Genes specifying long non-coding RNAs (lncRNAs) occupy a large fraction of the genomes of complex organisms. The term 'lncRNAs' encompasses RNA polymerase I (Pol I), Pol II and Pol III transcribed ...RNAs, and RNAs from processed introns. The various functions of lncRNAs and their many isoforms and interleaved relationships with other genes make lncRNA classification and annotation difficult. Most lncRNAs evolve more rapidly than protein-coding sequences, are cell type specific and regulate many aspects of cell differentiation and development and other physiological processes. Many lncRNAs associate with chromatin-modifying complexes, are transcribed from enhancers and nucleate phase separation of nuclear condensates and domains, indicating an intimate link between lncRNA expression and the spatial control of gene expression during development. lncRNAs also have important roles in the cytoplasm and beyond, including in the regulation of translation, metabolism and signalling. lncRNAs often have a modular structure and are rich in repeats, which are increasingly being shown to be relevant to their function. In this Consensus Statement, we address the definition and nomenclature of lncRNAs and their conservation, expression, phenotypic visibility, structure and functions. We also discuss research challenges and provide recommendations to advance the understanding of the roles of lncRNAs in development, cell biology and disease.
Necrotic cell death during
(Mtb) infection is considered host detrimental since it facilitates mycobacterial spread. Ferroptosis is a type of regulated necrosis induced by accumulation of free iron ...and toxic lipid peroxides. We observed that Mtb-induced macrophage necrosis is associated with reduced levels of glutathione and glutathione peroxidase-4 (Gpx4), along with increased free iron, mitochondrial superoxide, and lipid peroxidation, all of which are important hallmarks of ferroptosis. Moreover, necrotic cell death in Mtb-infected macrophage cultures was suppressed by ferrostatin-1 (Fer-1), a well-characterized ferroptosis inhibitor, as well as by iron chelation. Additional experiments in vivo revealed that pulmonary necrosis in acutely infected mice is associated with reduced Gpx4 expression as well as increased lipid peroxidation and is likewise suppressed by Fer-1 treatment. Importantly, Fer-1-treated infected animals also exhibited marked reductions in bacterial load. Together, these findings implicate ferroptosis as a major mechanism of necrosis in Mtb infection and as a target for host-directed therapy of tuberculosis.
Summary
Nitrogen‐fixing rhizobacteria can promote plant growth; however, it is controversial whether biological nitrogen fixation (BNF) from associative interaction contributes to growth promotion. ...The roots of Setaria viridis, a model C4 grass, were effectively colonized by bacterial inoculants resulting in a significant enhancement of growth. Nitrogen‐13 tracer studies provided direct evidence for tracer uptake by the host plant and incorporation into protein. Indeed, plants showed robust growth under nitrogen‐limiting conditions when inoculated with an ammonium‐excreting strain of Azospirillum brasilense. 11C‐labeling experiments showed that patterns in central carbon metabolism and resource allocation exhibited by nitrogen‐starved plants were largely reversed by bacterial inoculation, such that they resembled plants grown under nitrogen‐sufficient conditions. Adoption of S. viridis as a model should promote research into the mechanisms of associative nitrogen fixation with the ultimate goal of greater adoption of BNF for sustainable crop production.
Significance Statement
The results indicate that, under the appropriate conditions, the C4 model grass species, Setaria viridis, can obtain 100% of its nitrogen needs from biological nitrogen fixation, as a result of inoculation with plant growth promoting bacteria. The work supports the future use of S. viridis as a model system to explore the mechanistic aspects of associative nitrogen fixation with the goal of transferring this knowledge to important crop species, such as corn.
Quest for a sustainable university: a review Amaral, Luís P; Martins, Nelson; Gouveia, Joaquim B
International journal of sustainability in higher education,
01/2015, Letnik:
16, Številka:
2
Journal Article
Recenzirano
Purpose
– The paper aims to deliver a general review of the methods used to pursue the concept of a “sustainable university”.
Design/methodology/approach
– The research was Internet based, and it ...included research papers, books, conference proceedings, technical reports and Internet Web sites. The review was divided in two main parts: sustainability implementation methods and assessment and report tools. In turn, the practices used on universities to implement included more “traditional” environmental sustainability initiatives and a more updated sustainable management systems.
Findings
– Because “traditional” sustainability environmental sustainability initiatives have flaws, more recent tools were developed to help manage sustainability. Two sustainability management systems specifically oriented to universities are outlined on this paper. They both highlight the advantage of disposing a systematized management system; the need of address environmental issues and putting special attention on the use of resources, especially energy, on campus buildings; the social responsibility of the institution; and educational and research sustainability activities that must be taken on universities. Managing sustainability in a university would be facilitated if the procedure used to implement sustainability is aligned with the tool used that assesses its performance.
Originality/value
– The paper presents an updated review of the efforts that universities have made in contributing to a sustainable development. It includes methods and tools used to manage sustainability within a university, including the ones used to implement, assess and report it. The paper also intends to highlight the need of consistency and coherence between the implementation method and the assessment and report tools.
Vanadium Compounds with Antidiabetic Potential Amaral, Luísa M. P. F; Moniz, Tânia; Silva, André M. N ...
International journal of molecular sciences,
11/2023, Letnik:
24, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Over the last four decades, vanadium compounds have been extensively studied as potential antidiabetic drugs. With the present review, we aim at presenting a general overview of the most promising ...compounds and the main results obtained with in vivo studies, reported from 1899–2023. The chemistry of vanadium is explored, discussing the importance of the structure and biochemistry of vanadate and the impact of its similarity with phosphate on the antidiabetic effect. The spectroscopic characterization of vanadium compounds is discussed, particularly magnetic resonance methodologies, emphasizing its relevance for understanding species activity, speciation, and interaction with biological membranes. Finally, the most relevant studies regarding the use of vanadium compounds to treat diabetes are summarized, considering both animal models and human clinical trials. An overview of the main hypotheses explaining the biological activity of these compounds is presented, particularly the most accepted pathway involving vanadium interaction with phosphatase and kinase enzymes involved in the insulin signaling cascade. From our point of view, the major discoveries regarding the pharmacological action of this family of compounds are not yet fully understood. Thus, we still believe that vanadium presents the potential to help in metabolic control and the clinical management of diabetes, either as an insulin-like drug or as an insulin adjuvant. We look forward to the next forty years of research in this field, aiming to discover a vanadium compound with the desired therapeutic properties.
RNA molecules undergo a vast array of chemical post-transcriptional modifications (PTMs) that can affect their structure and interaction properties. In recent years, a growing number of PTMs have ...been successfully mapped to the transcriptome using experimental approaches relying on high-throughput sequencing. Oxford Nanopore direct-RNA sequencing has been shown to be sensitive to RNA modifications. We developed and validated Nanocompore, a robust analytical framework that identifies modifications from these data. Our strategy compares an RNA sample of interest against a non-modified control sample, not requiring a training set and allowing the use of replicates. We show that Nanocompore can detect different RNA modifications with position accuracy in vitro, and we apply it to profile m
A in vivo in yeast and human RNAs, as well as in targeted non-coding RNAs. We confirm our results with orthogonal methods and provide novel insights on the co-occurrence of multiple modified residues on individual RNA molecules.
The need to transition from fossil fuels to renewables arises from factors such as depletion, price fluctuations, and environmental considerations. Lignocellulosic biomass, being abundant, and ...quickly renewable, and not interfering with food supplies, offers a standout alternative for chemical production. This paper explores the energetic characteristics of two derivatives of furfural—a versatile chemical obtained from biomass with great potential for commercial sustainable chemical and fuel production. The standard (p° = 0.1 MPa) molar enthalpies of formation of the liquids furfurylamine and 5-methylfurfurylamine were derived from the standard molar energies of combustion, determined in oxygen and at T = 298.15 K, by static bomb combustion calorimetry. Their standard molar enthalpies of vaporization were also determined at the same temperature using high-temperature Calvet microcalorimetry. By combining these data, the gas-phase enthalpies of formation at T = 298.15 K were calculated as −(43.5 ± 1.4) kJ·mol−1 for furfurylamine, and −(81.2 ± 1.7) kJ·mol−1 for 5-methylfurfurylamine. Furthermore, a theoretical analysis using G3 level calculations was performed, comparing the calculated enthalpies of formation with the experimental values to validate both results. This method has been successfully applied to similar molecules. The discussion looks into substituent effects in terms of stability and compares them with similar compounds.
Tuberculosis remains second only to HIV/AIDS as the leading cause of mortality worldwide due to a single infectious agent. Despite chemotherapy, the global tuberculosis epidemic has intensified ...because of HIV co-infection, the lack of an effective vaccine and the emergence of multi-drug-resistant bacteria. Alternative host-directed strategies could be exploited to improve treatment efficacy and outcome, contain drug-resistant strains and reduce disease severity and mortality. The innate inflammatory response elicited by Mycobacterium tuberculosis (Mtb) represents a logical host target. Here we demonstrate that interleukin-1 (IL-1) confers host resistance through the induction of eicosanoids that limit excessive type I interferon (IFN) production and foster bacterial containment. We further show that, in infected mice and patients, reduced IL-1 responses and/or excessive type I IFN induction are linked to an eicosanoid imbalance associated with disease exacerbation. Host-directed immunotherapy with clinically approved drugs that augment prostaglandin E2 levels in these settings prevented acute mortality of Mtb-infected mice. Thus, IL-1 and type I IFNs represent two major counter-regulatory classes of inflammatory cytokines that control the outcome of Mtb infection and are functionally linked via eicosanoids. Our findings establish proof of concept for host-directed treatment strategies that manipulate the host eicosanoid network and represent feasible alternatives to conventional chemotherapy.
Chronic kidney disease (CKD) is a worldwide public health threat that increases risk of death due to cardiovascular complications, including left ventricular hypertrophy (LVH). Novel therapeutic ...targets are needed to design treatments to alleviate the cardiovascular burden of CKD. Previously, we demonstrated that circulating concentrations of fibroblast growth factor (FGF) 23 rise progressively in CKD and induce LVH through an unknown FGF receptor (FGFR)-dependent mechanism. Here, we report that FGF23 exclusively activates FGFR4 on cardiac myocytes to stimulate phospholipase Cγ/calcineurin/nuclear factor of activated T cell signaling. A specific FGFR4-blocking antibody inhibits FGF23-induced hypertrophy of isolated cardiac myocytes and attenuates LVH in rats with CKD. Mice lacking FGFR4 do not develop LVH in response to elevated FGF23, whereas knockin mice carrying an FGFR4 gain-of-function mutation spontaneously develop LVH. Thus, FGF23 promotes LVH by activating FGFR4, thereby establishing FGFR4 as a pharmacological target for reducing cardiovascular risk in CKD.
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•In the absence of α-klotho, FGF23 induces binding of FGFR4 to PLCγ•FGF23 activates calcineurin/NFAT signaling in cardiac myocytes via FGFR4•FGFR4 blockade protects CKD rats with high serum FGF23 from cardiac hypertrophy•Knockin mice carrying a FGFR4 gain-of-function mutation develop cardiac hypertrophy
Grabner et al. reveal that FGFR4 mediates the pro-hypertrophic cardiac effects of FGF23, a phosphate-regulating hormone elevated in patients with chronic kidney disease (CKD). Activation of FGFR4/calcineurin/NFAT signaling is sufficient to induce cardiac hypertrophy in mice, while FGFR4 blockade attenuates cardiac hypertrophy in a rat model of CKD.
Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates ...vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency-genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor-23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-β1-, angiotensin II-, or high phosphate-induced fibrosis and abolished TGF-β1- or angiotensin II-induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor-23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging.
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