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Anthracnose, white mold, powdery mildew, and root rot caused by Colletotrichum lindemuthianum, Scletorinia sclerotiorum, Erysiphe spp., and Pythium ultimum, respectively, are among the most frequent diseases that cause significant production losses worldwide in common bean (Phaseolus vulgaris L.). Reactions against these four fungal diseases were investigated under controlled conditions using a diversity panel of 311 bean lines for snap consumption (Snap bean Panel). The genomic regions involved in these resistance responses were identified based on a genome-wide association study conducted with 16,242 SNP markers. The highest number of resistant lines was observed against the three C. lindemuthianum isolates evaluated: 156 lines were resistant to CL124 isolate, 146 lines resistant to CL18, and 109 lines were resistant to C531 isolate. Two well-known anthracnose resistance clusters were identified, the Co-2 on chromosome Pv11 for isolates CL124 and CL18, and the Co-3 on chromosome Pv04 for isolates CL124 and C531. In addition, other lesser-known regions of anthracnose resistance were identified on chromosomes Pv02, Pv06, Pv08, and Pv10. For the white mold isolate tested, 24 resistant lines were identified and the resistance was localized to three different positions on chromosome Pv08. For the powdery mildew local isolate, only 12 resistant lines were identified, and along with the two previous resistance genes on chromosomes Pv04 and Pv11, a new region on chromosome Pv06 was also identified. For root rot caused by Pythium, 31 resistant lines were identified and two main regions were located on chromosomes Pv04 and Pv05. Relevant information for snap bean breeding programs was provided in this work. A total of 20 lines showed resistant or intermediate responses against four or five isolates, which can be suitable for sustainable farm production and could be used as resistance donors. Potential genes and genomic regions to be considered for targeted improvement were provided, including new or less characterized regions that should be validated in future works. Powdery mildew disease was identified as a potential risk for snap bean production and should be considered a main goal in breeding programs.

Common bean (Phaseolus vulgaris L.) is a crop of high nutritional interest which is widespread throughout the world as a result of which it is considered as a potential crop for ensuring future food security. The effect of organic and conventional farming systems on the nutritional and functional composition of two cultivars of market class fabada (a landrace and a modern elite cultivar) is described. The findings of our study have shown that the common beans from organic farming have a higher content of protein, phenolic compounds, and relevant microelements such as iron and zinc than the seeds from conventional farming trial. However, in conventional crops a higher content of polyunsaturated fatty acids and lower concentrations of phytic acid and raffinose oligosaccharides were also detected. In contrast, no significant differences were detected in the proximate composition of the two genotypes tested, nor in their antioxidant activity or levels of phenolic compounds. The elite cultivar maintains the nutritional characteristics of the landrace from which it derives, suggesting the genomic regions modified in the improvement do not play an important role in their genetic control.

Common bean has two distinct domestication centers in Mesoamerica and in the Andes. The authors show that the Andean is the first gene pool successfully introduced in Europe and identify signature of pervasive introgression among gene pools and of selection for flowering underlying adaptation.

Dry bean (Phaseolus vulgaris L.) is a crop of high nutritional interest widespread throughout the world. This research had two objectives. On the one hand, the development and validation of an analytical method to quantify fatty acids in dry beans based on the extraction and derivatization in a single step and later quantification by gas chromatography. On the other, its application to characterize the fatty acid content in a diversity panel consisting of 172 lines. The method was successfully validated in terms of accuracy, precision and robustness. Among the 14 fatty acids that constitute the fatty acid profile of dry bean, the most quantitatively important were linolenic acid, the major fatty acid in all cases, with an average value of 6.7 mg/g, followed by linoleic acid (3.9 mg/g), palmitic acid (2.9 mg/g) and oleic acid (1.5 mg/g). The concentrations of fatty acids in dry bean were influenced by the gene pool, with the Mesoamerican gene pool showing a higher content of palmitic, stearic, linoleic and linolenic acids and the Andean gene pool a higher level of cis-vaccenic acid. Also, the expression of fatty acid content showed high heritability. The information generated constitutes a robust database of interest in food technology, nutrition and breeding programs.

Abstract The Fabada market class within the dry beans has a well‐differentiated seed phenotype with very large white seeds. This work investigated the genetic diversity maintained in the seed collections within this market class and possible genetic erosion over the last 30 years. A panel with 100 accessions was maintained in seed collections for 30 years, 57 accessions collected from farmers in 2021, six cultivars developed in SERIDA, and 16 reference cultivars were gathered and genotyped with 108,585 SNPs using the genotyping‐by‐sequencing method. Filtering based on genotypic and phenotypic data was carried out in a staggered way to investigate the genetic diversity among populations. The dendrogram generated from genotyping revealed 90 lines forming 16 groups with identical SNP profiles (redundant lines) from 159 lines classified as market‐class Fabada according to their passport data. Seed phenotyping indicated that 19 lines were mistakenly classified as Fabada (homonymies), which was confirmed in the dendrogram built without redundant lines. Moreover, this study provides evidence of genetic erosion between the population preserved for 30 years and the currently cultivated population. The conserved population contains 54.6% segregation sites and 41 different SNP profiles, whereas the cultivated population has 19.6% segregation sites and 26 SNP profiles. The loss of genetic variability cannot be attributed to the diffusion of modern cultivars, which increase genetic diversity (six new SNP profiles). The results allow for the more efficient preservation of plant genetic resources in genebanks, minimizing redundant accessions and incorporating new variations based on genotypic and phenotypic data.

Abstract Background A large variation in seed coat colors and seed phenolic metabolites is present in common bean (Phaseolus vulgaris L.). The study of the relationships between seed coat color phenotype and the phenolic profile is an important step in the elucidation of the gene network involved in the phenylpropanoid biosynthetic pathway. However, this relationship is still poorly understood in this species. Results A genome-wide association study (GWAS) was used to investigate the genomic regions associated with the synthesis of 10 flavonoids (5 anthocyanins and 5 flavonols) and with 10 seed coat color traits using a set of 308 common bean lines of the Spanish Diversity Panel (SDP) which have been genotyped with 11,763 SNP markers.. A total of 31 significant SNP-trait associations (QTNs) were identified, grouped in 20 chromosome regions: 6 for phenolic metabolites on chromosomes Pv01, Pv02, Pv04, Pv08, and Pv09, 13 for seed coat color on chromosomes Pv01, Pv02, Pv06, Pv07, and Pv10, and 1 including both types of traits located on chromosome Pv08. In all, 58 candidate genes underlying these regions have been proposed, 31 of them previously described in the phenylpropanoid pathway in common bean, and 27 of them newly proposed in this work based on the association study and their homology with Arabidopsis anthocyanin genes. Conclusions Chromosome Pv08 was identified as the main chromosome involved in the phenylpropanoid pathway and in consequence in the common bean seed pigmentation, with three independent chromosome regions identified, Phe/C_Pv08(2.7) (expanding from 2.71 to 4.04 Mbp), C_Pv08(5.8) (5.89–6.59 Mbp), and Phe_Pv08(62.5) (62.58 to 63.28 Mbp). Candidate genes previously proposed by other authors for the color genes V and P were validated in this GWAS. Candidate genes have been tentatively proposed from this study for color genes B and Rk on Pv02, Asp on Pv07, and complex C on Pv08. These results help to clarify the complex network of genes involved in the genetic control of phenolic compounds and seed color in common bean and provide the opportunity for future validation studies.

Anthracnose is responsible for large yield losses in common bean crops. RNA-sequencing was used to investigate the differentially expressed genes (DEGs) in response to race 38 of Colletotrichum lindemuthianum in two near-isogenic lines (A25 and A4804) that differ in the presence of a resistance gene located in the cluster Co-2. Their responses were analyzed at different hours after inoculation (0, 24, and 48) and within and between genotypes. In all, 2,850 DEGs were detected, with 2,373 assigned to at least one functional GO term. Enriched GO terms in the resistant genotype were mainly related to functions as a response to stimulus, hormone signaling, cellular component organization, phosphorylation activities, and transcriptional regulation. The region containing the Co-2 cluster was delimited at the end of chromosome Pv11 (46.65–48.65 Mb) through a comparison with the SNP genotypes, obtained using ‘Genotyping by Sequencing,’ among seven resistant lines harboring the Co-2 gene and the susceptible line A25. The delimited region contained 23 DEGs, including 8 typical R genes, that showed higher expression levels in the resistant genotype and non-changes in the susceptible genotype after inoculation. Six R genes encoding protein kinases and an LRR domain formed a cluster in a core region between 46.98 and 47.04 Mb. The alignment of the raw transcriptome reads in the core region revealed structural changes that were used to design four potential breeder-friendly DNA markers, and it revealed some alignments with the intergenic regions, suggesting the presence of genes in addition to those annotated in the reference genome.

Abstract Background Common bean (Phaseolus vulgaris L.) is an important legume species which can be consumed as immature pods and dry seeds after re-hydration and cooking. Many genes and QTL, and epistatic interactions among them, condition pod morphological traits. However, not all them have been mapped or validated nor candidate genes proposed. We sought to investigate the genomic regions conditioning pod morphological and color characters through GWAS. Results Single and multi-locus genome wide association analysis was used to investigate pod traits for a set of 301 bean lines of the Spanish Diversity Panel (SDP). The SDP was genotyped with 32,812 SNPs obtained from Genotyping by Sequencing. The panel was grown in two seasons and phenotypic data were recorded for 17 fresh pods traits grouped in four pod characters: pod length, pod cross-section, pod color, and number of seeds per pod. In all, 23 QTL for pod length, 6 for cross-section, 18 for pod color, 6 for number of seeds per pod and 9 associated to two or more pod characters were detected. Most QTL were located in the telomeric region of chromosomes Pv01, Pv02, Pv04, Pv08, Pv09 and Pv10. Eighteen detected QTL co-localized with 28 previously reported QTL. Twenty-one potential candidate genes involving developmental processes were detected underlying 11 QTL for pod morphological characters, four of them homologous to A. thaliana genes FIS2, SPL10, TTG2 and AML4 affecting silique size. Eight potential candidate genes involved in pigment synthesis, were found underlying five QTL for pod color. Conclusions GWAS for pod morphological and color characters in the bean Spanish Diversity Panel revealed 62 QTL, 18 co-localized with previously reported QTL, and 16 QTL were underlain by 25 candidate genes. Overall 44 new QTL identified and 18 existing QTL contribute to a better understanding of the complex inheritance of pod size and color traits in common bean and open the opportunity for future validation works.

Summary: Background: The dominant effect of age on COVID-19 mortality obscures the impact of other risk factors. Although the elderly is at a greater risk of severe disease and death due to COVID-19, the interaction of obesity and age was not carefully assessed. This analysis is especially critical for prioritizing groups to receive COVID-19 vaccination. Methods: Starting with 1,120,767 unvaccinated individuals registered in a Brazilian surveillance system, we selected 313,898 hospitalized COVID-19 patients aged 20 to 89 who had a BMI ≥ 25 kg/m2 and cardiovascular diseases (CVD) or diabetes, as well as individuals with no risk factors associated with severe COVID-19. Patient data were stratified by age, obesity, BMI, and comorbidities, and subsequently, subjected to crude and adjusted odds ratio, hazard ratio, and Kaplan–Meier curves. Disease outcomes were invasive and non-invasive ventilatory support, intensive care unit (ICU) admission, and death. Findings: Obesity alone is a risk factor for in-hospital mortality and is more significant than cardiovascular disease and diabetes. Furthermore, obesity, cardiovascular disease, and diabetes increase the risk of severity and death by COVID-19 more significantly in young adults than in the elderly. When categorizing patients by obesity classes, the severity of obesity was found to be associated with a higher risk of admission to the ICU and death from COVID-19 than the non-obese young adults or elderly population. Interpretation: Our findings highlight the increased risk of severe COVID-19 on the Brazilian obese youth. As SARS-CoV-2 may become a recurrent seasonal infection, future vaccination campaigns against COVID-19 should prioritize obese young individuals. Fundings: This work was supported by the Brazilian National Council for Scientific and Technological Development (grant number 313662/2017-7 and 307356/2017-5; the São Paulo Research Foundation (grant numbers 2018/14933-2); and CAPES.

A set of 54 snap bean lines grown under organic farming was characterized for different traits: pod color, pod cross-section shape, pod section width (PSW), protein content (PC), and sugar content (S). After cooking, the lines were analyzed for firmness and color parameters (CIE-L*, a*, b*). The snap bean lines were grouped based on pod cross-section shape and pod color into eight groups, and significant differences were observed among lines and groups for all the traits investigated. In particular, the yellow pods were harder than the other snap beans and less sweet due to the negative correlation between firmness and sugar content. Fourteen selected lines with contrasting firmness and belonging to different color groups were investigated for their phenolic composition and antioxidant activity (TEAC) before and after domestic cooking. A general decrease was observed only for vanillic acid, quercetin, and apigenin-8-C-glucoside. Quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside were detected in all samples with the highest values in the SBP042 line in both raw and cooked samples. Antioxidant activity decreased with cooking (average of 39%), but purple line SBP053 showed the lowest and no significant loss (3.1%). The results reported in this study could be useful to design specific varieties for different markets and purposes.

Hazelnut is a traditional crop in northern Spain, where it grows wild as well as being cultivated. A field collection of 41 local and 17 non-local accessions, including 15 well-known cultivars, was established at SERIDA in Villaviciosa, Spain. Here, phenotypic variation was documented for phenological and morphological traits and chemical composition. A large degree of variation for most morphological and phenological traits, except nut maturity date, was revealed. Estimates of broad-sense heritability were high (>0.75) for most of the assessed characters, except for the first male bloom date (0.65), male and female flowering periods (0.40, 0.31), kernel weight (0.69), and kernel percentage (0.33). Local accessions produced smaller nuts and kernels than well-known cultivars but with higher kernel percentage. Limited overlapping between the male and female flowering periods (dychogamy) was observed, except for ‘Forcinas 1’, ‘Forcinas 2’, and ‘Morell’. The local accessions generally exhibited significantly later male and female flowering compared with the reference cultivars. The local materials showed similar nutritional values to those reported previously for hazelnut. Moreover, the local accessions presented average values similar to the non-local accessions for total fat, ash and carbohydrate contents, as well as energy value, but their protein contents were lower. Their oils were rich in functional compounds, such as unsaturated fatty acids (average: 90.1%), tocopherols (514 mg/kg) and squalene (294.3 mg/kg). A hierarchical clustering on principal components analysis grouped the accessions and differentiated eight local accessions from the rest, including the landrace ‘Casina’. This finding provides potential new cultivars, as well as sources of desirable traits, for European hazelnut breeding programs.

Patients infected with the Dengue virus (DENV) often present with a massive generation of DENV-specific antibody-secreting cells (ASCs) in the blood. In some cases, these ASCs represent more than 50% of the circulating B cells, a higher magnitude than those induced by other infections, vaccinations, and plasma cell lymphomas. However, it remains unclear how the DENV infection elicits this colossal response. To address this issue, we utilised an in vitro strategy to induce human PBMCs of healthy individuals incubated with DENV particles (DENV4 TVP/360) to differentiate into ASCs. As controls, PBMCs were incubated with a mitogen cocktail or supernatants of uninfected C6/36 cells (mock). The ASC phenotype and function were increasingly detected in the DENV and mitogen-cultured PBMCs as compared to mock-treated cells. In contrast to the in vivo condition, secreted IgG derived from the PBMC-DENV culture was not DENV-specific. Lower ASC numbers were observed when inactivated viral particles or purified B cells were added to the cultures. The physical contact was essential between B cells and the remaining PBMCs for the DENV-mediated ASC response. Considering the evidence for the activation of the tryptophan metabolism detected in the serum of Dengue patients, we assessed its relevance in the DENV-mediated ASC differentiation. For this, tryptophan and its respective metabolites were quantified in the supernatants of cell cultures through mass spectrophotometry. Tryptophan depletion and kynurenine accumulation were found in the supernatants of PBMC-DENV cultures, which presented enhanced detection of indoleamine 2,3-dioxygenase 1 and 2 transcripts as compared to controls. In PBMC-DENV cultures, tryptophan and kynurenine levels strongly correlated to the respective ASC numbers, while the kynurenine levels were directly proportional to the secreted IgG titers. Contrastingly, PBMCs incubated with Zika or attenuated Yellow Fever viruses showed no correlation between their kynurenine concentrations and ASC numbers. Therefore, our data revealed the existence of distinct pathways for the DENV-mediated ASC differentiation and suggest the involvement of the tryptophan metabolism in this cellular process triggered by flavivirus infections.

In the course of infection and intense endotoxemia processes, induction of a catabolic state leading to weight loss is observed in mice and humans. However, the late effects of acute inflammation on energy homeostasis, regulation of body weight and glucose metabolism are yet to be elucidated. Here, we addressed whether serial intense endotoxemia, characterized by an acute phase response and weight loss, could be an aggravating or predisposing factor to weight gain and associated metabolic complications. Male Swiss Webster mice were submitted to 8 consecutive doses of lipopolysaccharide (10 mg/kg LPS), followed by 10 weeks on a high-fat diet (HFD). LPS-treated mice did not show changes in weight when fed standard chow. However, when challenged by a high-fat diet, LPS-treated mice showed greater weight gain, with larger fat depot areas, increased serum leptin and insulin levels and impaired insulin sensitivity when compared to mice on HFD only. Acute endotoxemia caused a long-lasting increase in mRNA expression of inflammatory markers such as TLR-4, CD14 and serum amyloid A (SAA) in the adipose tissue, which may represent the key factors connecting inflammation to increased susceptibility to weight gain and impaired glucose homeostasis. In an independent experimental model, and using publicly available microarray data from adipose tissue from mice infected with Gram-negative bacteria, we performed gene set enrichment analysis and confirmed upregulation of a set of genes responsible for cell proliferation and inflammation, including TLR-4 and SAA. Together, we showed that conditions leading to intense and recurring endotoxemia, such as common childhood bacterial infections, may resound for a long time and aggravate the effects of a western diet. If confirmed in humans, infections should be considered an additional factor contributing to obesity and type 2 diabetes epidemics.

Snap beans are a group of bean cultivars grown for their edible immature pods. The objective of this work was to characterize the diversity of pod phenotypes in a snap bean panel (SBP), comprising 311 lines collected in Europe, and establish a core set (Core-SBP) with the maximum diversity of pod phenotypes. Phenotyping of the SBP was carried out over two seasons based on 14 quantitative pod dimension traits along with three qualitative traits: pod color, seed coat color, and growth habit. Phenotypes were grouped into 54 classes using a hierarchical method, and a Core-SBP with one line per phenotype class was established. A further field-based evaluation of the Core-SBP revealed higher diversity index values than those obtained for the SBP. The Core-SBP was also genotyped using 24 breeder-friendly DNA markers tagging 21 genomic regions previously associated with pod trait control. Significant marker-trait associations were found for 11 of the 21 analyzed regions as well as the locus fin. The established Core-SBP was a first attempt to classify snap bean cultivars based on pod morphology and constituted a valuable source of characteristics for future breeding programs and genetic analysis.

A complex landscape of anthracnose resistance genes (Co-) located at the telomeric regions of the bean chromosomes Pv01 and Pv04 has been reported. The aim of this work was to investigate the genetic and physical positions of genes conferring resistance to races 6, 38, 39, 357, 65, and 73 as well as the relationships among the resistance genes identified herein and the previously described Co- genes in these telomeric regions. The linkage analysis using a genetic map of 497 SNPs from the recombinant inbred line population Xana/BAT93 revealed that the gene conferring resistance to race 65 in cultivar Xana (Co-165-X) was located in the Co-1 cluster, at the distal end of chromosome Pv01. The fine mapping of Co-165-X indicated that it was positioned between the physical positions 49,512,545 and 49,658,821 bp. This delimited physical position agrees with the positions of the previously mapped genes Co- 14, Co-x, Co-14, Co-1HY, and Co-Pa. Responses to races 6, 38, 39, and 357 in BAT93 exhibited co-segregation suggesting that the same gene, or very closely linked genes, were involved in the control. The linkage analysis showed that the resistance gene to race 38 in the genotype BAT93 (Co-338-B) was located at the beginning of chromosome Pv04, in the genetic position of the Co-3 cluster, and was flanked by markers with physical positions between 1,286,490 and 2,047,754 bp. Thus, the genes Co-3, Co-9, Co-10, Co-16, and Co-338-B, found in this work, form part of the same anthracnose resistance cluster at the beginning of chromosome Pv04, which is consistent with the discontinuous distribution of typical R genes annotated in the underlying genomic region. Resistance loci involved in the response to race 73 in the genotypes Xana (R) and BAT93 (R) were mapped to the same positions on clusters Co-1 and Co-3, respectively. The positioning of the resistance genes in the bean genome based on fine linkage mapping should play an important role in the characterization and differentiation of the anthracnose resistance genes. The assignment of Co- genes to clusters of race specific genes can help simplify the current scenario of anthracnose resistance.

Dry bean (Phaseolus vulgaris L.) is one of the most important pulses consumed in the world. Total phenolic content, total flavonoid content, total monomeric anthocyanin content and antioxidant capacity were determined, using ferric reducing antioxidant power and free radical scavenging activity, in 255 lines grown under the same environmental conditions. For all parameters analysed, there was a wide range of variability, with differences always above one order of magnitude. Phenolic compounds in beans with coloured coats were found to be more efficient antioxidants than those with completely white coats, and samples with more strongly coloured coats (red, cream, black, pink and brown) showed the highest antioxidant capacities. Based on the strong correlation detected between the variables, total phenolic content can be considered an appropriate indicator of antioxidant activity. The results provide a robust database for selecting those lines of greater functional and nutritional interest in terms of cultivation for direct consumption, for inclusions in food formulations or for use in future breeding programs.

Blueberry is a small fruit crop which includes a complex group of different Vaccinium species of various ploidy levels. Commercial blueberries have been grown in Europe most recently, so there is not much information available about their adaptation into new regions. In this work we investigated adaptation to the environmental conditions of northern Spain, in terms of flowering and ripening seasons, of a set of 70 blueberry cultivars including several of the most important cultivated American species (V. corymbosum, V. virgatum, V. macrocarpon and V. uliginosum) in order to identify which types are best-suited in this geographical area of Europe. Most materials showed high chilling requirements for flowering under local conditions, while materials with low-chilling requirements showed problems in the maturation process of the flowers. Most cultivars were early or mid-season while a relative lack of late-season cultivars was observed. GBS was used for the analysis of genetic diversity in this sample of 70 cultivars. A total of 5255 SNP markers were obtained and a cluster analysis revealed three main groups associated with the ploidy level of the species. A Principal Component Analysis revealed a grouping of the V. corymbosum cultivars according to their chilling requirements. A total of 29 SNPs were identified as being highly informative for diversity analysis and potentially useful for cultivar identification and for breeding purposes. The results obtained from this research should contribute to the expansion of this crop, as well as providing data about genetic diversity useful for the preservation of genetic resources or for future breeding programs.

Genotyping-by-sequencing (GBS) was used to investigate and identify the introgressed genomic regions that corresponded to resistance alleles for anthracnose ( and ), (BCMV), and (BCMNV, and ) in a set of bean near-isogenic lines (NIL). The GBS analysis provided 12,697 single nucleotide polymorphisms (SNPs) although the densities along the chromosomes were not uniform, and some chromosomal regions, such as centromeric or pericentromeric regions, were less tagged. The backcrossing method resulted in the introgression of genomic regions into specific chromosomes. The number of introgressed region-tagging SNPs varied between 1 and 13, representing between 0.33 and 6.88% of the bean genome. The changes detected among the recurrent parent and NIL in chromosomal regions are candidate regions that may contain the introgressed genes. By comparing the NIL derived from the same resistance source, it was possible to delimit in chromosomes Pv02, Pv04, Pv06, and Pv11 the genomic regions containing the resistance genes , , , and . Results allowed verification of the physical positions of the resistance genes and a clearer physical position of the anthracnose resistance genes and . Two nonoverlapping regions were delimited in chromosome Pv11 from common regions in NIL with resistance loci mapped to the Co-2 cluster. Alleles of the loci included within these genomic regions show strong linkage disequilibrium. This knowledge can be used in selection programs involving these regions rich in resistance genes.

In this study, we evaluated whether human serum and lipoproteins, especially high-density lipoprotein (HDL), affected serum amyloid A (SAA)-induced cytokine release. We verified the effects of SAA on THP-1 cells in serum-free medium compared to medium containing human serum or lipoprotein-deficient serum. SAA-induced tumour necrosis factor-alpha (TNF-α) production was higher in the medium containing lipoprotein-deficient serum than in the medium containing normal human serum. The addition of HDL inhibited the SAA-induced TNF-α release in a dose-dependent manner. This inhibitory effect was specific for HDL and was not affected by low-density lipoprotein or very low-density lipoprotein. In human peripheral blood mononuclear cells, the inhibitory effect of HDL on TNF-α production induced by SAA was less pronounced. However, this effect was significant when HDL was added to lipoprotein-deficient medium. In addition, a similar inhibitory effect was observed for interleukin-1 beta release. These findings confirm the important role of HDL and support our previous hypothesis that HDL inhibits the effects of SAA during SAA transport in the bloodstream. Moreover, the HDL-induced reduction in the proinflammatory activity of SAA emphasizes the involvement of SAA in diseases, such as atherosclerosis, that are characterized by low levels of HDL.

Anthracnose caused by (Sacc. & Magnus) Lams.-Scrib. is a major disease affecting common bean ( L.) crops worldwide. Response to five isolates, classified as races 3, 6, 7, 38, and 73, were analyzed in 156 F families derived from the cross between line SEL1308 and cultivar Michigan Dark Red Kidney (MDRK). SEL1308 was resistant to all five races, while MDRK was susceptible to all except for race 73. Segregation ratio for response to races 3 and 7 indicated that single dominant genes were responsible for the resistance reaction to each race. Recombination between both race-specific genes was observed and no linkage was found with any of the molecular markers tagging Co-genes or clusters previously described. Linkage analyses allowed the location of both genes at the beginning of linkage group (LG) Pv03, a region tentatively named as Co-17. Segregation ratio for response to races 6 and 38 indicated that two dominant and independent genes conferred resistance to these races. Contingency tests and subpopulation analyses suggested the implication of one region on LG Pv08, corresponding to the Co-4 cluster, and the Co-17 region. For reaction to race 73, the most likely scenario was that two dominant and independent genes conferred resistance: in MDRK and in SEL1308. Results indicated that, in addition to , SEL1308 carries resistance genes located at the beginning of LG Pv03, in which no anthracnose resistance genes were previously mapped. In silico analysis revealed the presence of seven genes codifying typical resistance proteins (R-proteins) in the underlying physical position of the Co-17 region.

C-reactive protein (CRP) and serum amyloid A (SAA) are acute-phase proteins mainly synthesized by the liver in response to some cytokines. They are potentially useful to diagnosing infection and monitoring different clinical conditions. The aim of this study was to measure SAA and CRP in maternal and cord blood during and after delivery and try to correlate these proteins with tumor necrosis factor-α, interleukin -1β, and interleukin-8. Acute-phase proteins and cytokines were measured by ELISA in 24 healthy pregnant women undergoing vaginal delivery or Cesarean section. Cord blood samples in addition to maternal blood were collected. SAA and CRP reached the maximum maternal serum levels 24 hours after delivery, while cytokines remained constant over time. SAA and CRP were significantly higher in maternal serum than in newborn's (P

The acute phase response is a systemic reaction to inflammatory processes characterized by multiple physiological adaptations, including the hepatic synthesis of acute-phase proteins. In humans, serum amyloid A (SAA) is one of the most prominent of these proteins. Despite the huge increase of serum levels of SAA in inflammation, its biological role remains to be elucidated, even though SAA is undoubtedly active in neutrophils. In a previous study, we reported that SAA induces the release of tumor necrosis factor-α, interleukin (IL)-1β and IL-8 from human blood neutrophils. Here, we extend our earlier study, focusing on the effect of SAA on neutrophil IL-8 transcription and on the signaling pathways involved. We demonstrate herein that SAA, in relatively low concentrations (0.4-100 μg/ml) compared with those found in plasma in inflammatory conditions, induces a dose-dependent release of IL-8 from neutrophils. The p38 mitogen-activated protein kinase inhibitor SB 203580 inhibits the IL-8 mRNA expression and the release of protein from neutrophils. The release of IL-8 from SAA-stimulated neutrophils is strongly suppressed by the addition of N-acetyl-l-cysteine, α-mercaptoethanol, glutathione, and dexamethasone. SAA also induces IL-8 expression and release from monocytes. In conclusion, SAA appears to be an important mediator of the inflammatory process, possibly contributing to the pool of IL-8 produced in chronic diseases, which may play a role in degenerative diseases.

The serum amyloid A (SAA) protein is known to function in the acute phase response and immunoregulation. Recently, SAA has been shown to be involved in cell proliferation, differentiation and migratory behavior in different cell types. Here, we evaluated whether exogenous SAA could influence trophoblast invasion and differentiation using both the trophoblast-like BeWo cell line and fully differentiated human extravillous trophoblast cells (EVT) isolated from term placentae. SAA stimulated BeWo cell invasion, as measured in Matrigel invasion assays, and induced metalloprotease mRNA expression and activity. Given that BeWo cells express Toll-like receptor 4 (TLR4), a known receptor for SAA, we examined the role of TLR4 in SAA-induced invasion using a TLR4 neutralizing antibody. We also tested whether SAA could affect markers of trophoblast syncytialization in BeWo cells. We observed that SAA decreased βhCG secretion and did not influence trophoblast syncytialization. Using EVT cells isolated from human term basal plates, we confirmed that SAA at 1 and 10 µg/mL doubled EVT invasion in a TLR4-dependent manner, but at 20 µg/mL inhibited EVT cells invasiveness. In addition, we observed that SAA was expressed in both BeWo cells and human term placentae, specifically in the syncytiotrophoblast, decidual cells and EVT. In conclusion, SAA was identified as a molecule that functions in the placental microenvironment to regulate metalloprotease activity and trophoblast invasion, which are key processes in placentation and placental homeostasis.

Evidence sustains a role for the acute-phase protein serum amyloid A (SAA) in carcinogenesis and metastasis, and the protein has been suggested as a marker for tumor progression. Nevertheless, the demonstration of a direct activity of SAA on tumor cells is still incipient. We have investigated the effect of human recombinant SAA (rSAA) on two human glioma cell lines, A172 and T98G. rSAA stimulated the [3H]-thymidine incorporation of both lines, but had dual effects on migration and invasiveness which varied according to the cell line. In T98G, the rSAA increased migration and invasion behaviors whereas in A172 it decreased these behaviors. These findings agree with the effect triggered by rSAA on matrix metalloproteinases (MMPs) activities measured in a gelatinolytic assay. rSAA inhibited activity of both MMPs in A172 cells while increasing them in T98G cells. rSAA also affected the production of compounds present in the tumor microenvironment that orchestrate tumor progression, such as IL-8, the production of reactive oxygen species (ROS) and nitric oxide (NO). We also observed that both lines expressed all three of the isoforms of SAA: SAA1, SAA2, and SAA4. These data suggest that some tumor cells are responsive to SAA and, in these cases, SAA may have a role in cancer progression that varies according to the cell type.

The distinction between exudates and transudates is very important in the patient management. Here we evaluate whether the acute-phase protein serum amyloid A (SAA), in comparison with C reactive protein (CRP) and total protein (TP), can be useful in this discrimination. CRP, SAA, and TP were determined in 36 exudate samples (27 pleural and 9 ascitic) and in 12 transudates (9 pleural and 3 ascitic). CRP, SAA, and TP were measured. SAA present in the exudate corresponded to 10% of the amount found in serum, that is, the exudate/serum ratio (E/S) was 0.10±0.13. For comparison, the exudate/serum ratio for CRP and TP was 0.39±0.37 and 0.68±0.15, respectively. There was a strong positive correlation between serum and exudate SAA concentration (r=0.764;p

Electrochemotherapy is an innovative technology used to treat skin and mucosal cancers. It consists of intravenous administration of bleomycin followed by the application of electroporation pulses to the tumor at its margins. These pulses induce the formation of pores in the cell membrane, increasing the cytotoxic efficacy of bleomycin by more than 1,000- fold. As electroporation is a physical phenomenon, different types of tumors can be treated regardless of their histology. Generally, only one treatment session is needed to obtain a satisfactory response. Electrochemotherapy is a good option for recurrent tumors in which other therapies do not provide a response. Additionally, tumors can be shrunk with therapy, allowing for less aggressive surgeries and improving outcomes. Many treatment guidelines have begun to include the use of this non-ablative technique as a new treatment option when other therapies have failed or been rejected by the patient. Treatment is carried out on an outpatient basis with high response rates and few side effects.

IntroductionSystemic lupus erythematosus (SLE) is a clinically heterogeneous disease that presents a challenge for clinicians. To identify potential biomarkers for diagnosis and disease activity in SLE, we investigated a selected yet broad panel of cytokines and autoantibodies in patients with SLE, healthy controls (HC), and patients with other autoimmune diseases (AIDs).MethodsSerum samples from 422 SLE patients, 546 HC, and 1223 other AIDs were analysed within the frame of the European PRECISESADS project (NTC02890121). Cytokine levels were determined using Luminex panels, and autoantibodies using different immunoassays.ResultsOf the 83 cytokines analysed, 29 differed significantly between patients with SLE and HC. Specifically, CCL8, CXCL13, and IL-1RA levels were elevated in patients with active, but not inactive, SLE versus HC, as well as in patients with SLE versus other AIDs. The levels of these cytokines also correlated with SLE Disease Activity Index 2000 (SLEDAI-2K) scores, among five other cytokines. Overall, the occurrence of autoantibodies was similar across SLEDAI-2K organ domains, and the correlations between autoantibodies and activity in different organ domains were weak.DiscussionOur findings suggest that, upon validation, CCL8, CXCL13, and IL-1RA could serve as promising serum biomarkers of activity in SLE.