Mechanisms of neutralization of toxSAS from toxin-antitoxin modules.

Toxic small alarmone synthetase (toxSAS) enzymes constitute a family of bacterial effectors present in toxin-antitoxin and secretion systems. toxSASs act through either translation inhibition mediated by pyrophosphorylation of transfer RNA (tRNA) CCA ends or synthesis of the toxic alarmone adenosine pentaphosphate ((pp)pApp) and adenosine triphosphate (ATP) depletion, exemplified by FaRel2 and FaRel, respectively. However, structural bases of toxSAS neutralization are missing. Here we show that the pseudo-Zn2+ finger domain (pZFD) of the ATfaRel2 antitoxin precludes access of ATP to the pyrophosphate donor site of the FaRel2 toxin, without affecting recruitment of the tRNA pyrophosphate acceptor. By contrast, (pp)pApp-producing toxSASs are inhibited by Tis1 antitoxin domains though occlusion of the pyrophosphate acceptor-binding site. Consequently, the auxiliary pZFD of AT2faRel is dispensable for FaRel neutralization. Collectively, our study establishes the general principles of toxSAS inhibition by structured antitoxin domains, with the control strategy directly coupled to toxSAS substrate specificity.

Brassica oleracea L. var. italica Aquaporin Reconstituted Proteoliposomes as Nanosystems for Resveratrol Encapsulation.

Aquaporins (AQPs), membrane proteins responsible for facilitating water transport, found in plant membrane vesicles (MV), have been related to the functionality and stability of MV. We focused on AQPs obtained from broccoli, as they show potential for biotechnological applications. To gain further insight into the role of AQPs in MV, we describe the heterologous overexpression of two broccoli AQPs (BoPIP1;2 and BoPIP2;2) in Pichia pastoris, resulting in their purification with high yield (0.14 and 0.99 mg per gram cells for BoPIP1;2 and BoPIP2;2). We reconstituted AQPs in liposomes to study their functionality, and the size of proteoliposomes did not change concerning liposomes. BoPIP2;2 facilitated water transport, which was preserved for seven days at 4 °C and at room temperature but not at 37 °C. BoPIP2;2 was incorporated into liposomes to encapsulate a resveratrol extract, resulting in increased entrapment efficiency (EE) compared to conventional liposomes. Molecular docking was utilized to identify binding sites in PIP2s for resveratrol, highlighting the role of aquaporins in the improved EE. Moreover, interactions between plant AQP and human integrin were shown, which may increase internalization by the human target cells. Our results suggest AQP-based alternative encapsulation systems can be used in specifically targeted biotechnological applications.

Exploring Phenolic Compounds in Crop By-Products for Cosmetic Efficacy.

Phenolic compounds represent a group of secondary metabolites that serve essential functions in plants. Beyond their positive impact on plants, these phenolic metabolites, often referred to as polyphenols, possess a range of biological properties that can promote skin health. Scientific research indicates that topically using phenolics derived from plants can be advantageous, but their activity and stability highly depend on storage of the source material and the extraction method. These compounds have the ability to relieve symptoms and hinder the progression of different skin diseases. Because they come from natural sources and have minimal toxicity, phenolic compounds show potential in addressing the causes and effects of skin aging, skin diseases, and various types of skin damage, such as wounds and burns. Hence, this review provides extensive information on the particular crops from which by-product phenolic compounds can be sourced, also emphasizing the need to conduct research according to proper plant material storage practices and the choice of the best extracting method, along with an examination of their specific functions and the mechanisms by which they act to protect skin.

Exploring membrane vesicles in citrus fruits: a comparative analysis of conventional and organic farming approaches.

BACKGROUND: Recently, vesicles derived from plant cell membranes have received attention for their potential use as active biomolecules and nanocarriers, and obtaining them from organic crops may be an interesting option because different farming systems can affect production, plant secondary metabolism and biochemistry of cell membranes. The present study aimed to determine how organic and conventional farming affects the mineral nutrition, gas exchange, CO2 fixation and biochemical composition of lemon fruits, which could have an impact on the different fractions of cell membranes in pulp and juice. RESULTS: Organic trees had higher intrinsic water use efficiency (WUEi) but conventional trees had higher stomatal conductance (gs) and nitrogen use efficiency (NUtE). Also, organic lemons had significantly higher levels of some micronutrients (Ca, Cu, Fe and Zn). Second, the main differences in the membrane vesicles showed that organic pulp vesicles had a higher antioxidant activity and more oleic acid, whereas both types of vesicles from conventional lemons had more linoleic acid. CONCLUSION: In conclusion, organic farming did not alter carbon fixation parameters but impacted nitrogen fixation and water uptake, and resulted in higher micronutrient levels in lemons. These mineral nutritional changes could be related to the higher production of membranes that showed suitable morphological traits and a high antioxidant activity, positively correlated with a high amount of oleic acid, which could have stronger cell protection characteristics. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Transcriptomic Profiling of Pleural Effusions: Differences in Malignant and Infectious Fluids.

Background and Objectives: Different cellular and molecular processes are involved in the production of malignant and infectious pleural effusions. However, the underlying mechanisms responsible for these differences or their consequences remain incompletely understood. The objective of this study was to identify differences in gene expression in pleural exudates of malignant and infectious aetiology and establish the possible different biological processes involved in both situations. Materials and Methods: RNA transcriptomic analysis was performed on 46 pleural fluid samples obtained during diagnostic thoracocenteses from 46 patients. There were 35 exudates (19 malignant and 16 infectious effusions) and 11 transudates that were used as a reference control group. Differential gene expression analysis for both exudative groups was identified. An enrichment score using the Human Kegg Orthology database was used for establishing the biological processes associated with malignant and infectious pleural effusions. Results: When comparing malignant exudates with infectious effusions, 27 differentially expressed genes with statistical significance were identified. Network analysis showed ten different biological processes for malignant and for infectious pleural effusions. In malignant fluids, processes related to protein synthesis and processing predominate. In infectious exudates, biological processes in connection with ATP production prevail. Conclusions: This study demonstrates differentially expressed genes in malignant and infectious pleural effusions, which could have important implications in the search for diagnostic or prognostic biomarkers. In addition, for the first time, biological processes involved in these two causes of pleural exudates have been described.

Sapwood mycobiome varies across host, plant compartment and environments in Nothofagus forests from Northern Patagonia.

Global forests are increasingly being threatened by altered climatic conditions and increased attacks by pests and pathogens. The complex ecological interactions among pathogens, microbial communities, tree hosts and the environment are important drivers of forest dynamics. Little is known about the ecology of forest pathology and related microbial communities in temperate forests of the southern hemisphere. In this study, we used next-generation sequencing to characterize sapwood-inhabiting fungal communities in North Patagonian Nothofagus forests and assessed patterns of diversity of taxa and ecological guilds across climatic, site and host variables (health condition and compartment) as a contribution to Nothofagus autecology. The diversity patterns inferred through the metabarcoding analysis were similar to those obtained through culture-dependent approaches. However, we detected additional heterogeneity and greater richness with culture-free methods. Host species was the strongest driver of fungal community structure and composition, while host health status was the weakest. The relative impacts of site, season, plant compartment and health status were different for each tree species; these differences can be interpreted as a matter of water availability. For Nothofagus dombeyi, which is distributed across a wide range of climatic conditions, site was the strongest driver of community composition. The microbiome of N. pumilio varied more with season and temperature, a relevant factor for forest conservation in the present climate change scenario. Both species carry a number of potential fungal pathogens in their sapwood, whether they exhibit symptoms or not. Our results provide insight into the diversity of fungi associated with the complex pathobiome of the dominant Nothofagus species in southern South America.

Los bosques del mundo están cada vez más amenazados por las condiciones climáticas alteradas y el aumento de los ataques de plagas y patógenos. Las complejas interacciones ecológicas entre los patógenos, las comunidades microbianas, los árboles hospedantes y el medio ambiente son impulsores importantes de la dinámica forestal. Poco se sabe sobre la ecología de la patología forestal y las comunidades microbianas relacionadas en los bosques templados del hemisferio sur. En este estudio, utilizamos la secuenciación Illumina para caracterizar las comunidades de hongos que habitan en la albura en los bosques de Nothofagus de la Patagonia Norte y evaluamos los patrones de diversidad de taxones y gremios ecológicos a través de variables climáticas, de sitio y de hospedante (identidad, condición de salud y compartimento) como una contribución a la autoecología de los Nothofagus. Los patrones de diversidad inferidos a través del análisis metabarcoding fueron similares a los obtenidos a través de enfoques dependientes de cultivo. Sin embargo, detectamos mayor heterogeneidad y mayor riqueza con métodos independientes de cultivo. La especie hospedante fue el modelador más fuerte de la estructura y composición de la comunidad fúngica, mientras que el estado de salud del hospedante fue el más débil. El impacto relativo del sitio, la estación, el compartimento y el estado de salud fueron diferentes para cada especie de árbol; estas diferencias pueden interpretarse en clave de disponibilidad de agua. Para N. dombeyi, que se distribuye a lo largo de una amplia gama de condiciones climáticas, el sitio fue el principal modelador de la composición de la comunidad. El micobioma de Nothofagus pumilio varió más con la estación y la temperatura, un factor relevante para la conservación de los bosques en el escenario actual de cambio climático. Ambas especies portan una serie de patógenos fúngicos potenciales en su albura, ya sea que muestren síntomas o no. Nuestros resultados brindan una idea de la diversidad de hongos asociados con el complejo patobioma de las especies dominantes de Nothofagus en el sur de América del Sur.

Confronting Secondary Metabolites with Water Uptake and Transport in Plants under Abiotic Stress.

Phenolic compounds and glucosinolates are secondary plant metabolites that play fundamental roles in plant resistance to abiotic stress. These compounds have been found to increase in stress situations related to plant adaptive capacity. This review assesses the functions of phenolic compounds and glucosinolates in plant interactions involving abiotic stresses such as drought, salinity, high temperature, metals toxicity, and mineral deficiency or excess. Furthermore, their relation with water uptake and transport mediated through aquaporins is reviewed. In this way, the increases of phenolic compounds and glucosinolate synthesis have been related to primary responses to abiotic stress and induction of resistance. Thus, their metabolic pathways, root exudation, and external application are related to internal cell and tissue movement, with a lack of information in this latter aspect.

Thromboembolic and hemorrhagic complications in patients with prosthetic heart valves cared for in a tertiary care center. What have we learned?

BACKGROUND: Heart valve replacement surgery with mechanical or biological prostheses entails a risk of thromboembolism and bleeding complications. OBJECTIVE: To determine the complications related to complementary anticoagulation therapy and the probability of risk. METHODS: One-hundred and sixty-three patients who underwent heart valve replacement between 2002 and 2016 with either mechanical or biological prostheses, and who received vitamin K antagonists after hospital discharge, were studied. Anticoagulation therapy was categorized into optimal and non-optimal according to INR values prior to the development of complications. Patients with comorbidities and other risk factors for thrombosis and/or bleeding were excluded. RESULTS: In total, 68.7 % of patients received mechanical prostheses, and 31.3 %, biological prostheses (p ≤ 0.001); 25.2 % experienced the complications that motivated the study (p ≤ 0.001), which were hemorrhagic in 48.8 %, thromboembolic in 26.8 %, and of both types in 24.4 % (relative risk = 4.229). Among the patients with complications, 95.1 % received mechanical prostheses, and 4.9 %, biological (p = 0.005); non-optimal INR was identified in 49.7 % (p ≤ 0.001). CONCLUSIONS: Given the high risk of thromboembolic and hemorrhagic complications, valve prostheses must be carefully chosen, and care priorities should include prevention and follow-up, especially in those patients who require anticoagulation therapy.

ANTECEDENTES: El reemplazo valvular por prótesis mecánicas o biológicas implica riesgo de tromboembolismo y complicaciones hemorrágicas. OBJETIVO: Determinar las complicaciones relacionadas con la terapia de anticoagulación complementaria y la probabilidad de riesgo en pacientes portadores de prótesis valvulares del corazón. MÉTODOS: Se estudiaron 163 pacientes entre 2002 y 2016, portadores de prótesis mecánicas y biológicas, quienes recibieron antagonistas de la vitamina K posterior al egreso hospitalario. La terapia de anticoagulación se categorizó en óptima y no óptima conforme a los valores de INR previos a las complicaciones. Fueron excluidos los pacientes con comorbilidades y otros factores de riesgo de trombosis y/o sangrado. RESULTADOS: a 68.7 % de los pacientes se les colocó prótesis mecánica y a 31.3 %, biológica (p ≤ 0.001); 25.2 % presentó las complicaciones motivo de estudio (p ≤ 0.001), hemorrágicas en 48.8 %, tromboembólicas en 26.8 % y de ambos tipos en 24.4 % (riesgo relativo = 4.229); a 95.1 % de los pacientes con complicaciones se les colocó prótesis mecánica y a 4.9 %, biológica (p = 0.005); 49.7 % presentó INR no óptimo (p ≤ 0.001). CONCLUSIONES: Ante riesgo alto de complicaciones tromboembólicas y hemorrágicas, la elección de las prótesis valvulares, la prevención y el seguimiento son prioridades, principalmente en quienes requieren terapia de anticoagulación.

Epigenetic Deregulation in Human Primary Immunodeficiencies.

Primary immunodeficiencies (PIDs) are immune disorders resulting from defects in genes involved in immune regulation, and manifesting as an increased susceptibility to infections, autoimmunity, and cancer. However, the molecular basis of some prevalent entities remains poorly understood. Epigenetic control is essential for immune functions, and epigenetic alterations have been identified in different PIDs, including syndromes such as immunodeficiency-centromeric-instability-facial-anomalies, Kabuki, or Wolf-Hirschhorn, among others. Although the epigenetic changes may differ among these PIDs, the reversibility of epigenetic modifications suggests that they might become potential therapeutic targets. Here, we review recent mechanistic advances in our understanding of epigenetic alterations associated with certain PIDs, propose that a fully epigenetically driven mechanism might underlie some PIDs, and discuss the possible prophylactic and therapeutic implications.

Membrane Vesicles for Nanoencapsulated Sulforaphane Increased Their Anti-Inflammatory Role on an In Vitro Human Macrophage Model.

At present, there is a growing interest in finding new non-toxic anti-inflammatory drugs to treat inflammation, which is a key pathology in the development of several diseases with considerable mortality. Sulforaphane (SFN), a bioactive compound derived from Brassica plants, was shown to be promising due to its anti-inflammatory properties and great potential, though its actual clinical use is limited due to its poor stability and bioavailability. In this sense, the use of nanocarriers could solve stability-related problems. In the current study, sulforaphane loaded into membrane vesicles derived from broccoli plants was studied to determine the anti-inflammatory potential in a human-macrophage-like in vitro cell model under both normal and inflammatory conditions. On the one hand, the release of SFN from membrane vesicles was modeled in vitro, and two release phases were stabilized, one faster and the other slower due to the interaction between SFN and membrane proteins, such as aquaporins. Furthermore, the anti-inflammatory action of sulforaphane-loaded membrane vesicles was demonstrated, as a decrease in interleukins crucial for the development of inflammation, such as TNF-α, IL-1ß and IL-6, was observed. Furthermore, these results also showed that membrane vesicles by themselves had anti-inflammatory properties, opening the possibility of new lines of research to study these vesicles, not only as carriers but also as active compounds.

Potential of Sulforaphane and Broccoli Membrane Vesicles as Regulators of M1/M2 Human Macrophage Activity.

Macrophages have emerged as important therapeutic targets in many human diseases. The aim of this study was to analyze the effect of broccoli membrane vesicles and sulphoraphane (SFN), either free or encapsulated, on the activity of human monocyte-derived M1 and M2 macrophage primary culture. Our results show that exposure for 24 h to SFN 25 µM, free and encapsulated, induced a potent reduction on the activity of human M1 and M2 macrophages, downregulating proinflammatory and anti-inflammatory cytokines and phagocytic capability on C. albicans. The broccoli membrane vesicles do not represent inert nanocarriers, as they have low amounts of bioactive compounds, being able to modulate the cytokine production, depending on the inflammatory state of the cells. They could induce opposite effects to that of higher doses of SFN, reflecting its hormetic effect. These data reinforce the potential use of broccoli compounds as therapeutic agents not only for inflammatory diseases, but they also open new clinical possibilities for applications in other diseases related to immunodeficiency, autoimmunity, or in cancer therapy. Considering the variability of their biological effects in different scenarios, a proper therapeutic strategy with Brassica bioactive compounds should be designed for each pathology.

Bioactive peptides from broccoli stems strongly enhance regenerative keratinocytes by stimulating controlled proliferation.

CONTEXT: As the interest on the research of plant derived bioactive peptides (BPs) for nutraceutical, cosmeceutical and medical applications is increasing, in this work, the application of peptide derived from broccoli to keratinocytes was studied. OBJECTIVE: We focussed on the characterization of different peptides hydrolysates from broccoli stems [extracted from total protein (E) and from membrane protein (MF)], and their activity when applied to human keratinocytes. MATERIALS AND METHODS: Peptide mixtures from broccoli stems (E and MF) were characterized by proteomics. They were applied to HaCaT cells in order to study cytotoxicity in a concentration range between 20 and 0.15625 µg of protein/mL and wound healing was studied after 24 and 48 h of treatment application. Also, proteomic and gene expression of keratinocytes were analysed. RESULTS: Depending on the source, proteins varied in peptide and amino acid composition. An increased proliferation of keratinocytes was shown after the application of the E peptides mixtures, reaching 190% with the lowest concentrations, but enhanced wound healing repair with E and MF appeared, reaching 59% of wound closure after 48 h. At the gene expression and protein levels of keratinocytes, the upregulation of anti-oncogene p53 and keratinization factors were observed. DISCUSSION: These results suggest that peptide mixtures obtained from broccoli augmented cell proliferation and prevented the carcinogenic, uncontrolled growth of the cells, with different mechanisms depending on the protein source. CONCLUSIONS: The results encourage the opening of new lines of research involving the use of Brassica peptides for pharmaceutic or cosmetic use.

Interrelations of nutrient and water transporters in plants under abiotic stress.

Environmental changes cause abiotic stress in plants, primarily through alterations in the uptake of the nutrients and water they require for their metabolism and growth and to maintain their cellular homeostasis. The plasma membranes of cells contain transporter proteins, encoded by their specific genes, responsible for the uptake of nutrients and water (aquaporins). However, their interregulation has rarely been taken into account. Therefore, in this review we identify how the plant genome responds to abiotic stresses such as nutrient deficiency, drought, salinity and low temperature, in relation to both nutrient transporters and aquaporins. Some general responses or regulation mechanisms can be observed under each abiotic stress such as the induction of plasma membrane transporter expression during macronutrient deficiency, the induction of tonoplast transporters and reduction of aquaporins during micronutrients deficiency. However, drought, salinity and low temperatures generally cause an increase in expression of nutrient transporters and aquaporins in tolerant plants. We propose that both types of transporters (nutrients and water) should be considered jointly in order to better understand plant tolerance of stresses.

Nanoencapsulation of sulforaphane in broccoli membrane vesicles and their in vitro antiproliferative activity.

CONTEXT: The development of nanocarriers of plant origin, such as plant cell membranes, has recently been investigated. Also, plant bioactive compounds as sulforaphane (SFN) from broccoli have recognized antioxidant or anticancer properties. OBJECTIVE: To investigate the capacity of membrane vesicles from broccoli (BM-vesicles) to encapsulate SFN and their application in the cancer cell line. MATERIALS AND METHODS: Physicochemical analysis was carried out to characterize BM-vesicles through different approaches: dynamic light scattering, transmission electron microscopy, stopped-flow analysis, and proteomic analysis. They were applied at different concentrations (BM-vesicles at 0.04-0.00315% of protein and SFN at 5, 25, and 100 µM) in SK-MEL-28 cells during 24 h for studying cytotoxicity and gene expression. RESULTS: The entrapment efficiency was 41%. The anticancer activity tested in cells showed a decrease in proliferation when SFN in BM-vesicles was utilized. Expression patterns when SFN was applied in an encapsulated form showed a reduction of cancer markers and an increase of AQP3. Also, the metabolism of SFN occurred inside of cells, and higher SFN penetrated when it was encapsulated. DISCUSSION: The results showed that encapsulated SFN was better absorbed by melanoma cells providing metabolism products and a reduction of cancer molecular markers. Also aquaporin, AQP3 was pointed to as an important marker since it appeared to play a key role in homeostasis due to the importance of water transport in biological processes. CONCLUSION: These results indicate that SFN and SFN encapsulated in BM-vesicles have a high activity for the inhibition of melanocyte development. Therefore, BM-vesicles could serve as nanocarriers for drugs.

Platelet-to-Lymphocyte Ratio and Survival in Malignant Pleural Effusion.

BACKGROUND: Efforts have been made to search for parameters that facilitate the prediction of the 3-month survival for clinical decisions in patients with malignant pleural effusion (MPE). We sought to evaluate whether the platelet-to-lymphocyte ratio (PLR) may be a useful marker of 3-month survival in a series of consecutive patients with MPE. METHODS: A total of 81 patients with MPE were included, 46 (57%) of whom were female. Twenty-six patients (32%) died during the first 3 months according to thoracentesis data. RESULTS: The area under the receiver operating characteristics curve was 0.73 for PLR. Using a cutoff point of 158, patients with higher PLR values experienced higher mortality at 3 months (p = 0.001). CONCLUSIONS: PLR was able to successfully differentiate patients with different survival at 3 months. Outcomes of the PLR (a fast and inexpensive test) could be included among the prognostic factors able to guide the personalized management of MPE.

Prognostic Value of Hematological Inflammatory Markers in Patients with Pleural Effusion Due to Heart Failure.

BACKGROUND: Pleural effusions due to heart failure are associated with a high 1-year mortality. Several hematological parameters have been shown to provide prognostic information in patients with cardiovascular diseases. The objective was to assess whether hematological markers can also provide prognostic information in patients with pleural effusion caused by heart failure. METHODS: This was a retrospective study of patients with pleural effusion due to heart failure who underwent a diagnostic thoracentesis. The hematological parameters evaluated were as follows: neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, platelet count, platelet-to-lymphocyte ratio, mean platelet volume (MPV), and MPV-to-platelet ratio. Patients were divided into two groups: those who died within 1 year and survivors of more than 1 year. Differences and possible correlations were analyzed with non-parametric tests. Diagnostic values were estimated. Survival analysis was performed using the Kaplan-Meier method. Cox regression analysis was performed to identify independent variables. RESULTS: Twenty five of 55 (45%) patients died within 1-year from thoracentesis. Patients who died in this period were older, aged 83 years (73 - 87, median and interquartile range, IQR) vs. 74 (65 - 82); with lower platelet count: 181 x 103 (140 - 258 x 103) vs. 241 x 103 (198 - 324 x 103); and higher MPV/platelet: 48.1 (34.9 - 75.6) vs. 35.6 (27.1 - 42.9). In the regression analysis only the MPV/platelet had statistical significance (p = 0.002). MPV/platelet > 50 had a specificity of 87% for 1-year mortality, and a ratio > 30 had a sensitivity of 84%. CONCLUSIONS: Simple hematological parameters such as platelet count and MPV/platelet, may provide useful prognostic information for predicting 1-year mortality in patients with pleural effusion due to heart failure.

Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies.

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies, but their B-cell defects and underlying genetic alterations remain largely unknown. OBJECTIVE: We investigated patients with PADs for the distribution of 41 blood B-cell and plasma cell (PC) subsets, including subsets defined by expression of distinct immunoglobulin heavy chain subclasses. METHODS: Blood samples from 139 patients with PADs, 61 patients with common variable immunodeficiency (CVID), 68 patients with selective IgA deficiency (IgAdef), 10 patients with IgG subclass deficiency with IgA deficiency, and 223 age-matched control subjects were studied by using flow cytometry with EuroFlow immunoglobulin isotype staining. Patients were classified according to their B-cell and PC immune profile, and the obtained patient clusters were correlated with clinical manifestations of PADs. RESULTS: Decreased counts of blood PCs, memory B cells (MBCs), or both expressing distinct IgA and IgG subclasses were identified in all patients with PADs. In patients with IgAdef, B-cell defects were mainly restricted to surface membrane (sm)IgA+ PCs and MBCs, with 2 clear subgroups showing strongly decreased numbers of smIgA+ PCs with mild versus severe smIgA+ MBC defects and higher frequencies of nonrespiratory tract infections, autoimmunity, and affected family members. Patients with IgG subclass deficiency with IgA deficiency and those with CVID showed defects in both smIgA+ and smIgG+ MBCs and PCs. Reduced numbers of switched PCs were systematically found in patients with CVID (absent in 98%), with 6 different defective MBC (and clinical) profiles: (1) profound decrease in MBC numbers; (2) defective CD27+ MBCs with almost normal IgG3+ MBCs; (3) absence of switched MBCs; and (4) presence of both unswitched and switched MBCs without and; (5) with IgG2+ MBCs; and (6) with IgA1+ MBCs. CONCLUSION: Distinct PAD defective B-cell patterns were identified that are associated with unique clinical profiles.

Detergent Resistant Membrane Domains in Broccoli Plasma Membrane Associated to the Response to Salinity Stress.

Detergent-resistant membranes (DRMs) microdomains, or "raft lipids", are key components of the plasma membrane (PM), being involved in membrane trafficking, signal transduction, cell wall metabolism or endocytosis. Proteins imbibed in these domains play important roles in these cellular functions, but there are few studies concerning DRMs under abiotic stress. In this work, we determine DRMs from the PM of broccoli roots, the lipid and protein content, the vesicles structure, their water osmotic permeability and a proteomic characterization focused mainly in aquaporin isoforms under salinity (80 mM NaCl). Based on biochemical lipid composition, higher fatty acid saturation and enriched sterol content under stress resulted in membranes, which decreased osmotic water permeability with regard to other PM vesicles, but this permeability was maintained under control and saline conditions; this maintenance may be related to a lower amount of total PIP1 and PIP2. Selective aquaporin isoforms related to the stress response such as PIP1;2 and PIP2;7 were found in DRMs and this protein partitioning may act as a mechanism to regulate aquaporins involved in the response to salt stress. Other proteins related to protein synthesis, metabolism and energy were identified in DRMs independently of the treatment, indicating their preference to organize in DMRs.

Brassica Bioactives Could Ameliorate the Chronic Inflammatory Condition of Endometriosis.

Endometriosis is a chronic, inflammatory, hormone-dependent disease characterized by histological lesions produced by the presence of endometrial tissue outside the uterine cavity. Despite the fact that an estimated 176 million women are affected worldwide by this gynecological disorder, risk factors that cause endometriosis have not been properly defined and current treatments are not efficient. Although the interaction between diet and human health has been the focus of many studies, little information about the correlation of foods and their bioactive derivates with endometriosis is available. In this framework, Brassica crops have emerged as potential candidates for ameliorating the chronic inflammatory condition of endometriosis, due to their abundant content of health-promoting compounds such as glucosinolates and their hydrolysis products, isothiocyanates. Several inflammation-related signaling pathways have been included among the known targets of isothiocyanates, but those involving aquaporin water channels have an important role in endometriosis. Therefore, the aim of this review is to highlight the promising effects of the phytochemicals present in Brassica spp. as major candidates for inclusion in a dietary approach aiming to improve the inflammatory condition of women affected with endometriosis. This review points out the potential roles of glucosinolates and isothiocyanates from Brassicas as anti-inflammatory compounds, which might contribute to a reduction in endometriosis symptoms. In view of these promising results, further investigation of the effect of glucosinolates on chronic inflammatory diseases, either as diet coadjuvants or as therapeutic molecules, should be performed. In addition, we highlight the involvement of aquaporins in the maintenance of immune homeostasis. In brief, glucosinolates and the modulation of cellular water by aquaporins could shed light on new approaches to improve the quality of life for women with endometriosis.

Precursor B-cell development in bone marrow of Good syndrome patients.

Good syndrome is an immunodeficiency presenting with thymoma, hypogammaglobulinemia and almost absent B cells. To investigate the origin of the B-cell lymphopenia in these patients, we studied B cell differentiation in the bone marrow of Good syndrome patients. We found very low numbers of precursor B cells in bone marrow of Good syndrome patients and a differentiation arrest after the pro-B-cell stage; this is different from other agammaglobulinemia patients with a defect in pre B-cell receptor signaling.