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Domestic Cat Hepadnavirus and Pathogenic Retroviruses; A Sero-Molecular Survey of Cats in Santiago, Chile
(Multidisciplinary Digital Publishing Institute (MDPI), 0024) Choi, Yan Ru; Iturriaga, María Paz; Nekouei, Omid; Tu, Thomas; Van Brussel, Kate; Barrs, Vanessa R; Beatty, Julia A
Cat ownership is common in Chile, but data on the regional prevalence of infectious agents are limited. A sero-molecular survey of 120 client- or shelter-owned domestic cats in greater Santiago was performed. Whole blood DNA was tested for the novel hepatitis-B-like virus, domestic cat hepadnavirus (DCH) by conventional PCR (cPCR) and quantitative PCR (qPCR), and for feline leukaemia virus (FeLV) by qPCR. Point-of-care serology for FeLV p27 antigen and antibodies recognising feline immunodeficiency virus (FIV) p15 and p24 was performed. DCH DNA was detected in the serum of 2/120 cats (1.67%). Sequencing and phylogenetic analysis showed that the DCH detected in Chile occupies a position outside the main clustering of DCH in the near-complete genome tree. Progressive (antigen-positive, provirus-positive) and regressive (antigen-negative, provirus-positive) FeLV infections were identified in 6/120 (5%) and 9/120 (7.5%) of cats. A total of 2/120 (1.7%) cats had dual FeLV/FIV infection, and another 2 cats had FIV infection alone. This study shows that the global footprint of DCH includes South America with a low molecular frequency in Chile, similar to that reported in the USA. Progressive FeLV infection is relatively common in urban Chile, and male cats are at greater risk than females. Testing and control measures for pathogenic retroviruses are indicated. The potential impact of FeLV, FIV and DCH on Chile’s wildcat species is worthy of further investigation. © 2023 by the authors.
Functional characterization of two KCND3 variants associated with SCA 19/22 ataxia in Latin American families
(BioMed Central Ltd, 0025) Arancibia, Felipe; Martin, Fernanda; Ruiz-Fuentes, Jenny; Hermosilla, Tamara; Gonzalez, Wendy; Simon, Felipe; Avila-Jaque, Diana; Luna-Álvarez, Mariana; Dávila Ortiz de Montellano, David José; Miranda, Marcelo; Bustamante, M. Leonor
Background: Spinocerebellar ataxia 19/22 (SCA19/22) represents a rare autosomal dominant genetic disorder resulting in progressive ataxia and cerebellar atrophy. SCA19/22 is caused by variants in the KCND3 gene, which encodes a voltage-gated potassium channel subunit essential for cerebellar Purkinje cell function. To date, 22 variants have been reported worldwide, with incomplete functional studies. Results: We present four Chilean and Mexican cases in whom two single-nucleotide variants were identified through whole-exome sequencing of the probands. One variant (G371R) was initially cataloged as pathogenic and the other (S357W) as likely pathogenic according to the American College of Medical Genetics and Genomics criteria. The pathogenicity of the G371R variation was confirmed by in-silico mutagenesis. Our molecular models, that include electrostatic potential analysis and algorithms to analyze the pore dimensions (HOLE), indicated that the longer side chain of the arginine narrowed the channel’s selectivity filter, while the positive charge modified its surface electrostatic potential, presumably preventing potassium flux. Functional characterization of the S357W variant was performed in AD293 cells. When overexpressed, KV4.3S357W channels alone showed no current. Protein electrophoresis revealed that the total number of KV4.3 channels expressed did not differ between the wild-type and mutated phenotypes, suggesting a protein trafficking malfunction. Co-expression of the KChIP2 auxiliary subunit partially rescued the potassium currents when the variant was expressed, albeit with very different biophysical characteristics, including faster inactivation vs. wild-type channels. Conclusions: This functional characterization of two KCND3 variants associated with SCA19/22 adds new evidence for the pathogenic role of Kv4.3 loss-of-function mutations and establishes a correlation between functional dominance and clinical severity in SCA19/22. © The Author(s) 2025.
From STEM to STEAM: An Enactive and Ecological Continuum
(Frontiers Media S.A., 2021-09-24) Videla, Ronnie; Aguayo, Claudio; Veloz, Tomas
STEM and STEAM education promotes the integration between science, technology, engineering, mathematics, and the arts. The latter aims at favoring deep and collaborative learning on students, through curricular integration in K-12 science education. The enactive and ecological psychology approach to education puts attention on the role of the teacher, learning context and socio-cultural environment in shaping lived learning experiences. The approach describes education as a process of embodied cognitive assemblage of guided perception and action. The latter process depends on the interaction of learners with digital and/or analogue learning affordances existing within the socio-technological environment. This article proposes that the scope of an enactive-ecological approach can be extended to the domain of learning science, technology, engineering, arts, and mathematics (STEAM), especially when it comes to understanding deep roots of the learning process. We first present an exhaustive literature review regarding the foundations of both the enactive and the ecological learning theories, along with their differences and key similarities. We then describe the fundamentals and latest research advances of an integrated STEAM pedagogy, followed by the notion of mixed reality (XR) as an emerging educational technology approach, offering an understanding of its current foundations and general disposition on how to understand digital immersion from ecological psychology. Next, we propose a systems theoretical approach to integrate the enactive-ecological approach in STEAM pedagogy, framed in the Santiago school of cognition attending to the interactive dynamics occurring between learners and their interaction with learning affordances existing within their educational medium, establishing that sensorimotor contingencies and attentional anchors are important to restrict sensory variety and stabilize learning concepts. Finally, we consider two empirical studies, one from Chile and the other from New Zealand, in which we demonstrate how the enactive-ecological approach built upon a systems theory perspective can contribute to understanding the roots of STEAM learning and inform its learning design. © Copyright © 2021 Videla, Aguayo and Veloz.
Anti-parasitic drugs modulate the non-selective channels formed by connexins or pannexins
(Elsevier B.V., 2021-10-01) Güiza, Juan; Arriagada, Javiera; Rodríguez, Luis; Gutiérrez, Camila; Duarte, Yorley; Sáez, Juan C.; Vega, José L.
The proteins connexins, innexins, and pannexins are the subunits of non-selective channels present in the cell membrane in vertebrates (connexins and pannexins) and invertebrates (innexins). These channels allow the transfer of ions and molecules across the cell membrane or, and in many cases, between the cytoplasm of neighboring cells. These channels participate in various physiological processes, particularly under pathophysiological conditions, such as bacterial, viral, and parasitic infections. Interestingly, some anti-parasitic drugs also block connexin- or pannexin-formed channels. Their effects on host channels permeable to molecules that favor parasitic infection can further explain the anti-parasitic effects of some of these compounds. In this review, the effects of drugs with known anti-parasitic activity that modulate non-selective channels formed by connexins or pannexins are discussed. Previous studies that have reported the presence of these proteins in worms, ectoparasites, and protozoa that cause parasitic infections have also been reviewed. © 2021 Elsevier B.V.
Experimental and theoretical study of shyntesis of N-alkyl-nitroimidazoles
(Universidad de Antioquia, 2010) Salamanca M., Constain; Tiznado V., William; Jaramillo G., Paula
In this work we realized and experimental and theoretical study of the N-alkylation of nitroimidazoles. The N-alkyl-2-methyl-nitroimidazoles correspond to biologically active molecules, obtained by reaction of 2-methyl-5- nitroimidazole and different alkyl halides. This reaction showed the formation of a mixture of isomeric products in different proportions, denominated like N-alkyl-2-methyl-4-nitroimidazole and N-alkyl-2-methyl-5-nitroimidazole, respectively. The reaction suggestes the formation of a tautomeric equilibrium, which generates two nucleophilic sites susceptible to electrophilic attack by the alkyl halide. The local nucleophilic reactivity of the nitroimidazole ring is determined using local reactivity indices such as the Fukui function and the electrostatic potential, besides the electronic localization function (ELF). The Fukui function was integrated for each atom using partition schemes based on analysis of Mulliken charges and natural bond orbital (NBO). Finally the reaction profiles were assessed. The results show a minor difference in the local reactivity. Nevertheless a significant difference in energy barriers is observed explaining the formation of an isomeric product over another. These results agree quite well with the experimental data.
Widespread historical presence of Batrachochytrium dendrobatidis in African pipid frogs
(2010-01) Soto-Azat, Claudio; Clarke, Barry T.; Poynton, John C.; Cunningham, Andrew A.
Aim Amphibian chytridiomycosis, an emerging infectious disease caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), is associated with global amphibian population declines and species extinctions. Current evidence indicates that the pathogen has recently spread globally from an enzootic focus, with Xenopus spp. (family Pipidae) in South Africa having been identified as a likely source. The aim of this study was to investigate further the likelihood of African Xenopus spp. as the original source of Bd. Location We examined 665 museum specimens of 20 species of African and South American pipid frogs collected between 1844 and 1994 and held in the collection of the Natural History Museum, London. Methods Skin brushings taken from adult amphibians and brushings from the mouthparts, lips and developing hind limbs of larval pipid frogs were examined for the presence of Bd using real-time PCR. Results We found six cases of Bd infection in three Xenopus spp. (from Africa), but none of the South American pipids was positive, although only 45 South American frogs were available for examination. The earliest case of Bd infection was in a specimen of Xenopus fraseri collected from Cameroon in 1933. A consistently low prevalence of infection over time indicates that a historical equilibrium existed between Xenopus spp. and Bd infection in Africa. Main conclusions Our results suggest that Bd infection was present in Xenopus spp. across sub-Saharan Africa by the 1930s, providing additional support for the 'out of Africa' hypothesis. If this hypothesis is correct, it strengthens the argument for stringent control of human-assisted movements of amphibians and other wildlife world-wide to minimize the likelihood of pathogen introduction and disease emergence that can threaten species globally. Our findings help inform species selection for conservation in the face of the current Bd pandemic and also guide future research directions for selecting Bd isolates for sequencing and virulence testing. © 2009 Blackwell Publishing Ltd.
Comparative genomics sheds light on transcription factor-mediated regulation in the extreme acidophilic Acidithiobacillia representatives
(Elsevier Masson s.r.l., 2024-01) Sepúlveda-Rebolledo, Pedro; González-Rosales, Carolina; Dopson, Mark; Pérez-Rueda, Ernesto; Holmes, David S.; Valdés, Jorge H
Extreme acidophiles thrive in acidic environments, confront a multitude of challenges, and demonstrate remarkable adaptability in their metabolism to cope with the ever-changing environmental fluctuations, which encompass variations in temperature, pH levels, and the availability of electron acceptors and donors. The survival and proliferation of members within the Acidithiobacillia class rely on the deployment of transcriptional regulatory systems linked to essential physiological traits. The study of these transcriptional regulatory systems provides valuable insights into critical processes, such as energy metabolism and nutrient assimilation, and how they integrate into major genetic-metabolic circuits. In this study, we examined the transcriptional regulatory repertoires and potential interactions of forty-three Acidithiobacillia complete and draft genomes, encompassing nine species. To investigate the function and diversity of Transcription Factors (TFs) and their DNA Binding Sites (DBSs), we conducted a genome-wide comparative analysis, which allowed us to identify these regulatory elements in representatives of Acidithiobacillia. We classified TFs into gene families and compared their occurrence among all representatives, revealing conservation patterns across the class. The results identified conserved regulators for several pathways, including iron and sulfur oxidation, the main pathways for energy acquisition, providing new evidence for viable regulatory interactions and branch-specific conservation in Acidithiobacillia. The identification of TFs and DBSs not only corroborates existing experimental information for selected species, but also introduces novel candidates for experimental validation. Moreover, these promising candidates have the potential for further extension to new representatives within the class. © 2023 Institut Pasteur
From genes to systems: The role of food supplementation in the regulation of sepsis-induced inflammation
(Elsevier B.V., 2024-01) Prado, Yolanda; Aravena, Diego; Gatica, Sebastian; Llancalahuen, Felipe M.; Aravena, Cristobal; Gutiérrez-Vera, Cristián; Carreño, Leandro J.; Cabello-Verrugio, Claudio; Simon, Felipe
Systemic inflammation includes a widespread immune response to a harmful stimulus that results in extensive systemic damage. One common example of systemic inflammation is sepsis, which is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Under the pro-inflammatory environment of sepsis, oxidative stress contributes to tissue damage due to dysfunctional microcirculation that progressively causes the failure of multiple organs that ultimately triggers death. To address the underlying inflammatory condition in critically ill patients, progress has been made to assess the beneficial effects of dietary supplements, which include polyphenols, amino acids, fatty acids, vitamins, and minerals that are recognized for their immuno-modulating, anticoagulating, and analgesic properties. Therefore, we aimed to review and discuss the contribution of food-derived supplementation in the regulation of inflammation from gene expression to physiological responses and summarize the precedented potential of current therapeutic approaches during systemic inflammation. © 2023
Connexin46 in the nucleus of cancer cells: a possible role as transcription modulator
(BioMed Central Ltd, 2025-12) Fernández-Olivares, Ainoa; Orellana, Viviana P; Llanquinao, Jesús; Nuñez, Gonzalo; Pérez-Moreno, Pablo; Contreras-Riquelme, Sebastián; Martin, Alberto JM; Mammano, Fabio; Alfaro, Ivan E; Calderón, Juan F; Stehberg, Jimmy; Sáez, Mauricio A; Retamal, Mauricio A.
Background Oncogenes drive cancer progression, but few are active exclusively in tumor cells. Connexins (Cxs), traditionally recognized as ion channel proteins, can localize to the nucleus and regulate gene expression, playing key roles in both physiological and pathological processes. Cx46, once thought to be restricted to the eye lens, has been implicated in tumor growth, though its underlying mechanisms remain unclear. This study investigates the nuclear presence of Cx46 in cancer cells and its potential role as a transcriptional modulator. Methods We employed ChIP-Seq, confocal immunofuorescence, and nuclear protein purifcation to assess Cx46 localization and DNA interactions. Functional assays were conducted to evaluate its efects on invasion, division, spheroid formation, and mesenchymal marker expression. Single-point mutations and molecular dynamics simulations were used to explore potential Cx46-DNA interactions. Results Cx46 mRNA upregulation was found in a variety of tumors compared to adjacent healthy tissue. In HeLa cells, which do not express Cx46, its transfection promoted proliferation, invasion and self-renewal capacity, cancer stem cell traits and mesenchymal features. Consistently, in Sk-Mel-2, which naturally express Cx46, reduced Cx46 expression led to a decrease in the similar parameters. In HeLa cells, nuclear Cx46 was detected in two forms, full length 46 kDa and a 30 kDa fragment (GJA3-30 k), ChIP-Seq experiments revealed that Cx46 binds to the DNA at intergenic and promoter regions, leading to the activation of oncogenic pathways. Molecular dynamics simulations suggest that GJA3-30 k dimerizes in a RAD50-like structure, forming stable DNA complexes. Cx46 and in some cases GJA3-30 k were detected in the nuclei of multiple cancer cell lines, including prostate, breast and skin cancers. Conclusions Our fndings reveal a novel nuclear role for Cx46 in cancer, demonstrating its function as a transcriptional regulator and its potential as a therapeutic target
Functional characterization of two KCND3 variants associated with SCA 19/22 ataxia in Latin American families
(BioMed Central Ltd, 0025) Arancibia, Felipe; Martin, Fernanda; Ruiz-Fuentes, Jenny; Diaz, Erbio; Hermosilla, Tamara; Gonzalez, Wendy; Simon, Felipe; Avila-Jaque, Diana; Luna-Álvarez, Mariana; Dávila Ortiz de Montellano, David José; Miranda, Marcelo; Bustamante, M. Leonor
Background: Spinocerebellar ataxia 19/22 (SCA19/22) represents a rare autosomal dominant genetic disorder resulting in progressive ataxia and cerebellar atrophy. SCA19/22 is caused by variants in the KCND3 gene, which encodes a voltage-gated potassium channel subunit essential for cerebellar Purkinje cell function. To date, 22 variants have been reported worldwide, with incomplete functional studies. Results: We present four Chilean and Mexican cases in whom two single-nucleotide variants were identified through whole-exome sequencing of the probands. One variant (G371R) was initially cataloged as pathogenic and the other (S357W) as likely pathogenic according to the American College of Medical Genetics and Genomics criteria. The pathogenicity of the G371R variation was confirmed by in-silico mutagenesis. Our molecular models, that include electrostatic potential analysis and algorithms to analyze the pore dimensions (HOLE), indicated that the longer side chain of the arginine narrowed the channel’s selectivity filter, while the positive charge modified its surface electrostatic potential, presumably preventing potassium flux. Functional characterization of the S357W variant was performed in AD293 cells. When overexpressed, KV4.3S357W channels alone showed no current. Protein electrophoresis revealed that the total number of KV4.3 channels expressed did not differ between the wild-type and mutated phenotypes, suggesting a protein trafficking malfunction. Co-expression of the KChIP2 auxiliary subunit partially rescued the potassium currents when the variant was expressed, albeit with very different biophysical characteristics, including faster inactivation vs. wild-type channels. Conclusions: This functional characterization of two KCND3 variants associated with SCA19/22 adds new evidence for the pathogenic role of Kv4.3 loss-of-function mutations and establishes a correlation between functional dominance and clinical severity in SCA19/22. © The Author(s) 2025.
Regioselective cyclocondensations with thiobarbituric acid: spirocyclic and azocine products, X-ray characterization, and antioxidant evaluation
(Royal Society of Chemistry, 0025) Polo-Cuadrado, Efraín; Rojas-Peña, Cristian; Rodriguez-Nuñez, Yeray A.; Blanco-Acuña, Edgard Fabián; Lopez, Jhon J.; Brito, Iván; Cisterna, Jonathan; Alderete, Joel B; Gutiérrez, Margarita
Multicomponent cyclocondensations of 5-amino-3-methyl-1-phenyl-1H-pyrazole (AMPZ), thiobarbituric acid, and p-formaldehyde under conventional thermal heating or ultrasonic irradiation were studied. Treatment of the reaction mixture in ethanol in an ultrasonic bath for 3 h produced azocine compound 4b, while the same mixture in ethanol under reflux conditions for 15 h produced spiro compound 4a. This work encompasses intricate experimental details, X-ray diffraction measurements, and multifaceted computational analyses employing methods such as the density functional theory and Hirshfeld surface analysis. Crystallographic investigations revealed the molecular structure of the compound and clarified its interactions involving hydrogen bonds and weak intermolecular forces. This article describes the synthesis and characterization of a novel spirocyclic compound. The study also evaluated the antioxidant potential in vitro using the DPPH and ABTS methods. The results showed that these compounds showed the best free radical scavenging ability, even in very small amounts, and that even at very low concentrations, these compounds showed excellent radical scavenging potential. Surprisingly, these compounds exhibited strong (ABTS+) radical scavenging activities, mainly attributed to the HAT mechanism, indicating their potential as therapeutic agents. Facile multipurpose, three-component selective procedures for new spiroheterocycles have been proposed, presenting intriguing perspectives in the field of medicine, particularly in the field of antioxidants. The geometric values of the computationally optimized structure were calculated using the density functional theory in LC-BLYP/6-31(d), aligned with the X-ray diffraction data, reinforcing the precision of our findings. © 2025 The Royal Society of Chemistry
Successful use of daptomycin and cefazolin in a case of persistent bacteremia caused by community acquired-methicillin resistant Staphylococcus aureus in a pregnant woman. Case report
(Sociedad Medica de Santiago, 2023-12) Fica, Alberto; Chomali, Pascal R.; Ojeda, Javier; Galarce, Nicolás; Hormazabal, Juan Carlos; Fernández, Jorge O.
We present the case of a pregnant woman with community-acquired methicillin-resistant Staphylococcus aureus bacteremia who required combined treatment with daptomycin and cefazolin for control after failure of an initial treatment with vancomycin. She had a favorable evolution, and the study of family contacts revealed a phenotypic and genetically similar isolate in a nasal sample from his mother. The carriage study on three household cats was negative. This case reveals that bacteremia caused by methicillin-resistant Staphylococcus aureus can affect pregnant women, and that the use of combined therapies may be necessary for its control. Sometimes, family contacts can carry this agent, and an eradication treatment is suggested.. © 2023 Sociedad Medica de Santiago. All rights reserved.
Three-dimensional exploration of the chicken embryo, a comparative study of light sheet and histological visualisation
(Public Library of Science, 0025) Smallridge M.W.; Aktepe T.E.; Coppo M.J.C.; Vaz P.K; Diaz-Méndez A; Murray C.M.; Segal G.; Devlin J.M; Hartley C.A.
Ultramicroscopy has offered new avenues into the visualisation of tissues within animal models, providing three-dimensional visualisation through the use of light sheet fluorescence microscopy. This study aimed to develop and apply an optical tissue clearing method to investigate the application of light sheet fluorescence microscopy to image late-stage chicken embryos, and compare anatomical visualisation to traditional histological staining. Seventeen-day old specific pathogen free embryos were collected, fixed, and sectioned. Haematoxylin and eosin stained sections were prepared for histology, while light sheet imaging required the tissues to be optically clear. For this, an ethyl cinnamate-based method was utilised, allowing for acquisition of clear, unobstructed three-dimensional images of significant organ structures and systems using only autofluorescence. The use of established histological techniques provided anatomical mapping of structures between familiar histology images and the three-dimensional light sheet images. Rendering of organs using light sheet imaging provided contextual insights into the surrounding tissues and physiological architecture of major organ structures and systems. This was most apparent through the identification of the pulmonary vein and rendering of a volumetric projection of the vasculature branching within the lung and the subsequent merging of vasculature into the left side of the heart. Overall, the visualisation of the chicken embryo was enhanced by combining traditional histology with the information gained by three-dimensional light sheet fluorescence microscopy. © 2025 Smallridge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
View more Major antigenic differences in Aeromonas salmonicida isolates correlate with the emergence of a new strain causing furunculosis in Chilean salmon farms
(Frontiers Media SA, 2025) Mancilla, Marcos; Ojeda, Adriana; Yuivar, Yassef; Grandón, Maritza; Grothusen, Horst; Oyarzún, Marcela; Bisquertt, Alejandro; Ugalde, Juan A.; Fuentes, Francisco; Ibarra, Pablo; Bustos, Patricio
Aeromonas salmonicida is the etiological agent of furunculosis, a septicemic disease with high mortality rates affecting salmonids and other teleost species worldwide. Reviewing molecular diagnostic protocols for routine diagnostics, we realized that the amplification of the vapA target gene failed in some cases of furunculosis. Therefore, we hypothesized that the emergence of a new strain may be involved in recent outbreaks. In this work, we demonstrate that the vapA locus is absent in the new strain, which explains why it lacks the major membrane component VapA protein, a critical virulence factor. In addition, we found that the vapA-absent strain differs from its counterparts in outer membrane protein and lipopolysaccharide profiles, suggesting profound changes at the membrane structure level and in antigenic properties. These features along with sequence analysis information allowed us to infer that a complex genomic rearrangement, probably an indel encompassing the entire vapA locus, gave rise to this membrane phenotype. Although the causes for pathogen evolution and emergence were not fully elucidated, our results strongly suggest that the vapA-absent strain is responsible for a raising proportion of recent furunculosis cases, and that it may be related to a less virulent disease and a low serological response upon vaccination with the A. salmonicida antigen formulation currently used in Chile.
Exploring Alternative Splicing in Response to Salinity: A Tissue-Level Comparative Analysis Using Arabidopsis thaliana Public Transcriptomic Data
(Multidisciplinary Digital Publishing Institute (MDPI), 0025) Hernández-Urrieta, Jesús; Álvarez, José Miguel; O’Brien, José Antonio
Increased soil salinity is a major threat to global agriculture and food security, caused mainly by anthropogenic activities and changing climatic cycles. Plants responses to salinity involve multiple regulatory layers, from transcriptome reprogramming to proteomic and metabolomic changes. Alternative splicing (AS) plays a role in coordinating the response to salinity, yet its extent, tissue, and condition specificity, remain poorly understood aspects. In this study, we used 52 publicly available RNA-seq datasets of salinity treatment to identify differential alternative splicing (DAS) events and genes participating in the response to this stimulus. Our findings reveal that either independently or coordinately, AS can regulate up to 20% of the transcriptome detected in Arabidopsis, with treatment intensity being the most determining factor. Moreover, we show that AS regulation was highly tissue-specific, with roots displaying strong AS-mediated stress responses. Furthermore, cross-stress comparisons showed that roots have a core set of AS-regulated genes associated with stress response and development, with functionally distinct sets of genes when comparing salt with other stresses, while also conserving a relevant condition-specific response. We demonstrate the need to integrate AS analysis to better understand plant adaptation mechanisms and highlight the key role of AS in salinity responses, revealing shared AS regulation between salt, heat, and drought responses. © 2025 by the authors.
Connexin46 in the nucleus of cancer cells: a possible role as transcription modulator
(BioMed Central Ltd, 0025) Fernández-Olivares, Ainoa; Orellana, Viviana P; Llanquinao, Jesús; Nuñez, Gonzalo; Pérez-Moreno, Pablo; Contreras-Riquelme, Sebastián; Martin, Alberto JM; Mammano, Fabio; Alfaro, Ivan E; Calderón, Juan F; Stehberg, Jimmy; Sáez, Mauricio A
Background: Oncogenes drive cancer progression, but few are active exclusively in tumor cells. Connexins (Cxs), traditionally recognized as ion channel proteins, can localize to the nucleus and regulate gene expression, playing key roles in both physiological and pathological processes. Cx46, once thought to be restricted to the eye lens, has been implicated in tumor growth, though its underlying mechanisms remain unclear. This study investigates the nuclear presence of Cx46 in cancer cells and its potential role as a transcriptional modulator. Methods: We employed ChIP-Seq, confocal immunofluorescence, and nuclear protein purification to assess Cx46 localization and DNA interactions. Functional assays were conducted to evaluate its effects on invasion, division, spheroid formation, and mesenchymal marker expression. Single-point mutations and molecular dynamics simulations were used to explore potential Cx46-DNA interactions. Results: Cx46 mRNA upregulation was found in a variety of tumors compared to adjacent healthy tissue. In HeLa cells, which do not express Cx46, its transfection promoted proliferation, invasion and self-renewal capacity, cancer stem cell traits and mesenchymal features. Consistently, in Sk-Mel-2, which naturally express Cx46, reduced Cx46 expression led to a decrease in the similar parameters. In HeLa cells, nuclear Cx46 was detected in two forms, full length 46 kDa and a 30 kDa fragment (GJA3-30 k), ChIP-Seq experiments revealed that Cx46 binds to the DNA at intergenic and promoter regions, leading to the activation of oncogenic pathways. Molecular dynamics simulations suggest that GJA3-30 k dimerizes in a RAD50-like structure, forming stable DNA complexes. Cx46 and in some cases GJA3-30 k were detected in the nuclei of multiple cancer cell lines, including prostate, breast and skin cancers. Conclusions: Our findings reveal a novel nuclear role for Cx46 in cancer, demonstrating its function as a transcriptional regulator and its potential as a therapeutic target. © The Author(s) 2025.
Biodegradation of olive mill solid waste by Anthracophyllum discolor and Stereum hirsutum: effect of copper and manganese supplementation
(Springer, 0025) Benavides V; Serrano A; Pinto-Ibieta F; Rubilar O.; Ciudad G.
Anthracophyllum hirsutum and Stereum hirsutum produce manganese peroxidase (MnP) and laccase to break down lignin, a potential biological pretreatment for lignocellulosic biomass. This work aimed to evaluate the effect of copper (Cu) and manganese (Mn) added to olive mill solid waste (OMSW) inoculated with A. discolor and S. hirsutum on ligninolytic enzyme activity, lignin degradation, and phenolic compound removal. Different optimal metal dosages were determined for each fungal strain. For S. hirsutum, the addition of 6.1 mg Cu kg⁻1 and 7.3 mg Mn kg⁻1 resulted in 173 ± 5 U·L⁻1 MnP activity (an 863% increase compared to no metal addition) and 42 ± 3% lignin degradation (183% higher than with no metal addition, 15 ± 3%). These conditions also led to 65–75% phenol removal efficiencies in OMSW at 25 days and 80–95% in leachates between 20 and 30 days. For A. discolor, 14.6 mg Mn kg⁻1 yielded 37 ± 7 U·L⁻1 MnP activity (a 142% increase compared to no metal addition) and 38 ± 7% lignin degradation (150% higher than with no metal addition, 15 ± 3%). Under these conditions, A. discolor achieved 80–90% phenol removal in leachates at 20 days. These results demonstrate the positive effect of optimised metal supplementation, highlighting the potential of S. hirsutum and A. discolor for effective lignocellulosic biomass pretreatment and future mycoremediation processes. © The Author(s) 2025.
Ventilation-induced acute kidney injury in acute respiratory failure: Do PEEP levels matter?
(BioMed Central Ltd, 0025) Benites, Martín H.; Suarez-Sipmann, Fernando; Kattan, Eduardo; Cruces, Pablo; Retamal, Jaime
Acute Respiratory Distress Syndrome (ARDS) is a leading cause of morbidity and mortality among critically ill patients, and mechanical ventilation (MV) plays a critical role in its management. One of the key parameters of MV is the level of positive end-expiratory pressure (PEEP), which helps to maintain an adequate lung functional volume. However, the optimal level of PEEP remains controversial. The classical approach in clinical trials for identifying the optimal PEEP has been to compare “high” and “low” levels in a dichotomous manner. High PEEP can improve lung compliance and significantly enhance oxygenation but has been inconclusive in hard clinical outcomes such as mortality and duration of MV. This discrepancy could be related to the fact that inappropriately high or low PEEP levels may adversely affect other organs, such as the heart, brain, and kidneys, which could counteract its potential beneficial effects on the lung. Patients with ARDS often develop acute kidney injury, which is an independent marker of mortality. Three primary mechanisms have been proposed to explain lung-kidney crosstalk during MV: gas exchange abnormalities, such as hypoxemia and hypercapnia; remote biotrauma; and hemodynamic changes, including reduced venous return and cardiac output. As PEEP levels increase, lung volume expands to a variable extent depending on mechanical response. This dynamic underlies two potential mechanisms that could impair venous return, potentially leading to splanchnic and renal congestion. First, increasing PEEP may enhance lung aeration, particularly in highly recruitable lungs, where previously collapsed alveoli reopen, increasing lung volume and pleural pressure, leading to vena cava compression, which can contribute to systemic venous congestion and abdominal organ impairment function. Second, in lungs with low recruitability, PEEP elevation may induce minimal changes in lung volume while increasing airway pressure, resulting in alveolar overdistension, vascular compression, and increased pulmonary vascular resistance. Therefore, we propose that high PEEP settings can contribute to renal congestion, potentially impairing renal function. This review underscores the need for further rigorous research to validate these perspectives and explore strategies for optimizing PEEP settings while minimizing adverse renal effects. © The Author(s) 2025.
Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
(Nature Research, 2022-12) Munk, Patrick; Brinch, Christian; Møller, Frederik Duus; Petersen, Thomas N.; Hendriksen, Rene S.; Seyfarth, Anne Mette; Kjeldgaard, Jette S.; Svendsen, Christina Aaby; van Bunnik, Bram; Berglund, Fanny; Bego, Artan; Power, Pablo; Rees, Catherine; Lambrinidis, Dionisia; Neilson, Elizabeth Heather Jakobsen; Gibb, Karen; Coventry, Kris; Collignon, Peter; Cassar, Susan; Allerberger, Franz; Begum, Anowara; Hossain, Zenat Zebin; Worrell, Carlon; Vandenberg, Olivier; Pieters, Ilse; Victorien, Dougnon Tamègnon; Salazar Gutierrez, Angela Daniela; Soria, Freddy; Grujić, Vesna Rudić; Mazalica, Nataša; Rahube, Teddie O.; Tagliati, Carlos Alberto; Rodrigues, Dalia; Oliveira, Guilherme; de Souza, Larissa Camila Ribeiro; Ivanov, Ivan; Juste, Bonkoungou Isidore; Oumar, Traoré; Sopheak, Thet; Vuthy, Yith; Ngandijo, Antoinette; Nzouankeu, Ariane; Olivier, Ziem A. Abah Jacques; Yost, Christopher K.; Kumar, Pratik; Brar, Satinder Kaur; Tabo, Djim-Adjim; Adell, Aiko D.; Paredes-Osses, Esteban; Martinez, Maria Cristina; Sara, Cuadros-Orellana; Ke, Changwen; Zheng, Huanying; Baisheng, Li; Lau, Lok Ting; Chung, Teresa; Jiao, Xiaoyang; Yu, Yongjie; JiaYong, Zhao; Morales, Johan F. Bernal; Valencia, Maria Fernanda; Donado-Godoy, Pilar; Coulibaly, Kalpy Julien; Hrenovic, Jasna; Jergović, Matijana; Karpíšková, Renáta; Deogratias, Zozo Nyarukweba; Elsborg, Bodil; Hansen, Lisbeth Truelstrup; Jensen, Pernille Erland; Abouelnaga, Mohamed; Salem, Mohamed Fathy; Koolmeister, Marliin; Legesse, Mengistu; Eguale, Tadesse; Heikinheimo, Annamari; Le Guyader, Soizick; Schaeffer, Julien; Villacis, Jose Eduardo; Sanneh, Bakary; Malania, Lile; Nitsche, Andreas; Brinkmann, Annika; Schubert, Sara; Hesse, Sina; Berendonk, Thomas U.; Saba, Courage Kosi Setsoafia; Mohammed, Jibril; Feglo, Patrick Kwame; Banu, Regina Ama; Kotzamanidis, Charalampos; Lytras, Efthymios; Lickes, Sergio A.; Kocsis, Bela; Solymosi, Norbert; Thorsteinsdottir, Thorunn R.; Hatha, Abdulla Mohamed; Ballal, Mamatha; Bangera, Sohan Rodney; Fani, Fereshteh; Alebouyeh, Masoud; Morris, Dearbhaile; O’Connor, Louise; Cormican, Martin; Moran-Gilad, Jacob; Battisti, Antonio; Diaconu, Elena Lavinia; Corno, Gianluca; Di Cesare, Andrea; Alba, Patricia; Hisatsune, Junzo; Yu, Liansheng; Kuroda, Makoto; Sugai, Motoyuki; Kayama, Shizuo; Shakenova, Zeinegul; Kiiyukia, Ciira; Ng’eno, Eric; Raka, Lul; Jamil, Kazi; Fakhraldeen, Saja Adel; Alaati, Tareq; Bērziņš, Aivars; Avsejenko, Jeļena; Kokina, Kristina; Streikisa, Madara; Bartkevics, Vadims; Matar, Ghassan M.; Daoud, Ziad; Pereckienė, Asta; Butrimaite-Ambrozeviciene, Ceslova; Penny, Christian; Bastaraud, Alexandra; Rasolofoarison, Tiavina; Collard, Jean-Marc; Samison, Luc Hervé; Andrianarivelo, Mala Rakoto; Banda, Daniel Lawadi; Amin, Arshana; Rajandas, Heraa; Parimannan, Sivachandran; Spiteri, David; Haber, Malcolm Vella; Santchurn, Sunita J.; Vujacic, Aleksandar; Djurovic, Dijana; Bouchrif, Brahim; Karraouan, Bouchra; Vubil, Delfino Carlos; Pal, Pushkar; Schmitt, Heike; van Passel, Mark; Jeunen, Gert-Jan; Gemmell, Neil; Chambers, Stephen T.; Mendoza, Fania Perez; Huete-Pιrez, Jorge; Vilchez, Samuel; Ahmed, Akeem Olayiwola; Adisa, Ibrahim Raufu; Odetokun, Ismail Ayoade; Fashae, Kayode; Sørgaard, Anne-Marie; Wester, Astrid Louise; Ryrfors, Pia; Holmstad, Rune; Mohsin, Mashkoor; Hasan, Rumina; Shakoor, Sadia; Gustafson, Natalie Weiler; Schill, Claudia Huber; Rojas, Maria Luz Zamudio; Velasquez, Jorge Echevarria; Magtibay, Bonifacio B.; Catangcatang, Kris; Sibulo, Ruby; Yauce, Felipe Campos; Wasyl, Dariusz; Manaia, Celia; Rocha, Jaqueline; Martins, Jose; Álvaro, Pedro; Di Yoong Wen, Doris; Shin, Hanseob; Hur, Hor-Gil; Yoon, Sukhwan; Bosevska, Golubinka; Kochubovski, Mihail; Cojocaru, Radu; Burduniuc, Olga; Hong, Pei-Ying; Perry, Meghan Rose; Gassama, Amy; Radosavljevic, Vladimir; Tay, Moon Y. F.; Zuniga-Montanez, Rogelio; Wuertz, Stefan; Gavačová, Dagmar; Pastuchová, Katarína; Truska, Peter; Trkov, Marija; Keddy, Karen; Esterhuyse, Kerneels; Song, Min Joon; Quintela-Baluja, Marcos; Lopez, Mariano Gomez; Cerdà-Cuéllar, Marta; Perera R.R.D.P.; Bandara N.K.B.K.R.G.W.; Premasiri H.I.; Pathirage, Sujatha; Charlemagne, Kareem; Rutgersson, Carolin; Norrgren, Leif; Örn, Stefan; Boss, Renate; Van der Heijden, Tanja; Hong, Yu-Ping; Kumburu, Happiness Houka; Mdegela, Robinson Hammerthon; Hounmanou, Yaovi Mahuton Gildas; Chonsin, Kaknokrat; Suthienkul, Orasa; Thamlikitkul, Visanu; de Roda Husman, Ana Maria; Bidjada, Bawimodom; Njanpop-Lafourcade, Berthe-Marie; Nikiema-Pessinaba, Somtinda Christelle; Levent, Belkis; Kurekci, Cemil; Ejobi, Francis; Kalule, John Bosco; Thomsen, Jens; Obaidi, Ouidiane; Jassim, Laila Mohamed; Moore, Andrew; Leonard, Anne; Graham, David W.; Bunce, Joshua T.; Zhang, Lihong; Gaze, William H.; Lefor, Brett; Capone, Drew; Sozzi, Emanuele; Brown, Joe; Meschke, John Scott; Sobsey, Mark D.; Davis, Michael; Beck, Nicola Koren; Sukapanpatharam, Pardi; Truong, Phuong; Lilienthal, Ronald; Kang, Sanghoon; Wittum, Thomas E.; Rigamonti, Natalia; Baklayan, Patricia; Van, Chinh Dang; Tran, Doan Minh Nguyen; Do Phuc, Nguyen; Kwenda, Geoffrey; Larsson, D. G. Joakim; Koopmans, Marion; Woolhouse, Mark; Aarestrup, Frank M.
Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention. © 2022, The Author(s).
Baseline Corticosterone, Stress Responses, and Leukocyte Profiles in Chicks of Precocial Birds in Rural and Urban Environments
(Multidisciplinary Digital Publishing Institute (MDPI), 2023-11) Quirici, Verónica; Valeris-Chacín, Carlos E.; Parada, Pablo; Cuevas, Elfego; Wingfield, John C.
The urban environment produces complex relationship among urban stressors that could change the levels of the steroid hormone, glucocorticoid (GCs). Studies that have evaluated baseline corticosterone (Cort) levels (the main GC in birds) and stress responses during development in urban and rural environments have obtained contrasting results. This ambiguity could partially be because the studies were carried out in altricial species, where parental care and sibling competition can affect Cort levels. Therefore, in this study, we compared levels of circulating baseline levels of CORT (blood sample obtained within 3 min of capture) and stress responses (blood sample obtained 30 min after capture) and the H/L ratio (an alternative method to measure stress) in chicks of a precocial bird, southern lapwings (Vanellus chilensis), from one rural (6 chicks), one urban low-polluted (13 chicks), and one urban high-polluted (10 chicks) site of Metropolitan Region of Santiago de Chile. We observed higher baseline Cort (2.41 ± 1.78 ng/mL) in the urban high-polluted site, a higher H/L ratio (0.51 ± 0.20) in the urban low-polluted site, and similar stress response across the three sites. We propose that the difference in stress physiology we observed within Santiago de Chile is because the two zones are at extremes in terms of stressors (noise, light, chemical, and human presence). It is unusual to find a precocious bird that lives in both urban and rural areas; therefore, the results of this study will advance our knowledge of the effect of the urban environment during the development of wildlife, which is relevant in terms of management and conservation. © 2023 by the authors.

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