ALBERT

Beschreibung: This study was to investigate the effects of UPro as a new nutritive fortifier on high-quality egg production from the perspective of egg properties, intestinal histomorphology, and oviduct function of laying hens. Four hundred thirty-two Hy-Line Brown laying hens aged 56 weeks were allocated to four groups. Layers were given a basal diet or supplemented with different levels of small peptides (0.2, 0.4, and 0.8%) to replace soybean meal. After 1-week adaptation period, the feeding trial was conducted for 12 weeks. The results showed that UPro addition significantly decreased (P 〈 0.05) the hardness, stickiness, and chewiness of albumen of layers on weeks 12. A linear elevation (P 〈 0.05) in the albumen height, Haugh unit (HU), and crude protein content of albumen of layers were noted on week 12 along with dietary UPro addition increasing, and the villus height (VH) and villus height-to-crypt depth radio (VCR) of jejunum also linearly increasing (P 〈 0.05). In addition, there were linear elevations (P 〈 0.05) in the relative mRNA expression of Sec23 homolog A (Sec23A) and protein-O-mannosyltransferase1 (POMT1) in layers as dietary UPro addition increased. In conclusion, dietary UPro addition could improve intestinal health, increase the absorption of nutrients, and improve egg quality of laying hens. The possible mechanism underlying UPro improving the quality and processing characteristics of albumen is up-regulating Sec23A and POMT1 expression of magnum. These findings will promote the application of UPro as a new nutritional additive in the production of high-quality eggs.

Beschreibung: Milk polar lipids provide choline, ethanolamine, and polyunsaturated fatty acids, which are needed for the growth and plasticity of the tissues in a suckling child. They may also inhibit cholesterol absorption by interacting with cholesterol during micelle formation. They may also have beneficial luminal, mucosal, and metabolic effects in both the neonate and the adult. The milk fat globule membrane contains large proportions of sphingomyelin (SM), phosphatidylcholine (PC), and phosphatidylethanolamine (PE), and some phosphatidylserine (PS), phosphatidylinositol (PI), and glycosphingolipids. Large-scale technical procedures are available for the enrichment of milk fat globule membrane (MFGM) in milk replacement formulations and food additives. Pancreatic phospholipase A2 (PLA2) and mucosal phospholipase B digest glycero-phospholipids in the adult. In the neonate, where these enzymes may be poorly expressed, pancreatic lipase-related protein 2 probably has a more important role. Mucosal alkaline SM-ase and ceramidase catalyze the digestion of SM in both the neonate and the adult. In the mucosa, the sphingosine is converted into sphingosine-1-phosphate, which is both an intermediate in the conversion to palmitic acid and a signaling molecule. This reaction sequence also generates ethanolamine. Here, we summarize the pathways by which digestion and absorption may be linked to the biological effects of milk polar lipids. In addition to the inhibition of cholesterol absorption and the generation of lipid signals in the gut, the utilization of absorbed choline and ethanolamine for mucosal and hepatic phospholipid synthesis and the acylation of absorbed lyso-PC with polyunsaturated fatty acids to chylomicron and mucosal phospholipids are important.

Beschreibung: Identification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understand the biology of alcohol use disorder (AUD) and drinks per week (DPW). Multi-omics integration approaches have shown potential for fine mapping complex loci to obtain biological insights to disease mechanisms. In this study, we use multi-omics approaches, to fine-map AUD and DPW associations at single SNP resolution to demonstrate that rs56030824 on chromosome 11 significantly reduces SPI1 mRNA expression in myeloid cells and lowers risk for AUD and DPW. Our analysis also identifies MAPT as a candidate causal gene specifically associated with DPW. Genes prioritized in this study show overlap with causal genes associated with neurodegenerative disorders. Multi-omics integration analyses highlight, genetic similarities and differences between alcohol intake and disordered drinking, suggesting molecular heterogeneity that might inform future targeted functional and cross-species studies.

Beschreibung: Asymmetric inheritance of organelles and compounds between daughter cells is considered a hallmark for differentiation and rejuvenation in stem-like and cancer cells, as much as a mechanism for enhancing resistance in bacteria populations. In non-differentiating homogeneous cancer cells, asymmetric division is still poorly investigated. Here, we present a method based on the binomial partitioning process that allows the measurement of asymmetric organelle partitioning with multiple live cell markers without genetically mutating the cells. We demonstrate our method by measuring simultaneously the partitioning of three cellular elements, i.e., cytoplasm, membrane, and mitochondria in human Jurkat T-cells. We found that although cell cytoplasm is partitioned symmetrically, mitochondria and membrane lipids are asymmetrically partitioned between daughter cells. Moreover, we observe that mitochondria and membrane lipids present a stable positive correlation with cytoplasm, incompatibly with a binomial partition mechanism produced by two independent partitioning processes. Our experimental apparatus, combined with our theoretical framework, could be generalized to different cell kinds, providing a tool for understanding partitioning-driven biological processes.

Beschreibung: In this study, we demonstrated generation and transmission of 114 Gbaud and 126 Gbaud faster-than-Nyquist (FTN) discrete Fourier transform-spread (DFT-spread) quadrature phase shift keying orthogonal frequency division multiplexing (QPSK-OFDM) with 88-Gsa/s sampling rate digital-to-analog converters (DACs) experimentally. It is the first time to realize 400G FTN DFT-spread QPSK-OFDM signal per optical carrier for metro and regional applications, which will be a solution for network operators to address the issue of increasing bandwidth derived from the rapid popularization of mobile Internet and the wide application of IoT (Internet of Things technology). Delay-and-add filter (DAF) is adopted to realize frequency shaping at the transmitter to keep higher portions of energy of signal at low frequencies, which makes the OFDM much more robust to strong filtering effect. After pre-equalization, bit error rate (BER) performance of 114 GBaud and 126 GBaud FTN DFT-spread QPSK-OFDM has been significantly improved, and maximum-likelihood sequence estimation (MLSE) shows a better effect than binary decoding in the aspect of against the inter symbol interference (ISI) introduced by spectrum compression. The effective bit rate of dual polarization 126 Gbaud FTN DFT-spread QPSK-OFDM which is generated with 88 GSa/s sampling rate is 410.08 Gb/s, to the exclusion of all overhead including TSs, cyclic prefix (CP), and 20% forward error correction (FEC) coding. We successfully transmit 8 × 400 Gbit/s FTN DFT-spread QPSK-OFDM signal generated from 88 Gsa/s sampling rate DAC over 420 km single mode fiber (SMF) with the BER under 2.4 × 10−2.

Beschreibung: The impact of heat-absorbing viscoelastic nanofluidic flow along with a convectively heated porous Riga plate with Cattaneo-Christov double flux was analytically investigated. The Buongiorno model nanofluid was implemented with the diversity of Brownian motion and thermophoresis. Making use of the transformations; the PDE systems are altered into an ODE system. We use the homotopy analysis method to solve these systems analytically. The reaction of the apposite parameters on fluid velocity, fluid temperature, nanoparticle volume fraction skin friction coefficients (SFC), local Nusselt number and local Sherwood number are shown with vividly explicit details. It is found that the fluid velocities reflect a declining nature for the development of viscoelastic and porosity parameters. The liquid heat becomes rich when escalating the radiation parameter. In addition, the nanoparticle volume fraction displays a declining nature towards the higher amount of thermophoresis parameter, whereas the inverse trend was obtained for the Brownian motion parameter. We also found that the fluid temperature is increased in viscoelastic nanofluid compared to the viscous nanofluid. When we change the fluid nature from heat absorption to heat generation, the liquid temperature also rises. In addition, the fluid heat is suppressed when we change the flow medium from a stationary plate to a Riga plate for heat absorption/generation cases.

Beschreibung: Graphene-based photodetectors have attracted significant attention for high-speed optical communication due to their large bandwidth, compact footprint, and compatibility with silicon-based photonics platform. Large-bandwidth silicon-based optical coherent receivers are crucial elements for large-capacity optical communication networks with advanced modulation formats. Here, we propose and experimentally demonstrate an integrated optical coherent receiver based on a 90-degree optical hybrid and graphene-on-plasmonic slot waveguide photodetectors, featuring a compact footprint and a large bandwidth far exceeding 67 GHz. Combined with the balanced detection, 90 Gbit/s binary phase-shift keying signal is received with a promoted signal-to-noise ratio. Moreover, receptions of 200 Gbit/s quadrature phase-shift keying and 240 Gbit/s 16 quadrature amplitude modulation signals on a single-polarization carrier are realized with a low additional power consumption below 14 fJ/bit. This graphene-based optical coherent receiver will promise potential applications in 400-Gigabit Ethernet and 800-Gigabit Ethernet technology, paving another route for future high-speed coherent optical communication networks.

Beschreibung: An overarching challenge of the electrochemical carbon dioxide reduction reaction (eCO2RR) is finding an earth-abundant, highly active catalyst that selectively produces hydrocarbons at relatively low overpotentials. Here, we report the eCO2RR performance of two-dimensional transition metal carbide class of materials. Our results indicate a maximum methane (CH4) current density of −421.63 mA/cm2 and a CH4 faradic efficiency of 82.7% ± 2% for di-tungsten carbide (W2C) nanoflakes in a hybrid electrolyte of 3 M potassium hydroxide and 2 M choline-chloride. Powered by a triple junction photovoltaic cell, we demonstrate a flow electrolyzer that uses humidified CO2 to produce CH4 in a 700-h process under one sun illumination with a CO2RR energy efficiency of about 62.3% and a solar-to-fuel efficiency of 20.7%. Density functional theory calculations reveal that dissociation of water, chemisorption of CO2 and cleavage of the C-O bond—the most energy consuming elementary steps in other catalysts such as copper—become nearly spontaneous at the W2C surface. This results in instantaneous formation of adsorbed CO—an important reaction intermediate—and an unlimited source of protons near the tungsten surface sites that are the main reasons for the observed superior activity, selectivity, and small potential.

Beschreibung: The contents of numerous membrane lipids change upon ageing. However, it is unknown whether and how any of these changes are causally linked to lifespan regulation. Acyl chains contribute to the functional specificity of membrane lipids. In this study, working with C. elegans, we identified an acyl chain-specific sphingolipid, C22 glucosylceramide, as a longevity metabolite. Germline deficiency, a conserved lifespan-extending paradigm, induces somatic expression of the fatty acid elongase ELO-3, and behenic acid (22:0) generated by ELO-3 is incorporated into glucosylceramide for lifespan regulation. Mechanistically, C22 glucosylceramide is required for the membrane localization of clathrin, a protein that regulates membrane budding. The reduction in C22 glucosylceramide impairs the clathrin-dependent autophagic lysosome reformation, which subsequently leads to TOR activation and longevity suppression. These findings reveal a mechanistic link between membrane lipids and ageing and suggest a model of lifespan regulation by fatty acid-mediated membrane configuration.

Beschreibung: Reactive oxygen species (ROS) oxidize cellular nucleotide pools and cause double strand breaks (DSBs). Non-homologous end-joining (NHEJ) attaches broken chromosomal ends together in mammalian cells. Ribonucleotide insertion by DNA polymerase (pol) μ prepares breaks for end-joining and this is required for successful NHEJ in vivo. We previously showed that pol μ lacks discrimination against oxidized dGTP (8-oxo-dGTP), that can lead to mutagenesis, cancer, aging and human disease. Here we reveal the structural basis for proficient oxidized ribonucleotide (8-oxo-rGTP) incorporation during DSB repair by pol μ. Time-lapse crystallography snapshots of structural intermediates during nucleotide insertion along with computational simulations reveal substrate, metal and side chain dynamics, that allow oxidized ribonucleotides to escape polymerase discrimination checkpoints. Abundant nucleotide pools, combined with inefficient sanitization and repair, implicate pol μ mediated oxidized ribonucleotide insertion as an emerging source of widespread persistent mutagenesis and genomic instability.

Beschreibung: Previous studies have suggested that PTEN loss is associated with p110β signaling dependency, leading to the clinical development of p110β-selective inhibitors. Here we use a panel pre-clinical models to reveal that PI3K isoform dependency is not governed by loss of PTEN and is impacted by feedback inhibition and concurrent PIK3CA/PIK3CB alterations. Furthermore, while pan-PI3K inhibition in PTEN-deficient tumors is efficacious, upregulation of Insulin Like Growth Factor 1 Receptor (IGF1R) promotes resistance. Importantly, we show that this resistance can be overcome through targeting AKT and we find that AKT inhibitors are superior to pan-PI3K inhibition in the context of PTEN loss. However, in the presence of wild-type PTEN and PIK3CA-activating mutations, p110α-dependent signaling is dominant and selectively inhibiting p110α is therapeutically superior to AKT inhibition. These discoveries reveal a more nuanced understanding of PI3K isoform dependency and unveil novel strategies to selectively target PI3K signaling nodes in a context-specific manner.

Beschreibung: Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients. Combining fragmentation features, clinical risk factors, and CEA levels, followed by CT imaging, detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites distinguished individuals with small cell lung cancer from those with non-small cell lung cancer with high accuracy (AUC = 0.98). A higher fragmentation score represented an independent prognostic indicator of survival. This approach provides a facile avenue for non-invasive detection of lung cancer.

Beschreibung: The preparation of thermal equilibrium states is important for the simulation of condensed matter and cosmology systems using a quantum computer. We present a method to prepare such mixed states with unitary operators and demonstrate this technique experimentally using a gate-based quantum processor. Our method targets the generation of thermofield double states using a hybrid quantum-classical variational approach motivated by quantum-approximate optimization algorithms, without prior calculation of optimal variational parameters by numerical simulation. The fidelity of generated states to the thermal-equilibrium state smoothly varies from 99 to 75% between infinite and near-zero simulated temperature, in quantitative agreement with numerical simulations of the noisy quantum processor with error parameters drawn from experiment.

Beschreibung: From the flashing of fireflies to autonomous robot swarms, synchronization phenomena are ubiquitous in nature and technology. They are commonly described by the Kuramoto model that, in this paper, we generalise to networks over n-dimensional spheres. We show that, for almost all initial conditions, the sphere model converges to a set with small diameter if the model parameters satisfy a given bound. Moreover, for even n, a special case of the generalized model can achieve phase synchronization with nonidentical frequency parameters. These results contrast with the standard n = 1 Kuramoto model, which is multistable (i.e., has multiple equilibria), and converges to phase synchronization only if the frequency parameters are identical. Hence, this paper shows that the generalized network Kuramoto models for n ≥ 2 displays more coherent and predictable behavior than the standard n = 1 model, a desirable property both in flocks of animals and for robot control.

Beschreibung: The discovery of moiré superlattices (MSLs) opened an era in the research of ‘twistronics’. Engineering MSLs and realizing unique emergent properties are key challenges. Herein, we demonstrate an effective synthetic strategy to fabricate MSLs based on mechanical flexibility of WS2 nanobelts by a facile one-step hydrothermal method. Unlike previous MSLs typically created through stacking monolayers together with complicated method, WS2 MSLs reported here could be obtained directly during synthesis of nanobelts driven by the mechanical instability. Emergent properties are found including superior conductivity, special superaerophobicity and superhydrophilicity, and strongly enhanced electro-catalytic activity when we apply ‘twistronics’ to the field of catalytic hydrogen production. Theoretical calculations show that such excellent catalytic performance could be attributed to a closer to thermoneutral hydrogen adsorption free energy value of twisted bilayers active sites. Our findings provide an exciting opportunity to design advanced WS2 catalysts through moiré superlattice engineering based on mechanical flexibility.

Beschreibung: The cascades prediction aims to predict the possible information diffusion path in the future based on cascades of the social network. Recently, the existing researches based on deep learning have achieved remarkable results, which indicates the great potential to support cascade prediction task. However, most prior arts only considered either cascade features or user relationship network to predict cascade, which leads to the performance limitation because of the lack of unified modeling for the potential relationship between them. To that end, in this paper, we propose a recurrent neural network model with graph attention mechanism, which constructs a seq2seq framework to learn the spatial-temporal cascade features. Specifically, for user spatial feature, we learn potential relationship among users based on social network through graph attention network. Then, for temporal feature, a recurrent neural network is built to learn their structural context in several different time intervals based on timestamp with a time-decay attention. Finally, we predict the next user with the latest cascade representation which obtained by above method. Experimental results on two real-world datasets show that our model achieves better performance than the baselines on the both evaluation metrics of HITS and mean average precision.

Beschreibung: Increasing demand on water resources, reduced land water availability, and concerns over food security have spurred the evolution of many innovative and complex food production. An aquaponic system is a productive, innovative, and sustainable fish and vegetable production system that is revolutionizing agriculture in the face of drought, soil fertility losses, and climate change. Aquaponics, as an advanced aquaculture-agriculture system, is expected to improve food security in developing countries. However, as an emerging technology, there is very limited information on the system in Africa. Questions about the ecological and socio-economic sustainability of aquaponics are answered in this comprehensive review. This review considers aquaponics projects in Africa, categorizes the technology by evidences of their effectiveness, fish and plant yields, and juxtaposes the technology within best-use practices to make recommendations that will inform evidence-based policymaking. It also maps the present spatial adoption of the technology in sub-Saharan Africa and highlights the system's contribution to improving food security on the continent. Egypt and South Africa are countries where aquaponics is emerging and being adopted at faster rates and contributing to food security. In West Africa, significantly lower net-discounted benefit-cost ratios were realized when aquaponics systems were constructed using imported materials compared to using locally available materials. Despite aquaponics systems generally having higher start-up costs currently, its potential to be economically viable when undertaken with local materials is very high.

Beschreibung: With excellent creep resistance, good high-temperature microstructural stability and good irradiation resistance, oxide dispersion strengthened (ODS) alloys are a class of important alloys that are promising for high-temperature applications. However, plagued by a nerve-wracking fact that the oxide particles tend to aggregate at grain boundary of metal matrix, their improvement effect on the mechanical properties of metal matrix tends to be limited. In this work, we employ a unique in-house synthesized oxide@W core-shell nanopowder as precursor to prepare W-based ODS alloy. After low-temperature sintering and high-energy-rate forging, high-density oxide nanoparticles are dispersed homogeneously within W grains in the prepared alloy, accompanying with the intergranular oxide particles completely disappearing. As a result, our prepared alloy achieves a great enhancement of strength and ductility at room temperature. Our strategy using core-shell powder as precursor to prepare high-performance ODS alloy has potential to be applied to other dispersion-strengthened alloy systems.

Beschreibung: Flows with chemical reactions in porous media are fundamental phenomena encountered in many natural, industrial, and scientific areas. For such flows, most existing studies use continuum assumptions and focus on volume-averaged properties on macroscopic scales. Considering the complex porous structures and fluid–solid interactions in realistic situations, this study develops a sophisticated lattice Boltzmann (LB) model for simulating reactive flows in porous media on the pore scale. In the present model, separate LB equations are built for multicomponent flows and chemical species evolutions, source terms are derived for heat and mass transfer, boundary schemes are formulated for surface reaction, and correction terms are introduced for temperature-dependent density. Thus, the present LB model offers a capability to capture pore-scale information of compressible/incompressible fluid motions, homogeneous reaction between miscible fluids, and heterogeneous reaction at the fluid–solid interface in porous media. Different scenarios of density fingering with homogeneous reaction are investigated, with effects of viscosity contrast being clarified. Furthermore, by introducing thermal flows, the solid coke combustion is modeled in porous media. During coke combustion, fluid viscosity is affected by heat and mass transfer, which results in unstable combustion fronts.

Beschreibung: The widespread UbiD enzyme family utilises the prFMN cofactor to achieve reversible decarboxylation of acrylic and (hetero)aromatic compounds. The reaction with acrylic compounds based on reversible 1,3-dipolar cycloaddition between substrate and prFMN occurs within the confines of the active site. In contrast, during aromatic acid decarboxylation, substantial rearrangement of the substrate aromatic moiety associated with covalent catalysis presents a molecular dynamic challenge. Here we determine the crystal structures of the multi-subunit vanillic acid decarboxylase VdcCD. We demonstrate that the small VdcD subunit acts as an allosteric activator of the UbiD-like VdcC. Comparison of distinct VdcCD structures reveals domain motion of the prFMN-binding domain directly affects active site architecture. Docking of substrate and prFMN-adduct species reveals active site reorganisation coupled to domain motion supports rearrangement of the substrate aromatic moiety. Together with kinetic solvent viscosity effects, this establishes prFMN covalent catalysis of aromatic (de)carboxylation is afforded by UbiD dynamics.

Beschreibung: Melanoma cells rely on developmental programs during tumor initiation and progression. Here we show that the embryonic stem cell (ESC) factor Sall4 is re-expressed in the Tyr::NrasQ61K; Cdkn2a−/− melanoma model and that its expression is necessary for primary melanoma formation. Surprisingly, while Sall4 loss prevents tumor formation, it promotes micrometastases to distant organs in this melanoma-prone mouse model. Transcriptional profiling and in vitro assays using human melanoma cells demonstrate that SALL4 loss induces a phenotype switch and the acquisition of an invasive phenotype. We show that SALL4 negatively regulates invasiveness through interaction with the histone deacetylase (HDAC) 2 and direct co-binding to a set of invasiveness genes. Consequently, SALL4 knock down, as well as HDAC inhibition, promote the expression of an invasive signature, while inhibition of histone acetylation partially reverts the invasiveness program induced by SALL4 loss. Thus, SALL4 appears to regulate phenotype switching in melanoma through an HDAC2-mediated mechanism.

Beschreibung: Omega-3 (n-3) fatty acids (FA) play an essential role in human physiology and health. As a result, a variety of n-3 FA-fortified functional foods have become commercially available for human consumption. These fortified functional foods are created through various processes; however, nutri-priming, a potentially promising fortification approach, has not been utilized to develop plant-based n-3 fortified foods. We sought to determine whether nutri-priming is a viable option to enrich seeds and sprouts with n-3 FA. Additionally, we assessed whether n-3 FA nutri-priming would inhibit germination of the primed seeds. To address these goals, we nutri-primed brown flax in three priming solutions, control [0% fish oil (FO)], 10% FO and a 20% FO solution, and determined the FA content and profile of seeds and sprouts and germination percentage of primed seeds. n-3 FA nutri-priming with FO altered the FA profile in seeds and sprouts, with increases in the absolute content of 20:5 n-3, 22:6 n-3, 22:5 n3, 18:4 n-3, and 20:4 n-6. However, n-3 FA nutri-priming did not increase the absolute content of 18:2 n-6, 18:3 n-3, total saturated FA, total monounsaturated FA, total polyunsaturated FA, total n-6 FA, or total n-3 FA. Our results also showed that n-3 nutri-priming decreased the germination percentage of primed seeds, with 10 and 20% FO priming solution reducing germination by 4.3 and 6.2%, respectively. Collectively, n-3 nutri-priming modified the n-3 FA profile in flax; however, the process does not increase the total n-3 FA content and inhibits germination of primed seeds. Further research utilizing different seed types, oil types, and oil concentrations needs to be conducted to fully determine if n-3 nutri-priming is a commercially viable approach for n-3 fortification of seeds and sprouts.

Beschreibung: Pozol is an acidic, refreshing, and non-alcoholic traditional Mayan beverage made with nixtamalized corn dough that is fermented spontaneously. The extensive analysis of the microbiology, biochemistry and metaproteomics of pozol allowed the construction of a comprehensive image of the fermentation system. The main changes in both the substrate and the microbiota occurred in the first 9 h of fermentation. The increase in microorganisms correlated with the drop in pH and with the decrease in the contents of carbohydrates, lipids, and nitrogen, which shows that this stage has the highest metabolic activity. Bacterial proteins were mainly represented by those of lactic acid bacteria, and among them, the proteins from genus Streptococcus was overwhelmingly the most abundant. Yeast proteins were present in all the analyzed samples, while proteins from filamentous fungi increased up to 48 h. The metaproteomic approach allowed us to identify several previously unknown enzyme complexes in the system. Additionally, enzymes for hydrolysis of starch, hemicellulose and cellulose were found, indicating that all these substrates can be used as a carbon source by the microbiota. Finally, enzymes related to the production of essential intermediates involved in the synthesis of organic acids, acetoin, butanediol, fatty acids and amino acids important for the generation of compounds that contribute to the sensorial quality of pozol, were found.

Beschreibung: This study was performed to determine the antifungal activity of loquat (Eriobotrya japonica Lindl) leaf extract (LLE) against the citrus postharvest pathogen Penicillium digitatum (P. digitatum). The LLE exhibited an antifungal activity against P. digitatum, with a minimum inhibitory concentration (MIC) of 0.625 mg/ml and a minimum fungicidal concentration (MFC) of 1.25 mg/ml. Significant inhibitory effects of LLE on mycelial growth and spore germination of P. digitatum were seen in a dose-dependent manner. Simultaneously, to investigate possible antifungal mechanisms by LLE, we analyzed their influence on morphological changes, cell membrane permeability, cell wall and cell membrane integrity, and adenosine phosphates (ATP, ADP, and AMP) levels. Alterations, such as sunken surface and malformation, occurred in the LLE-treated P. digitatum spores. Furthermore, intracellular inclusion content decreased after LLE treatment, indicating an increase in cell membrane permeability. Besides, the LLE treatment induced a significant decline in the level of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) with a noticeable addition of extracellular ATP, ADP, and AMP during the entire treatment period. Overall, the results manifested that the antifungal activity of LLE against P. digitatum can be attributed to the derangement of cell membrane permeability and disordered energy metabolism. This is the first report on the mechanism of antifungal activity of LLE and could be useful in the development of targeted fungicides from natural origin.

Beschreibung: β cells may participate and contribute to their own demise during Type 1 diabetes (T1D). Here we report a role of their expression of Tet2 in regulating immune killing. Tet2 is induced in murine and human β cells with inflammation but its expression is reduced in surviving β cells. Tet2-KO mice that receive WT bone marrow transplants develop insulitis but not diabetes and islet infiltrates do not eliminate β cells even though immune cells from the mice can transfer diabetes to NOD/scid recipients. Tet2-KO recipients are protected from transfer of disease by diabetogenic immune cells.Tet2-KO β cells show reduced expression of IFNγ-induced inflammatory genes that are needed to activate diabetogenic T cells. Here we show that Tet2 regulates pathologic interactions between β cells and immune cells and controls damaging inflammatory pathways. Our data suggests that eliminating TET2 in β cells may reduce activating pathologic immune cells and killing of β cells.

Beschreibung: Ghrelin, also called “the hunger hormone”, is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward, cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of Gq-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor.

Beschreibung: One of the most important aspects of time series is their degree of stochasticity vs. chaoticity. Since the discovery of chaotic maps, many algorithms have been proposed to discriminate between these two alternatives and assess their prevalence in real-world time series. Approaches based on the combination of “permutation patterns” with different metrics provide a more complete picture of a time series’ nature, and are especially useful to tackle pathological chaotic maps. Here, we provide a review of such approaches, their theoretical foundations, and their application to discrete time series and real-world problems. We compare their performance using a set of representative noisy chaotic maps, evaluate their applicability through their respective computational cost, and discuss their limitations.

Beschreibung: In vivo bioprinting has recently emerged as a direct fabrication technique to create artificial tissues and medical devices on target sites within the body, enabling advanced clinical strategies. However, existing in vivo bioprinting methods are often limited to applications near the skin or require open surgery for printing on internal organs. Here, we report a ferromagnetic soft catheter robot (FSCR) system capable of in situ computer-controlled bioprinting in a minimally invasive manner based on magnetic actuation. The FSCR is designed by dispersing ferromagnetic particles in a fiber-reinforced polymer matrix. This design results in stable ink extrusion and allows for printing various materials with different rheological properties and functionalities. A superimposed magnetic field drives the FSCR to achieve digitally controlled printing with high accuracy. We demonstrate printing multiple patterns on planar surfaces, and considering the non-planar surface of natural organs, we then develop an in situ printing strategy for curved surfaces and demonstrate minimally invasive in vivo bioprinting of hydrogels in a rat model. Our catheter robot will permit intelligent and minimally invasive bio-fabrication.

Beschreibung: Ultrasound-assisted extraction (UAE) is an effective tool for the extraction of natural antioxidants. Thus, differentially roasted Arabica-coffee beans known as light (LC), medium (MC), and dark coffee (DC) were prepared and extracted under the influence of UAE. Following that, they were examined specifically on theirs physicochemical and biological characteristics: nutritional values, pH, °Brix, antioxidant activities, polyphenol content, caffeine, and chlorogenic-acid levels. Various parameters, such as extraction temperatures (20, 40, and 80°C) and extraction time periods (5, 10, and 20 min), were examined. DC extract was less acidic than those on MC and LC extracts. LC showed higher moisture content than the MC and DC (1.56, 1.3, and 0.92%, respectively). MC displayed the highest polyphenol content and potent antioxidant activity. Caffeine and chlorogenic acid contents trend to decrease during roasting. The maximum caffeine level was found in MC at 80°C for 5 min (27.65 mg/g extract). The highest chlorogenic acid content was in LC at 80°C for 10 min (16.67 mg/g extract). The caffeine and chlorogenic acid contents were related to the polyphenol content and depended on the roasting and extraction conditions. These results suggest that the UAE at various temperature and extraction time period may alter the physicochemical and biological characteristics of different coffee roasts.

Beschreibung: Depression is a common mental disorder. The standard medical treatment is the selective serotonin reuptake inhibitors (SSRIs). All characterized SSRIs are competitive inhibitors of the serotonin transporter (SERT). A non-competitive inhibitor may produce a more favorable therapeutic profile. Vilazodone is an antidepressant with limited information on its molecular interactions with SERT. Here we use molecular pharmacology and cryo-EM structural elucidation to characterize vilazodone binding to SERT. We find that it exhibits non-competitive inhibition of serotonin uptake and impedes dissociation of [3H]imipramine at low nanomolar concentrations. Our SERT structure with bound imipramine and vilazodone reveals a unique binding pocket for vilazodone, expanding the boundaries of the extracellular vestibule. Characterization of the binding site is substantiated with molecular dynamics simulations and systematic mutagenesis of interacting residues resulting in decreased vilazodone binding to the allosteric site. Our findings underline the versatility of SERT allosteric ligands and describe the unique binding characteristics of vilazodone.

Beschreibung: p53 regulates several signaling pathways to maintain the metabolic homeostasis of cells and modulates the cellular response to stress. Deficiency or excess of nutrients causes cellular metabolic stress, and we hypothesized that p53 could be linked to glucose maintenance. We show here that upon starvation hepatic p53 is stabilized by O-GlcNAcylation and plays an essential role in the physiological regulation of glucose homeostasis. More specifically, p53 binds to PCK1 promoter and regulates its transcriptional activation, thereby controlling hepatic glucose production. Mice lacking p53 in the liver show a reduced gluconeogenic response during calorie restriction. Glucagon, adrenaline and glucocorticoids augment protein levels of p53, and administration of these hormones to p53 deficient human hepatocytes and to liver-specific p53 deficient mice fails to increase glucose levels. Moreover, insulin decreases p53 levels, and over-expression of p53 impairs insulin sensitivity. Finally, protein levels of p53, as well as genes responsible of O-GlcNAcylation are elevated in the liver of type 2 diabetic patients and positively correlate with glucose and HOMA-IR. Overall these results indicate that the O-GlcNAcylation of p53 plays an unsuspected key role regulating in vivo glucose homeostasis.

Beschreibung: Argonaute is the primary mediator of metazoan miRNA targeting (MT). Among the currently identified 〉1,500 human RNA-binding proteins (RBPs), there are only a handful of RBPs known to enhance MT and several others reported to suppress MT, leaving the global impact of RBPs on MT elusive. In this study, we have systematically analyzed transcriptome-wide binding sites for 150 human RBPs and evaluated the quantitative effect of individual RBPs on MT efficacy. In contrast to previous studies, we show that most RBPs significantly affect MT and that all of those MT-regulating RBPs function as MT enhancers rather than suppressors, by making the local secondary structure of the target site accessible to Argonaute. Our findings illuminate the unappreciated regulatory impact of human RBPs on MT, and as these RBPs may play key roles in the gene regulatory network governed by metazoan miRNAs, MT should be understood in the context of co-regulating RBPs.

Beschreibung: Increased global production of animal-based protein results in high greenhouse gas (GHG) emissions and other adverse consequences for human and planetary health. Recently, commercial insect rearing has been claimed a more sustainable source of animal protein. However, this system also leaves residues called frass, which—depending on the insect diet—is rich in carbon (C) and nitrogen (N), and could thus be used as fertilizer in agriculture. The impact of this kind of fertilizer on soil GHG emissions is yet unknown. Therefore, we investigated the effect of black soldier fly (Hermetia illucens L.) frass derived from a carbohydrate (Carb-) or a protein (Prot-) based diet applied at two different application rates to an arable soil on C and N fluxes and microbial properties in a 40-day incubation experiment. CO2, N2O, NO, N2, CH4, water extractable organic C (WEOC), and inorganic N were continuously measured quantitatively. At the end of the incubation, microbial biomass (MB), stoichiometry, community composition, and abundance of functional genes were assessed. Along with a strong increase in WEOC and CO2, Carb-frass caused strong initial N2O emissions associated with high N and C availability. In contrast, Prot-frass showed lower CO2 emissions and N2O release, although soil nitrate levels were higher. At the end of incubation, MB was significantly increased, which was more pronounced following Carb-frass as compared to Prot-frass application, and at higher amendment rates. Fungal abundance increased most from both frass types with an even stronger response at higher application rates, whereas bacterial abundance rose following Carb-frass as compared to Prot-application. Abundance of functional genes related to ammonia-oxidizing bacteria and archaea were enhanced by high frass application but did not clearly differ between frass types. C use efficiency of microorganisms, as revealed by the metabolic quotient, was most strongly reduced in the high Prot-frass application rate. Overall, insect diet influenced available C and N in frass and thus affected mineralization dynamics, GHG emissions, and microbial growth. Overall, emissions were very high undermining the potential environmental benefit of insect based protein production and calling for more detailed analyses before frass is widely applied in agriculture.

Beschreibung: From the observed datasets, we should be able to produce curve surfaces that have the same characteristics as the original datasets. For instance, if the given data are positive, then the resulting curve or surface must be positive on entire given intervals, i.e., everywhere. In this study, a new partial blended rational bi-quartic spline with C1 continuity is constructed through the partially blended scheme. This rational spline is defined on four corners of the rectangular meshes. The sufficient condition for the positivity of rational bi-quartic spline is derived on four boundary curve networks. There are eight free parameters that can be used for shape modification. The first-order partial derivatives are estimated by using numerical techniques. We also show that the proposed scheme is local quadratic reproducing such that it can exactly reproduce the quadratic surface. We test the proposed scheme to interpolate various types of positive surface data. Based on statistical indicators such as the root mean square error (RMSE) and coefficient of determination (R2), we found that the proposed scheme is on par with some established schemes. In fact, it requires less CPU times (in seconds) to generate the interpolating surface on rectangular meshes. Furthermore, by combining the statistical indicators’ result and graphically visualizing the test functions, the proposed method has the capability to reconstruct very comparable smoothing interpolating positive surfaces compared to some existing schemes. This finding is significant in producing a better interpolating surface for computer graphics applications since the proposed scheme has a smaller error compared with existing schemes.

Beschreibung: The past decade has seen a proliferation of topological materials for both insulators and semimetals in electronic systems and classical waves. Topological semimetals exhibit topologically protected band degeneracies, such as nodal points and nodal lines. Dirac nodal line semimetals (DNLS), which own four-fold line degeneracy, have drawn particular attention. DNLSs have been studied in electronic systems but there is no photonic DNLS. Here in this work, we provide a new mechanism, which is unique for photonic systems to investigate a stringent photonic DNLS. When truncated, the photonic DNLS exhibits double-bowl states (DBS), which comprise two sets of perpendicularly polarized surface states. In sharp contrast to nondegenerate surface states in other photonic systems, here the two sets of surface states are almost degenerate over the whole-spectrum range. The DBS and the bulk Dirac nodal ring (DNR) dispersion along the relevant directions, are experimentally resolved.

Beschreibung: We study theoretically the properties of local heat originated from energy exchange between electrons passing through a quantum dot (QD) coupled to a phonon bath. The dot is sandwiched between two normal metal leads and also side-coupled to Majorana bound states (MBSs) formed at opposite ends of a topological superconductor nanowire. We find that in addition to the negative differential of heat generation (NDHG) in the Coulomb blockade regime, another NDHG emerges near the leads’ Fermi level due to the dot-MBS coupling. This dual NDHG effect is robust against the variation of intradot Coulomb interaction strength, and disappears if the QD is coupled to regular Fermions. Direct hybridization between the MBSs reduces their impacts on the electronic transport processes, and eliminates the dual NDHG effect. Our results show that the dual NDHG effect is quite efficient for inferring the existence of MBSs, and may remedy some limitations of the detection schemes relying on tunneling spectroscopy technique.

Beschreibung: Novel human coronavirus disease (COVID-19), an infectious respiratory disease, has affected more than 50 million people around the world up to November 2020, thereby becoming the fifth documented pandemic since the Spanish flu in 1918. SARS-CoV-2 virus originated in China and evolved for 4 months within the country before becoming a global threat. There is currently no drug approved by the Food and Drug Administration (FDA) for which efficacy on the virus has been proved. Therefore, the only strategy against this virus is to apply measures that are capable of reducing its spread, such as isolation and quarantine, social distancing, community-wide containment, and strict enforcement of hygiene. Quarantine has proved to be effective in combating the spread of the virus; however, it has inevitably led to a radical change in the lives of people. Studies have been conducted in Italy and some European countries to highlight the role that quarantine has played in determining the lifestyle changes both in eating habits and physical activity and their possible correlation with increase in weight. The selection criteria involved answering a questionnaire that included information on the weight status and at least one of the other two aspects: changes in eating habits and/or physical activity during the quarantine period. The results obtained indicate, in general, that the negative effect of quarantine was on eating habits and physical activity. This was based on the observation that there has been an increase in food consumption and a reduction in physical activity with a consequent increase in weight.

Beschreibung: We numerically calculate the quasinormal frequencies of the Klein-Gordon and Dirac fields propagating in a two-dimensional asymptotically anti-de Sitter black hole of the dilaton gravity theory. For the Klein-Gordon field we use the Horowitz-Hubeny method and the asymptotic iteration method for second order differential equations. For the Dirac field we first exploit the Horowitz-Hubeny method. As a second method, instead of using the asymptotic iteration method for second order differential equations, we propose to take as a basis its formulation for coupled systems of first order differential equations. For the two fields we find that the results that produce the two numerical methods are consistent. Furthermore for both fields we obtain that their quasinormal modes are stable and we compare their quasinormal frequencies to analyze whether their spectra are isospectral. Finally we discuss the main results.

Beschreibung: In this review, we report on recent progress in the generation and application of multichromatic polarization-tailored pulse sequences for the coherent control of multiphoton ionization (MPI) dynamics and present unpublished experimental results that complement our previous findings. Specifically, we utilize single-color, bichromatic, and trichromatic polarization-controlled pulse sequences generated by spectral amplitude, phase and polarization modulation of a carrier-envelope phase (CEP)-stable white light supercontinuum for MPI. The analysis of the number of ionization pathways and the number of distinct final free electron states shows that both increase significantly, but scale differently with the number of absorbed photons and the number of pulses in the sequence. In our experiments, ultrafast polarization shaping is combined with high-resolution photoelectron tomography to generate, control, and reconstruct three-dimensional photoelectron momentum distributions from atomic and molecular MPI. We discuss the use of polarization-controlled single-color and bichromatic pulse sequences in perturbative and non-perturbative coherent control of coupled electron-nuclear dynamics in molecules, atomic spin-orbit wave packet dynamics and the directional photoemission from atoms and chiral molecules. We compare the coherent control of CEP-insensitive intraband multipath interference in the MPI with a fixed number of photons with CEP-sensitive interband multipath interference in the ionization with a different number of photons. The generation and control of free electron vortices with even-numbered rotational symmetry by MPI with single-color pulse sequences is contrasted with the bichromatic control of CEP-sensitive electron vortices with odd-numbered rotational symmetry. To illustrate the potential of multichromatic pulse sequences for coherent control, we present a trichromatic scheme for shaper-based quantum state holography.

Beschreibung: On the 〉1 µm scale the morphology of semicrystalline plastics like polyethylene or Nylon features spherulites, “shish-kebabs”, cylinddrites and other crystalline aggregates which strongly affect mechanical and other material properties. Current imaging techniques give only a 2D picture of these objects. Here we show how they can be visualized in 3D using fluorescent labels and confocal microscopy. As a result, we see spherulites in 3D, both in neat polymers and their nanocomposites, and observe how unevenly nanoparticles and other additives are distributed in the material. Images of i-polypropylene and biodegradable poly(lactic acid) reveal previously unsuspected morphologies such as “vases” and “goblets”, nonspherical “spherulites” and, unexpectedly, “shish-kebabs” grown from quiescent melt. Also surprisingly, in nanocomposite sheets spherulite nucleation is seen to be copied from one surface to another, mediated by crystallization-induced pressure drop and local melt-flow. These first results reveal unfamiliar modes of self-assembly in familiar plastics and open fresh perspectives on polymer microstructure.

Beschreibung: Objective: At present, the association of body mass index (BMI) with the prognosis of liver cirrhosis is controversial. Our retrospective study aimed to evaluate the impact of BMI on the outcome of liver cirrhosis.Methods: In the first part, long-term death was evaluated in 436 patients with cirrhosis and without malignancy from our prospectively established single-center database. In the second part, in-hospital death was evaluated in 379 patients with cirrhosis and with acute gastrointestinal bleeding (AGIB) from our retrospective multicenter study. BMI was calculated and categorized as underweight (BMI

Beschreibung: Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa.

Beschreibung: The neural mechanisms of fear-associated thermoregulation remain unclear. Innate fear odor 2-methyl-2-thiazoline (2MT) elicits rapid hypothermia and elevated tail temperature, indicative of vasodilation-induced heat dissipation, in wild-type mice, but not in mice lacking Trpa1–the chemosensor for 2MT. Here we report that Trpa1−/− mice show diminished 2MT-evoked c-fos expression in the posterior subthalamic nucleus (PSTh), external lateral parabrachial subnucleus (PBel) and nucleus of the solitary tract (NTS). Whereas tetanus toxin light chain-mediated inactivation of NTS-projecting PSTh neurons suppress, optogenetic activation of direct PSTh-rostral NTS pathway induces hypothermia and tail vasodilation. Furthermore, selective opto-stimulation of 2MT-activated, PSTh-projecting PBel neurons by capturing activated neuronal ensembles (CANE) causes hypothermia. Conversely, chemogenetic suppression of vGlut2+ neurons in PBel or PSTh, or PSTh-projecting PBel neurons attenuates 2MT-evoked hypothermia and tail vasodilation. These studies identify PSTh as a major thermoregulatory hub that connects PBel to NTS to mediate 2MT-evoked innate fear-associated hypothermia and tail vasodilation.

Beschreibung: The discovery of superconducting H3S with a critical temperature Tc∼200 K opened a door to room temperature superconductivity and stimulated further extensive studies of hydrogen-rich compounds stabilized by high pressure. Here, we report a comprehensive study of the yttrium-hydrogen system with the highest predicted Tcs among binary compounds and discuss the contradictions between different theoretical calculations and experimental data. We synthesized yttrium hydrides with the compositions of YH3, YH4, YH6 and YH9 in a diamond anvil cell and studied their crystal structures, electrical and magnetic transport properties, and isotopic effects. We found superconductivity in the Im-3m YH6 and P63/mmc YH9 phases with maximal Tcs of ∼220 K at 183 GPa and ∼243 K at 201 GPa, respectively. Fm-3m YH10 with the highest predicted Tc 〉 300 K was not observed in our experiments, and instead, YH9 was found to be the hydrogen-richest yttrium hydride in the studied pressure and temperature range up to record 410 GPa and 2250 K.

Beschreibung: Histone lysine methylations have primarily been linked to selective recruitment of reader or effector proteins that subsequently modify chromatin regions and mediate genome functions. Here, we describe a divergent role for histone H4 lysine 20 mono-methylation (H4K20me1) and demonstrate that it directly facilitates chromatin openness and accessibility by disrupting chromatin folding. Thus, accumulation of H4K20me1 demarcates highly accessible chromatin at genes, and this is maintained throughout the cell cycle. In vitro, H4K20me1-containing nucleosomal arrays with nucleosome repeat lengths (NRL) of 187 and 197 are less compact than unmethylated (H4K20me0) or trimethylated (H4K20me3) arrays. Concordantly, and in contrast to trimethylated and unmethylated tails, solid-state NMR data shows that H4K20 mono-methylation changes the H4 conformational state and leads to more dynamic histone H4-tails. Notably, the increased chromatin accessibility mediated by H4K20me1 facilitates gene expression, particularly of housekeeping genes. Altogether, we show how the methylation state of a single histone H4 residue operates as a focal point in chromatin structure control. While H4K20me1 directly promotes chromatin openness at highly transcribed genes, it also serves as a stepping-stone for H4K20me3-dependent chromatin compaction.

Beschreibung: The human gut microbiota is increasingly recognized as an important factor in modulating innate and adaptive immunity through release of ligands and metabolites that translocate into circulation. Urbanizing African populations harbor large intestinal diversity due to a range of lifestyles, providing the necessary variation to gauge immunomodulatory factors. Here, we uncover a gradient of intestinal microbial compositions from rural through urban Tanzanian, towards European samples, manifested both in relative abundance and genomic variation observed in stool metagenomics. The rural population shows increased Bacteroidetes, led by Prevotella copri, but also presence of fungi. Measured ex vivo cytokine responses were significantly associated with 34 immunomodulatory microbes, which have a larger impact on circulating metabolites than non-significant microbes. Pathway effects on cytokines, notably TNF-α and IFN-γ, differential metabolome analysis and enzyme copy number enrichment converge on histidine and arginine metabolism as potential immunomodulatory pathways mediated by Bifidobacterium longum and Akkermansia muciniphila.

Beschreibung: Although layered van der Waals (vdW) materials involve vast interface areas that are often subject to contamination, vdW interactions between layers may squeeze interfacial contaminants into nanopockets. More intriguingly, those nanopockets could spontaneously coalesce into larger ones, which are easier to be squeezed out the atomic channels. Such unusual phenomena have been thought of as an Ostwald ripening process that is driven by the capillarity of the confined liquid. The underlying mechanism, however, is unclear as the crucial role played by the sheet’s elasticity has not been previously appreciated. Here, we demonstrate the coalescence of separated nanopockets and propose a cleaning mechanism in which both elastic and capillary forces are at play. We elucidate this mechanism in terms of control of the nanopocket morphology and the coalescence of nanopockets via a mechanical stretch. Besides, we demonstrate that bilayer graphene interfaces excel in self-renewal phenomena.

Beschreibung: Managed and wild bee populations contribute over $15 billion in pollination services to US agriculture, yet both are declining or becoming increasingly vulnerable to parasites and disease. The loss of healthy and diverse forage is a key driver in bee declines, so incentivizing land managers to adopt diversified bee-friendly management practices such as forage plantings and reduced pesticide use can directly increase food security, pollinator health, and farmer adaptive capacity. To better understand what might incentivize growers to adopt bee-friendly practices, we conducted a survey of California almond growers, whose orchards are entirely dependent on bee pollination and draw nearly 88% of US bee colonies each February to pollinate almond bloom. We asked 329 respondents across all major almond growing regions of CA about their adoption rate and incentives for planting cover crops, pollinator habitat, and practicing the recommended and legally required bee-friendly best management practices, as well as their interest in bee-friendly certification programs. Using a model selection framework, we evaluated which geographic, social, operational, and pollination-service related factors were predictive of bee-friendly practice adoption. We found that no single factor was a statistically significant predictor of adoption across all models, suggesting there is no silver bullet determining bee-friendly practice adoption. However, we discovered that region and concerns about future pollination services consistently emerged as important factors related to all the practices we investigated, except the adoption of legally required BMPs. These findings suggest that a regionally flexible pollinator conservation strategy focused on supporting honey bee colonies might have the highest likelihood of grower participation and adoption.

Beschreibung: Edible insects are proposed as a nutritious and environmentally sustainable alternative source to animal proteins, due to their numerous advantages in terms of reduced ecological impact and high nutritional value. However, the novelty for edible insects relies on the content of bioactive ingredients potentially able to induce a functional effect in the body. The present review summarizes the main findings on the antioxidant properties of edible insects available in the literature. A total of 30 studies involving animals, cell cultures, or in vitro experimental studies evaluating the antioxidant effect of edible insects are presented in this work. When the antioxidant activity was investigated, using a wide variety of in vitro tests and in cellular models, positive results were shown. Dietary supplementation with edible insects was also able to counteract dietary oxidative stress in animal models, restoring the balance of antioxidant enzymes and reducing the formation of oxidation damage markers. On the basis of the reviewed evidences, edible insects might represent a source of novel redox ingredients at low ecological impact able to modulate oxidative stress. However, due to the fact that majority of these evidences have been obtained in vitro and in cellular and animal models, dietary intervention trials are needed to assess the efficacy of edible insect consumption to modulate redox status in humans.

Beschreibung: Infants hospitalized for critical illnesses are at a high risk of undernutrition because of increased nutrient requirements (due to increased metabolism) and decreased nutrient intake (due to disease-related problems such as anorexia or feeding difficulties). This can result in a slowing down of their normal growth, referred to as “growth faltering.” Appropriate nutritional management of these infants is extremely important to avoid long-term adverse outcomes. Administration of energy- and nutrient-dense formula (ENDF; 100 kcal energy and 2.6 g protein per 100 mL, with added micronutrients) can be an effective means of increasing the nutrient and energy intake of these children. Despite the high prevalence of undernutrition and growth faltering among pediatric patients in India, there is a paucity of literature on the use of ENDF in Indian infants. Herein, we report the successful use of ENDF for the nutritional management of two infants hospitalized for growth faltering because of severe upper airway obstruction. The aim of nutritional management was to achieve satisfactory weight gain, which can lead to spontaneous resolution of upper airway obstruction. ENDF was initially administered to provide 50–100 kcal/kg/day, and the dose was gradually increased to 160–185 kcal/kg/day. Both infants tolerated the formula well and showed satisfactory weight gain. These cases clearly demonstrate that early administration of ENDF is an effective means of increasing nutrient and energy intake of critically ill infants, thereby facilitating catchup growth, without any notable adverse effects.

Beschreibung: Insulin resistance in obesity coincides with abnormalities in lipid profile and lipoprotein subclass distribution and size even before abnormalities in glucose homeostasis manifest. We aimed to assess this relationship in the absence of obesity. Insulin sensitivity (3-h intravenous glucose tolerance test and minimal modeling) and lipoprotein particle concentrations and sizes (proton nuclear magnetic resonance spectroscopy) were evaluated in 15 insulin-resistant and 15 insulin-sensitive lean Asians of Chinese descent with normal glucose tolerance, matched on age, sex, and body mass index. Despite a ~50% lower insulin sensitivity index (Si) in insulin-resistant than in insulin-sensitive subjects, which was accompanied by significantly greater acute insulin response to glucose (AIRg) and fasting insulin concentration but not different fasting glucose concentration, there were no significant differences between groups in the blood lipid profile (p ≥ 0.44) or the lipoprotein subclass concentrations (p ≥ 0.30) and particle sizes (p ≥ 0.43). We conclude that, contrary to observations in subjects with obesity, insulin resistance is not accompanied by unfavorable changes in the plasma lipid profile and lipoprotein particle concentrations and sizes in lean Asians with normal glucose tolerance. Therefore, insulin resistance at the level of glucose metabolism is mechanistically or temporally dissociated from lipid and lipoprotein metabolism.Trial Registration:clinicaltrials.gov, NCT03264001.

Beschreibung: Atmospheric gravity waves (GWs) are generated in the lower atmosphere by various weather phenomena. They propagate upward, carry energy and momentum to higher altitudes, and appreciably influence the general circulation upon depositing them in the middle and upper atmosphere. We use a three-dimensional first-principle general circulation model (GCM) with implemented nonlinear whole atmosphere GW parameterization to study the global climatology of wave activity and produced effects at altitudes up to the upper thermosphere. The numerical experiments were guided by the GW momentum fluxes and temperature variances as measured in 2010 by the SABER (Sounding of the Atmosphere using Broadband Emission Radiometry) instrument onboard NASA’s TIMED (Thermosphere Ionosphere Mesosphere Energetics Dynamics) satellite. This includes the latitudinal dependence and magnitude of GW activity in the lower stratosphere for the boreal summer season. The modeling results were compared to the SABER temperature and total absolute momentum flux and Upper Atmosphere Research Satellite (UARS) data in the mesosphere and lower thermosphere. Simulations suggest that, in order to reproduce the observed circulation and wave activity in the middle atmosphere, GW fluxes that are smaller than observed fluxes have to be used at the source level in the lower atmosphere. This is because observations contain a broader spectrum of GWs, while parameterizations capture only a portion relevant to the middle and upper atmosphere dynamics. Accounting for the latitudinal variations of the source appreciably improves simulations.

Beschreibung: Lasers are the pillars of modern optics and sensing. Microlasers based on whispering-gallery modes (WGMs) are miniature in size and have excellent lasing characteristics suitable for biosensing. WGM lasers have been used for label-free detection of single virus particles, detection of molecular electrostatic changes at biointerfaces, and barcode-type live-cell tagging and tracking. The most recent advances in biosensing with WGM microlasers are described in this review. We cover the basic concepts of WGM resonators, the integration of gain media into various active WGM sensors and devices, and the cutting-edge advances in photonic devices for micro- and nanoprobing of biological samples that can be integrated with WGM lasers.

Beschreibung: Large-scale disturbances such as ice storms may increase in frequency and intensity as climate changes. While disturbances are a natural component of forest ecosystems, climatically driven alteration to historical patterns may impart fundamental change to ecosystem function. At Hubbard Brook Experimental Forest, NH, experimental ice storms of varying severity were applied to replicate plots of mature northern hardwoods to quantify their effects on forested ecosystems. We assessed ice storm treatment effects on insectivorous foliage-gleaning birds and evaluated insectivore predation on model caterpillars in the understory vegetation. These birds are charismatic, of conservation concern, and are major predators of caterpillars. In turn, lepidopterans are the dominant herbivores in temperate forests and are integral to ecosystem function. We predicted that avian abundance would increase due to additional structural heterogeneity caused by ice treatments, with a concomitant increase in caterpillar predation. Point counts were used to measure insectivorous bird activity in the ice storm experiment plots and additional control plots before and after treatments. We deployed and retrieved plasticine model caterpillars and estimated predation from characteristic marks to these surrogates. Abundance of foliage-gleaning birds was higher in the ice storm plots and birds responded to treatments as a single diffuse disturbance rather than on an individual plot level. All species except one were observed both before and after the ice treatments. Surprisingly, predation on caterpillar models was unaffected by ice storm treatments but rather was a function of caterpillar density. The increase in avian abundance in the ice storm treatment plots corroborates other studies of bird responses to relatively small-scale disturbances in forests and the limited change in species composition was expected given the plot size. We conclude that ice storms may provide beneficial changes for foliage-gleaning birds in the growing season following the disturbance.

Beschreibung: We previously discovered that gut microbiota can serve as universal microbial biomarkers for diagnosis, disease activity assessment, and predicting the response to infliximab treatment for inflammatory bowel diseases (IBD). Much still remains unknown about the relationship between alterations in gut microbiota and IBD affected bowel region, in particular in the case of ulcerative colitis (UC) and colonic Crohn's disease (cCD) without endoscopic and biopsy data. In the current study gut microbiota from a population in China was found to be distinct from that of the Western world [Human Microbiome Project (HMP) data]. Furthermore, both gut microbiota greatly differed from microbiota of other anatomical locations (oral, skin, airway, and vagina), with higher alpha-diversity (Chinese gut 〉 HMP gut 〉 oral microbiome 〉 airway microbiome 〉 skin microbiome 〉 vaginal microbiome), and marked differences in microbiome composition. In patients with IBD in China, UC was characterized by the presence of Gardnerella, while cCD was characterized by the presence of Fusobacterium. Moreover, gut microbiota, such as Gardnerella and Fusobacterium, may be potential biomarkers for identifying UC from cCD. Together, this study revealed crucial differences in microbial communities across anatomical locations, and demonstrated that there was an important association between IBD affected bowel region and gut microbiota.

Beschreibung: The thermodynamic properties of the parabolic-well fluid are considered. The intermolecular interaction potential of this model, which belongs to the class of the so-called van Hove potentials, shares with the square-well and the triangular well potentials the inclusion of a hard-core and an attractive well of relatively short range. The analytic second virial coefficient for this fluid is computed explicitly and an equation of state is derived with the aid of the second-order thermodynamic perturbation theory in the macroscopic compressibility approximation and taking the hard-sphere fluid as the reference system. For this latter, the fully analytical expression of the radial distribution function, consistent with the Carnahan-Starling equation of state as derived within the rational function approximation method, is employed. The results for the reduced pressure of the parabolic-well fluid as a function of the packing fraction and two values of the range of the parabolic-well potential at different temperatures are compared with Monte Carlo and Event‐driven molecular dynamics simulation data. Estimates of the values of the critical temperature are also provided.

Beschreibung: Humans are participating in the sixth mass extinction, and for the first time in 200,000 years, our species may be on the brink of extinction. We are facing the greatest challenges we have ever encountered, namely how to nourish eight billion people in the face of changing climates ecologically, diminish disparity between the haves and the have-nots economically, and ease xenophobia, fear, and hatred socially? Historically, our tribal nature served us well, but the costs of tribalism are now far too great for one people inhabiting one tiny orb. If we hope to survive, we must mend the divides that isolate us from one another and the communities we inhabit. While not doing so could be our undoing, doing so could transform our collective consciousness into one that respects, nourishes, and embraces our interdependence with life on Earth. At a basic level, we can cultivate life by using nature as a model for how to produce and consume food; by decreasing our dependence on fossil fuels for energy to grow, process, and transport food; and by transcending persistent battles over one-size-fits-all plant- or animal-based diets. If we learn to do so in ways that nourish life, we may awaken individually and collectively to the wisdom of the Maori proverb Ko au te whenua. Ko te whenua Ko au: I am the land. The land is me. In this paper, we use “scapes” —foodscapes, landscapes, heartscapes, and thoughtscapes—as unifying themes to discuss our linkages with communities. We begin by considering how palates link animals with foodscapes. Next, we address how palates link foodscapes with landscapes. We then consider how, through our reverence for life, heartscapes link palates with foodscapes and landscapes. We conclude with transformations of thoughtscapes needed to appreciate life on Earth as a community to which we belong, rather than as a commodity that belongs to us.

Beschreibung: Malnutrition among children of school-going age is a challenge of serious concern in developing countries especially Sub-Saharan Africa. Many programs focus on mothers and under-5-year-old children, leaving the school going age unattended. It has been shown that school meals can reduce school absenteeism, improve concentration in class and reduce early dropouts. In Tanzania, successful home-grown school feeding programs are localized in few areas but have not been scaled-out. The objective of this study was to analyze the policy and organizational environment which enables or promotes home-grown school feeding approaches. The study consisted of a systematic review, key informant interviews and focus group discussions in Arumeru and Babati Districts, Tanzania. In total, 21 key informant interviews with 27 participants and 27 focus group discussions with 217 participants were conducted. The results show that Tanzania lacks a clear policy on school feeding; there are no guidelines for school meal quality, participation in school feeding programs is not mandatory, leading to many students being left out and going hungry. Students in private schools tend to be better off than those in public schools in terms of provision and quality of school meals. We recommend that policies and practices are developed based on positive experiences of home-grown school feeding programs implemented in Tanzania by the World Food Programme and Project Concern International and emphasize that these policies need to be developed in a multi-sectoral manner. A conceptual framework for improving home-grown school feeding in public schools in Tanzania highlights four critical components: leadership and public awareness; operational modalities; contributions from parents; and meal diversity and nutrition. The home-grown school feeding model provides mechanisms to improve diversity of meals and their nutritional value, increase participation of communities and inclusion of students. Parents will still be responsible for the largest part of food supplies, but the model also requires participation of multiple stakeholders, and provision of natural resources such as land and water by the local government for production of nutritious food for young students. Minimum levels of social protection are recommended to ensure that no student is denied school meals.

Beschreibung: A Correction to this paper has been published: https://doi.org/10.1038/s41377-021-00481-1

Beschreibung: While commission reports and nutritional guidelines raise concerns about the effects of consuming red meat on human health, the impacts of how livestock are raised and finished on consumer health are generally ignored. Meat and milk, irrespective of rearing practices, provide many essential nutrients including bioavailable protein, zinc, iron, selenium, calcium, and/or B12. Emerging data indicate that when livestock are eating a diverse array of plants on pasture, additional health-promoting phytonutrients—terpenoids, phenols, carotenoids, and anti-oxidants—become concentrated in their meat and milk. Several phytochemicals found in grass-fed meat and milk are in quantities comparable to those found in plant foods known to have anti-inflammatory, anti-carcinogenic, and cardioprotective effects. As meat and milk are often not considered as sources of phytochemicals, their presence has remained largely underappreciated in discussions of nutritional differences between feedlot-fed (grain-fed) and pasture-finished (grass-fed) meat and dairy, which have predominantly centered around the ω-3 fatty acids and conjugated linoleic acid. Grazing livestock on plant-species diverse pastures concentrates a wider variety and higher amounts of phytochemicals in meat and milk compared to grazing monoculture pastures, while phytochemicals are further reduced or absent in meat and milk of grain-fed animals. The co-evolution of plants and herbivores has led to plants/crops being more productive when grazed in accordance with agroecological principles. The increased phytochemical richness of productive vegetation has potential to improve the health of animals and upscale these nutrients to also benefit human health. Several studies have found increased anti-oxidant activity in meat and milk of grass-fed vs. grain-fed animals. Only a handful of studies have investigated the effects of grass-fed meat and dairy consumption on human health and show potential for anti-inflammatory effects and improved lipoprotein profiles. However, current knowledge does not allow for direct linking of livestock production practices to human health. Future research should systematically assess linkages between the phytochemical richness of livestock diets, the nutrient density of animal foods, and subsequent effects on human metabolic health. This is important given current societal concerns about red meat consumption and human health. Addressing this research gap will require greater collaborative efforts from the fields of agriculture and medicine.

Beschreibung: Organic farming systems are gaining popularity as agronomically and environmentally sound soil management strategies with potential to enhance soil microbial diversity and fertility, environmental quality and sustainable crop production. This work aimed at understanding the effect of organic and conventional farming on the diversity of soybean nodulating bradyrhizobia species. Field trapping of indigenous soybean Bradyrhizobium was done by planting promiscuous soybeans varieties SB16 and SC squire as well as non-promiscuous Gazelle in three organic and three conventional farms in Tharaka-Nithi County of Kenya. After 45 days of growth, 108 nodule isolates were obtained from the soybean nodules and placed into 13 groups based on their morphological characteristics. Genetic diversity was done by polymerase chain reaction (PCR) targeting 16S rDNA gene using universal primers P5-R and P3-F and sequencing was carried out using the same primer. High morphological and genetic diversity of the nodule isolates was observed in organic farms as opposed to conventional farms. There was little or no genetic differentiation between the nodule isolates from the different farms with the highest molecular variation (91.12%) being partitioned within populations as opposed to among populations (8.88%). All the isolates were identified as bradyrhizobia with close evolutionary ties with Bradyrhizobium japonicum and Bradyrhizobium yuanminense. Organic farming systems favor the proliferation of bradyrhizobia species and therefore a suitable environmentally friendly alternative for enhancing soybean production.

Beschreibung: Treatment with immune checkpoint inhibitors (ICI) has demonstrated clinical benefit for a wide range of cancer types. Because only a subset of patients experience clinical benefit, there is a strong need for biomarkers that are easily accessible across diverse practice settings. Here, in a retrospective cohort study of 1714 patients with 16 different cancer types treated with ICI, we show that higher neutrophil-to-lymphocyte ratio (NLR) is significantly associated with poorer overall and progression-free survival, and lower rates of response and clinical benefit, after ICI therapy across multiple cancer types. Combining NLR with tumor mutational burden (TMB), the probability of benefit from ICI is significantly higher (OR = 3.22; 95% CI, 2.26-4.58; P 

Beschreibung: Cellular senescence is induced by stresses and results in a stable proliferation arrest accompanied by a pro-inflammatory secretome. Senescent cells accumulate during aging, promoting various age-related pathologies and limiting lifespan. The endoplasmic reticulum (ER) inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) calcium-release channel and calcium fluxes from the ER to the mitochondria are drivers of senescence in human cells. Here we show that Itpr2 knockout (KO) mice display improved aging such as increased lifespan, a better response to metabolic stress, less immunosenescence, as well as less liver steatosis and fibrosis. Cellular senescence, which is known to promote these alterations, is decreased in Itpr2 KO mice and Itpr2 KO embryo-derived cells. Interestingly, ablation of ITPR2 in vivo and in vitro decreases the number of contacts between the mitochondria and the ER and their forced contacts induce premature senescence. These findings shed light on the role of contacts and facilitated exchanges between the ER and the mitochondria through ITPR2 in regulating senescence and aging.