We present a one-line closed-form expression for the three-parameter breather of the nonlinear Schrödinger equation. This provides an analytic proof of the time period doubling observed in ...experiments. The experimental check that some pulses generated in optical fibers are indeed such generalized breathers will be drastically simplified.
We measure and analyze the chirality of Dzyaloshinskii-Moriya-interaction (DMI) stabilized spin textures in multilayers of Ta|Co_{20}F_{60}B_{20}|MgO. The effective DMI is measured experimentally ...using domain wall motion measurements, both in the presence (using spin-orbit torques) and absence of driving currents (using magnetic fields). We observe that the current-induced domain wall motion yields a change in effective DMI magnitude and opposite domain wall chirality when compared to field-induced domain wall motion (without current). We explore this effect, which we refer to as current-induced DMI, by providing possible explanations for its emergence, and explore the possibility of its manifestation in the framework of recent theoretical predictions of DMI modifications due to spin currents.
Medulloblastoma (MB) is the most common malignant brain tumour in children. High-risk MB patients harbouring MYC amplification or overexpression exhibit a very poor prognosis. Aberrant activation of ...MYC markedly reprograms cell metabolism to sustain tumorigenesis, yet how metabolism is dysregulated in MYC-driven MB is not well understood. Growing evidence unveiled the potential of BET-bromodomain inhibitors (BETis) as next generation agents for treating MYC-driven MB, but whether and how BETis may affect tumour cell metabolism to exert their anticancer activities remains unknown. In this study, we explore the metabolic features characterising MYC-driven MB and examine how these are altered by BET-bromodomain inhibition. To this end, we employed an NMR-based metabolomics approach applied to the MYC-driven MB D283 and D458 cell lines before and after the treatment with the BETi OTX-015. We found that OTX-015 triggers a metabolic shift in both cell lines resulting in increased levels of myo-inositol, glycerophosphocholine, UDP-N-acetylglucosamine, glycine, serine, pantothenate and phosphocholine. Moreover, we show that OTX-015 alters ascorbate and aldarate metabolism, inositol phosphate metabolism, phosphatidylinositol signalling system, glycerophospholipid metabolism, ether lipid metabolism, aminoacyl-tRNA biosynthesis, and glycine, serine and threonine metabolism pathways in both cell lines. These insights provide a metabolic characterisation of MYC-driven childhood MB cell lines, which could pave the way for the discovery of novel druggable pathways. Importantly, these findings will also contribute to understand the downstream effects of BETis on MYC-driven MB, potentially aiding the development of new therapeutic strategies to combat medulloblastoma.
Cell migration is crucial for cancer dissemination. We find that AMP-activated protein kinase (AMPK) controls cell migration by acting as an adhesion sensing molecular hub. In 3-dimensional matrices, ...fast-migrating amoeboid cancer cells exert low adhesion/low traction linked to low ATP/AMP, leading to AMPK activation. In turn, AMPK plays a dual role controlling mitochondrial dynamics and cytoskeletal remodelling. High AMPK activity in low adhering migratory cells, induces mitochondrial fission, resulting in lower oxidative phosphorylation and lower mitochondrial ATP. Concurrently, AMPK inactivates Myosin Phosphatase, increasing Myosin II-dependent amoeboid migration. Reducing adhesion or mitochondrial fusion or activating AMPK induces efficient rounded-amoeboid migration. AMPK inhibition suppresses metastatic potential of amoeboid cancer cells in vivo, while a mitochondrial/AMPK-driven switch is observed in regions of human tumours where amoeboid cells are disseminating. We unveil how mitochondrial dynamics control cell migration and suggest that AMPK is a mechano-metabolic sensor linking energetics and the cytoskeleton.
Intermittent (or bolus) feeding regimens in critically ill patients have been of increasing interest to clinicians and scientists. Changes in amino acid, fat and carbohydrate metabolites over time ...might yet deliver other benefits (e.g. modulation of the circadian rhythm and sleep, and impacts on ghrelin secretion, insulin resistance and autophagy). We set out to characterise these changes in metabolite concentration. The Intermittent versus Continuous Feeding in Critically Ill paitents study (NCT02358512) was an eight-centre single-blinded randomised controlled trial. Patients were randomised to received a continuous (control arm) or intermittent (6x/day, intervention arm) enteral feeding regimen. Blood samples were taken on trial days 1, 7 and 10 immediately before and 30 min after intermittent feeds, and at equivalent timepoints in the control arm. A pre-planned targeted metabolomic analysis was performend using Nuclear Resonance Spectroscopy. Five hundred and ninety four samples were analysed from 75 patients. A total of 24 amino acid-, 19 lipid based-, and 44 small molecule metabolite features. Across the main two axes of variation (40-60% and 6-8% of variance), no broad patterns distinguished between intermittent or continuous feeding arms, across intra-day sampling times or over the 10 days from initial ICU admission. Logfold decreases in abundance were seen in metabolites related to amino acids (Glutamine - 0.682; Alanine - 0.594), ketone body metabolism (Acetone - 0.64; 3-Hydroxybutyric Acid - 0.632; Acetonacetic Acid - 0.586), fatty acid (carnitine - 0.509) and carbohydrate metabolism ( Maltose - 0.510; Citric Acid - 0.485). 2-3 Butanediol, a by-product of sugar-fermenting microbial metabolism also decreased (- 0.489). No correlation was seen with change in quadriceps muscle mass for any of the 20 metabolites varying with time (all p > 0.05). Increasing severity of organ failure was related to increasing ketone body metabolism (3 Hydroxybutyric Acid-1 and - 3; p = 0.056 and p = 0.014), carnitine deficiency (p = 0.002) and alanine abundancy (p - 0.005). A 6-times a day intermittent feeding regimen did not alter metabolite patterns across time compared to continuous feeding in critically ill patients, either within a 24 h period or across 10 days of intervention. Future research on intermittent feeding regimens should focus on clinical process benefits, or extended gut rest and fasting.
Polymers constitute the most employed reinforced matrices to achieve composite materials. Carbon and glass fibers are the reinforcements that are mainly utilized to improve specific properties for ...both thermoplastics and thermosets creating a new class of materials, which has been applied in several industrial fields. Various products made of fiber reinforced polymers are available on the market and at their own end-of-life, they must be reclaimed and remanufactured, properly, in an ideal recycling circular economy. The aim of this review is to point out the progress on fiber reclaiming from these materials, providing an overview on the most employed strategies and highlighting their main technological limits. Specifically, first, mechanical, thermal and chemical reclaiming processes have been contextualized introducing their peculiarities. Subsequently, the attention has been focalized on the new research trends proposed in the last years showing the direction, where the research is moving to. The processes have been also classified in terms of tensile strength of the reclaimed fibers and in terms of the energy required to be performed. Finally, design for reclaiming and remanufacturing treatments have been also considered pointing out the different approaches that can be pursued as valuable solutions to strengthen the recycling capabilities encouraging as much as possible the recovering of the polymeric matrix composites.
The use of environmentally friendly refrigerants and the improvement of the system performance are two main topics in the research on heat pump technology. Given the recent limitations imposed on the ...usage of high global warming potential refrigerants, there is a growing demand in the market for the adoption of natural refrigerants, like CO2. Nevertheless, CO2 heat pumps operate under transcritical conditions, which can adversely affect its efficiency. Therefore, incorporating a solar heat source into a CO2 heat pump can offer a solution to mitigate low system performance issues. In the present study, a photovoltaic module integrated with the evaporator of a CO2 heat pump is experimentally studied. The PV-T evaporator exploits solar radiation to both generate electricity in the PV cells and ensure the evaporation of CO2 in the collector’s tubes. Simultaneously, the PV conversion efficiency is improved by the cooling effect of the evaporation. The present evaporator works in dry expansion mode, thus the refrigerant flow after the expansion device is sent to the solar collectors, where it evaporates before returning to the compressor. When using a PV-T evaporator, it is necessary to prevent superheating in the evaporator to keep a uniform and efficient cooling of the PV cells. The current heat pump design prevents the occurrence of superheated vapor at the PV-T evaporator’s outlet. Beside the experimental activity a dynamic numerical model of the system has been developed and validated.
Abstract
The Drosophila behaviour/human splicing (DBHS) proteins are a family of RNA/DNA binding cofactors liable for a range of cellular processes. DBHS proteins include the non-POU ...domain-containing octamer-binding protein (NONO) and paraspeckle protein component 1 (PSPC1), proteins capable of forming combinatorial dimers. Here, we describe the crystal structures of the human NONO and PSPC1 homodimers, representing uncharacterized DBHS dimerization states. The structures reveal a set of conserved contacts and structural plasticity within the dimerization interface that provide a rationale for dimer selectivity between DBHS paralogues. In addition, solution X-ray scattering and accompanying biochemical experiments describe a mechanism of cooperative RNA recognition by the NONO homodimer. Nucleic acid binding is reliant on RRM1, and appears to be affected by the orientation of RRM1, influenced by a newly identified ‘β-clasp’ structure. Our structures shed light on the molecular determinants for DBHS homo- and heterodimerization and provide a basis for understanding how DBHS proteins cooperatively recognize a broad spectrum of RNA targets.
Graphical Abstract
Graphical Abstract
Binding of nucleic acids by DBHS protein dimers involves RRM1 and RRM2 of each monomer. Although the two identical binding sites in a homodimer are not linked, independent rearrangement of RRM1 domains to accommodate nucleic acid requires the unfastening of the N-terminal β-clasp.
Increasing evidence suggests that posttranscriptional regulation is a key player in the transition between mature pollen and the progamic phase (from pollination to fertilization). Nonetheless, the ...actors in this messenger RNA (mRNA)-based gene expression reprogramming are poorly understood. We demonstrate that the evolutionarily conserved RNA-binding protein LARP6C is necessary for the transition from dry pollen to pollen tubes and the guided growth of pollen tubes towards the ovule in Arabidopsis thaliana. In dry pollen, LARP6C binds to transcripts encoding proteins that function in lipid synthesis and homeostasis, vesicular trafficking, and polarized cell growth. LARP6C also forms cytoplasmic granules that contain the poly(A) binding protein and possibly represent storage sites for translationally silent mRNAs. In pollen tubes, the loss of LARP6C negatively affects the quantities and distribution of storage lipids, as well as vesicular trafficking. In Nicotiana benthamiana leaf cells and in planta, analysis of reporter mRNAs designed from the LARP6C target MGD2 provided evidence that LARP6C can shift from a repressor to an activator of translation when the pollen grain enters the progamic phase. We propose that LARP6C orchestrates the timely posttranscriptional regulation of a subset of mRNAs in pollen during the transition from the quiescent to active state and along the progamic phase to promote male fertilization in plants.
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