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The Thermal And Near infrared Sensor for carbon Observation – Fourier Transform Spectrometer (TANSO-FTS) on the Japanese Greenhouse gases Observing SATellite (GOSAT) has been returning data since April 2009. The version 9 (v9) Atmospheric Carbon Observations from Space (ACOS) Level 2 Full Physics (L2FP) retrieval algorithm (Kiel et al., 2019) was used to derive estimates of carbon dioxide (CO2) dry air mole fraction (XCO2) from the TANSO-FTS measurements collected over its first 11 years of operation. The bias correction and quality filtering of the L2FP XCO2 product were evaluated using estimates derived from the Total Carbon Column Observing Network (TCCON) as well as values simulated from a suite of global atmospheric inversion systems (models) which do not assimilate satellite-derived CO2. In addition, the v9 ACOS GOSAT XCO2 results were compared with collocated XCO2 estimates derived from NASA's Orbiting Carbon Observatory-2 (OCO-2), using the version 10 (v10) ACOS L2FP algorithm. These tests indicate that the v9 ACOS GOSAT XCO2 product has improved throughput, scatter, and bias, when compared to the earlier v7.3 ACOS GOSAT product, which extended through mid 2016. Of the 37 million soundings collected by GOSAT through June 2020, approximately 20 % were selected for processing by the v9 L2FP algorithm after screening for clouds and other artifacts. After post-processing, 5.4 % of the soundings (2×106 out of 37×106) were assigned a “good” XCO2 quality flag, as compared to 3.9 % in v7.3 ( ×106 out of 24×106). After quality filtering and bias correction, the differences in XCO2 between ACOS GOSAT v9 and both TCCON and models have a scatter (1σ) of approximately 1 ppm for ocean-glint observations and 1 to 1.5 ppm for land observations. Global mean biases against TCCON and models are less than approximately 0.2 ppm. Seasonal mean biases relative to the v10 OCO-2 XCO2 product are of the order of 0.1 ppm for observations over land. However, for ocean-glint observations, seasonal mean biases relative to OCO-2 range from 0.2 to 0.6 ppm, with substantial variation in time and latitude. The ACOS GOSAT v9 XCO2 data are available on the NASA Goddard Earth Science Data and Information Services Center (GES-DISC) in both the per-orbit full format (https://doi.org/10.5067/OSGTIL9OV0PN, OCO-2 Science Team et al., 2019b) and in the per-day lite format (https://doi.org/10.5067/VWSABTO7ZII4, OCO-2 Science Team et al., 2019a). In addition, a new set of monthly super-lite files, containing only the most essential variables for each satellite observation, has been generated to provide entry level users with a light-weight satellite product for initial exploration (CaltechDATA, https://doi.org/10.22002/D1.2178, Eldering, 2021). The v9 ACOS Data User's Guide (DUG) describes best-use practices for the GOSAT data (O'Dell et al., 2020). The GOSAT v9 data set should be especially useful for studies of carbon cycle phenomena that span a full decade or more and may serve as a useful complement to the shorter OCO-2 v10 data set, which begins in September 2014.

The Tibetan Plateau, known as the “Roof of the World” and “The Third Pole”, harbors numerous saline lakes primarily distributed in the Northern Tibetan Plateau. However, the challenging conditions of high altitude, low oxygen level, and harsh climate have limited investigations into the actinobacteria from these saline lakes. This study focuses on investigating the biodiversity and bioactive secondary metabolites of cultivable actinobacteria isolated from the sediments of four saline lakes on the Northern Tibetan Plateau. A total of 255 actinobacterial strains affiliated with 21 genera in 12 families of 7 orders were recovered by using the pure culture technique and 16S rRNA gene phylogenetic analysis. To facilitate a high-throughput bioactivity evaluation, 192 isolates underwent OSMAC cultivation in a miniaturized 24-well microbioreactor system (MATRIX cultivation). The antibacterial activity of crude extracts was then evaluated in a 96-well plate antibacterial assay. Forty-six strains demonstrated antagonistic effects against at least one tested pathogen, and their underlying antibacterial mechanisms were further investigated through a dual-fluorescent reporter assay (pDualrep2). Two Streptomyces strains (378 and 549) that produce compounds triggering DNA damage were prioritized for subsequent chemical investigations. Metabolomics profiling involving HPLC-UV/vis, UPLC-QTOF-MS/MS, and molecular networking identified three types of bioactive metabolites belonging to the aromatic polyketide family, i.e., cosmomycin, kidamycin, and hedamycin. In-depth analysis of the metabolomic data unveiled some potentially novel anthracycline compounds. A genome mining study based on the whole-genome sequences of strains 378 and 549 identified gene clusters potentially responsible for cosmomycin and kidamycin biosynthesis. This work highlights the effectiveness of combining metabolomic and genomic approaches to rapidly identify bioactive chemicals within microbial extracts. The saline lakes on the Northern Tibetan Plateau present prospective sources for discovering novel actinobacteria and biologically active compounds.

Patients with advanced prostate cancer (PCa) invariably develop resistance to anti-androgen therapy and taxane-based chemotherapy. Glucocorticoid receptor (GR) has been implicated in PCa therapy resistance; however, the mechanisms underlying GR-mediated chemoresistance remain unclear. Lens epithelium-derived growth factor p75 (LEDGF/p75, also known as PSIP1 and DFS70) is a glucocorticoid-induced transcription co-activator implicated in cancer chemoresistance. We investigated the contribution of the GR–LEDGF/p75 axis to docetaxel (DTX)-resistance in PCa cells. GR silencing in DTX-sensitive and -resistant PCa cells decreased LEDGF/p75 expression, and GR upregulation in enzalutamide-resistant cells correlated with increased LEDGF/p75 expression. ChIP-sequencing revealed GR binding sites in the LEDGF/p75 promoter. STRING protein–protein interaction analysis indicated that GR and LEDGF/p75 belong to the same transcriptional network, and immunochemical studies demonstrated their co-immunoprecipitation and co-localization in DTX-resistant cells. The GR modulators exicorilant and relacorilant increased the sensitivity of chemoresistant PCa cells to DTX-induced cell death, and this effect was more pronounced upon LEDGF/p75 silencing. RNA-sequencing of DTX-resistant cells with GR or LEDGF/p75 knockdown revealed a transcriptomic overlap targeting signaling pathways associated with cell survival and proliferation, cancer, and therapy resistance. These studies implicate the GR–LEDGF/p75 axis in PCa therapy resistance and provide a pre-clinical rationale for developing novel therapeutic strategies for advanced PCa.

In Sweden, routine deworming has been used for several decades; however, to slow down the development of anthelmintic resistance, selective treatment is currently recommended. As part of a monitoring programme, equestrian premises submitted faecal samples to the National Veterinary Institute (SVA) twice per year between 2008 and 2017. Analyses for strongyles (small and large), tapeworms and ascarids, followed by premise-specific advice regarding deworming and parasite control strategies, were provided. In total, 43,330 faecal samples, collected from 26,625 horses on 935 premises in springtime (March to June), were analysed by quantitative or semi-quantitative flotation. Moreover, Strongylus vulgaris was detected by larval culture or PCR. Between 4 and 11% of individual horses tested positive for S. vulgaris and 3–10% were shedding tapeworm eggs. There were recurrent high and low egg shedders; 75% of horses with S. vulgaris appeared to have been recently introduced into the herd; the proportion of S. vulgaris-positive premises increased when individual samples rather than pooled samples were used. Based on the results of S. vulgaris diagnostics and strongyle egg-shedding level, 59% of the horses did not need to be dewormed.

This article presents the use of phase-change material (PCM) thermal storage within the Horizon 2020 HEART project (Holistic Energy and Architectural Retrofit Toolkit), aimed at decarbonising the European building sector through the retrofitting of existing structures into energy-efficient smart buildings. These buildings not only reduce energy consumption, but also incorporate advanced technologies for harnessing green energy, thereby promoting environmental sustainability. The HEART project employs state-of-the-art technologies for electricity production/dispatching and heat generation/storage, managed by a cloud-based platform for the real-time monitoring of parameters and optimising energy utilisation, enabling users to control their environmental comfort. The article provides a detailed examination of one of the project’s demonstration sites in Italy, focusing on various components such as heat pumps, photovoltaic systems (PV), controllers, and particularly emphasising the significance of storage tanks. The study involved the measurement and analysis of three heat storage tanks, each with a total volume of 3000 L. These tanks utilised PCM modules for latent heat storage, significantly enhancing overall heat accumulation. Water served as the heat transfer fluid within the tanks. Through meticulous calculations, the article quantifies the accumulated heat and presents a comparative evaluation between PCM-based storage tanks and conventional water tanks, showcasing the advantages of PCM technology in terms of increased heat retention and efficiency.

The functions of most proteins are yet to be determined. The function of an enzyme is often defined by its interacting partners, including its substrate and product, and its role in larger metabolic networks. Here, we describe a computational method that predicts the functions of orphan enzymes by organizing them into a linear metabolic pathway. Given candidate enzyme and metabolite pathway members, this aim is achieved by finding those pathways that satisfy structural and network restraints implied by varied input information, including that from virtual screening, chemoinformatics, genomic context analysis, and ligand -binding experiments. We demonstrate this integrative pathway mapping method by predicting the L-gulonate catabolic pathway in Haemophilus influenzae Rd KW20. The prediction was subsequently validated experimentally by enzymology, crystallography, and metabolomics. Integrative pathway mapping by satisfaction of structural and network restraints is extensible to molecular networks in general and thus formally bridges the gap between structural biology and systems biology.

The functions of most proteins are yet to be determined. The function of an enzyme is often defined by its interacting partners, including its substrate and product, and its role in larger metabolic networks. Here, we describe a computational method that predicts the functions of orphan enzymes by organizing them into a linear metabolic pathway. Given candidate enzyme and metabolite pathway members, this aim is achieved by finding those pathways that satisfy structural and network restraints implied by varied input information, including that from virtual screening, chemoinformatics, genomic context analysis, and ligand -binding experiments. We demonstrate this integrative pathway mapping method by predicting the L-gulonate catabolic pathway in Haemophilus influenzae Rd KW20. The prediction was subsequently validated experimentally by enzymology, crystallography, and metabolomics. Integrative pathway mapping by satisfaction of structural and network restraints is extensible to molecular networks in general and thus formally bridges the gap between structural biology and systems biology.

PLPHP (pyridoxal-phosphate homeostasis protein) deficiency is caused by biallelic pathogenic variants in PLPBP and is a rare cause of pyridoxine-responsive disorders. We describe three French-Canadian individuals with PLPHP deficiency, including one with unusual paroxysmal episodes lacking EEG correlation with a suspicious movement disorder, rarely reported in B6RDs. In addition, we review the clinical features and treatment responses of all 51 previously published individuals with PLPHP deficiency. Our case series underlines the importance of considering PLPBP mutations in individuals with partially B6-responsive seizures and highlights the presence of a founder effect in the French-Canadian population.

ABSTRACT Bifidobacterium longum subsp. infantis is a prevalent beneficial bacterium that colonizes the human neonatal gut and is uniquely adapted to efficiently use human milk oligosaccharides (HMOs) as a carbon and energy source. Multiple studies have focused on characterizing the elements of HMO utilization machinery in B. longum subsp. infantis; however, the regulatory mechanisms governing the expression of these catabolic pathways remain poorly understood. A bioinformatic regulon reconstruction approach used in this study implicated NagR, a transcription factor from the ROK family, as a negative global regulator of gene clusters encoding lacto-N-biose/galacto-N-biose (LNB/GNB), lacto-N-tetraose (LNT), and lacto-N-neotetraose (LNnT) utilization pathways in B. longum subsp. infantis. This conjecture was corroborated by transcriptome profiling upon nagR genetic inactivation and experimental assessment of binding of recombinant NagR to predicted DNA operators. The latter approach also implicated N-acetylglucosamine (GlcNAc), a universal intermediate of LNT and LNnT catabolism, and its phosphorylated derivatives as plausible NagR transcriptional effectors. Reconstruction of NagR regulons in various Bifidobacterium lineages revealed multiple potential regulon expansion events, suggesting evolution from a local regulator of GlcNAc catabolism in ancestral bifidobacteria to a global regulator controlling the utilization of mixtures of GlcNAc-containing host glycans in B. longum subsp. infantis and Bifidobacterium bifidum. IMPORTANCE The predominance of bifidobacteria in the gut of breastfed infants is attributed to the ability of these bacteria to metabolize human milk oligosaccharides (HMOs). Thus, individual HMOs such as lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) are considered promising prebiotics that would stimulate the growth of bifidobacteria and confer multiple health benefits to preterm and malnourished children suffering from impaired (stunted) gut microbiota development. However, the rational selection of HMO-based prebiotics is hampered by the incomplete knowledge of regulatory mechanisms governing HMO utilization in target bifidobacteria. This study describes NagR-mediated transcriptional regulation of LNT and LNnT utilization in Bifidobacterium longum subsp. infantis. The elucidated regulatory network appears optimally adapted to simultaneous utilization of multiple HMOs, providing a rationale to add HMO mixtures (rather than individual components) to infant formulas. The study also provides insights into the evolutionary trajectories of complex regulatory networks controlling carbohydrate metabolism in bifidobacteria.