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In this work, we demonstrate that in a regime of strong modulation, by generating pulses of the length of the order of a few cavity lifetimes (hundreds of ps), a broadband quantum cascade laser can be driven to lase on a bandwidth (250 cm−1) limited by the gain. In addition, the amplitude noise of the radiation was shown to be limited by the detector. A laser linewidth study has been performed under different operating conditions, finding values spanning from 20 to 800 MHz, indicating a trade-off between emission bandwidth, amplitude stability, and coherence. The pulsed intensity of the output arises from the gain switching dynamics of the laser, while the self-seeded nature of the emission is responsible for the low amplitude noise and the relatively narrow linewidth of the individual spectral lines of the multimode emission.

The authors examined task-based (i.e., executive function), surveyed (i.e., effortful control), and physiological (i.e., resting cardiac respiratory sinus arrhythmia [RSA]) measures of child and maternal regulation as distinct moderators of longitudinal bidirectional links between child externalizing (EXT) behaviors and harsh parenting (HP) from 6 to 9 years. The sample size was 299 (50.9% female; 1% Asian, 4% multiple races; 14% Black; 78% White), and participants were recruited in the United States (a rural college town in Virginia and a midsized city in North Carolina). Higher child EXT at 6 years predicted higher HP at 7-8 years, which predicted higher EXT at 9 years. Also, this path was moderated by 6-year child effortful control, 6-year resting RSA, and 9-year executive function. In contrast, there was no moderating effect of any measure of maternal regulation. Findings suggest it is important to consider child self-regulation when examining bidirectionality in parent and child effects for HP and child EXT.

Oxalic precipitation is usually used in nuclear industry to process radioactive wastes and recover actinides from a multi-component solution. To facilitate the development of experimental methods and data acquisitions, actinides are often simulated using lanthanides, thereby gaining experience in harmless conditions. Precipitation reactions being highly sensitive to many operation parameters, modelling appear to be a very effective tool to predict the evolutions of the system under various operating conditions, especially in nuclear environment in which experiments are limited. The aim of this article is to describe the modelling approach of neodymium oxalate precipitation in a continuous MSMPR (Mixed Suspension Mixed Product Removal). Primary nucleation, crystal growth and agglomeration are taken into account in the model. Thermodynamic effects are modelled through activity coefficients which are calculated using the Bromley model. For the nucleation study, experimental runs have been performed in a specific device that allows a micromixing time less than a millisecond. The homogeneous nucleation rate follows the Volmer-Weber equation. The crystal growth rate is first order with respect to the supersaturation and controlled by the surface integration into the crystal lattice according to a screw dislocation mechanism. The agglomeration kernel has been found to be independent of the crystal size. The population balance of the particulate suspension is solved by the method of classes. The particle sizes predicted by the model are in good agreement with the experimental measurements.

[fr] L'étude de la chorologie et de l'écologie de la malacofaune terrestre d'Andalousie (sud de la Péninsule Ibérique), a permis de déterminer la présence, dans les cordillères Bétiques Orientales, d'un groupe de reliques climatiques propres à la région Euro-sibérienne. L'écologie et la distribution de deux de ces espèces (Vitrina pellucida O. F. Müller, 1774 et Cepaea nemoralis Linnaeux, 1758) sont exposées ici, et on montre que le principal facteur limitant est la sécheresse estivale caractéristique du climat méditerranéen. La réponse adaptative de dex deux espèces face à la rareté de l'eau durant l'été est déterminée par leurs écophysiologies différentes, Vitrina pellucida (eurytherme) utilise aussi bien les écosystèmes des terres basses là où la disponibilité en eau est constante tout au long de l'année (zones humides), que les écosystèmes secs de haute montagne, profitant de leur climat froid. En revanche, Cepaea nemoralis (sténotherme) occupe seulement les habitats de sols humides, de couverture végétale dense et constante, a une altitude inférieure à 1500 m. L'absence de ce type de végétation et les conditions climatiques dures de la haute montagne méditerranéenne empêchent sa présence à une plus haute altitude, contrairement a ce qui se passe dans la haute montagne euro-sibérienne. [es] A partir del estudio de la corología y ecología de la malacofauna terrestre de Andalucía (sur de la Península Ibérica) se determina la presencia en las cordilleras Bélicas Orientales de dos relictos climáticos propios de la región Eurosiberiana: Vitrina pellucida (O. F. Millier, 1774) y Cepaea nemoralis (Linnaeus, 1758). Se expone su ecología y distribución y se muestra que el principal factor que las limita es la sequía estival característica del clima mediterráneo. Sus respuestas adaptativas ante la escasez de agua del verano están definidas por diferencias ecofisiológicas. Vitrina pellucida (euriterma) hace uso tanto de los ecosistemas de tierras bajas en los que la disponibilidad de agua es constante a lo largo del año (zonas húmedas) como de los secos de alta montaña, gracias al clima frío. Cepaea nemoralis (estenoterma) ocupa sólo hábitats de suelos húmedos y cobertura vegetal densa y constante situados por debajo de los 1500 m. La ausencia de este tipo de vegetación y la dureza del clima de la alta montaña mediterránea impiden su presencia a mayor altitud, al contrario de lo que ocurre en las montarías eurosiberianas.

Oxalic precipitation is used in the nuclear industry. To facilitate the development of experimental methods and data acquisitions, actinides are often simulated using lanthanides, thereby gaining experience in harmless conditions. Precipitation reactions being highly sensitive to many operation parameters, modelling appear to be a very effective tool to predict the evolutions of the system subjected to various operating conditions, especially in nuclear environment in which experiments are limited. The aim of this article is to describe the modelling approach and its application to the neodymium oxalate precipitation in a continuous MSMPR (Mixed Suspension Mixed Product Removal). The model takes into account the kinetic laws of primary nucleation, crystal growth and agglomeration. Thermodynamic effects are taken into account through activity coefficients which are calculated using the Bromley model. For the nucleation study, experimental runs have been performed in a specific device that allows a micromixing time less than a millisecond. The homogeneous nucleation rate follows the Volmer-Weber equation. The crystal growth rate is first order with respect to the supersaturation and controlled by the surface integration into the crystal lattice according to a screw dislocation mechanism. The agglomeration kernel has been found to be independent of the crystal size. The particle sizes predicted for two different mean shear rates are in good agreement with the experimental measurements.

Abstract Coastal upwelling regions are among the most productive marine ecosystems but may be threatened by amplified ocean acidification. Increased acidification is hypothesized to reduce iron bioavailability for phytoplankton thereby expanding iron limitation and impacting primary production. Here we show from community to molecular levels that phytoplankton in an upwelling region respond to short-term acidification exposure with iron uptake pathways and strategies that reduce cellular iron demand. A combined physiological and multi-omics approach was applied to trace metal clean incubations that introduced 1200 ppm CO2 for up to four days. Although variable, molecular-level responses indicate a prioritization of iron uptake pathways that are less hindered by acidification and reductions in iron utilization. Growth, nutrient uptake, and community compositions remained largely unaffected suggesting that these mechanisms may confer short-term resistance to acidification; however, we speculate that cellular iron demand is only temporarily satisfied, and longer-term acidification exposure without increased iron inputs may result in increased iron stress.

Model output statistics (MOS) approaches relying on machine learning algorithms were applied to downscale regional air quality forecasts produced by CAMS (Copernicus Atmosphere Monitoring Service) at hundreds of monitoring sites across Europe. Besides the CAMS forecast, the predictors in the MOS typically include meteorological variables but also ancillary data. We explored first a “local” approach where specific models are trained at each site. An alternative “global” approach where a single model is trained with data from the whole geographical domain was also investigated. In both cases, local predictors are used for a given station in predictive mode. Because of its global nature, the latter approach can capture a variety of meteorological situations within a very short training period and is thereby more suited to cope with operational constraints in relation to the training of the MOS (frequent upgrades of the modelling system, addition of new monitoring sites). Both approaches have been implemented using a variety of machine learning algorithms: random forest, gradient boosting, and standard and regularized multi-linear models. The quality of the MOS predictions is evaluated in this work for four key pollutants, namely particulate matter (PM10 and PM2.5), ozone (O3) and nitrogen dioxide (NO2), according to scores based on the predictive errors and on the detection of pollution peaks (exceedances of the regulatory thresholds). Both the local and the global approaches significantly improve the performances of the raw ensemble forecast. The most important result of this study is that the global approach competes with and can even outperform the local approach in some cases. This global approach gives the best RMSE scores when relying on a random forest model for the prediction of daily mean, daily max and hourly concentrations. By contrast, it is the gradient boosting model which is better suited for the detection of exceedances of the European Union regulated threshold values for O3 and PM10.

ABSTRACT Vitamin B1 (thiamin) is a vital nutrient for most cells in nature, including marine plankton. Early and recent experiments show that B1 degradation products instead of B1 can support the growth of marine bacterioplankton and phytoplankton. However, the use and occurrence of some degradation products remains uninvestigated, namely N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine (FAMP), which has been a focus of plant oxidative stress research. We investigated the relevance of FAMP in the ocean. Experiments and global ocean meta-omic data indicate that eukaryotic phytoplankton, including picoeukaryotes and harmful algal bloom species, use FAMP while bacterioplankton appear more likely to use deformylated FAMP, 4-amino-5-aminomethyl-2-methylpyrimidine. Measurements of FAMP in seawater and biomass revealed that it occurs at picomolar concentrations in the surface ocean, heterotrophic bacterial cultures produce FAMP in the dark—indicating non-photodegradation of B1 by cells, and B1-requiring (auxotrophic) picoeukaryotic phytoplankton produce intracellular FAMP. Our results require an expansion of thinking about vitamin degradation in the sea, but also the marine B1 cycle where it is now crucial to consider a new B1-related compound pool (FAMP), as well as generation (dark degradation—likely via oxidation), turnover (plankton uptake), and exchange of the compound within the networks of plankton. IMPORTANCE Results of this collaborative study newly show that a vitamin B1 degradation product, N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine (FAMP), can be used by diverse marine microbes (bacteria and phytoplankton) to meet their vitamin B1 demands instead of B1 and that FAMP occurs in the surface ocean. FAMP has not yet been accounted for in the ocean and its use likely enables cells to avoid B1 growth deficiency. Additionally, we show FAMP is formed in and out of cells without solar irradiance—a commonly considered route of vitamin degradation in the sea and nature. Altogether, the results expand thinking about oceanic vitamin degradation, but also the marine B1 cycle where it is now crucial to consider a new B1-related compound pool (FAMP), as well as its generation (dark degradation—likely via oxidation), turnover (plankton uptake), and exchange within networks of plankton.

Abstract Oxidative stress plays a role in many aspects of cellular metabolism, and as a result, antioxidants have the potential to impact cellular stoichiometry and biogeochemical cycles. We reviewed how antioxidant systems influence macronutrient and micronutrient stoichiometry in marine phytoplankton and identified that antioxidant systems have important implications for micronutrient stoichiometry. By leveraging diatom proteomic data, we empirically estimated the level of micronutrient quota variation that can be attributed to antioxidant systems. Fe‐containing antioxidant expression may contribute to 3.3–10 μmol : mol variation in Fe : C, and superoxide dismutases appear to be important contributors to variation in Mn, Ni, Zn, and Cu quotas in phytoplankton. Critical next steps for the study of phytoplankton antioxidant systems are to (1) distinguish between oxidative stress and redox‐based gene regulation and (2) determine how antioxidants influence variation or consistency in micronutrient quotas under various environmental conditions.

Receptor-Interacting serine/threonine-Protein Kinase 1 (RIPK1) emerged as an important driver of inflammation and, consequently, inflammatory pathologies. The enzymatic activity of RIPK1 is known to indirectly promote inflammation by triggering cell death, in the form of apoptosis, necroptosis and pyroptosis. Small molecule Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitors have therefore recently entered clinical trials for the treatment of a subset of inflammatory pathologies. We previously identified GSK2656157 (GSK’157), a supposedly specific inhibitor of protein kinase R (PKR)-like ER kinase (PERK), as a much more potent type II Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitor. We now performed further structural optimisation on the GSK’157 scaffold in order to develop a novel class of more selective Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitors. Based on a structure-activity relationship (SAR) reported in the literature, we anticipated that introducing a substituent on the para-position of the pyridinyl ring would decrease the interaction with PERK. Herein, we report a series of novel GSK’157 analogues with different para-substituents with increased selectivity for Receptor-Interacting serine/threonine-Protein Kinase 1. The optimisation led to UAMC-3861 as the best compound of this series in terms of activity and selectivity for Receptor-Interacting serine/threonine-Protein Kinase 1 over PERK. The most selective compounds were screened in vitro for their ability to inhibit RIPK1-dependent apoptosis and necroptosis. With this work, we successfully synthesised a novel series of potent and selective type II Receptor-Interacting serine/threonine-Protein Kinase 1 inhibitors based on the GSK’157 scaffold.

The Inhibitor of Kappa B Kinase (IKK) complex is a critical regulator of NF-κB activation. More recently, IKK has also been shown to repress RIPK1 dependent extrinsic cell death pathways by directly phosphorylating RIPK1 at serine 25. In T cells, IKK expression is essential for normal development in the thymus, by promoting survival of thymocytes independently of NF-κB activation. RIPK1 undergoes extensive phosphorylation following TNF stimulation in T cells, though which targets are required to repress RIPK1 has not been defined. Here, we show that TNF induced phosphorylation of RIPK1 at S25 is IKK dependent. We test the relevance of this phosphorylation event in T cells using mice with a RIPK1S25D phosphomimetic point mutation to endogenous RIPK1. We find that this mutation protects T cells from TNF induced cell death when IKK activity is inhibited in vitro, and can rescues development of IKK deficient thymocytes in vivo to a degree comparable with kinase dead RIPK1D138N. Together, these data show that phosphorylation of RIPK1S25 by IKK represents a key regulatory event promoting survival of T cells by IKK.

Delphinium montanum DC. 1815, is an endangered larkspur endemic to the Eastern Pyrenees. For biogeographic and conservation purpose, a hybrid assembly approach based on long- and short-read genomic data allowed us to successfully assemble whole plastid genome of Delphinium montanum. The complete plastome is 154,185 bp in length, consisting of a pair of inverted repeats (IRs) of 26,559 bp, a large single-copy (LSC) region and a small single-copy region (SSC) of 84,746 and 16,320 bp, respectively. It was found to contain 136 genes, including 84 protein-coding genes, 44 trRNA genes and 8 rRNA genes. The overall GC content of the plastid genome is 38.3%. Phylogenetic inference supports the polyphyly of the Delphinium genus.

The simultaneous limitation of productivity by two or more nutrients, commonly referred to as nutrient co-limitation, affects microbial communities throughout the marine environment and is of profound importance because of its impacts on various biogeochemical cycles. Multiple types of co-limitation have been described, enabling distinctions based on the hypothesized mechanisms of co-limitation at a biochemical level. These definitions usually pertain to individuals and do not explicitly, or even implicitly, consider complex ecological dynamics found within a microbial community. However, limiting and co-limiting nutrients can be produced in situ by a subset of microbial community members, suggesting that interactions within communities can underpin co-limitation. To address this, we propose a new category of nutrient co-limitation, community interaction co-limitation (CIC). During CIC, one part of the community is limited by one nutrient, which results in the insufficient production or transformation of a biologically produced nutrient that is required by another part of the community, often primary producers. Using cobalamin (vitamin B12) and nitrogen fixation as our models, we outline three different ways CIC can arise based on current literature and discuss CIC’s role in biogeochemical cycles. Accounting for the inherent and complex roles microbial community interactions play in generating this type of co-limitation requires an expanded toolset – beyond the traditional approaches used to identify and study other types of co-limitation. We propose incorporating processes and theories well-known in microbial ecology and evolution to provide meaningful insight into the controls of community-based feedback loops and mechanisms that give rise to CIC in the environment. Finally, we highlight the data gaps that limit our understanding of CIC mechanisms and suggest methods to overcome these and further identify causes and consequences of CIC. By providing this framework for understanding and identifying CIC, we enable systematic examination of the impacts this co-limitation can have on current and future marine biogeochemical processes.

Abstract Iron and temperature are important drivers controlling phytoplankton growth in the Southern Ocean (SO). Most studies examining phytoplankton responses to these variables consider them independently, testing responses to changing temperature under constant iron and vice versa. Consequently, we lack a phenomenological and mechanistic understanding of how concurrent changes in these variables influence primary productivity. Here, we used a matrix of three temperatures and eight iron levels to examine changes in growth rate, photophysiology, and size in Fragilariopsis cylindrus. Temperature and iron interactively influenced growth; warming decreased iron demand, allowing cells to maintain half‐maximal growth rate at lower iron concentrations. We also observed possible mechanisms underpinning this phenomenon: warming increased light‐harvesting cross section and reduced cell size, thereby increasing light energy availability and iron uptake efficiency. These results suggest that interactive iron‐warming effects could lead to larger increases in SO phytoplankton growth than those currently predicted by marine ecosystem models.

Abstract Background Amyotrophic lateral sclerosis (ALS) is a multifactorial fatal motoneuron disease without a cure. Ten percent of ALS cases can be pointed to a clear genetic cause, while the remaining 90% is classified as sporadic. Our study was aimed to uncover new connections within the ALS network through a bioinformatic approach, by which we identified C13orf18, recently named Pacer, as a new component of the autophagic machinery and potentially involved in ALS pathogenesis. Methods Initially, we identified Pacer using a network-based bioinformatic analysis. Expression of Pacer was then investigated in vivo using spinal cord tissue from two ALS mouse models (SOD1G93A and TDP43A315T) and sporadic ALS patients. Mechanistic studies were performed in cell culture using the mouse motoneuron cell line NSC34. Loss of function of Pacer was achieved by knockdown using short-hairpin constructs. The effect of Pacer repression was investigated in the context of autophagy, SOD1 aggregation, and neuronal death. Results Using an unbiased network-based approach, we integrated all available ALS data to identify new functional interactions involved in ALS pathogenesis. We found that Pacer associates to an ALS-specific subnetwork composed of components of the autophagy pathway, one of the main cellular processes affected in the disease. Interestingly, we found that Pacer levels are significantly reduced in spinal cord tissue from sporadic ALS patients and in tissues from two ALS mouse models. In vitro, Pacer deficiency lead to impaired autophagy and accumulation of ALS-associated protein aggregates, which correlated with the induction of cell death. Conclusions This study, therefore, identifies Pacer as a new regulator of proteostasis associated with ALS pathology.

Ophrys aveyronensis is an orchid with disjunct geographic distribution. For biogeographic and conservation purpose, we sequenced its complete plastome using Illumina data. The complete plastome is 146,816 bp in length, consisting of a pair of inverted repeats (IRs) of 25,006 bp, a large single-copy (LSC) region and a small single-copy region (SSC) of 80,495 and 16,309 bp, respectively. It was found to contain 133 genes, including 86 protein-coding genes, up to 39 trRNA genes and 8 rRNA genes. The overall GC content of the plastid genome is 36.9%. Phylogenetic inference confirms that O. aveyronensis is very close to O. sphegodes.

Understanding the mechanisms responsible for phenotypic diversification within and among species ultimately rests with linking naturally occurring mutations to functionally and ecologically significant traits. Colour polymorphisms are of great interest in this context because discrete colour patterns within a population are often controlled by just a few genes in a common environment. We investigated how and why phenotypic diversity arose and persists in the Zosterops borbonicus white-eye of Reunion (Mascarene archipelago), a colour polymorphic songbird in which all highland populations contain individuals belonging to either a brown or a grey plumage morph. Using extensive phenotypic and genomic data, we demonstrate that this melanin-based colour polymorphism is controlled by a single locus on chromosome 1 with two large-effect alleles, which was not previously described as affecting hair or feather colour. Differences between colour morphs appear to rely upon complex cis-regulatory variation that either prevents the synthesis of pheomelanin in grey feathers, or increases its production in brown ones. We used coalescent analyses to show that, from a ‘brown’ ancestral population, the dominant ‘grey’ allele spread quickly once it arose from a new mutation. Since colour morphs are always found in mixture, this implies that the selected allele does not go to fixation, but instead reaches an intermediate frequency, as would be expected under balancing selection.