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ABSTRACT Cellular lipid metabolism plays a pivotal role in human cytomegalovirus (HCMV) infection, as increased lipogenesis in HCMV-infected cells favors the envelopment of newly synthesized viral particles. As all cells are equipped with restriction factors (RFs) able to exert a protective effect against invading pathogens, we asked whether a similar defense mechanism would also be in place to preserve the metabolic compartment from HCMV infection. Here, we show that gamma interferon (IFN-γ)-inducible protein 16 (IFI16), an RF able to block HCMV DNA synthesis, can also counteract HCMV-mediated metabolic reprogramming in infected primary human foreskin fibroblasts (HFFs), thereby limiting virion infectivity. Specifically, we find that IFI16 downregulates the transcriptional activation of the glucose transporter 4 (GLUT4) through cooperation with the carbohydrate-response element-binding protein (ChREBP), thereby reducing HCMV-induced transcription of lipogenic enzymes. The resulting decrease in glucose uptake and consumption leads to diminished lipid synthesis, which ultimately curbs the de novo formation of enveloped viral particles in infected HFFs. Consistently, untargeted lipidomic analysis shows enhanced cholesteryl ester levels in IFI16 KO versus wild-type (WT) HFFs. Overall, our data unveil a new role of IFI16 in the regulation of glucose and lipid metabolism upon HCMV replication and uncover new potential targets for the development of novel antiviral therapies. IMPORTANCE Human cytomegalovirus (HCMV) gathers all the substrates and enzymes necessary for the assembly of new virions from its host cell. For instance, HCMV is known to induce cellular metabolism of infected cells to favor virion assembly. Cells are, however, equipped with a first-line defense represented by restriction factors (RFs), which after sensing viral DNA can trigger innate and adaptive responses, thereby blocking HCMV replication. One such RF is IFN-γ-inducible protein 16 (IFI16), which we have shown to downregulate viral replication in human fibroblasts. Thus, we asked whether IFI16 would also play a role in preserving cellular metabolism upon HCMV infection. Our findings highlight an unprecedented role of IFI16 in opposing the metabolic changes elicited by HCMV, thus revealing new promising targets for antiviral therapy.

Abstract Increased wealth and per capita energy use have transformed lives and shaped societies, but energy poverty remains a global challenge. Previous research has shown positive relationships among metrics of health and happiness and economic indices such as income and gross domestic product and between energy use and human development. To our knowledge, however, no comprehensive assessment has examined to what extent energy use may limit national‐level trends in such metrics. We analyze the maximum global performance of nine health, economic, and environmental metrics by country, determining which metrics increase with per capita energy use and which show thresholds or plateaus in maximum performance. Across the dataset, eight of nine metrics, including life expectancy, infant mortality, happiness, food supply, and access to basic sanitation services, improve steeply and then plateau at levels of average primary annual energy consumption between 10 and 75 GJ person−1 computed nationally (five metrics plateau between 10 and 30 GJ person−1). One notable exception is air quality (energy threshold of 125 GJ person−1 across 133 countries). Averaged across metrics, the 10 countries (with at least seven metrics) showing the best performance given their per capita primary energy use are Malta, Sri Lanka, Cuba, Albania, Iceland, Finland, Bangladesh, Norway, Morocco, and Denmark. If distributed equitably, today's average global energy consumption of 79 GJ person−1 could, in principle, allow everyone on Earth to realize 95% or more of maximum performance across all metrics (and assuming no other limiting factors). Dozens of countries have average per capita energy use below this 79 GJ energy sufficiency threshold, highlighting the need to combat energy poverty. Surprisingly, our analysis also suggests that reduced per capita primary energy consumption could in principle occur in many higher energy‐consuming countries with little or no loss in health, happiness, or other outcomes, reducing the need for global energy infrastructure and increasing global equity.

Abstract Glutamine synthetase (GS) generates glutamine from glutamate and controls the release of inflammatory mediators. In macrophages, GS activity, driven by IL10, associates to the acquisition of M2‐like functions. Conditional deletion of GS in macrophages inhibits metastasis by boosting the formation of anti‐tumor, M1‐like, tumor‐associated macrophages (TAMs). From this basis, we evaluated the pharmacological potential of GS inhibitors in targeting metastasis, identifying glufosinate as a specific human GS inhibitor. Glufosinate was tested in both cultured macrophages and on mice bearing metastatic lung, skin and breast cancer. We found that glufosinate rewires macrophages toward an M1‐like phenotype both at the primary tumor and metastatic site, countering immunosuppression and promoting vessel sprouting. This was also accompanied to a reduction in cancer cell intravasation and extravasation, leading to synchronous and metachronous metastasis growth inhibition, but no effects on primary tumor growth. Glufosinate treatment was well‐tolerated, without liver and brain toxicity, nor hematopoietic defects. These results identify GS as a druggable enzyme to rewire macrophage functions and highlight the potential of targeting metabolic checkpoints in macrophages to treat cancer metastasis.

The intermittency of solar resources is one of the primary challenges for the large-scale integration of the renewable energy. Here Yin et al. used satellite data and climate model outputs to evaluate the geographic patterns of future solar power reliability, highlighting the tradeoff between the maximum potential power and the power reliability.

Soil drying and wetting cycles promote carbon (C) release through large heterotrophic respiration pulses at rewetting, known as the “Birch” effect. Empirical evidence shows that drier conditions before rewetting and larger changes in soil moisture at rewetting cause larger respiration pulses. Because soil moisture varies in response to rainfall, these respiration pulses also depend on the random timing and intensity of precipitation. In addition to rewetting pulses, heterotrophic respiration continues during soil drying, eventually ceasing when soils are too dry to sustain microbial activity. The importance of respiration pulses in contributing to the overall soil heterotrophic respiration flux has been demonstrated empirically, but no theoretical investigation has so far evaluated how the relative contribution of these pulses may change along climatic gradients or as precipitation regimes shift in a given location. To fill this gap, we start by assuming that heterotrophic respiration rates during soil drying and pulses at rewetting can be treated as random variables dependent on soil moisture fluctuations, and we develop a stochastic model for soil heterotrophic respiration rates that analytically links the statistical properties of respiration to those of precipitation. Model results show that both the mean rewetting pulse respiration and the mean respiration during drying increase with increasing mean precipitation. However, the contribution of respiration pulses to the total heterotrophic respiration increases with decreasing precipitation frequency and to a lesser degree with decreasing precipitation depth, leading to an overall higher contribution of respiration pulses under future more intermittent and intense precipitation. Specifically, higher rainfall intermittency at constant total rainfall can increase the contribution of respiration pulses up to ∼10 % or 20 % of the total heterotrophic respiration in mineral and organic soils, respectively. Moreover, the variability of both components of soil heterotrophic respiration is also predicted to increase under these conditions. Therefore, with future more intermittent precipitation, respiration pulses and the associated nutrient release will intensify and become more variable, contributing more to soil biogeochemical cycling.

Background: Tumors are highly plastic metabolic entities composed of cancer and host cells that can adopt different metabolic phenotypes. For energy production, cancer cells may use 4 main fuels that are shuttled in 5 different metabolic pathways. Glucose fuels glycolysis that can be coupled to the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) in oxidative cancer cells or to lactic fermentation in proliferating and in hypoxic cancer cells. Lipids fuel lipolysis, glutamine fuels glutaminolysis, and lactate fuels the oxidative pathway of lactate, all of which are coupled to the TCA cycle and OXPHOS for energy production. This review focuses on the latter metabolic pathway. Scope of review: Lactate, which is prominently produced by glycolytic cells in tumors, was only recently recognized as a major fuel for oxidative cancer cells and as a signaling agent. Its exchanges across membranes are gated by monocarboxylate transporters MCT1-4. This review summarizes the current knowledge about MCT structure, regulation and functions in cancer, with a specific focus on lactate metabolism, lactate-induced angiogenesis and MCT-dependent cancer metastasis. It also describes lactate signaling via cell surface lactate receptor GPR81. Major conclusions: Lactate and MCTs, especially MCT1 and MCT4, are important contributors to tumor aggressiveness. Analyses of MCT-deficient (MCT+/- and MCT−/-) animals and (MCT-mutated) humans indicate that they are druggable, with MCT1 inhibitors being in advanced development phase and MCT4 inhibitors still in the discovery phase. Imaging lactate fluxes non-invasively using a lactate tracer for positron emission tomography would further help to identify responders to the treatments. Keywords: Cancer metabolism, Monocarboxylate transporters (MCTs), GPR81, Metabolic symbiosis, Angiogenesis, Metastasis

Abstract Breast cancer is the most prevalent cancer and a major cause of death in women worldwide. Although early diagnosis and therapeutic intervention significantly improve patient survival rate, metastasis still accounts for most deaths. Here it is reported that, in a cohort of more than 2000 patients with breast cancer, overexpression of PI3KC2α occurs in 52% of cases and correlates with high tumor grade as well as increased probability of distant metastatic events, irrespective of the subtype. Mechanistically, it is demonstrated that PI3KC2α synthetizes a pool of PI(3,4)P2 at focal adhesions that lowers their stability and directs breast cancer cell migration, invasion, and metastasis. PI(3,4)P2 locally produced by PI3KC2α at focal adhesions recruits the Ras GTPase activating protein 3 (RASA3), which inactivates R‐RAS, leading to increased focal adhesion turnover, migration, and invasion both in vitro and in vivo. Proof‐of‐concept is eventually provided that inhibiting PI3KC2α or lowering RASA3 activity at focal adhesions significantly reduces the metastatic burden in PI3KC2α‐overexpressing breast cancer, thereby suggesting a novel strategy for anti‐breast cancer therapy.

Este trabajo examina cómo un gobierno municipal utiliza la transparencia de información como un mecanismo de gestión organizacional para subvertir la configuración de relaciones de poder con el sindicato que representa a todos sus empleados. Desde un diseño de caso único y exploratorio, se estudia el municipio de una ciudad de más de 1 millón de habitantes en Argentina. El caso se construye desde artículos periodísticos, entrevistas, conversaciones in situ y actas de un proceso judicial. Basados en la sociología institucional de Bourdieu y usando el concepto de habitus en la vida organizacional del municipio, el análisis revela cómo el entorno, las organizaciones y sus sistemas se corrompen con el tiempo ya que el campo está conformado y limitado por las condiciones históricas del mismo. El artículo concluye que las prácticas de transparencia afectan la corrupción en países como Argentina basado en la tradición del derecho civil y calificados como carteles de élite debido al rol de poderosas redes profesionales, tales como sindicatos. Las redes profesionales juegan un papel importante en la creación y mantenimiento de prácticas de corrupción cuando los mecanismos de control son débiles; se sugiere que los gobiernos pueden usar la transparencia para limitar la corrupción.

The introduction and expansion of the Asian yellow-legged hornet (Vespa velutina nigrithorax) in Europe poses concern for multiple reasons, including biodiversity conservation. In addition to the predation of native insects (e.g., bees and wasps), this species may compete with native hornets due to an overlap of their climatic and trophic niches. The aim of this study is to investigate the realised climatic niche of V. v. nigrithorax and its response to climatic conditions and to evaluate the degree of overlap with the niches of the two native Vespa species present in Europe, Vespa crabro and Vespa orientalis. The niches of both native species partially overlap with the niche of the invasive species (Schoener’s D, 0.43 for V. crabro and 0.28 for V. orientalis), although some differences can be detected. V. crabro appears to be more adapted to cold and dry conditions than the invasive species, and V. orientalis is more adapted to arid climates. These differences may provide a competitive advantage to both native species in areas with a lower environmental suitability for V. v. nigrithorax, in the probable event that this species continues to spread, reaching all areas predicted to be suitable in Europe and in the Mediterranean basin.

Large areas in the tropics and at mid-latitudes experience pronounced seasonality and inter-annual variability in rainfall and hence water availability. Despite the importance of these seasonally dry ecosystems (SDEs) for the global carbon cycling and in providing ecosystem services, a unifying ecohydrological framework to interpret the effects of climatic variability on SDEs is still lacking. A synthesis of existing data about plant functional adaptations in SDEs, covering some 400 species, shows that leaf phenological variations, rather than physiological traits, provide the dominant control on plant-water-carbon interactions. Motivated by this result, the combined implications of leaf phenology and climatic variability on plant water use strategies are here explored with a minimalist model of the coupled soil water and plant carbon balances. The analyses are extended to five locations with different hydroclimatic forcing, spanning seasonally dry tropical climates (without temperature seasonality) and Mediterranean climates (exhibiting out of phase seasonal patterns of rainfall and temperature). The most beneficial leaf phenology in terms of carbon uptake depends on the climatic regime: evergreen species are favoured by short dry seasons or access to persistent water stores, whereas high inter-annual variability of rainy season duration favours the coexistence of multiple drought-deciduous phenological strategies. We conclude that drought-deciduousness may provide a competitive advantage in face of predicted declines in rainfall totals, while reduced seasonality and access to deep water stores may favour evergreen species. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

This essay provides a first insight on the recently resumed production of the “Gigante (Giant) Vercelli”, a rice cultivar created in 1936, but whose production had ceased in the 1960s. We conducted our survey in the Vercelli area, the heart of one of the largest Italian agro-industrial districts. Today the cultivation of this variety of rice, which has a peculiar, natural resilience to rice blast, the most serious fungal disease on the planet, is possible everywhere, but its growing areal is limited to Piedmont. In 2018, the Slow Food “Gigante Vercelli” rice presidium was established, with a product specification highly attentive to sustainability issues.

Nowadays, face masks play an essential role in limiting coronavirus diffusion. However, their disposable nature represents a relevant environmental issue. In this work, we propose the utilization of two types of disposed (waste) face masks to prepare hard carbons (biochar) by pyrolytic conversion in mild conditions. Moreover, we evaluated the application of the produced hard carbons as anode materials in Na-ion batteries. Pristine face masks were firstly analyzed through infrared spectroscopy and thermogravimetric analysis. The pyrolysis of both mask types resulted in highly disordered carbons, as revealed by field-emission scanning electron microscopy and Raman spectroscopy, with a very low specific surface area. Anodes prepared with these carbons were tested in laboratory-scale Na-metal cells through electrochemical impedance spectroscopy, cyclic voltammetry and galvanostatic cycling, displaying an acceptable specific capacity along a wide range of current regimes, with a good coulombic efficiency (>98% over at least 750 cycles). As a proof of concept, the anodes were also used to assemble a Na-ion cell in combination with a Na3V2(PO4)2F3 (NVPF) cathode and tested towards galvanostatic cycling, with an initial capacity of almost 120 mAhg−1 (decreasing at about 47 mAhg−1 after 50 cycles). Even though further optimization is required for a real application, the achieved electrochemical performances represent a preliminary confirmation of the possibility of repurposing disposable face masks into higher-value materials for Na-ion batteries.

Este articulo reporta los antecedentes, proceso y cambios experimentados en una empresa de servicios cuando se cambia la asignación de costos que a su vez informa la fijación de precios. El foco está más en la práctica que en el desarrollo teórico, por ello se detallan los pasos seguidos en una empresa de servicios en el sector automotriz operando la provincia de Córdoba (Argentina). El investigador ha sido parte del cambio por lo que el método se asemeja a un “interventionist research” (Jonsson y Lukka, 2007). Adoptar una reasignación de costos en función del método del costeo basado en las actividades (ABC) tiene el potencial de generar ventajas estratégicas según las ideas detrás del gerenciamiento basado en actividades (ABM) según documentó Gosselin (2007). Una de ellas es usar los precios como señales a los clientes que se autoseleccionan y mejoran la mezcla de clientes de la empresa. Emplear el ABC destaca las ineficiencias de los procesos de la empresa, ya que, al momento de generar el mapa de procesos de la misma, se detectaron ciertas actividades que causan costos significativamente más altos y otras que no agregan valor. El método de ABC identifica las mejores oportunidades para iniciar una mejora de procesos.

Journals and citations are networks of practice in which management accounting, management control systems, and performance management carry significance. A total of 2,560 publications and 43,425 citations from the Web of Science between 2000-2020 were used to perform a citation analysis of articles, authors, and journals, along with a bibliometric study to map keywords co-occurrence. Citations and publications had an explosive growth due to new journals and Web of Science expansion, with the number and share of top journals decreasing over time. Performance management is eclectic with journals and authors from various disciplines; bibliometric maps suggest that management accounting and performance literature rooted in strategy are competing to integrate this emerging topic. Regardless of the increase in citations and publications, there are only 28 Latin American articles (1% of the total). Despite calls for more diversity in accounting research, we observe the pre-eminence of Western academic norms and practices. Although management accounting is an active field in Latin America with many local publications, few appear in internationally ranked academic journals. [ABSTRACT FROM AUTHOR]