Origin of Evolution versus Origin of Life: A Shift of Paradigm

The question of the primordial ancestor must be approached through the search for the origin of evolution, not through the search for the origin of life. There is a major issue with the concept of life because it is impossible to define, thus is not a scientific but a metaphysical concept. On the contrary, evolution may be defined by as few as three conditions. These do not necessarily involve biopolymers. However, such an approach must give clues to explain the emergence of distinct lineages to allow Darwinian natural selection. A plausible solution exists within an autotrophic lipidic vesicle-based model that is presented. The model requires the existence of hydrothermal sites such as the Lost City Hydrothermal Field leading to specific constraints. For this reason Mars and Europa may be questioned as possible cradles of evolution. If we replace the search for the origin of life by the one for the origin of evolution our priority first is to find a consensus on the minimal conditions that would allow evolution to emerge and persist anywhere in the universe.     

Omics-Based Strategies in Precision Medicine: Toward a Paradigm Shift in Inborn Errors of Metabolism Investigations

The rise of technologies that simultaneously measure thousands of data points represents the heart of systems biology. These technologies have had a huge impact on the discovery of next-generation diagnostics, biomarkers, and drugs in the precision medicine era. Systems biology aims to achieve systemic exploration of complex interactions in biological systems. Driven by high-throughput omics technologies and the computational surge, it enables multi-scale and insightful overviews of cells, organisms, and populations. Precision medicine capitalizes on these conceptual and technological advancements and stands on two main pillars: data generation and data modeling. High-throughput omics technologies allow the retrieval of comprehensive and holistic biological information, whereas computational capabilities enable high-dimensional data modeling and, therefore, accessible and user-friendly visualization. Furthermore, bioinformatics has enabled comprehensive multi-omics and clinical data integration for insightful interpretation. Despite their promise, the translation of these technologies into clinically actionable tools has been slow. In this review, we present state-of-the-art multi-omics data analysis strategies in a clinical context. The challenges of omics-based biomarker translation are discussed. Perspectives regarding the use of multi-omics approaches for inborn errors of metabolism (IEM) are presented by introducing a new paradigm shift in addressing IEM investigations in the post-genomic era.     

The Dynamics of Pheromone Gland Synthesis and Release: a Paradigm Shift for Understanding Sex Pheromone Quantity in Female Moths

Moths are exemplars of chemical communication, especially with regard to specificity and the minute amounts they use. Yet, little is known about how females manage synthesis and storage of pheromone to maintain release rates attractive to conspecific males and why such small amounts are used. We developed, for the first time, a quantitative model, based on an extensive empirical data set, describing the dynamical relationship among synthesis, storage (titer) and release of pheromone over time in a moth (Heliothis virescens). The model is compartmental, with one major state variable (titer), one time-varying (synthesis), and two constant (catabolism and release) rates. The model was a good fit, suggesting it accounted for the major processes. Overall, we found the relatively small amounts of pheromone stored and released were largely a function of high catabolism rather than a low rate of synthesis. A paradigm shift may be necessary to understand the low amounts released by female moths, away from the small quantities synthesized to the (relatively) large amounts catabolized. Future research on pheromone quantity should focus on structural and physicochemical processes that limit storage and release rate quantities. To our knowledge, this is the first time that pheromone gland function has been modeled for any animal.     

Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus

Although ^99mTc is not an ideal Auger electron (AE) emitter for Targeted Radionuclide Therapy (TRT) due to its relatively low Auger electron yield, it can be considered a readily available “model” radionuclide useful to validate the design of new classes of AE-emitting radioconjugates. With this in mind, we performed a detailed study of the radiobiological effects and mechanisms of cell death induced by the dual-targeted radioconjugates ^99mTc-TPP-BBN and ^99mTc-AO-BBN (TPP = triphenylphosphonium; AO = acridine orange; BBN = bombesin derivative) in human prostate cancer PC3 cells. ^99mTc-TPP-BBN and ^99mTc-AO-BBN caused a remarkably high reduction of the survival of PC3 cells when compared with the single-targeted congener ^99mTc-BBN, leading to an augmented formation of γH2AX foci and micronuclei. ^99mTc-TPP-BBN also caused a reduction of the mtDNA copy number, although it enhanced the ATP production by PC3 cells. These differences can be attributed to the augmented uptake of ^99mTc-TPP-BBN in the mitochondria and enhanced uptake of ^99mTc-AO-BBN in the nucleus, allowing the irradiation of these radiosensitive organelles with the short path-length AEs emitted by ^99mTc. In particular, the results obtained for ^99mTc-TPP-BBN reinforce the relevance of targeting the mitochondria to promote stronger radiobiological effects by AE-emitting radioconjugates.     

Experimental Evidence of an Age-Specific Shift in Chemical Detection of Predators in a Lizard

The risk posed by predation is one of the most fundamental aspects of an animal's environment. Avoidance of predators implies an ability to obtain reliable information about the risk of predation, and for many species, chemosensory cues are likely to be an important source of such information. Chemosensory cues reliably reveal the presence of predators or their presence in the recent past. We used retreat site selection experiments to test whether the Australian scincid lizard Eulamprus heatwoleiM uses chemical cues for predator detection and avoidance. Both adult and juvenile lizards were given the choice of retreat sites treated with scents from invertebrate predators, as well as sympatric and allopatric snake predators. Some of the snake predators were known to eat E. heatwolei, while others did not pose a predation threat. All invertebrate predators posed a risk to juveniles, but not adults because of their size. We found that juvenile E. heatwolei avoided predator odors more strongly than adults. Juveniles avoided both invertebrate predators and snakes, and the strongest response was toward the funnelweb spider, the only ambush predator used in this experiment. This result may demonstrate the importance of predator ecology in the evolution of predator detection mechanisms, with chemical cues being more useful in detecting sedentary predators than active predators. Adult lizards showed no avoidance behavior toward predator odors. This result suggests an age specific shift in predator avoidance behavior as lizards get older and become too large for many predators. However, adults showed no response to the odor from the red-bellied black snake, a known predator of adult E. heatwolei. This finding further demonstrates the importance of predator ecology when examining communication between predators and prey. Chemical cues, which are persistent long after predators have vacated the area, may not be useful in detecting the red-bellied black snake, a wide-ranging active forager.     

Oncometabolism: A Paradigm for the Metabolic Remodeling of the Failing Heart

Heart failure is associated with profound alterations in cardiac intermediary metabolism. One of the prevailing hypotheses is that metabolic remodeling leads to a mismatch between cardiac energy (ATP) production and demand, thereby impairing cardiac function. However, even after decades of research, the relevance of metabolic remodeling in the pathogenesis of heart failure has remained elusive. Here we propose that cardiac metabolic remodeling should be looked upon from more perspectives than the mere production of ATP needed for cardiac contraction and relaxation. Recently, advances in cancer research have revealed that the metabolic rewiring of cancer cells, often coined as oncometabolism, directly impacts cellular phenotype and function. Accordingly, it is well feasible that the rewiring of cardiac cellular metabolism during the development of heart failure serves similar functions. In this review, we reflect on the influence of principal metabolic pathways on cellular phenotype as originally described in cancer cells and discuss their potential relevance for cardiac pathogenesis. We discuss current knowledge of metabolism-driven phenotypical alterations in the different cell types of the heart and evaluate their impact on cardiac pathogenesis and therapy.     

CO变换系统的几点节能措施

本文分析了变换系统能耗高的主要原因。采取了不开电炉、强化保温、减少热损失、防止蒸气带水和热交腐蚀及强化操作与管理等措施,从而降低参耗提高经济效益。     

Trail-following in termites: Evidence for a multicomponent system

Several African termite species from different subfamilies and different habitats are sensitive to trail-active extracts or to naturally laid trails from other species. Using single-extract bioassays, it is shown that the response threshold for trail-following is nearly identical for all tested species (except forHodotermes mossambicus). However, when termite workers have a choice between trails from their own species and from other species, conspecific trail-following is exclusively observed. This phenomenon can be counteracted by dilution (110) of the conspecific trail-pheromone extract. Tests of the trail activity of various synthetic alcohols show that among these, the highest sensitivity of termite workers is to (Z)-3-dodecen-1-ol. Based on our experimental data, we postulate that, in addition to a generally active trail-pheromone constituent (an unsaturated primary C₁₂ alcohol) or a pool of chemically closely related alcohols, other species-specific components are present in termite trails.     

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

The quantity of high-density lipoproteins (HDL) is represented as the serum HDL-C concentration (mg/dL), while the HDL quality manifests as the diverse features of protein and lipid content, extent of oxidation, and extent of glycation. The HDL functionality represents several performance metrics of HDL, such as antioxidant, anti-inflammatory, and cholesterol efflux activities. The quantity and quality of HDL can change during one’s lifetime, depending on infection, disease, and lifestyle, such as dietary habits, exercise, and smoking. The quantity of HDL can change according to age and gender, such as puberty, middle-aged symptoms, climacteric, and the menopause. HDL-C can decrease during disease states, such as acute infection, chronic inflammation, and autoimmune disease, while it can be increased by regular aerobic exercise and healthy food consumption. Generally, high HDL-C at the normal level is associated with good HDL quality and functionality. Nevertheless, high HDL quantity is not always accompanied by good HDL quality or functionality. The HDL quality concerns the morphology of the HDL, such as particle size, shape, and number. The HDL quality also depends on the composition of the HDL, such as apolipoproteins (apoA-I, apoA-II, apoC-III, serum amyloid A, and α-synuclein), cholesterol, and triglyceride. The HDL quality is also associated with the extent of HDL modification, such as glycation and oxidation, resulting in the multimerization of apoA-I, and the aggregation leads to amyloidogenesis. The HDL quality frequently determines the HDL functionality, which depends on the attached antioxidant enzyme activity, such as the paraoxonase and cholesterol efflux activity. Conventional HDL functionality is regression, the removal of cholesterol from atherosclerotic lesions, and the removal of oxidized species in low-density lipoproteins (LDL). Recently, HDL functionality was reported to expand the removal of β-amyloid plaque and inhibit α-synuclein aggregation in the brain to attenuate Alzheimer’s disease and Parkinson’s disease, respectively. More recently, HDL functionality has been associated with the susceptibility and recovery ability of coronavirus disease 2019 (COVID-19) by inhibiting the activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The appearance of dysfunctional HDL is frequently associated with many acute infectious diseases and chronic aging-related diseases. An HDL can be a suitable biomarker to diagnose many diseases and their progression by monitoring the changes in its quantity and quality in terms of the antioxidant and anti-inflammatory abilities. An HDL can be a protein drug used for the removal of plaque and as a delivery vehicle for non-soluble drugs and genes. A dysfunctional HDL has poor HDL quality, such as a lower apoA-I content, lower antioxidant ability, smaller size, and ambiguous shape. The current review analyzes the recent advances in HDL quantity, quality, and functionality, depending on the health and disease state during one’s lifetime.     

Interspecific recognition among termites of the genusReticulitermes: Evidence for a role for the cuticular hydrocarbons

Two species of termites,Reticulitermes (lucifugus) grassei andR. (l.) banyulensis, show a high degree of aggressivity toward each other. The epicuticular signature, recognized by contact, can be extracted using organic solvents, and the removal of the signature abolished all types of aggressive behavior. The signature can be transferred to lures, where it triggers interspecies aggression. It was found to be mainly present in the apolar fraction of the cuticular extracts, which contained only hydrocarbons, are determined by GC/MS techniques. Chemical recognition contributes towards isolation of the two species belonging to theR. lucifugus complex.     

Heat Stress Decreases Rice Grain Weight: Evidence and Physiological Mechanisms of Heat Effects Prior to Flowering

Heat stress during the preflowering panicle initiation stage seriously decreases rice grain weight in an invisible way and has not been given enough attention. The current review aims to (i) specify the heat effects on rice grain weight during the panicle initiation stage compared with the most important grain-filling stage; and (ii) discuss the physiological mechanisms of the decreased rice grain weight induced by heat during panicle initiation in terms of assimilate supply and phytohormone regulation, which are key physiological processes directly regulating rice grain weight. We emphasize that the effect of heat during the panicle initiation stage on rice grain weight is more serious than that during the grain-filling stage. Heat stress during the panicle initiation stage induces alterations in endogenous phytohormones, leading to the inhibition of the photosynthesis of functional leaves (source) and the formation of vascular bundles (flow), thus reducing the accumulation and transport of nonstructural carbohydrates and the growth of lemmata and paleae. The disruptions in the “flow” and restrictions in the preanthesis “source” tissue reduce grain size directly and decrease grain plumpness indirectly, resulting in a reduction in the final grain weight, which could be the direct physiological causes of the lower rice grain weight induced by heat during the panicle initiation stage. We highlight the seriousness of preflowering heat stress on rice grain weight, which can be regarded as an invisible disaster. The physiological mechanisms underlying the lower grain weight induced by heat during panicle initiation show a certain novelty because they distinguish this stage from the grain-filling stage. Additionally, a number of genes that control grain size through phytohormones have been summarized, but their functions have not yet been fully tested under heat conditions, except for the Grain Size and Abiotic stress tolerance 1 (GSA1) and BRASSINOSTEROID INSENSITIVE1 (OsBRI1) genes, which are reported to respond rapidly to heat stress. The mechanisms of reduced rice grain weight induced by heat during the panicle initiation stage should be studied in more depth in terms of molecular pathways.     

Development of a Method for Evaluating Alumina Ceramic Material the Wear Resistance

Refractories and Industrial Ceramics - Amethod is developed for rapid evaluation of the wear resistance of ceramic materials by changing the roughness parameter Rt. The method is tested...     

Opinion: On the Way towards the New Paradigm of Atherosclerosis

Atherosclerosis is a multicausal disease characterized by the formation of cholesterol-containing plaque in the pronounced intima nearest to the heart’s elastic-type arteries that have high levels of blood circulation. Plaques are formed due to arterial pressure-induced damage to the endothelium in areas of turbulent blood flow. It is found in the majority of the Western population, including young people. This denies the monogenic mechanism of atherogenesis. In 1988, Orekhov et al. and Kawai et al. discovered that the presence of atherogenic (modified, including oxidized ones) LDLs is necessary for atherogenesis. On the basis of our discovery, suggesting that the overloading of enterocytes with lipids could lead to the formation of modified LDLs, we proposed a new hypothesis explaining the main factors of atherogenesis. Indeed, when endothelial cells are damaged and then pass through the G2 phase of their cell cycle they secrete proteins into their basement membrane. This leads to thickening of the basement membrane and increases its affinity to LDL especially for modified ones. When the enterocyte transcytosis pathway is overloaded with fat, very large chylomicrons are formed, which have few sialic acids, circulate in the blood for a long time, undergo oxidation, and can induce the production of autoantibodies. It is the sialic acids that shield the short forks of the polysaccharide chains to which autoantibodies are produced. Here, these data are evaluated from the point of view of our new model.     

New Beta-lactamases in Candidate Phyla Radiation: Owning Pleiotropic Enzymes Is a Smart Paradigm for Microorganisms with a Reduced Genome

The increased exploitation of microbial sequencing methods has shed light on the high diversity of new microorganisms named Candidate Phyla Radiation (CPR). CPR are mainly detected via 16S rRNA/metabarcoding analyses or metagenomics and are found to be abundant in all environments and present in different human microbiomes. These microbes, characterized by their symbiotic/epiparasitic lifestyle with bacteria, are directly exposed to competition with other microorganisms sharing the same ecological niche. Recently, a rich repertoire of enzymes with antibiotic resistance activity has been found in CPR genomes by using an in silico adapted screening strategy. This reservoir has shown a high prevalence of putative beta-lactamase-encoding genes. We expressed and purified five putative beta-lactamase sequences having the essential domains and functional motifs from class A and class B beta-lactamase. Their enzymatic activities were tested against various beta-lactam substrates using liquid chromatography-mass spectrometry (LC-MS) and showed some beta-lactamase activity even in the presence of a beta-lactamase inhibitor. In addition, ribonuclease activity was demonstrated against RNA that was not inhibited by sulbactam and EDTA. None of these proteins could degrade single- and double-stranded-DNA. This study is the first to express and test putative CPR beta-lactamase protein sequences in vitro. Our findings highlight that the reduced genomes of CPR members harbor sequences encoding for beta-lactamases known to be multifunction hydrolase enzymes.     

Testing for the Cointegrating Rank of a VAR Process with Level Shift and Trend Break

Abstract. A test for the cointegrating rank of a vector autoregressive (VAR) process with a possible shift and broken linear trend is proposed. The break point is assumed to be known. Our test is not a likelihood ratio test but the deterministic terms including the broken trends are removed first by a generalized least squares procedure. Then, a likelihood ratio‐type test is applied to the adjusted series. The asymptotic null distribution of the test is derived and it is shown by a Monte Carlo experiment that the test has better small‐sample properties in many cases than a corresponding Gaussian likelihood ratio test for the cointegrating rank. Moreover, response surface techniques can be used to easily obtain p‐values of the test for any possible break date.     

Ribosome: The Structure–Function Relation and a New Paradigm to the Protein Folding Problem

The rate of protein synthesis is about seven and fifteen amino acids per second, in the eukaryotic and the bacterial ribosome, respectively. Hence, a few minutes is required to synthesize a polypeptide of an average length. This is much longer than the time needed for the hydrophobic collapse (folding) to take place. So a polypeptide gets enough time to form its local secondary to tertiary structures cotranslationally and put such segments in proper order while in association with the ribosome, unless something prevents its entire length from folding. As reported earlier, ribosomes from prokaryotes, eukaryotes, and mitochondria act as molds for protein folding, and each mold has a set of recognition sites for all proteins. More specifically, the mold is the peptidyl transferase center (PTC), a part of the large RNA of the large ribosomal subunit. Specific amino acids from different random coil regions in a protein interact with specific nucleotides in the PTC, which brings the entire length of the protein into the small space of the PTC mold. The mold thus helps to stabilize the entropy-driven collapsed state of the polypeptide. The process also divides the protein into small segments; each segment is connected at two ends with two nucleotides and can fold in the ribosomal environment. The segments dissociate in such a sequence that the organization proceeds hierarchically from the core of the globular protein radially towards the outer surface. Then the protein dissociates from the ribosome in a “folding competent state” which does the final fine tuning in folding outside the ribosome. While the ribosomal contact and release are over in 1–2 minutes in vitro, the fine tuning takes about 5–10 minutes. Release from the ribosome needs no added energy factor from outside, like ATP.     

Evidence for a Dioxetane Intermediate in the Lucigenin Light Reaction

10,10′-Dimethyl-9,9′-biacrilydene in pinacolone reacts with ozone at −45°C to give a thermally unstable product, the decomposition of which results in N-methylacridone and emission of light with a quantum yield of over 10⁻² Einstein · mole⁻¹, showing the reaction to be one of the most efficient chemiluminescent reactions known. As the chemical reaction is known to yield dioxetanes and the primary exited product is shown to be N-methylacridone, positive evidence is provided that the Lucigenin light reaction proceeds via a dioxetane intermediate.