Unique and redundant roles of mouse BCMA, TACI, BAFF, APRIL, and IL-6 in supporting antibody-producing cells in different tissues.

Antibody-producing plasma cells fuel humoral immune responses. They also contribute to autoimmune diseases such as systemic lupus erythematosus or IgA nephropathy. Interleukin-6 and the tumor necrosis factor (TNF) family ligands BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) participate in plasma cell survival. BAFF binds to three receptors, BAFFR (BAFF receptor), TACI (transmembrane activator and CAML interactor), and BCMA (B cell maturation antigen), while APRIL binds to TACI, BCMA, and proteoglycans. However, which ligand-receptor pair(s) are required to maintain plasma cells in different body locations remains unknown. Here, by combining mouse genetic and pharmacological approaches, we found that plasma cells required BCMA and/or TACI but not BAFFR. BCMA responded exclusively to APRIL, while TACI responded to both BAFF and APRIL, identifying three self-sufficient ligand-receptor pairs for plasma cell maintenance: BAFF-TACI, APRIL-TACI, and APRIL-BCMA. Together, these actors accounted for 90% of circulating antibodies. In BAFF-ko mice, the reduction of plasma cells upon APRIL inhibition indicated that APRIL could function in the absence of BAFF-APRIL heteromers. No evidence was found that in the absence of BCMA and TACI, binding of APRIL to proteoglycans would help maintain plasma cells. IL-6, alone or together with BAFF and APRIL, supported mainly splenic plasmablasts and plasma cells and contributed to circulating IgG but not IgA levels. In conclusion, survival factors for plasma cells can vary with body location and with the antibody isotype that plasma cells produce. To efficiently target plasma cells, in particular IgA-producing ones, dual inhibition of BAFF and APRIL is required.

Spontaneous pneumopericardium in a dog with bronchopulmonary disease complicated by pyothorax and pneumothorax.

Spontaneous pneumopericardium is a rare condition consisting of pericardial gas in the absence of iatrogenic or traumatic causes; it has been described secondary to pneumonia, lung abscess, and bronchopulmonary disease. This report describes a case of spontaneous pneumopericardium in a dog presenting with dyspnea secondary to pyopneumothorax complicating a bronchopulmonary disease.

Pneumopéricarde spontané chez un chien avec une maladie broncho-pulmonaire compliquée par la pleurésie et le pneumothorax. Un pneumopéricarde spontané est une rare affection qui cause des gaz péricardiques en l'absence de causes iatrogéniques ou traumatiques; il a été décrit comme secondaire à la pneumonie, à un abcès pulmonaire et à la maladie broncho-pulmonaire. Ce rapport décrit un cas de pneumopéricarde spontané chez un chien présenté avec une dyspnée secondaire au pyopneumothorax compliquant une maladie broncho-pulmonaire.(Traduit par Isabelle Vallières).

ECPUB5 Polyubiquitin Gene in Euphorbia characias: Molecular Characterization and Seasonal Expression Analysis.

The spurge Euphorbia characias is known for its latex, which is rich in antioxidant enzymes and anti-phytopathogen molecules. In this study, we identified a novel polyubiquitin protein in the latex and leaves, leading to the first molecular characterization of its coding gene and expressed protein in E. characias. Using consensus-degenerate hybrid oligonucleotide primers (CODEHOP) and rapid amplification of cDNA ends (5'/3'-RACE), we reconstructed the entire open reading frame (ORF) and noncoding regions. Our analysis revealed that the polyubiquitin gene encodes five tandemly repeated sequences, each coding for a ubiquitin monomer with amino acid variations in four of the five repeats. In silico studies have suggested functional differences among monomers. Gene expression peaked during the summer, correlating with high temperatures and suggesting a role in heat stress response. Western blotting confirmed the presence of polyubiquitin in the latex and leaf tissues, indicating active ubiquitination processes. These findings enhance our understanding of polyubiquitin's regulatory mechanisms and functions in E. characias, highlighting its unique structural and functional features.

HLA Genotyping in Children With Celiac Disease Allows to Establish the Risk of Developing Type 1 Diabetes.

INTRODUCTION: Celiac disease (CD) and type 1 diabetes (T1D) often co-occur and share genetic components in the human leukocyte antigen (HLA) class II region. We aimed to study the usefulness of HLA genotyping in predicting the risk of developing T1D in patients with CD and the temporal relationship between these diseases. METHODS: A cohort of 1,886 Sardinian patients, including 822 with CD, 1,064 with T1D, and 627 controls, underwent HLA class II typing. Seventy-six of 822 patients with CD were also affected by T1D (CD-T1D), and their HLA genotypes were analyzed for specific HLA associations with CD, T1D, and controls. RESULTS: High-risk HLA-DQ genotypes, including HLA-DQ2.5/DQ8, -DQ2.5/DQ2.5, and -DQ2.5/DQ2.3, were strongly associated with CD-T1D with frequencies of 34.5%, 15.9%, and 18.8%, respectively. Conversely, certain HLA genotypes associated with CD seemed to confer protection against T1D development. Therefore, HLA genotyping allows for the identification of those patients with CD who might develop T1D. The frequency of patients with CD preceding T1D is higher in younger children than older ones, with implications for the early childhood approach to diabetes prevention. DISCUSSION: CD is a condition for future T1D development, and specific HLA genotypes can predict this risk. Early screening for celiac autoimmunity and subsequent HLA typing in CD children could help identify those at high risk of T1D, allowing for proactive interventions and immunotherapies to preserve ß-cell function. These findings may support the re-evaluation of HLA typing in children with CD.

Clinical features of patients with hands arthralgia referred from primary care physicians to rheumatologists: A cohort study.

PURPOSE: Early referral of patients with suspicious of rheumatoid arthritis (RA) has an impact on prognosis. Our study aimed to evaluate the clinical characteristics of patients with hands arthralgia who were referred from primary care physicians (PCP) to the rheumatologist. METHODS: A descriptive, observational, prospective cohort study was performed. We included patients who visited a PCP for the first time for hands arthralgia. Demographics and the European Alliance of Associations for Rheumatology criteria for arthralgia suspicious for progression to RA plus seven complementary questions, the time to referral, the pressure needed to provoke pain with an automatic squeeze test machine in the metacarpophalangeal joints of both hands, and the diagnoses established at the last review of medical charts from patients on follow-up were documented. The primary outcome was the referral to a rheumatologist. RESULTS: A total of 109 patients were included. The mean age was 49.9 years, 81.6% were women. 30.3% were referred to the rheumatologist. The time to referral was a median of 38 days. The main clinical characteristics associated with referral to the rheumatologist were the "most severe symptoms are present after midnight" (OR=6.29) and the "difficulty with making a fist" (OR=3.67). An isolated "positive squeeze test of metacarpophalangeal joints" was not associated with a referral to the rheumatologist. CONCLUSIONS: Among patients with hands arthralgia who attended PCP, those with most severe symptoms after midnight and difficulty making a fist were more likely to be referred to the rheumatology clinic. Isolated positive squeeze tests are not a parameter for referral, it should only be performed if arthralgia is clinically suspected.

Peroxiredoxin 6 suppresses ferroptosis in lung endothelial cells.

Peroxiredoxin 6 (Prdx6) repairs peroxidized membranes by reducing oxidized phospholipids, and by replacing oxidized sn-2 fatty acyl groups through hydrolysis/reacylation by its phospholipase A2 (aiPLA2) and lysophosphatidylcholine acyltransferase activities. Prdx6 is highly expressed in the lung, and intact lungs and cells null for Prdx6 or with single-point mutations that inactivate either Prdx6-peroxidase or aiPLA2 activity alone exhibit decreased viability, increased lipid peroxidation, and incomplete repair when exposed to paraquat, hyperoxia, or organic peroxides. Ferroptosis is form of cell death driven by the accumulation of phospholipid hydroperoxides. We studied the role of Prdx6 as a ferroptosis suppressor in the lung. We first compared the expression Prdx6 and glutathione peroxidase 4 (GPx4) and visualized Prdx6 and GPx4 within the lung. Lung Prdx6 mRNA levels were five times higher than GPx4 levels. Both Prdx6 and GPx4 localized to epithelial and endothelial cells. Prdx6 knockout or knockdown sensitized lung endothelial cells to erastin-induced ferroptosis. Cells with genetic inactivation of either aiPLA2 or Prdx6-peroxidase were more sensitive to ferroptosis than WT cells, but less sensitive than KO cells. We then conducted RNA-seq analyses in Prdx6-depleted cells to further explore how the loss of Prdx6 sensitizes lung endothelial cells to ferroptosis. Prdx6 KD upregulated transcriptional signatures associated with selenoamino acid metabolism and mitochondrial function. Accordingly, Prdx6 deficiency blunted mitochondrial function and increased GPx4 abundance whereas GPx4 KD had the opposite effect on Prdx6. Moreover, we detected Prdx6 and GPx4 interactions in intact cells, suggesting that both enzymes cooperate to suppress lipid peroxidation. Notably, Prdx6-depleted cells remained sensitive to erastin-induced ferroptosis despite the compensatory increase in GPx4. These results show that Prdx6 suppresses ferroptosis in lung endothelial cells and that both aiPLA2 and Prdx6-peroxidase contribute to this effect. These results also show that Prdx6 supports mitochondrial function and modulates several coordinated cytoprotective pathways in the pulmonary endothelium.

Oxidative Stress Is a Potential Cost of Synchronous Nesting in Olive Ridley Sea Turtles.

Olive ridley sea turtles, Lepidochelys olivacea, exhibit a polymorphic reproductive behavior, nesting solitarily or in mass aggregations termed "arribadas", where thousands of individuals nest synchronously. Arribada nesting provides fitness benefits including mate finding during nearshore aggregations and predator satiation at the time of hatching, but it is unknown if such benefits come with a physiological cost. We used plasma metabolite profiling, stable isotope analysis, biochemical and endocrine assays to test whether metabolic parameters differ between nesting modes, and if arribada nesting is associated with increased levels of oxidative damage compared to solitary nesting. Arribada nesters were bigger and had higher circulating thyroid hormone levels than solitary nesters. Similarly, pathways related to phospholipid and amino acid metabolism, catabolic processes, and antioxidant defense were enriched in individuals nesting in arribada. Stable isotope signatures in skin samples showed differences in feeding zones with arribada nesters likely feeding on benthic and potentially more productive grounds. Arribada nesters had increased levels of plasma lipid peroxidation and protein oxidation products compared to solitary nesters. These results suggest that metabolic profiles differ between nesting modes and that oxidative stress is a trade-off for the fitness benefits associated with arribada nesting.

Bone erosions by MRI in first-degree relatives of patients with RA: an exploratory study.

INTRODUCTION/OBJECTIVES: First-degree relatives (FDR) of patients with rheumatoid arthritis (RA) are at increased risk of RA diagnosis. Magnetic resonance imaging (MRI) has been proposed as a useful tool to detect subclinical synovitis and bone abnormalities as predictors of progression to RA. The presence of grade ≥ 2 bone erosions in RA MRI scoring system (RAMRIS) was reported to be RA-specific. We aim to describe the prevalence and characteristics of MRI findings in RA patients and FDR. METHODS: A cross-sectional and exploratory study of 60 individuals was performed in 38 RA patients and 22 FDR with hand arthralgia without clinical arthritis and positive rheumatoid factor or anticitrullinated protein antibodies. All patients underwent an MRI and were evaluated for synovitis, bone erosion, and bone marrow edema. We evaluated second to fifth metacarpophalangeal joints of the dominant hand according to RAMRIS. RESULTS: Among the total population, eighteen (30%) subjects had grade ≥ 2 bone erosions, and 42 (70%) had at least one erosion of any grade. In patients with grade ≥ 2 bone erosions, 12 (31.6%) were from RA patients and 6 (27.2%) from FDR (p = 0.72). In patients with erosions of any grade, 26 (68.4%) were from RA patients and 15 (68.2%) were from FDR (p = 0.98). CONCLUSION: A high prevalence of bone erosions was found in RA patients' FDR who had symptoms without clinical arthritis and positive serology. MRI might be helpful in this population for an early detection of RA-specific erosions. The prognosis and the treatment decisions in these subjects should be elucidated. KEY POINTS: • First-degree relatives (FDR) of rheumatoid arthritis (RA) patients with positive serology and joint symptoms constitute a select subpopulation of individuals with an increased risk of developing RA. • Magnetic resonance imaging (MRI) of FDR shows a high prevalence of bone erosions of any grade, grade ≥ 2 erosions, and synovitis. • MRI might be helpful in FDR of RA patients to screen for the presence of RA-specific erosions or clinically undetectable synovitis.

Evaluación preclínica de la actividad antiinflamatoria de un gel con aceite de árbol de té / Preclinical evaluation of the anti-inflammatory activity of a gel with tea tree oil

Objetivo: Evaluar la actividad antiinflamatoria de una formulación semisólida que contiene Aceite de Árbol de Té (AAT), a dos concentraciones (2 % y 2,5 %), para futuro tratamiento de enfermedad periodontal.Método: Prueba preclínica de edema auricular por aceite de crotón, con una muestra de 30 ratones, para ser com-parados con Indometacina y Diclofenaco.Resultados: La concentración al 2 % mostró un 51,21 % de inhibición de la actividad inflamatoria, mientras que para la concentración del 2,5 %, fue de 54,74 %. Las pruebas estadísticas para conocer la eficacia de los tratamien-tos demostraron que no existen diferencias significativas entre las combinaciones de tratamientos, indicando que todos tratamientos son similares (p>0,05).Conclusiones: Los resultados de este estudio demuestran que la forma semi solida de AAT, en los estudios preclíni-cos en la fase de ensayos in vivo con animales no humanos demostró poseer una actividad antiinflamatoria. (AU)

Objective: To evaluate the anti-inflammatory activity of a semi-solid Tea Tree Oil (TTO) form at 2 % and 2,5% con-centrations for treating periodontal disease.Method: A preclinical test in a sample of 30 mice with ear edema induced by croton oil was divided into two groups to compare treatment with Indomethacin and Diclofenac.Results: TTO at 2,5 % concentration showed a higher inhibition activity of inflammation (54,74 %) than TTO at 2 % (51,21 %). Statistical analysis showed no significative differences between treatment combinations (p>0,05).Conclusions: The tea tree oil in semi-solid form, applied in 2 - 2,5 % concentration in this preclinical study, showed consistent anti-inflammatory activity. (AU)

Método LAMP como alternativa diagnostica para la detección del virus SARS-CoV-2 / LAMP method as a diagnostic alternative for the detection of the SARS-CoV-2 virus / Método LAMP como alternativa de diagnóstico para a detecção do vírus SARS-CoV-2

RESUMEN Introducción: el coronavirus SARS-CoV-2, causante de la enfermedad COVID-19 se ha convertido en un problema de salud pública mundial que requiere la implemen-tación de pruebas de diagnóstico rápidas y sensibles. Objetivo: evaluar y comparar el límite de detección del método LAMP con respecto al método estándar y aplicar el método RT-LAMP para el diagnóstico de SARS-CoV-2 en muestras clínicas de pacientes colombianos. Métodos: se realizó un estudio descriptivo y transversal, analizando un total de 25 muestras de hisopado nasofaríngeo incluyendo muestras negativas y positivas para SARS-CoV-2, a través del método RT-LAMP comparado con el método estándar RT-qPCR. Resultados: el método LAMP detectó ~18 copias del gen N, en 30 min, demostrando un límite de detección similar al obtenido con el método estándar, en un menor tiempo y una concordancia en RT-LAMP del 100 % con los resultados. Conclusiones: RT-LAMP es un método sensible, específico y rápido que puede ser empleado para el diagnóstico de la enfermedad COVID-19.

SUMMARY Introduction: The SARS-CoV-2 coronavirus, that causes the COVID-19 disease, has become a global public health problem that requires the implementation of rapid and sensitive diagnostic tests. Aim: To evaluate and compare the sensitivity of LAMP assay to a standard method and use RT-LAMP for the diagnosis of SARS-CoV-2 in clinical samples from Colombian patients. Methods: A descriptive and cross-sectional study was conducted. A total of 25 nasopharyngeal swab samples including negative and positive samples for SARS-CoV-2 were analyzed, through the RT-LAMP method compared to the RT-qPCR assay. Results: LAMP method detected ~18 copies of the N gene, in 30 min, evidenced a detection limit similar to the standard method, in a shorter time and a concordance in RT-LAMP of 100% with the results. Conclusions: RT-LAMP is a sensitive, specific, and rapid method that can be used as a diagnostic aid of COVID-19 disease.

RESUMO Introdução: o coronavírus SARS-CoV-2, causador da doença de COVID-19, tornou-se um problema de saúde pública global que requer a implementação de testes diagnósticos rápidos e sensíveis. Objetivo: avaliar e comparar o limite de detecção do método LAMP em relação ao método padrão e aplicar o método RT-LAMP para o diagnóstico de SARS-CoV-2 em amostras clínicas de pacientes colombianos. Métodos: foi realizado um estudo descritivo e transversal, analisando um total de 25 amostras de hissopado nasofaríngeo, incluindo amostras negativas e positivas para SARS-CoV-2, pelo método RT-LAMP em comparação ao método RT-qPCR padrão. Resultados: o método LAMP detectou ~18 cópias do gene N, em 30 min., demonstrando um limite de detecção semelhante ao obtido com o método padrão, em um tempo menor e uma concordância no RT-LAMP de 100% com os resultados. Conclusões: RT-LAMP é um método sensível, específico e rápido que pode ser usado para o diagnóstico da doença de COVID-19.

Clinical features of patients with hands arthralgia referred from primary care physicians to rheumatologists: A cohort study / Características clínicas de los pacientes con artralgia de manos que son referidos a la clínica de reumatología por médicos de atención primaria: un estudio de cohorte

Purpose: Early referral of patients with suspicious of rheumatoid arthritis (RA) has an impact on prognosis. Our study aimed to evaluate the clinical characteristics of patients with hands arthralgia who were referred from primary care physicians (PCP) to the rheumatologist.Methods: A descriptive, observational, prospective cohort study was performed. We included patients who visited a PCP for the first time for hands arthralgia. Demographics and the European Alliance of Associations for Rheumatology criteria for arthralgia suspicious for progression to RA plus seven complementary questions, the time to referral, the pressure needed to provoke pain with an automatic squeeze test machine in the metacarpophalangeal joints of both hands, and the diagnoses established at the last review of medical charts from patients on follow-up were documented. The primary outcome was the referral to a rheumatologist. Results: A total of 109 patients were included. The mean age was 49.9 years, 81.6% were women. 30.3% were referred to the rheumatologist. The time to referral was a median of 38 days. The main clinical characteristics associated with referral to the rheumatologist were the “most severe symptoms are present after midnight” (OR=6.29) and the “difficulty with making a fist” (OR=3.67). An isolated “positive squeeze test of metacarpophalangeal joints” was not associated with a referral to the rheumatologist. Conclusions: Among patients with hands arthralgia who attended PCP, those with most severe symptoms after midnight and difficulty making a fist were more likely to be referred to the rheumatology clinic. Isolated positive squeeze tests are not a parameter for referral, it should only be performed if arthralgia is clinically suspected.(AU)

Objetivo: Derivar tempranamente a los pacientes con sospecha de artritis reumatoide (AR) tiene un impacto en su pronóstico. Nuestro estudio tuvo como objetivo evaluar las características clínicas de los pacientes con artralgia de manos que fueron remitidos desde médicos de atención primaria (MAP) al reumatólogo. Métodos: Se realizó un estudio de cohorte descriptivo, observacional, y prospectivo. Incluimos pacientes que acudieron con un MAP por artralgia de manos. Se documentaron criterios demográficos y de la European Alliance of Associations for Rheumatology (EULAR) para artralgia con sospecha de progresión a AR más siete preguntas complementarias, el tiempo de derivación, la presión necesaria para provocar dolor con una máquina automática que comprime las articulaciones metacarpofalángicas, y los diagnósticos establecidos en la última revisión documentados en los expedientes médicos de los pacientes en seguimiento. El resultado principal fue la referencia al reumatólogo. Resultados: Un total de 109 pacientes fueron incluidos. El promedio de edad fue de 49,9 años, 81,6% fueron mujeres, 30,3% fueron referidos al reumatólogo. El tiempo de derivación al reumatólogo tuvo una mediana de 38 días. Las principales características clínicas asociadas con lo anterior fueron: «síntomas más severos presentes después de la medianoche» (OR=6,29) y «dificultad para hacer un puño» (OR=3,67). Una «prueba de compresión positiva de las articulaciones metacarpofalángicas» aislada no se asoció con una derivación al reumatólogo. Conclusión: Entre los pacientes que acudieron con MAP por artralgia de manos, aquellos con síntomas más severos después de la medianoche y que refirieron dificultad para realizar un puño fueron más frecuentemente referidos a una clínica de reumatología. Sin embargo, una prueba de compresión aislada no fue útil para la derivación temprana.(AU)

La biotecnología de Bacillus thuringiensis en la agricultura / Bacillus thuringiensis biotechnology in agriculture

Bacillus thuringiensis es un bacilo Gram positivo que durante su fase de esporulación produce unainclusión parasporal, conformada por proteínas Cry con actividad biológica contra insectos-plaga. Gracias a estas proteínas Bacillus thuringiensis presenta toxicidad contra larvas de insectos-plaga de los órdenes Lepidóptera, Coleóptera y Díptera, entre otros. Además es amigable con el medioambiente, razones por la cuales se ha hecho común el uso y desarrollo de productos comerciales y plantas transgénicas a base de toxinas Cry en el sector agrícola. En esta revisión se describirá los aspectos más importantes de Bt y su aplicación como herramienta biotecnológica para el sector agrícola, con una consideración sobre bioensayos usando esta bacteria.

Bacillus thuringiensis (Bt) is a Gram-positive rod-shape bacterium that during its sporulation phase produces a parasporal inclusion formed by Cry proteins having biological activity against pest insects. Because of these proteins, Bt shows toxicity toward pest insect larvae of Lepidoptera, Coleoptera and Diptera orders among others, besides of friendly with the environment, and for this reason Bt has a very common use for commercial products and transgenic plants with Cry protein basis in agriculture. In this review is described the most important Bt factors and their application as biotechnological tool in agrobusiness, considering Bt bioassays.

Bacillus thuringiensis: en el manejo del agente de la pudrición blanda de la papa Erwinia carotovora / Bacillus thuringiensis control of the potato soft rot Erwinia carotovora

En Colombia el cultivo de papa es el cuarto en importancia en la economía del país, y su producción alcanza las 300 millones de toneladas aproximadamente. Erwinia carotovora es una bacteria Gram negativa, anaeróbica facultativa causante de la pudrición blanda de la papa, puede llegar a generar hasta el 100% de daño en la cosecha, lo cual ocasiona grandes pérdidas económicas. Se ha establecido que la bacteria Bacillus thuringiensis es capaz de suprimir la virulencia de E. caratovora debido a que produce N-acil-homoserina-lactonasa, una potente enzima que degrada de N-acil-homoserinolactonas, que son indispensables en el mecanismo de quorum-sensing de E. caratovora. Esta circunstancia, puede ser una alternativa importante para el control de la enfermedad de la pudrición blanda de la papa. Considerando lo anterior, en este artículo se describe el proceso que emplea la bacteria Bacillus thuringiensis para inhibir la actividad de E. caratovora.

In Colombia the potato crop is the fourth in importance in the economy of the country, its production reached 300 million tons. Erwinia carotovora is a Gram-negative bacterium, facultative anaerobic which causes the soft rotting of the potato; it can potentially generate up to 100% damage in the crop, which causes large economic losses. It has been established that the bacterium Bacillus thuringiensis is able to suppress the virulence of E. caratovora because it produces N-acyl-homoserine-lactonasa, a powerful enzyme that degrades of N-acyl-homoserinolactonas, which are indispensable in the quorum-sensing mechanism of E. caratovora. This can be an important alternative for the control of the disease of the soft rotting of the potato. Considering the above, this article describes the process used by the bacterium B. thuringiensis to inhibit the activity of E. caratovora.