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Reticulated platelets are immature platelets freshly released from the bone marrow into the circulation and contain vestigial amounts of ribonucleic acid. Thus, they can serve as an indicator for the activity of thrombopoiesis. Despite the current lack of a standardized reference method, two types of hematology analyzers have incorporated a fully automated measurement of reticulated platelets. The “immature platelet fraction” (IPF; Sysmex XE-/XN-series) has some clinical utility in the differential diagnosis of thrombocytopenia. This is less clear for “reticulated platelets” (retPLT; Abbott CELL-DYN Sapphire/Alinity HQ). The usefulness of these parameters in the prediction of platelet recovery after chemotherapy or stem cell transplantation and as a decision aid for platelet transfusions has not been unequivocally confirmed. Recent findings have shown an association of reticulated platelets with an adverse risk in patients with coronary artery disease and stroke as well as resistance to anti-platelet therapy. Furthermore, a role of reticulated platelets for the prediction of sepsis was indicated. However, validation in larger prospective trials is necessary to establish the clinical benefit of reticulated platelets in these conditions. This review gives an overview of the available analytical methods and summarizes the current knowledge regarding the clinical application of reticulated platelets.

Mining is known to cause high ecological and social impacts especially due to its extractive nature on one hand and its resources and reserves mostly being located in developing or emerging economies on the other hand. Thus, it can be considered to have a paramount role in terms of making a significant contribution to sustainable development. Bearing in mind the growing economic output generated by humans and the growing world population, it is no wonder that related human-driven activities have never had such a strong (and at the same time burdening) influence on the biosphere resulting in exceedance of the planetary system boundaries. The critical reflection of the interaction between material cycles and economic growth is essential for reducing environmental burdens resulting from unthinking consumption patterns and production, and initial material extraction. The latest findings in academia confirm this assumption and point out that most practitioners are already aware of the urgent need for a redefinition of the sector’s understanding of success, taking into account the needs of both shareholders and stakeholders. Furthermore, the extractive sector has gained an image of being outdated. Agrowing number of decision-makers sees the necessity for a sustainable approach to business models that also embraces digitalization. The purpose of the paper is to analyze the standard business model that still dominates the mining industry, followed by a comparison of recent scientific findings on sustainability-oriented business model innovation and values-based innovation management to derive recommendations for potential sector-specific business model archetypes that contribute to the urgent redefinition.

Abstract Background Heart failure (HF) patients have a high risk of death, and implantable cardioverter defibrillators (ICDs) are effective in preventing sudden cardiac death (SCD). However, a certain percentage of patients may not be immediate candidates for ICDs, particularly those having a short duration of risk or an uncertain amount of risk. This includes the newly diagnosed patients, as well as those on the cardiac transplant list or NYHA class IV heart failure patients who do not already have an ICD. In these patients, a wearable cardioverter defibrillator (WCD) may be used until long term risk of SCD is defined. The purpose of this study was to determine the incidence of SCD in this population, and the efficacy of early defibrillation by a WCD. Methods Ten enrolling centers identified 89 eligible HF patients who were either listed for cardiac transplantation, diagnosed with dilated cardiomyopathy, or receiving inotropic medications. Data collected included medical history, device records, and outcomes (including 90 day mortality). Results Out of 89 patients, final data on 82 patients has been collected. Patients wore the device for 75±58 days. Mean age was 56.8±13.2, and 72% were male. Most patients (98.8%) were diagnosed with dilated cardiomyopathy with a low ejection fraction ( Conclusions In conclusion, the WCD monitored HF patients until further assessment of risk. The leading reasons for end of WCD use were improvement in left ventricular ejection fraction (LVEF) or ICD implantation if there was no significant improvement in LVEF.

Abstract Background The importance of voltage-dependent conductances in sensory information processing is well-established in insect photoreceptors. Here we present the characterization of electrical properties in photoreceptors of the cockroach (Periplaneta americana), a nocturnal insect with a visual system adapted for dim light. Results Whole-cell patch-clamped photoreceptors had high capacitances and input resistances, indicating large photosensitive rhabdomeres suitable for efficient photon capture and amplification of small photocurrents at low light levels. Two voltage-dependent potassium conductances were found in the photoreceptors: a delayed rectifier type (KDR) and a fast transient inactivating type (KA). Activation of KDR occurred during physiological voltage responses induced by light stimulation, whereas KA was nearly fully inactivated already at the dark resting potential. In addition, hyperpolarization of photoreceptors activated a small-amplitude inward-rectifying (IR) current mediated at least partially by chloride. Computer simulations showed that KDR shapes light responses by opposing the light-induced depolarization and speeding up the membrane time constant, whereas KA and IR have a negligible role in the majority of cells. However, larger KA conductances were found in smaller and rapidly adapting photoreceptors, where KA could have a functional role. Conclusions The relative expression of KA and KDR in cockroach photoreceptors was opposite to the previously hypothesized framework for dark-active insects, necessitating further comparative work on the conductances. In general, the varying deployment of stereotypical K+ conductances in insect photoreceptors highlights their functional flexibility in neural coding.

Nigella sativa (Black cumin) has many applications in food and pharmaceutical industries. Thymoquinone has been considered as a main effective compound in N. sativa seeds and attracted researchers' attention mainly due to its medicinal potential. In this study, the essential oil components of leaves, flowers and seed developmental stages including half black seeds, soft black seeds and hard black seeds were analyzed in N. sativa. Whereas no terpenes were detected in flowers and leaves, seeds showed an essential oil composition that increased in its thymoquinone content during seed maturation. To study the proposed first step of thymoquinone biosynthesis, the formation of γ-terpinene from geranyl diphosphate (GDP), we identified and functionally characterized a γ-terpinene synthase (NsTPS1) in N. sativa. This monoterpene synthase was identified in RNA sequence data derived from seeds. After heterologous expression in Escherichia coli, partially purified NsTPS1 converted GDP to γ-terpinene. NsTPS1 is the first functionally characterized terpene synthase from N. sativa and displays a higher similarity to other terpene synthases from Ranunculaceae than known γ-terpinene synthases from more distant plant species. Characterization of NsTPS1 elucidates the first dedicated step in the biosynthesis of thymoquinone in N. sativa and paves the way towards metabolic engineering for high-level thymoquinone production., (Copyright © 2022. Published by Elsevier Ltd.)

Thymol and carvacrol are phenolic monoterpenes found in thyme, oregano, and several other species of the Lamiaceae. Long valued for their smell and taste, these substances also have antibacterial and anti-spasmolytic properties. They are also suggested to be precursors of thymohydroquinone and thymoquinone, monoterpenes with anti-inflammatory, antioxidant, and antitumor activities. Thymol and carvacrol biosynthesis has been proposed to proceed by the cyclization of geranyl diphosphate to γ-terpinene, followed by a series of oxidations via p -cymene. Here, we show that γ-terpinene is oxidized by cytochrome P450 monooxygenases (P450s) of the CYP71D subfamily to produce unstable cyclohexadienol intermediates, which are then dehydrogenated by a short-chain dehydrogenase/reductase (SDR) to the corresponding ketones. The subsequent formation of the aromatic compounds occurs via keto-enol tautomerisms. Combining these enzymes with γ-terpinene in in vitro assays or in vivo in Nicotiana benthamiana yielded thymol and carvacrol as products. In the absence of the SDRs, only p -cymene was formed by rearrangement of the cyclohexadienol intermediates. The nature of these unstable intermediates was inferred from reactions with the γ-terpinene isomer limonene and by analogy to reactions catalyzed by related enzymes. We also identified and characterized two P450s of the CYP76S and CYP736A subfamilies that catalyze the hydroxylation of thymol and carvacrol to thymohydroquinone when heterologously expressed in yeast and N. benthamiana Our findings alter previous views of thymol and carvacrol formation, identify the enzymes involved in the biosynthesis of these phenolic monoterpenes and thymohydroquinone in the Lamiaceae, and provide targets for metabolic engineering of high-value terpenes in plants., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Plants use a wide array of secondary metabolites including terpenes as defense against herbivore and pathogen attack, which can be constitutively expressed or induced. Here, we investigated aspects of the chemical and molecular basis of resistance against the exotic rust fungus Austropuccinia psidii in Melaleuca quinquenervia , with a focus on terpenes. Foliar terpenes of resistant and susceptible plants were quantified, and we assessed whether chemotypic variation contributed to resistance to infection by A. psidii . We found that chemotypes did not contribute to the resistance and susceptibility of M. quinquenervia . However, in one of the chemotypes (Chemotype 2), susceptible plants showed higher concentrations of several terpenes including α-pinene, limonene, 1,8-cineole, and viridiflorol compared with resistant plants. Transcriptome profiling of these plants showed that several TPS genes were strongly induced in response to infection by A. psidii . Functional characterization of these TPS showed them to be mono- and sesquiterpene synthases producing compounds including 1,8-cineole, β-caryophyllene, viridiflorol and nerolidol. The expression of these TPS genes correlated with metabolite data in a susceptible plant. These results suggest the complexity of resistance mechanism regulated by M .  quinquenervia and that modulation of terpenes may be one of the components that contribute to resistance against A. psidii ., Competing Interests: The authors declare that there is no conflict of interest., (© 2021 The Authors. Plant‐Environment Interactions published by John Wiley & Sons Ltd and New Phytologist Foundation.)

Background: Terpene rich leaves are a characteristic of Myrtaceae. There is significant qualitative variation in the terpene profile of plants within a single species, which is observable as "chemotypes". Understanding the molecular basis of chemotypic variation will help explain how such variation is maintained in natural populations as well as allowing focussed breeding for those terpenes sought by industry. The leaves of the medicinal tea tree, Melaleuca alternifolia, are used to produce terpinen-4-ol rich tea tree oil, but there are six naturally occurring chemotypes; three cardinal chemotypes (dominated by terpinen-4-ol, terpinolene and 1,8-cineole, respectively) and three intermediates. It has been predicted that three distinct terpene synthases could be responsible for the maintenance of chemotypic variation in this species., Results: We isolated and characterised the most abundant terpene synthases (TPSs) from the three cardinal chemotypes of M. alternifolia. Functional characterisation of these enzymes shows that they produce the dominant compounds in the foliar terpene profile of all six chemotypes. Using RNA-Seq, we investigated the expression of these and 24 additional putative terpene synthases in young leaves of all six chemotypes of M. alternifolia., Conclusions: Despite contributing to the variation patterns observed, variation in gene expression of the three TPS genes is not enough to explain all variation for the maintenance of chemotypes. Other candidate terpene synthases as well as other levels of regulation must also be involved. The results of this study provide novel insights into the complexity of terpene biosynthesis in natural populations of a non-model organism.

Stream ecosystems show gradual variation of various selection factors, which can result in a zonation of species distributions and gradient evolution of morphological and life-history traits within species. Identifying the selective agents underlying such phenotypic evolution is challenging as different species could show shared and/or unique (species-specific) responses to components of the river gradient. We studied a stream gradient inhabited by two mosquitofishes (genus Gambusia) in the Río Grijalva basin in southern Mexico and found a patchy distribution pattern of both congeners along a stretch of 100 km, whereby one species was usually dominant at a given site. We uncovered both shared and unique patterns of diversification: some components of the stream gradient, including differences in piscine predation pressure, drove shared patterns of phenotypic divergence, especially in females. Other components of the gradient, particularly abiotic factors (max. annual temperature and temperature range) resulted in unique patterns of divergence, especially in males. Our study highlights the complexity of selective regimes in stream ecosystems. It exemplifies that even closely related, congeneric species can respond in unique ways to the same components of the river gradient and shows how both sexes can exhibit quite different patterns of divergence in multivariate phenotypic character suites.

Background: Terpenoids are abundant in the foliage of Eucalyptus, providing the characteristic smell as well as being valuable economically and influencing ecological interactions. Quantitative and qualitative inter- and intra- specific variation of terpenes is common in eucalypts., Results: The genome sequences of Eucalyptus grandis and E. globulus were mined for terpene synthase genes (TPS) and compared to other plant species. We investigated the relative expression of TPS in seven plant tissues and functionally characterized five TPS genes from E. grandis. Compared to other sequenced plant genomes, Eucalyptus grandis has the largest number of putative functional TPS genes of any sequenced plant. We discovered 113 and 106 putative functional TPS genes in E. grandis and E. globulus, respectively. All but one TPS from E. grandis were expressed in at least one of seven plant tissues examined. Genomic clusters of up to 20 genes were identified. Many TPS are expressed in tissues other than leaves which invites a re-evaluation of the function of terpenes in Eucalyptus., Conclusions: Our data indicate that terpenes in Eucalyptus may play a wider role in biotic and abiotic interactions than previously thought. Tissue specific expression is common and the possibility of stress induction needs further investigation. Phylogenetic comparison of the two investigated Eucalyptus species gives insight about recent evolution of different clades within the TPS gene family. While the majority of TPS genes occur in orthologous pairs some clades show evidence of recent gene duplication, as well as loss of function.

Phenotypic mosaic trees offer an ideal system for studying differential gene expression. We have investigated two mosaic eucalypt trees from two closely related species (Eucalyptus melliodora and E. sideroxylon), which each support two types of leaves: one part of the canopy is resistant to insect herbivory and the remaining leaves are susceptible. Driving this ecological distinction are differences in plant secondary metabolites. We used these phenotypic mosaics to investigate genome wide patterns of foliar gene expression with the aim of identifying patterns of differential gene expression and the somatic mutation(s) that lead to this phenotypic mosaicism. We sequenced the mRNA pool from leaves of the resistant and susceptible ecotypes from both mosaic eucalypts using the Illumina HiSeq 2000 platform. We found large differences in pathway regulation and gene expression between the ecotypes of each mosaic. The expression of the genes in the MVA and MEP pathways is reflected by variation in leaf chemistry, however this is not the case for the terpene synthases. Apart from the terpene biosynthetic pathway, there are several other metabolic pathways that are differentially regulated between the two ecotypes, suggesting there is much more phenotypic diversity than has been described. Despite the close relationship between the two species, they show large differences in the global patterns of gene and pathway regulation.

The essential oil of Thymus vulgaris consists of a complex blend of mono- and sesquiterpenes that provides the plant with its characteristic aromatic odor. Several chemotypes have been described for thyme. In this study, we identified two enzymes of the sabinene hydrate chemotype which are responsible for the biosynthesis of its major monoterpene alcohols, (1S,2R,4S)-(Z)-sabinene hydrate and (1S,2S,4R)-(E)-sabinene hydrate. Both TPS6 and TPS7 are multiproduct enzymes that formed 16 monoterpenes and thus cover almost the whole monoterpene spectrum of the chemotype. Although the product spectra of both enzymes are similar, they form opposing enantiomers of their chiral products. Incubation of the enzymes with the potential reaction intermediates revealed that the stereospecificity of TPS6 and TPS7 is determined by the formation of the first intermediate, linalyl diphosphate. Since TPS6 and TPS7 shared an amino acid sequence identity of 85%, a mutagenesis study was employed to identify the amino acids that determine the stereoselectivity. One amino acid position had a major influence on the stereochemistry of the formed products. Based on comparative models of TPS6 and TPS7 protein structures with the GPP substrate docked in the active site pocket, the influence of this amino acid residue on the reaction mechanism is discussed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The flavor and taste of fruits are often determined by terpenes. We identified three cDNAs encoding putative terpene synthases from olive fruits of cv. Frantoio and Grignano. Heterologous expression in a bacterial system demonstrated that one of the terpene synthases, OeGES1, was an active monoterpene synthase that converted geranyl diphosphate to the monoterpene alcohol geraniol. The transcript accumulation pattern of this gene showed a peak during fruit ripening in both genotypes, indicating that the enzyme may be involved in the production of monoterpene flavor compounds in olive fruit. Although the putative terpene synthases OeTPS2 and OeTPS3 clustered with α-farnesene synthases and angiosperm monoterpene synthases, no detectable in vitro activity was found after expression in a bacterial system. Nevertheless, their transcripts sharply accumulated during fruit ripening starting from véraison., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Background: The essential oil of chamomile, one of the oldest and agronomically most important medicinal plant species in Europe, has significant antiphlogistic, spasmolytic and antimicrobial activities. It is rich in chamazulene, a pharmaceutically active compound spontaneously formed during steam distillation from the sesquiterpene lactone matricine. Chamomile oil also contains sesquiterpene alcohols and hydrocarbons which are produced by the action of terpene synthases (TPS), the key enzymes in constructing terpene carbon skeletons., Results: Here, we present the identification and characterization of five TPS enzymes contributing to terpene biosynthesis in chamomile (Matricaria recutita). Four of these enzymes were exclusively expressed in above-ground organs and produced the common terpene hydrocarbons (-)-(E)-β-caryophyllene (MrTPS1), (+)-germacrene A (MrTPS3), (E)-β-ocimene (MrTPS4) and (-)-germacrene D (MrTPS5). A fifth TPS, the multiproduct enzyme MrTPS2, was mainly expressed in roots and formed several Asteraceae-specific tricyclic sesquiterpenes with (-)-α-isocomene being the major product. The TPS transcript accumulation patterns in different organs of chamomile were consistent with the abundance of the corresponding TPS products isolated from these organs suggesting that the spatial regulation of TPS gene expression qualitatively contribute to terpene composition., Conclusions: The terpene synthases characterized in this study are involved in the organ-specific formation of essential oils in chamomile. While the products of MrTPS1, MrTPS2, MrTPS4 and MrTPS5 accumulate in the oils without further chemical alterations, (+)-germacrene A produced by MrTPS3 accumulates only in trace amounts, indicating that it is converted into another compound like matricine. Thus, MrTPS3, but also the other TPS genes, are good markers for further breeding of chamomile cultivars rich in pharmaceutically active essential oils.