Instability of the HLA-E peptidome of HIV presents a major barrier to therapeutic targeting.

Naturally occurring T cells that recognize microbial peptides via HLA-E, a nonpolymorphic HLA class Ib molecule, could provide the foundation for new universal immunotherapeutics. However, confidence in the biological relevance of putative ligands is crucial, given that the mechanisms by which pathogen-derived peptides can access the HLA-E presentation pathway are poorly understood. We systematically interrogated the HIV proteome using immunopeptidomic and bioinformatic approaches, coupled with biochemical and cellular assays. No HIV HLA-E peptides were identified by tandem mass spectrometry analysis of HIV-infected cells. In addition, all bioinformatically predicted HIV peptide ligands (>80) were characterized by poor complex stability. Furthermore, infected cell elimination assays using an affinity-enhanced T cell receptor bispecific targeted to a previously reported HIV Gag HLA-E epitope demonstrated inconsistent presentation of the peptide, despite normal HLA-E expression on HIV-infected cells. This work highlights the instability of the HIV HLA-E peptidome as a major challenge for drug development.

Biosynthesis of photostable CdS quantum dots by UV-resistant psychrotolerant bacteria isolated from Union Glacier, Antarctica.

BACKGROUND: Quantum Dots (QDs) are fluorescent nanoparticles with exceptional optical and optoelectronic properties, finding widespread utility in diverse industrial applications. Presently, chemically synthesized QDs are employed in solar cells, bioimaging, and various technological domains. However, many applications demand QDs with prolonged lifespans under conditions of high-energy radiation. Over the past decade, microbial biosynthesis of nanomaterials has emerged as a sustainable and cost-effective process. In this context, the utilization of extremophile microorganisms for synthesizing QDs with unique properties has recently been reported. RESULTS: In this study, UV-resistant bacteria were isolated from one of the most extreme environments in Antarctica, Union Glacier at the Ellsworth Mountains. Bacterial isolates, identified through 16 S sequencing, belong to the genera Rhodococcus, Pseudarthrobacter, and Arthrobacter. Notably, Rhodococcus sp. (EXRC-4 A-4), Pseudarthrobacter sp. (RC-2-3), and Arthrobacter sp. (EH-1B-1) tolerate UV-C radiation doses ≥ 120 J/m². Isolated UV-resistant bacteria biosynthesized CdS QDs with fluorescence intensities 4 to 8 times higher than those biosynthesized by E. coli, a mesophilic organism tolerating low doses of UV radiation. Transmission electron microscopy (TEM) analysis determined QD sizes ranging from 6 to 23 nm, and Fourier-transform infrared (FTIR) analysis demonstrated the presence of biomolecules. QDs produced by UV-resistant Antarctic bacteria exhibit high photostability after exposure to UV-B radiation, particularly in comparison to those biosynthesized by E. coli. Interestingly, red fluorescence-emitting QDs biosynthesized by Rhodococcus sp. (EXRC-4 A-4) and Arthrobacter sp. (EH-1B-1) increased their fluorescence emission after irradiation. Analysis of methylene blue degradation after exposure to irradiated QDs biosynthesized by UV-resistant bacteria, indicates that the QDs transfer their electrons to O2 for the formation of reactive oxygen species (ROS) at different levels. CONCLUSIONS: UV-resistant Antarctic bacteria represent a novel alternative for the sustainable generation of nanostructures with increased radiation tolerance-two characteristics favoring their potential application in technologies requiring continuous exposure to high-energy radiation.

Minicells as an Escherichia coli mechanism for the accumulation and disposal of fluorescent cadmium sulphide nanoparticles.

BACKGROUND: Bacterial biosynthesis of fluorescent nanoparticles or quantum dots (QDs) has emerged as a unique mechanism for heavy metal tolerance. However, the physiological pathways governing the removal of QDs from bacterial cells remains elusive. This study investigates the role of minicells, previously identified as a means of eliminating damaged proteins and enhancing bacterial resistance to stress. Building on our prior work, which unveiled the formation of minicells during cadmium QDs biosynthesis in Escherichia coli, we hypothesize that minicells serve as a mechanism for the accumulation and detoxification of QDs in bacterial cells. RESULTS: Intracellular biosynthesis of CdS QDs was performed in E. coli mutants ΔminC and ΔminCDE, known for their minicell-producing capabilities. Fluorescence microscopy analysis demonstrated that the generated minicells exhibited fluorescence emission, indicative of QD loading. Transmission electron microscopy (TEM) confirmed the presence of nanoparticles in minicells, while energy dispersive spectroscopy (EDS) revealed the coexistence of cadmium and sulfur. Cadmium quantification through flame atomic absorption spectrometry (FAAS) demonstrated that minicells accumulated a higher cadmium content compared to rod cells. Moreover, fluorescence intensity analysis suggested that minicells accumulated a greater quantity of fluorescent nanoparticles, underscoring their efficacy in QD removal. Biosynthesis dynamics in minicell-producing strains indicated that biosynthesized QDs maintained high fluorescence intensity even during prolonged biosynthesis times, suggesting continuous QD clearance in minicells. CONCLUSIONS: These findings support a model wherein E. coli utilizes minicells for the accumulation and removal of nanoparticles, highlighting their physiological role in eliminating harmful elements and maintaining cellular fitness. Additionally, this biosynthesis system presents an opportunity for generating minicell-coated nanoparticles with enhanced biocompatibility for diverse applications.

Co-Culture of P. gingivalis and F. nucleatum Synergistically Elevates IL-6 Expression via TLR4 Signaling in Oral Keratinocytes.

Periodontitis, characterized by persistent inflammation in the periodontium, is intricately connected to systemic diseases, including oral cancer. Bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, play a pivotal role in periodontitis development because they contribute to dysbiosis and tissue destruction. Thus, comprehending the interplay between these bacteria and their impacts on inflammation holds significant relevance in clinical understanding and treatment advancement. In the present work, we explored, for the first time, their impacts on the expressions of pro-inflammatory mediators after infecting oral keratinocytes (OKs) with a co-culture of pre-incubated P. gingivalis and F. nucleatum. Our results show that the co-culture increases IL-1ß, IL-8, and TNF-α expressions, synergistically augments IL-6, and translocates NF-kB to the cell nucleus. These changes in pro-inflammatory mediators-associated with chronic inflammation and cancer-correlate with an increase in cell migration following infection with the co-cultured bacteria or P. gingivalis alone. This effect depends on TLR4 because TLR4 knockdown notably impacts IL-6 expression and cell migration. Our study unveils, for the first time, crucial insights into the outcomes of their co-culture on virulence, unraveling the role of bacterial interactions in polymicrobial diseases and potential links to oral cancer.

Pseudomonas violetae sp. nov. and Pseudomonas emilianonis sp. nov., two new species with the ability to degrade TNT isolated from soil samples at Deception Island, maritime Antarctica.

Two motile, rod-shaped, Gram-stain-negative bacterial strains, TNT11T and TNT19T, were isolated from soil samples collected at Deception Island, Antarctica. According to the 16S rRNA gene sequence similarity, both strains belong to the genus Pseudomonas. Further genomic analyses based on ANI and dDDH suggested that these strains were new species. Growth of strain TNT11T is observed at 0-30 â„ƒ (optimum, 20 â„ƒ), pH 4.0-9.0 (optimum, pH 6.0) and in the presence of 0-5.0% NaCl (optimum, 1% NaCl), while for TNT19T is observed at 0-30 â„ƒ (optimum between 15 and 20 â„ƒ), pH 5.0-9.0 (optimum, pH 6.0) and in the presence of 0-5.0% NaCl (optimum between 0 and 1% NaCl). The fatty acid profile consists of the major compounds; C16:0 and C16:1 ω6 for TNT11T, and C16:0 and C12:0 for TNT19T. Based on the draft genome sequences, the DNA G + C content for TNT11T is 60.43 mol% and 58.60 mol% for TNT19T. Based on this polyphasic study, TNT11T and TNT19T represent two novel species of the genus Pseudomonas, for which the proposed names are Pseudomonas violetae sp. nov. and Pseudomonas emilianonis sp. nov., respectively. The type strains are Pseudomonas violetae TNT11T (= RGM 3443T = LMG 32959T) and Pseudomonas emilianonis TNT19T (= RGM 3442T = LMG 32960T). Strains TNT11T and TNT19T were deposited to CChRGM and BCCM/LMG with entry numbers RGM 3443/LMG 32959 and RGM 3442/LMG 32960, respectively.

New insights into xenobiotic tolerance of Antarctic bacteria: transcriptomic analysis of Pseudomonas sp. TNT3 during 2,4,6-trinitrotoluene biotransformation.

The xenobiotic 2,4,6-trinitrotoluene (TNT) is a highly persistent environmental contaminant, whose biotransformation by microorganisms has attracted renewed attention. In previous research, we reported the discovery of Pseudomonas sp. TNT3, the first described Antarctic bacterium with the ability to biotransform TNT. Furthermore, through genomic analysis, we identified distinctive features in this isolate associated with the biotransformation of TNT and other xenobiotics. However, the metabolic pathways and genes active during TNT exposure in this bacterium remained unexplored. In the present transcriptomic study, we used RNA-sequencing to investigate gene expression changes in Pseudomonas sp. TNT3 exposed to 100 mg/L of TNT. The results showed differential expression of 194 genes (54 upregulated and 140 downregulated), mostly encoding hypothetical proteins. The most highly upregulated gene (> 1000-fold) encoded an azoreductase enzyme not previously described. Other significantly upregulated genes were associated with (nitro)aromatics detoxification, oxidative, thiol-specific, and nitrosative stress responses, and (nitro)aromatic xenobiotic tolerance via efflux pumps. Most of the downregulated genes were involved in the electron transport chain, pyrroloquinoline quinone (PQQ)-related alcohol oxidation, and motility. These findings highlight a complex cellular response to TNT exposure, with the azoreductase enzyme likely playing a crucial role in TNT biotransformation. Our study provides new insights into the molecular mechanisms of TNT biotransformation and aids in developing effective TNT bioremediation strategies. To the best of our knowledge, this report is the first transcriptomic response analysis of an Antarctic bacterium during TNT biotransformation.

Biosynthesis of Cu-In-S Nanoparticles by a Yeast Isolated from Union Glacier, Antarctica: A Platform for Enhanced Quantum Dot-Sensitized Solar Cells.

In recent years, the utilization of extremophile microorganisms for the synthesis of metal nanoparticles, featuring enhanced properties and diverse compositions, has emerged as a sustainable strategy to generate high-quality nanomaterials with unique characteristics. Our study focuses on the biosynthesis of Cu-In-S (CIS) nanoparticles, which has garnered considerable attention in the past decade due to their low toxicity and versatile applications in biomedicine and solar cells. Despite this interest, there is a notable absence of reports on biological methods for CIS nanoparticle synthesis. In this research, three yeast species were isolated from soil samples in an extreme Antarctic environment-Union Glacier, Ellsworth Mountains. Among these isolates, Filobasidium stepposum demonstrated the capability to biosynthesize CIS nanoparticles when exposed to copper sulfate, indium chloride, glutathione, and cysteine. Subsequent purification and spectroscopic characterization confirmed the presence of characteristic absorbance and fluorescence peaks for CIS nanoparticles at 500 and 650 nm, respectively. Transmission electron microscopy analysis revealed the synthesis of monodisperse nanoparticles with a size range of 3-5 nm. Energy dispersive X-ray spectroscopy confirmed the composition of the nanoparticles, revealing the presence of copper, indium, and sulfur. The copper/indium ratio ranged from 0.15 to 0.27, depending on the reaction time. The biosynthesized CIS nanoparticles showed higher photostability than biomimetic nanoparticles and demonstrated successful application as photosensitizers in quantum dot-sensitized solar cells (QDSSC), achieving a conversion efficiency of up to 0.0247%. In summary, this work presents a cost-effective, straightforward, and environmentally friendly method for CIS nanoparticle synthesis. Furthermore, it constitutes the first documented instance of a biological procedure for producing these nanoparticles, opening avenues for the development of environmentally sustainable solar cells.

Antimicrobial Effect of Copper Nanoparticles on Relevant Supragingival Oral Bacteria.

Copper nanoparticles (Cu NPs) show promise in dentistry for combating bacterial dysbiosis and tooth decay. Understanding their effects on commensal versus pathogenic bacteria is vital for maintaining oral health balance. While Cu NPs demonstrate antibacterial properties against various oral bacteria, including common pathogens associated with tooth decay, their impact on commensal bacteria requires careful examination. In our work, we analyzed three types of Cu NPs for their effects on the growth, viability, and biofilm formation of representative caries-associated and commensal oral bacteria. S. sanguinis showed high tolerance to all Cu NPs, while L. rhamnosus was highly sensitive. Oxide-Cu NPs exhibited a stronger inhibitory effect on pathobionts compared with commensal bacteria. Moreover, the biofilm formation of the key cariogenic bacteria S. mutans was reduced, with minimal negative effects on commensal species' biofilm formation. All our results showed that CuO nanoparticles (CuO NPs) exhibit reduced toxicity toward commensal bacteria growth and development but have a strong impact on pathogens. This suggests their potential for targeted treatments against pathogenic bacteria, which could help in maintaining the balance of the oral bacterial community.

Osteomalacia. Diagnóstico y tratamiento / Osteomalacia. Diagnosis and treatment

Introducción: la osteomalacia se caracteriza por la falta de mineralización de la sustancia osteoide, que afecta al hueso cortical y al hueso esponjoso maduro. Es una enfermedad que se presenta en adultos y niños, aunque la causa es diferente en cada uno. Objetivo: exponer la generalidad de la osteomalacia por ser una enfermedad que produce serias afectaciones a la población que la padece, especialmente a los niños. Se enfatiza en el diagnóstico y su tratamiento. Desarrollo: a fin de resumir los elementos esenciales para establecer el diagnóstico de osteomalacia hay que plantear en primer lugar, la presencia de un trastorno de la mineralización ósea, de ahí que además de tener en cuenta las causas de la enfermedad, su curso clínico y la sintomatología. Conclusiones: una recomendación importante es no tener en cuenta la posibilidad de complicaciones en el curso de la enfermedad, como las fracturas, que, aunque sean parte del cuadro clínico, al producirse pueden ocasionar graves problemas, como el caso de las que aparecen en las costillas, que si se desplazan pueden interesar órganos vitales, de modo que en este tipo de pacientes no debe excluirse la posibilidad de emergencias o de urgencias reumatológicas tanto en los adultos como en los niños(AU)

Introduction: osteomalacia is characterized by the lack of mineralization of the osteoid substance, which affects cortical bone and mature cancellous bone. It is a disease that occurs in adults and children, although the cause is different in each. Objective: to expose the generality of osteomalacia for being a disease that causes serious affectations to the population that suffers it, especially to children. Emphasis is placed on the diagnosis and its treatment. Development: in order to summarize the essential elements to establish the diagnosis of osteomalacia, we must first consider the presence of a bone mineralization disorder, hence, in addition to taking into account the causes of the disease, its clinical course and the symptomatology. Conclusions: an important recommendation is not to take into account the possibility of complications in the course of the disease, such as fractures, which, although they are part of the clinical picture, can cause serious problems when they occur, as in the case of those that appear in the ribs, which if they move may involve vital organs, so that in this type of patients should not exclude the possibility of emergencies or rheumatological emergencies in both adults and children(AU)

Conocimientos de los estudiantes de medicina sobre las afecciones oftalmológicas más frecuentes en la práctica de la reumatología / Medical student´s knowledge about the most common ophthalmological conditions in the practice of rheumatology

Introducción: en la formación de pregrado debe concederse la debida importancia a la enseñanza de la reumatología dado su carácter multidisciplinar, que demanda un futuro profesional de la salud capaz de valorar y reconocer aún desde aulas y laboratorios, las implicaciones sociales y de salud entre enfermedades reumáticas y oculares ya que el diagnóstico correcto de estas, puede ayudar a destacar el rol del proceso sistémico y viceversa. Objetivo: evaluar el nivel de conocimientos de estudiantes de medicina sobre las afecciones oftalmológicas más frecuentes en la práctica de la reumatología. Métodos: la investigación se realizó en la facultad de Medicina perteneciente a la Universidad Regional Autónoma de los Andes en el período comprendido de marzo a mayo de 2017. Se trata de un estudio descriptivo, transversal y analítico. El universo estuvo constituido por 166 estudiantes de VI y VII semestres y la muestra de estudio la constituyeron 75 estudiantes de cada semestre seleccionados al azar. Resultados: la presencia mayoritaria de mujeres caracteriza a la muestra objeto de estudio (53.3 por ciento, contra 46,7 por ciento de hombres). Las edades máximas y mínimas fueron 21 y 26 años respectivamente, con edad promedio superior en el VII semestre. Se aplicó una encuesta validada previamente que permitió evaluar el conocimiento relacionado con las manifestaciones oftalmológicas más frecuentes. Conclusiones: el nivel de conocimiento sobre las manifestaciones oftalmológicas en la práctica de la reumatología no es bueno, por lo que se sugiere redimensionar el proceso docente, privilegiando la formación práctica que debe caracterizar la enseñanza de pregrado al profundizar en el manejo de estas entidades(AU)

Introduction: In the undergraduate training must be given due importance to the teaching of rheumatology because of its multidisciplinary character, which demands a future health professional able to assess and recognize even from classrooms and laboratories, the social and health implications between rheumatic and ocular diseases because the correct diagnosis of these can help highlighting the role of the systemic process and vice versa. Objective: To assess the level of medical students´ knowledge about the most common ophthalmological conditions in the practice of rheumatology. Methods: The research was carried out in the Faculty of Medicine belonging to the Universidad Regional Autónoma de los Andes from March to May, 2017. It is a descriptive, transversal and analytical study. The universe was constituted by 166 students of sixth and seventh semesters and the sample of study was constituted by 75 students of each semester selected at random. Development: The majority presence of women characterizes the sample object of study (53.3 percent against 46.7 percent of men). The maximum and minimum wages were 21 and 26 years old respectively, with a higher average age in the seventh semester. A previously validated survey was applied that allowed evaluating the knowledge related to the most frequent ophthalmologic manifestations. Conclusions: The level of knowledge on the ophthalmologic manifestations in the practice of rheumatology is not good, so it is suggested to resize the teaching process, favoring the practical training that must characterize the teaching of undergraduate to deepen the management of these entities(AU)

Crítica de la razón autonómica / sss

La investigación realiza una crítica de la razón autonómica, es decir, en este trabajo se discuten las acepciones, los usos y los argumentos que conlleva el término autonomía y se los valora a la luz del horizonte de la vida humana. hay que aceptar que aunque no descuida una mirada al contexto internacional, sobre todo se concentra en la construcción autonómica que se vive en Bolivia