 in suppressing caspase-8-mediated cell death and maintaining intestinal homeostasis independently of its kinase activity. RIPK1 both activates and inhibits cell death Receptor-interacting protein 1 kinase (RIPK1) is involved in the activation of various cell death pathways and in the control of inflammatory signalling. Two separate groups reporting in this issue use contrasting techniques to show that as well as promoting cell death, RIPK1 has a paradoxical function in supporting the survival of mouse epithelial cells that is independent of its kinase function. RIPK1 suppresses epithelial cell apoptosis and necroptosis by preventing FADD/caspase-8-mediated apoptosis and RIPK3-dependent necroptosis. These findings, together with genetic data, suggest that RIPK1 is a master regulator of epithelial cell survival, homeostasis and inflammation in the intestine and the skin. Receptor interacting protein kinase 1 (RIPK1) has an essential role in the signalling triggered by death receptors and pattern recognition receptors 1 , 2 . RIPK1 is believed to function as a node driving NF-κB-mediated cell survival and inflammation as well as caspase-8 (CASP8)-dependent apoptotic or RIPK3/MLKL-dependent necroptotic cell death. The physiological relevance of this dual function has remained elusive because of the perinatal death of RIPK1 full knockout mice 3 . To circumvent this problem, we generated RIPK1 conditional knockout mice, and show that mice lacking RIPK1 in intestinal epithelial cells (IECs) spontaneously develop severe intestinal inflammation associated with IEC apoptosis leading to early death. This early lethality was rescued by antibiotic treatment, MYD88 deficiency or tumour-necrosis factor (TNF) receptor 1 deficiency, demonstrating the importance of commensal bacteria and TNF in the IEC Ripk1 knockout phenotype. CASP8 deficiency, but not RIPK3 deficiency, rescued the inflammatory phenotype completely, indicating the indispensable role of RIPK1 in suppressing CASP8-dependent apoptosis but not RIPK3-dependent necroptosis in the intestine. RIPK1 kinase-dead knock-in mice did not exhibit any sign of inflammation, suggesting that RIPK1-mediated protection resides in its kinase-independent platform function. Depletion of RIPK1 in intestinal organoid cultures sensitized them to TNF-induced apoptosis, confirming the in vivo observations. Unexpectedly, TNF-mediated NF-κB activation remained intact in these organoids. Our results demonstrate that RIPK1 is essential for survival of IECs, ensuring epithelial homeostasis by protecting the epithelium from CASP8-mediated IEC apoptosis independently of its kinase activity and NF-κB activation.

This study pertains to a secondary data analysis aimed at determining differences between oral and maxillofacial surgeons (OMFSs) and dentists handling dental extractions without an evident clinical indication. A survey of 18 questions was conducted among 256 OMFSs in the Netherlands and a random sample of 800 dentists Respondents could answer the questions in writing or online. The data was collected in the period from November 2019 to January 2020, during which two reminders were sent. Analysis of the data took place via descriptive statistics and Chi Square test. The response rate was 28.1% (n = 72) for OMFSs and 30.3% (n = 242) for dentists. In the past three years, 81.9% (n = 59) of the OMFSs and 68.0% (n = 164) of the dentists received a request for extraction without a clinical indication. The most common reasons were financial and severe dental fear (OMFSs: 64.9 and 50.9% vs dentists: 77.4 and 36.5%). Dentists were significantly more likely (75.6%, n = 114) than OMFS (60.7%, n = 34) to comply with their last extraction request without a clinical indication. Almost none of them regretted the extraction afterwards. As for the request itself, it was found that 17.5% (n = 10) of the OMFSs and 12.5% (n = 20) of the dentists did not check for patients' mental competency (p = 0.352). Given that most of the interviewed dental professionals complied with non-dental extraction requests when such extractions are ethically and legally precarious, recommendations for handling such requests are greatly needed.

Fungicides are widely used in agriculture for crop protection. Succinate dehydrogenase inhibitors (SDHIs) and strobilurins inhibit mitochondria electron transport chain (ETC) in fungi, by blocking complex II and complex III, respectively. Questions regarding their selectivity of action for fungi have been raised in the literature, and we previously showed that boscalid and bixafen (SDHIs) alter the mitochondrial function of human hepatocytes. Here, we analyzed the impact of the exposure of human hepatocytes to pyraclostrobin, a fungicide belonging to the class of strobilurins. Using electron paramagnetic resonance (EPR), we observed a decrease in oxygen consumption rate (OCR) and an increase in mitochondrial superoxide levels after 24 h exposure to 0.5 µM concentration. As a consequence, the content in ATP amount in the cells was reduced, the ratio reduced/oxidized glutathione was decreased, and a decrease in cell viability was observed using three different assays (PrestoBlue, crystal violet, and annexin V assays). In addition, as SDHIs and strobilurins are commonly associated in commercial preparations, we evaluated a potential “cocktail” toxic effect. We selected low concentrations of boscalid (0.5 µM) and pyraclostrobin (0.25 µM) that did not induce a mitochondrial dysfunction in liver cells when used separately. In sharp contrast, when both compounds were used in combination at the same concentration, we observed a decrease in OCR, an increase in mitochondrial superoxide production, a decrease in the ratio reduced/oxidized glutathione, and a decrease in cell viability in three different assays.

The quantum cascade laser has evolved to be a compact, powerful source of coherent mid-infrared light; however, its fast gain dynamics strongly restricts the formation of ultrashort pulses. As such, the shortest pulses reported so far were limited to a few picoseconds with some hundreds of milliwatts of peak power, strongly narrowing their applicability for time-resolved and nonlinear experiments. Here we demonstrate an approach capable of producing near-transform-limited subpicosecond pulses with several watts of peak power. Starting from a frequency-modulated phase-locked state, ultrashort high-peak-power pulses are generated via spectral filtering, gain modulation-induced spectral broadening and external pulse compression. We assess their temporal nature by means of a novel asynchronous sampling method, coherent beat note interferometry and interferometric autocorrelation. These results open new pathways for nonlinear physics in the mid-infrared.Near-transform-limited 630 fs pulses with 4.5 W of peak power are generated by compensating the dispersion of a quantum cascade laser emitting around 8 μm. Their temporal nature is assessed by a new method called asynchronous upconversion sampling.

Butylate hydroxyanisole (BHA) is a synthetic phenol that is widely utilized as a preservative by the food and cosmetic industries. The antioxidant properties of BHA are also frequently used by scientists to claim the implication of reactive oxygen species (ROS) in various cellular processes, including cell death. We report on the surprising finding that BHA functions as a direct inhibitor of RIPK1, a major signaling hub downstream of several immune receptors. Our in silico analysis predicts binding of 3-BHA, but not 2-BHA, to RIPK1 in an inactive DLG-out/Glu-out conformation, similar to the binding of the type III inhibitor Nec-1s to RIPK1. This predicted superior inhibitory capacity of 3-BHA over 2-BHA was confirmed in cells and using in vitro kinase assays. We demonstrate that the reported protective effect of BHA against tumor necrosis factor (TNF)-induced necroptotic death does not originate from ROS scavenging but instead from direct RIPK1 enzymatic inhibition, a finding that most probably extends to other reported effects of BHA. Accordingly, we show that BHA not only protects cells against RIPK1-mediated necroptosis but also against RIPK1 kinase-dependent apoptosis. We found that BHA treatment completely inhibits basal and induced RIPK1 enzymatic activity in cells, monitored at the level of TNFR1 complex I under apoptotic conditions or in the cytosol under necroptosis. Finally, we show that oral administration of BHA protects mice from RIPK1 kinase-dependent lethality caused by TNF injection, a model of systemic inflammatory response syndrome. In conclusion, our results demonstrate that BHA can no longer be used as a strict antioxidant and that new functions of RIPK1 may emerge from previously reported effects of BHA.

In December 2022, highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus emerged in Chile. We detected H5N1 virus in 93 samples and obtained 9 whole-genome sequences of strains from wild birds. Phylogenetic analysis suggests multiple viral introductions into South America. Continued surveillance is needed to assess risks to humans and domestic poultry.

Vector-boson scattering processes are of great importance for the current run-II and future runs of the Large Hadron Collider. The presence of triple and quartic gauge couplings in the process gives access to the gauge sector of the Standard Model (SM) and possible new-physics contributions there. To test any new-physics hypothesis, sound knowledge of the SM contributions is necessary, with a precision which at least matches the experimental uncertainties of existing and forthcoming measurements. In this article we present a detailed study of the vector-boson scattering process with two positively-charged leptons and missing transverse momentum in the final state. In particular, we first carry out a systematic comparison of the various approximations that are usually performed for this kind of process against the complete calculation, at LO and NLO QCD accuracy. Such a study is performed both in the usual fiducial region used by experimental collaborations and in a more inclusive phase space, where the differences among the various approximations lead to more sizeable effects. Afterwards, we turn to predictions matched to parton showers, at LO and NLO: we show that on the one hand, the inclusion of NLO QCD corrections leads to more stable predictions, but on the other hand the details of the matching and of the parton-shower programs cause differences which are considerably larger than those observed at fixed order, even in the experimental fiducial region. We conclude with recommendations for experimental studies of vector-boson scattering processes.