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Abstract Anthropic activities such as industries, agriculture and mining has generated public concern for its numerous irregular disposals of its waste, the incorrect deposition of heavy metals such as nickel (Ni) has caused the degradation and contamination of groundwater and water. Studies that point out cheap and efficient solutions have been an obstacle to the advancement of solutions for degraded area recovery programs. For this, a vegetable home experiment was developed, with an entirely randomized design with 5 treatments being a control (no metal) and 4 nickel concentrations (200 μM/L; 400 μM/L; 600 μM/L and 800 μM/L) with 6 repetitions. The variables analyzed were growth and biochemical activity. Plant height and diameter were not affected by increasing nickel concentrations and this response was due to the low leaf and leaflet production capacity of the species under these conditions, consequently reducing biomass production. Metabolic parameters such as sucrose, carbohydrates, proline and glycine increase under stressful conditions, which does not occur for nutritional configurations that decrease with increasing nickel stress.

Abstract Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT’s activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75–98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3–4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.

The Amazon and Congo basins are the two largest continuous blocks of tropical forest with a central role for global biogeochemical cycles and ecology. However, both biomes differ in structure and species richness and composition. Understanding future directions of the response of both biomes to environmental change is paramount. We used one elevational gradient on both continents to investigate functional and stoichiometric trait shifts of tropical forest in South America and Africa. We measured community-weighted functional canopy traits and canopy and topsoil δ15N signatures. We found that the functional forest composition response along both transects was parallel, with a shift towards more nitrogen-conservative species at higher elevations. Moreover, canopy and topsoil δ15N signals decreased with increasing altitude, suggesting a more conservative N cycle at higher elevations. This cross-continental study provides empirical indications that both South American and African tropical forest show a parallel response with altitude, driven by nitrogen availability along the elevational gradients, which in turn induces a shift in the functional forest composition. More standardized research, and more research on other elevational gradients is needed to confirm our observations.

Uncertainties for upper-air trend patterns are still substantial. Observations from the radio occultation (RO) technique offer new opportunities to assess the existing observational records there. Long-term time series are available from radiosondes and from the (Advanced) Microwave Sounding Unit (A)MSU. None of them were originally intended to deliver data for climate applications. Demanding intercalibration and homogenization procedures are required to account for changes in instrumentation and observation techniques. In this comparative study three (A)MSU anomaly time series and two homogenized radiosonde records are compared to RO data from the CHAMP, SAC-C, GRACE-A and F3C missions for September 2001 to December 2010. Differences of monthly anomalies are examined to assess the differences in the datasets due to structural uncertainties. The difference of anomalies of the (A)MSU datasets relative to RO shows a statistically significant trend within about (−0.2±0.1) K/10 yr (95% confidence interval) at all latitudes. This signals a systematic deviation of the two datasets over time. The radiosonde network has known deficiencies in its global coverage, with sparse representation of most of the southern hemisphere, the tropics and the oceans. In this study the error that results from sparse sampling is estimated and accounted for by subtracting it from radiosonde and RO datasets. Surprisingly the sampling error correction is also important in the Northern Hemisphere (NH), where the radiosonde network is dense over the continents but does not capture large atmospheric variations in NH winter. Considering the sampling error, the consistency of radiosonde and RO anomalies is improving substantially; the trend in the anomaly differences is generally very small. Regarding (A)MSU, its poor vertical resolution poses another problem by missing important features of the vertical atmospheric structure. This points to the advantage of homogeneously distributed measurements with high vertical resolution.

As a promising photocathode candidate, tetragonal CuBi 2 O 4 (CBO) has been studied extensively in recent years. As an intrinsically p-type material, its acceptor sites originate from the cation vacancies, which are also a potential cause of hindered hole utilization in photocathodes. In this study, the ultrafast transport dynamics of the valence band hole states in CBO photocathodes were investigated by varying their atomic composition and manipulating the p-type character. As a comprehensive ultrafast optical transient absorption spectroscopy (TAS) investigation of compositionally manipulated CBO that combines both ex situ and in situ TAS experiments with photoelectrochemical (PEC) performance tests, the study reveals the polaron formation tendencies of the valence band (VB) holes at cationic vacancy sites. Therefore, it draws a complete picture of the ultrafast hole transport dynamics and provides valuable insights into the hindrance of the photocurrent generated in CBO., (© 2024 Wiley-VCH GmbH.)

The tumor suppressor p14/19ARF regulates ribosomal RNA (rRNA) synthesis by controlling the nucleolar localization of Transcription Termination Factor 1 (TTF1). However, the role played by TTF1 in regulating the rRNA genes and in potentially controlling growth has remained unclear. We now show that TTF1 expression regulates cell growth by determining the cellular complement of ribosomes. Unexpectedly, it achieves this by acting as a "roadblock" to synthesis of the noncoding LncRNA and pRNA that we show are generated from the "Spacer Promoter" duplications present upstream of the 47S pre-rRNA promoter on the mouse and human ribosomal RNA genes. Unexpectedly, the endogenous generation of these noncoding RNAs does not induce CpG methylation or gene silencing. Rather, it acts in cis to suppress 47S preinitiation complex formation and hence de novo pre-rRNA synthesis by a mechanism reminiscent of promoter interference or occlusion. Taken together, our data delineate a pathway from p19ARF to cell growth suppression via the regulation of ribosome biogenesis by noncoding RNAs and validate a key cellular growth law in mammalian cells., (© 2024 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)

Transcription-factor binding to cis-regulatory regions regulates the gene expression program of a cell, but occupancy is often a poor predictor of the gene response. Here, we show that glucocorticoid stimulation led to the reorganization of transcriptional coregulators MED1 and BRD4 within topologically associating domains (TADs), resulting in active or repressive gene environments. Indeed, we observed a bias toward the activation or repression of a TAD when their activities were defined by the number of regions gaining and losing MED1 and BRD4 following dexamethasone (Dex) stimulation. Variations in Dex-responsive genes at the RNA levels were consistent with the redistribution of MED1 and BRD4 at the associated cis-regulatory regions. Interestingly, Dex-responsive genes without the differential recruitment of MED1 and BRD4 or binding by the glucocorticoid receptor were found within TADs, which gained or lost MED1 and BRD4, suggesting a role of the surrounding environment in gene regulation. However, the amplitude of the response of Dex-regulated genes was higher when the differential recruitment of the glucocorticoid receptor and transcriptional coregulators was observed, reaffirming the role of transcription factor-driven gene regulation and attributing a lesser role to the TAD environment. These results support a model where a signal-induced transcription factor induces a regionalized effect throughout the TAD, redefining the notion of direct and indirect effects of transcription factors on target genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tav, Fournier, Fournier, Khadangi, Baguette, Côté, Silveira, Bérubé-Simard, Bourque, Droit and Bilodeau.)

Recent advances have shown that some biologically active non-coding RNAs (ncRNAs) are actually translated into polypeptides that have a physiological function as well. This paradigm shift requires adapted computational methods to predict this new class of 'bifunctional RNAs'. Previously, we developed IRSOM, an open-source algorithm to classify non-coding and coding RNAs. Here, we use the binary statistical model of IRSOM as a ternary classifier, called IRSOM2, to identify bifunctional RNAs as a rejection of the two other classes. We present its easy-to-use web interface, which allows users to perform predictions on large datasets of RNA sequences in a short time, to re-train the model with their own data, and to visualize and analyze the classification results thanks to the implementation of self-organizing maps (SOM). We also propose a new benchmark of experimentally validated RNAs that play both protein-coding and non-coding roles, in different organisms. Thus, IRSOM2 showed promising performance in detecting these bifunctional transcripts among ncRNAs of different types, such as circRNAs and lncRNAs (in particular those of shorter lengths). The web server is freely available on the EvryRNA platform: https://evryrna.ibisc.univ-evry.fr., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Poly(ethylene oxide) (PEO)-based polymer electrolytes are a promising class of materials for use in lithium-ion batteries due to their high ionic conductivity and flexibility. In this study, the effects of polymer architecture including linear, star, and hyperbranched and salt (lithiumbis(trifluoromethanesulfonyl)imide (LiTFSI)) concentration on the glass transition ( T g ), microstructure, phase diagram, free volume, and bulk viscosity, all of which play a significant role in determining the ionic conductivity of the electrolyte, have been systematically studied for PEO-based polymer electrolytes. The branching of PEO widens the liquid phase toward lower salt concentrations, suggesting decreased crystallization and improved ion coordination. At high salt loadings, ion clustering is common for all electrolytes, yet the cluster size and distribution appear to be strongly architecture-dependent. Also, the ionic conductivity is maximized at a salt concentration of [Li/EO ≈ 0.085] for all architectures, and the highly branched polymers displayed as much as three times higher ionic conductivity (with respect to the linear analogue) for the same total molar mass. The architecture-dependent ionic conductivity is attributed to the enhanced free volume measured by positron annihilation lifetime spectroscopy. Interestingly, despite the strong architecture dependence of ionic conductivity, the salt addition in the highly branched architectures results in accelerated yet similar monomeric friction coefficients for these polymers, offering significant potential toward decoupling of conductivity from segmental dynamics of polymer electrolytes, leading to outstanding battery performance., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Tumor-associated macrophages (TAMs) support tumor progression within the tumor microenvironment (TME). Many questions remain as to the origin, development, and function of TAMs within the prostate TME. Evaluation of TAMs in prostate cancer (PCa) patients identified the immunosuppressive TAM marker CD163 in adjacent normal epithelium as an independent predictor of metastases or PCa death. Flow cytometry analyses identified prostate TAMs as frequently expressing both proinflammatory M1 (CCR7+) and immunosuppressive M2 (CD163+) markers. In vitro, we demonstrate PCa cells similarly subvert human M1 macrophages toward a mixed M1/M2 macrophage phenotype favoring tumor growth. Further the cytokine milieu-induced transition between immunosuppressive M2 to proinflammatory M1 (M2→M1) macrophages is abrogated by the presence of PCa cells. RNA sequencing suggests alterations in chemokine expression in prostate TAMs due to the presence of PCa cells. Together, our results suggest that prostate TAMs originate from inflammatory infiltrating macrophages, which are then reprogrammed mainly by PCa cells, but also the cytokine milieu. A better understanding of this subversion of macrophages within the prostate may lead to novel treatment strategies., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

This work reports the effects of free volume on curcumin release in various polymer-based composite films. Curcumin-reinforced biocomposite films were fabricated with natural biopolymers (carrageenan and chitosan) and bioplastics (poly(lactide) (PLA) and poly (butylene adipate-co-terephthalate) (PBAT)) via the solvent casting method. The curcumin release test was performed using an aqueous medium, and it was found that it was released the fastest in the carrageenan film, followed by the chitosan, PLA, and PBAT films, presumably owing to the dissimilarity of the polymer matrix. The free volume of the polymer films was determined using positron annihilation lifetime spectroscopy (PALS) to understand the release phenomena of curcumin. The free volume fraction was varied and reliant on the type of polymer, with the highest in the PBAT-based film followed by the PLA-, chitosan-, and carrageenan-based films. The free volume method helps analyze the release of bioactive compounds in a polymer matrix and may help to achieve a better understanding of the release of bioactive compounds.

Yeasts have wide applicability in the industrial field, as in the production of enzymes used in biocatalysts. Biocatalysts are more efficient when compared to chemical catalysts, with emphasis on hydrolytic enzymes, such as amylase, cellulase and protease. Here we focused on prospecting yeasts, with a high capacity to synthesize hydrolytic enzymes, from a continental lotic ecosystem environment in Brazil. 75 yeasts were grown in Yeast Extract-Peptone-Dextrose (YPD) medium supplemented with antibacterial and their capacity for enzymatic production was tested in specific media. Accordingly, 64 yeasts showed enzyme production capacity. From those, six showed good enzyme indexes, 3 for amylase, 2 for cellulase and 1 for protease. All showed at least one hydrolytic enzyme activity for the tested enzymes (amylase, cellulase and protease), which suggested that the yeasts are metabolically active. By sequencing the 26S gene, we identified Naganishia diffluens and Apiotrichum mycotoxinivorans as the species with highest enzyme production activities. Those species showed potential for application as biological catalysts in the biotechnological scope, collaborating in a sustainable way for the development of industrial products., Competing Interests: The authors report no declarations of interest., (© 2021 The Author(s).)

Master transcription factors control the transcriptional program and are essential to maintain cellular functions. Among them, steroid nuclear receptors, such as the estrogen receptor α (ERα), are central to the etiology of hormone-dependent cancers which are accordingly treated with corresponding endocrine therapies. However, resistance invariably arises. Here, we show that high levels of the stress response master regulator, the heat shock factor 1 (HSF1), are associated with antiestrogen resistance in breast cancer cells. Indeed, overexpression of HSF1 leads to ERα degradation, decreased expression of ERα-activated genes, and antiestrogen resistance. Furthermore, we demonstrate that reducing HSF1 levels reinstates expression of the ERα and restores response to antiestrogens. Last, our results establish a proof of concept that inhibition of HSF1, in combination with antiestrogens, is a valid strategy to tackle resistant breast cancers. Taken together, we are proposing a mechanism where high HSF1 levels interfere with the ERα-dependent transcriptional program leading to endocrine resistance in breast cancer., (© 2021 Silveira et al.)

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the third cause of cancer mortality. PCa initiation and growth are driven by the androgen receptor (AR). The AR is activated by androgens such as testosterone and controls prostatic cell proliferation and survival. Here, we report an AR signaling network generated using BioID proximity labeling proteomics in androgen-dependent LAPC4 cells. We identified 31 AR-associated proteins in nonstimulated cells. Strikingly, the AR signaling network increased to 182 and 200 proteins, upon 24 h or 72 h of androgenic stimulation, respectively, for a total of 267 nonredundant AR-associated candidates. Among the latter group, we identified 213 proteins that were not previously reported in databases. Many of these new AR-associated proteins are involved in DNA metabolism, RNA processing, and RNA polymerase II transcription. Moreover, we identified 44 transcription factors, including the Kru¨ppel-like factor 4 (KLF4), which were found interacting in androgen-stimulated cells. Interestingly, KLF4 repressed the well-characterized AR-dependent transcription of the KLK3 (PSA) gene; AR and KLF4 also colocalized genome-wide. Taken together, our data report an expanded high-confidence proximity network for AR, which will be instrumental to further dissect the molecular mechanisms underlying androgen signaling in PCa cells., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Computational methods are required for prediction of non-coding RNAs (ncRNAs), which are involved in many biological processes, especially at post-transcriptional level. Among these ncRNAs, miRNAs have been largely studied and biologists need efficient and fast tools for their identification. In particular, ab initio methods are usually required when predicting novel miRNAs. Here we present a web server dedicated for miRNA precursors identification at a large scale in genomes. It is based on an algorithm called miRNAFold that allows predicting miRNA hairpin structures quickly with high sensitivity. miRNAFold is implemented as a web server with an intuitive and user-friendly interface, as well as a standalone version. The web server is freely available at: http://EvryRNA.ibisc.univ-evry.fr/miRNAFold., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)