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The biotechnological development of monoclonal antibodies and their immunotherapeutic use in oncology have grown exponentially in the last decade, becoming the first-line therapy for some types of cancer. Their mechanism of action is based on the ability to regulate the immune system or by interacting with targets that are either overexpressed in tumor cells, released into the extracellular milieu or involved in processes that favor tumor growth. In addition, the intrinsic characteristics of each subclass of antibodies provide specific effector functions against the tumor by activating antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis, among other mechanisms. The rational design and engineering of monoclonal antibodies have improved their pharmacokinetic and pharmacodynamic features, thus optimizing the therapeutic regimens administered to cancer patients and improving their clinical outcomes. The selection of the immunoglobulin G subclass, modifications to its crystallizable region (Fc), and conjugation of radioactive substances or antineoplastic drugs may all improve the antitumor effects of therapeutic antibodies. This review aims to provide insights into the immunological and pharmacological aspects of therapeutic antibodies used in oncology, with a rational approach at molecular modifications that can be introduced into these biological tools, improving their efficacy in the treatment of cancer., (© 2024. The Author(s).)

The Ecuadorian Amazon rainforest stands out as one of the world's most biodiverse regions, yet faces significant threats due to oil extraction activities dating back to the 1970s in the northeastern provinces. This research investigates the environmental and societal consequences of prolonged petroleum exploitation and oil spills in Ecuador's Amazon. Conducted in June 2015, the study involved a comprehensive analysis of freshwater sediment samples from 24 locations in the Rio Aguarico and Napo basins. Parameters such as water and air temperature, conductivity, soil pH, and hydrocarbon concentrations were examined. Total petroleum hydrocarbon (TPH) concentrations ranged from 9.4 to 847.4 mg kg -1 , with polycyclic aromatic hydrocarbon (PAH) levels varying from 10.15 to 711.1 mg kg -1 . The pristane/phytane ratio indicated historic hydrocarbon pollution in 8 of the 15 chemically analyzed sediments. Using non-culturable techniques (Illumina), bacterial analyses identified over 350 ASV, with prominent families including Comamonadaceae , Chitinophagaceae , Anaeromyxobacteraceae , Sphingomonadaceae , and Xanthobacteraceae . Bacterial diversity, assessed in eight samples, exhibited a positive correlation with PAH concentrations. The study provides insights into how microbial communities respond to varying levels of hydrocarbon pollution, shedding light on the enduring impact of oil exploitation in the Amazonian region. Its objective is to deepen our understanding of the environmental and human well-being in the affected area, underscoring the pressing need for remedial actions in the face of ongoing ecological challenges.

MicroRNAs (miRNAs) are small non-coding RNAs that participate as powerful genetic regulators. MiRNAs can interfere with cellular processes by interacting with a broad spectrum of target genes under physiological and pathological states, including cancer development and progression. Major histocompatibility complex major histocompatibility complex class I-related chain A (MICA) belongs to a family of proteins that bind the natural-killer group 2, member D (NKG2D) receptor on Natural Killer cells and other cytotoxic lymphocytes. MICA plays a crucial role in the host's innate immune response to several disease settings, including cancer. MICA harbors various single nucleotide polymorphisms (SNPs) located in its 3'-untranslated region (3'UTR), a characteristic that increases the complexity of MICA regulation, favoring its post-transcriptional modulation by miRNAs under physiological and pathological conditions. Here, we conducted an in-depth analysis of MICA 3'UTR sequences according to each MICA allele described to date using NCBI database. We also systematically evaluated interactions between miRNAs and their putative targets on MICA 3'UTR containing SNPs using in silico analysis. Our in silico results showed that MICA SNPs rs9266829, rs 1880, and rs9266825, located in the target sequence of miRNAs hsa-miR-106a-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-20b-5p, hsa-miR-93, hsa-miR-1207.5p, and hsa-miR-711 could modify the binding free energy between -8.62 and -18.14 kcal/mol, which may affect the regulation of MICA expression. We believe that our results may provide a starting point for further exploration of miRNA regulatory effects depending on MICA allelic variability; they may also be a guide to conduct miRNA in silico analysis for other highly polymorphic genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Toledo-Stuardo, Ribeiro, Campos, Tello, Latorre, Altamirano, Dubois-Camacho and Molina.)

Objective: Remembering and imagining personal events that are rich in episodic (i.e., event-specific) detail is compromised in older adults who have mild cognitive impairment, a known risk factor for Alzheimer's disease dementia. Less clear is whether lower episodic detail generation is associated with higher risk for Alzheimer's disease dementia before mild clinical decline is detectable., Method: We compared past and future autobiographical thinking in clinically normal older adult carriers of the Alzheimer's disease-associated apolipoprotein E e4 allele (APOE4; n = 39) to demographically and neuropsychologically similar non-APOE4 carriers ( n = 43)., Results: APOE4 carriers showed a significant reduction for episodic details when remembering past events ( d = .47) and imagining future events ( d = .46), but not for nonepisodic details., Conclusions: These findings suggest that APOE4 is associated with a selective reduction of episodic detail during past and future autobiographical thinking among clinically normal older adults. Reduced episodic detail generation, therefore, may be an early cognitive associate of higher risk for Alzheimer's disease dementia. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Huanglongbing (HLB), the current major threat for Citrus species, is caused by intracellular alphaproteobacteria of the genus Candidatus Liberibacter ( Ca L), with Ca L asiaticus ( C Las) being the most prevalent species. This bacterium inhabits phloem cells and is transmitted by the psyllid Diaphorina citri . A gene encoding a putative serralysin-like metalloprotease (CLIBASIA_01345) was identified in the C Las genome. The expression levels of this gene were found to be higher in citrus leaves than in psyllids, suggesting a function for this protease in adaptation to the plant environment. Here, we study the putative role of C Las-serralysin (Las1345) as virulence factor. We first assayed whether Las1345 could be secreted by two different surrogate bacteria, Rhizobium leguminosarum bv. viciae A34 ( A34 ) and Serratia marcescens . The protein was detected only in the cellular fraction of A34 and S. marcescens expressing Las1345, and increased protease activity of those bacteria by 2.55 and 4.25-fold, respectively. In contrast, Las1345 expressed in Nicotiana benthamiana leaves did not show protease activity nor alterations in the cell membrane, suggesting that Las1345 do not function as a protease in the plant cell. Las1345 expression negatively regulated cell motility, exopolysaccharide production, and biofilm formation in Xanthomonas campestris pv. campestris ( Xcc ). This bacterial phenotype was correlated with reduced growth and survival on leaf surfaces as well as reduced disease symptoms in N. benthamiana and Arabidopsis. These results support a model where Las1345 could modify extracellular components to adapt bacterial shape and appendages to the phloem environment, thus contributing to virulence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garcia, Molina, Padgett-Pagliai, Torres, Bruna, Garciía Véscovi, González, Gadea and Marano.)

The worldwide, ecologically relevant lichen-forming genus Parmelia currently includes 41 accepted species, of which the Parmelia sulcata group (PSULgp) and the Parmelia saxatilis group (PSAXgp) have received considerable attention over recent decades; however, phycobiont diversity is poorly known in Parmelia s. lat. Here, we studied the diversity of Trebouxia microalgae associated with 159 thalli collected from 30 locations, including nine Parmelia spp.: P. barrenoae, P. encryptata, P. ernstiae, P. mayi, P. omphalodes, P. saxatilis, P. serrana, P. submontana , and P. sulcata . The mycobionts were studied by carrying out phylogenetic analyses of the nrITS. Microalgae genetic diversity was examined by using both nrITS and LSU rDNA markers. To evaluate putative species boundaries, three DNA species delimitation analyses were performed on Trebouxia and Parmelia . All analyses clustered the mycobionts into two main groups: PSULgp and PSAXgp. Species delimitation identified 13 fungal and 15 algal species-level lineages. To identify patterns in specificity and selectivity, the diversity and abundance of the phycobionts were identified for each Parmelia species. High specificity of each Parmelia group for a given Trebouxia clade was observed; PSULgp associated only with clade I and PSAXgp with clade S. However, the degree of specificity is different within each group, since the PSAXgp mycobionts were less specific and associated with 12 Trebouxia spp., meanwhile those of PSULgp interacted only with three Trebouxia spp. Variation-partitioning analyses were conducted to detect the relative contributions of climate, geography, and symbiotic partner to phycobiont and mycobiont distribution patterns. Both analyses explained unexpectedly high portions of variability (99 and 98%) and revealed strong correlations between the fungal and algal diversity. Network analysis discriminated seven ecological clusters. Even though climatic conditions explained the largest proportion of the variation among these clusters, they seemed to show indifference relative to climatic parameters. However, the cluster formed by P. saxatilis A/ P. saxatilis B/ Trebouxia sp. 2/ Trebouxia sp. S02/ Trebouxia sp. 3A was identified to prefer cold-temperate as well as humid summer environments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Moya, Molins, Škaloud, Divakar, Chiva, Dumitru, Molina, Crespo and Barreno.)

FR235222 is a natural tetra-cyclopeptide with a strong inhibition effect on histone deacetylases, effective on mammalian cells as well as on intracellular apicomplexan parasites, such as Toxoplasma gondii, in the tachyzoite and bradyzoite stages. This molecule is characterized by two parts: the zinc-binding group, responsible for the binding to the histone deacetylase, and the cyclic tetrapeptide moiety, which plays a crucial role in cell permeability. Recently, we have shown that the cyclic tetrapeptide coupled with a fluorescent diethyl-amino-coumarin was able to maintain properties of cellular penetration on human cells. Here, we show that this property can be extended to the crossing of the Toxoplasma gondii cystic cell wall and the cell membrane of the parasite in its bradyzoite form, while maintaining a high efficacy as a histone deacetylase inhibitor. The investigation by molecular modeling allows a better understanding of the penetration mechanism.

Seed microbiota is becoming an emergent area of research. Host plant microbial diversity is increasingly well described, yet relatively little is known about the stressors driving plant endomicrobiota at the metaorganism level. The present work examines the role of horizontal and vertical transmission of bacterial microbiota in response to abiotic stress generated by arsenic. Horizontal transmission is achieved by bioaugmentation with the endophyte Rhodococcus rhodochrous , while vertical transmission comes via maternal inheritance from seeds. To achieve this goal, all experiments were conducted with two Jasione species. J. montana is tolerant to arsenic (As), whereas J. sessiliflora , being phylogenetically close to J. montana , was not previously described as As tolerant. The Jasione core bacterial endophytes are composed of genera Pseudomonas , Ralstonia , Undibacterium , Cutibacterium , and Kocuria and family Comamanadaceae across different environmental conditions. All these operational taxonomic units (OTUs) coexisted from seeds to the development of the seedling, independently of As stress, or bioaugmentation treatment and Jasione species. R. rhodochrous colonized efficiently both species, driving the endomicrobiota structure of Jasione with a stronger effect than As stress. Despite the fact that most of the OTUs identified inside Jasione seeds and seedlings belonged to rare microbiota, they represent a large bacterial reservoir offering important physiological and ecological traits to the host. Jasione traits co-regulated with R. rhodochrous , and the associated microbiota improved the host response to As stress. NGS-Illumina tools provided further knowledge about the ecological and functional roles of plant endophytes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 González-Benítez, Martín-Rodríguez, Cuesta, Arrayás, White and Molina.)

Background: Natural killer (NK) cells are paramount for immunity against infectious agents and tumors. Their cytokine and cytolytic responses can be mediated by natural killer group 2, member D (NKG2D), an activating receptor whose ligands (NKG2DL) expression is induced in conditions of cell stress and malignant transformation. Since sustained expression of NKG2DL MICA is related to lower survival rates in gastric adenocarcinoma patients, and Helicobacter pylori infection contributes to tumorigenesis; we asked whether H. pylori stimulus could promote NKG2DL expression on human gastric adenocarcinoma cells., Methods: Heat-killed H. pylori (HKHP) was used to stimulate MKN45 cells before analysis of NKG2DL and Toll-like receptor 4 (TLR4) protein levels by flow cytometry and transcripts by real-time PCR. LPS from Rhodobacter sphaeroides and inhibitory peptide Pepinh MYD were used to inhibit TLR4/MyD88 signaling pathway to assess its participation on NKG2DL expression. NK cell-mediated cytotoxicity was measured by lactate dehydrogenase (LDH) and CD107a mobilization assays., Results: Stimulation of MKN45 cells with HKHP increased MICA, ULBP4 (another NKG2DL), and TLR4 at the protein and transcriptional levels. MICA, but not ULBP4 expression, was upregulated in a TLR4/MyD88-dependent manner. Furthermore, the presence of NKG2DL on the surface of HKHP-stimulated MKN45 cells enabled NK cell cytotoxic activation., Conclusions: Our data indicate that induction of NKG2DL expression on gastric adenocarcinoma cells by H. pylori promotes an immune response that may ultimately contribute to either gastric tissue damage, as a consequence of persistent activation of immunity, or tumor immune evasion due to chronic NKG2DL expression., (© 2021 John Wiley & Sons Ltd.)

Gastric cancer (GC) is the fifth most prevalent type of cancer worldwide. Gastric tumor cells express MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination. MICA gene is highly polymorphic, thus originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work was to study MICA gene polymorphisms and their relationship with the susceptibility and prognosis of GC. Fifty patients with GC and 50 healthy volunteers were included in this study. MICA alleles were identified using Sanger sequencing methods. The analysis of MICA gene sequence revealed 13 MICA sequences and 5 MICA-short tandem repeats (STR) alleles in the studied cohorts We identified MICA * 002 ( * A9) as the most frequent allele in both, patients and controls, followed by MICA * 008 allele ( * A5.1). MICA * 009/049 allele was significantly associated with increased risk of GC (OR: 5.11 [95% CI: 1.39-18.74], p = 0.014). The analysis of MICA-STR alleles revealed a higher frequency of MICA * A5 in healthy individuals than GC patients (OR = 0.34 [95% CI: 0.12-0.98], p = 0.046). Survival analysis after gastrectomy showed that patients with MICA * 002/002 or MICA * 002/004 alleles had significantly higher survival rates than those patients bearing MICA * 002/008 ( p = 0.014) or MICA * 002/009 (MICA * 002/049) alleles ( p = 0.040). The presence of threonine in the position MICA-181 (MICA * 009/049 allele) was more frequent in GC patients than controls ( p = 0.023). Molecular analysis of MICA-181 showed that the presence of threonine provides greater mobility to the protein than arginine in the same position (MICA * 004), which could explain, at least in part, some immune evasion mechanisms developed by the tumor. In conclusion, our findings suggest that the study of MICA alleles is crucial to search for new therapeutic approaches and may be useful for the evaluation of risk and prognosis of GC and personalized therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Toledo-Stuardo, Ribeiro, Canals, Morales, Gárate, Rodríguez-Siza, Tello, Bustamante, Armisen, Matthies, Zapata-Torres, González-Hormazabal and Molina.)

Diesel fuel storage tanks are not hostile environments for microorganisms and tend to form sludges in the water deposited at the bottom of the tanks. The lack of nutrient, carbon and energy limitations within these habitats boost the abundance and the metabolic activity of microorganisms providing microbial hotspots with high growing rates of diesel degradation (0.10 ± 0.021 d -1 ). Five different Phyla (Thermotogae, Spirochaetes, Firmicutes, Bacteroidetes Proteobacteria) were identified within the aqueous/sludge phase from in situ diesel storage tanks, by cultured independent molecular surveys using the 16S rDNA gene fragment. The identified dominant strains were Geotoga aestuarianus, Flavobacterium ceti, Spirochaeta thermophila, Propionispira arboris, Sporobacterium olearium and Dysgonomonas genera. The altitude where the storage tanks are located and the organic carbon concentration within the aqueous/sludge phases affected the bacterial diversity. Therefore, the more diverse the microbial communities are, the more probability of the presence of bacteria with capacity to metabolized diesel and eliminate organic matter. Despite, only phosphate showed an effect on the bacterial distribution within the storage tanks, there was an apparent lack of deterministic process in structuring microbial communities. Consequently, preventative protocols are a priority to avoid the microbial growth within diesel fuel storage tanks. A new focus of this worldwide problem within the oil industry would be to explore deeply the wide range of metabolic and adaptive capacities of these microorganisms. These microbial consortia are potential tools with new specific services to apply in bioremediation among others.

'Okitsu' is a mandarin cultivar showing substantial resistance to X. citri subsp. citri ( X. citri ). We have previously shown that this cultivar has significantly lower canker incidence and severity than 'Clemenules', particularly during early stages of leaf development in the field. This differential response is only seen when the leaves are inoculated by spraying, suggesting that leaf surface contributes to resistance. In this work, we have studied structural and chemical properties of leaf surface barriers of both cultivars. Ultrastructural analysis showed a thicker cuticle covering epidermal surface and guard cells in young 'Okitsu' leaves than in 'Clemenules'. This thicker cuticle was associated with a smaller stomatal aperture and reduced cuticle permeability. These findings correlated with an accumulation of cuticular wax components, including primary alcohols, alkanes, and fatty acids. None of these differences were observed in mature leaves, where both cultivars are equally resistant to the bacterium. Remarkably, mechanical alteration of cuticular thickness of young 'Okitsu' leaves allows canker development. Furthermore, cuticular waxes extracted from young 'Okitsu' leaves have higher antibacterial activity against X. citri than 'Clemenules'. Taken together, these data suggest that a faster development of epicuticular waxes in 'Okitsu' leaves play a central role in its resistance to X. citri.

In young adults, valence not only alters the degree to which future events are imagined in rich episodic detail, but also how memorable these events are later on. For older adults, how valence influences episodic detail generation while imagining future events, or recalling these details at another time, remains unclear. We investigated the effect of valence on the specificity and memorability of episodic future thinking (EFT) in young and older adults. Among young and older adults, negative EFT was accompanied by less episodic detail generation relative to positive and neutral EFT. A similar reduction in episodic specificity for negative EFT was found two days later when participants recalled their previously imagined events. Notably, while older adults generated less episodically specific future thoughts relative to young adults, age did not influence the effect of valence on episodic detail generation at imagination or recollection., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Toxoplasma gondii is a major cause of abortion in small ruminants and presents a zoonotic risk when undercooked meat containing cysts is consumed. The aim of the present study was to investigate the genetic diversity among the T. gondii strains circulating in ovine livestock in Spain., Methods: Selected samples collected from abortion outbreaks due to toxoplasmosis (n = 31) and from chronically infected adult sheep at slaughterhouses (n = 50) in different Spanish regions were bioassayed in mice, aiming at parasite isolation. In addition, all original clinical samples and the resulting isolates were genotyped by multi-nested PCR-RFLP analysis of 11 molecular markers and by PCR-DNA sequencing of portions of the SAG3, GRA6 and GRA7 genes., Results: As a result, 30 isolates were obtained from 9 Spanish regions: 10 isolates from abortion-derived samples and 20 isolates from adult myocardial tissues. Overall, 3 genotypes were found: ToxoDB#3 (type II PRU variant) in 90% (27/30) of isolates, ToxoDB#2 (clonal type III) in 6.7% (2/30), and ToxoDB#1 (clonal type II) in 3.3% (1/30). When T. gondii-positive tissue samples (n = 151) were directly subjected to RFLP genotyping, complete restriction profiles were obtained for 33% of samples, and up to 98% of the specimens belonged to the type II PRU variant. A foetal brain showed a clonal type II pattern, and four specimens showed unexpected type I alleles at the SAG3 marker, including two foetal brains that showed I + II alleles as co-infection events. Amplicons of SAG3, GRA6 and GRA7 obtained from isolates and clinical samples were subjected to sequencing, allowing us to confirm RFLP results and to detect different single-nucleotide polymorphisms., Conclusions: The present study informed the existence of a predominant type II PRU variant genotype (ToxoDB#3) infecting domestic sheep in Spain, in both abortion cases and chronic infections in adults, coexisting with other clonal (ToxoDB#1 and ToxoDB#2), much less frequent genotypes, as well as polymorphic strains as revealed by clinical sample genotyping. The use of multilocus sequence typing aided in accurately estimating T. gondii intragenotype diversity.

Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. Invariant natural killer T (iNKT) cells are innate-like cytotoxic T lymphocytes involved in tumor immune surveillance. They can be activated either through CD1d-presented glycolipid antigens recognized by their invariant T-cell receptor, cytokines or by sensing tumor-associated stress-induced ligands through the natural killer group 2, member D (NKG2D) receptor. Although the number and functionality of iNKT cells may be decreased in several types of cancer, here we show that GC patients presented a mild increase in iNKT cell frequencies and numbers in the blood compared with healthy donors. In GC patients, iNKT cells, expanded in vitro with α-galactosyl ceramide and stimulated with phorbol 12-myristate 13-acetate and ionomycin, produced higher levels of interleukin-2 and transforming growth factor-beta, while their capacity to degranulate remained preserved. Because tumor-derived epithelial cell adhesion molecule-positive epithelial cells did not display surface CD1d, and NKG2D ligands (NKG2DLs) were detected in the gastric tumor milieu, we envisioned a role for NKG2D in iNKT cell functions. Peripheral iNKT cells from GC patients and controls presented similar levels of NKG2D; nevertheless, the percentages of interferon-γ-producing and CD107a-positive iNKT cells from patients were reduced upon challenge with CD1d-negative, NKG2DL-positive K562 cells, suggesting a compromised response by iNKT cells in GC patients, which may not result from impaired NKG2D/NKG2DL signaling. The decreased response of iNKT cells may explain the fact that higher frequencies of circulating iNKT cells did not confer a survival benefit for GC patients. Therefore, functional impairment of iNKT cells in GC may contribute to tumor immune escape and favor disease progression., (© 2020 Australian and New Zealand Society for Immunology Inc.)

An in-situ experiment was performed to study metabolic responses of the freshwater mussel Diplodon chilensis to water contaminated by leachates from an open dump and cattle activity, in order to analyze both the effects of those contaminants on aquatic environments and the potential use of a native bivalve to evaluate the effects of anthropic influence and eutrophication. Bivalves from a reference site were cage-transplanted to a control site (site A) and to a temporal water pond (site B) over 30 and 60 periods. Water quality analyses revealed that the site B was affected by anthropogenic influence. Mussel's hemocytes from site B showed 50% lower reactive oxygen species production and 130% higher lysosomal membrane stability in the site B mussels. In addition, no oxidative stress was evident in gills, despite the elevated copper and iron concentrations recorded in the site B water samples (Cu B  = 0.3350 ± 0.0636 mg. L -1 vs. Cu A  = 0.0045 ± 0.0007 mg. L -1 ; Fe B  = 3.8650 ± 0.4031 mg. L -1 vs. Fe A  = 0.0365 ± 0.0049 mg. L -1 ). In contrast, the adductor muscle accumulated more Fe (~10-20-fold) than the gills and showed signs of oxidative stress, e.g. superoxide dismutase activity and TBARS levels were increased by 10% were 34%, respectively, in the site B compared with the site A after 60 days of exposure. Additionally, the adductor muscle showed signs of anaerobic metabolism activation. Cu is accumulated in gills from both sites' individuals, at 60 days, in concordance with the increase in the activity of the cu-containing enzyme cytochrome-c-oxidase. There was a reduction in the overall condition and digestive gland index in bivalves exposed at site B, associated with diminished levels of lipid and protein contents. Metal-pollution and eutrophication affects D. chilensis metabolism and is associated to tissue-specific exposure, anaerobic metabolism and general energetic condition depletion., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Parent training programs (PTPs) have been used extensively in Anglo-Saxon countries, but less so in Southern Europe. Several characteristics of families have been linked to effective parenting and positive development of children, but few studies have examined the social determinants of the effectiveness of PTPs. The Parenting Skills Program for families (PSP) is a PTP from Spain. This study aimed to identify the social characteristics (sex, age, country of birth, marital status, educational level, and employment status) of parents that determine the success of the PSP in relation to social support, parenting skills, parental stress, and negative behaviors among children. A quasi-experimental study with a prepost design with no control group was used. We conducted a survey before (T0) and after the intervention (T1). Sample size was 216. We fit multiple logistic regression models. Parenting skills increased more among parents with a lower educational level. Parents' stress decreased more among parents who had a lower educational level, were unemployed, and were men. Social support increased among parents who were younger, unemployed, or non-cohabiting. We found no significant differences in the effect on children's negative behaviors according to the social factors evaluated. The PSP is effective for socioeconomically diverse families, but the success differs according to the parents' social profile. Unlike most previous studies, the results were better among more socially disadvantaged people, highlighting the potential of this kind of intervention for reducing the social inequality gap between groups.

Propagation of emerging pollutants (EPs) in wastewater treatment plants has become a warning sign, especially for novel resource-recovery concepts. The fate of EPs on purple phototrophic bacteria (PPB)-based systems has not yet been determined. This work analyzes the performance of a photo-anaerobic membrane bioreactor treating a low-N wastewater contaminated with 25 EPs. The chemical oxygen demand (COD), N and P removal efficiencies were stable (76 ± 8, 62 ± 15 and 36 ± 8 %, respectively) for EPs loading rate ranging from 50 to 200 ng L -1 d -1 . The PPB community adapted to changes in both the EPs concentration and the organic loading rate (OLR) and maintained dominance with >85 % of total 16S gene copies. Indeed, an increment of the OLR caused an increase of the biomass growth and activity concomitantly with a higher EPs removal efficiency (30 ± 13 vs 54 ± 11 % removal for OLR of 307 ± 4 and 590 ± 8 mgCOD L -1 d -1 , respectively). Biodegradation is the main mechanism of EPs removal due to low EPs accumulation on the biomass, the membrane or the reactor walls. Low EPs adsorption avoided biomass contamination, resulting in no effect on its biological methane potential. These results support the use of PPB technologies for resource recovery with low EPs contamination of the products., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The apoplast, i.e. the cellular compartment external to the plasma membrane, undergoes important changes during senescence. Apoplastic fluid volume increases quite significantly in senescing leaves, thereby diluting its contents. Its pH elevates by about 0.8 units, similar to the apoplast alkalization in response to abiotic stresses. The levels of 159 proteins decrease, whereas 24 proteins increase in relative abundance in the apoplast of senescing leaves. Around half of the apoplastic proteins of non-senescent leaves contain a N-terminal signal peptide for secretion, while all the identified senescence-associated apoplastic proteins contain the signal peptide. Several of the apoplastic proteins that accumulate during senescence also accumulate in stress responses, suggesting that the apoplast may constitute a compartment where developmental and stress-related programs overlap. Other senescence-related apoplastic proteins are involved in cell wall modifications, proteolysis, carbohydrate, ROS and amino acid metabolism, signaling, lipid transport, etc. The most abundant senescence-associated apoplastic proteins, PR2 and PR5 (e.g. pathogenesis related proteins PR2 and PR5) are related to leaf aging rather than to the chloroplast degradation program, as their levels increase only in leaves undergoing developmental senescence, but not in dark-induced senescent leaves. Changes in the apoplastic space may be relevant for signaling and molecular trafficking underlying senescence., (Copyright © 2020 Borniego, Molina, Guiamét and Martinez.)

Relative to young adults, cognitively normal older adults commonly generate more semantic details and fewer episodic details in their descriptions of unique life events. It remains unclear whether this reflects a specific change to episodic memory or a broader alteration to autobiographical narration. To explore age differences across different types of autobiographical narration, we created a lifetime period narrative task that involves describing extended events. For comparison, participants also described unique life events. All autobiographical narratives were scored for episodic, semantic, and other detail generation. Relative to young adults, older adults generated more detailed narratives for remote and recent lifetime periods, which was driven by their increased retrieval of personal and general semantic details. Older adults also generated more semantic details for unique life event narratives, along with reduced episodic detail. More broadly, in both groups lifetime period narratives were largely based on semantic details, whereas episodic details were more prominent in the descriptions of unique life events. These findings indicate that the elevated generation of semantic details associated with normal cognitive aging is reflected in multiple types of autobiographical narration. We suggest that lifetime period narration is a spared aspect of autobiographical memory among older adults.

Recombinant protein expression for structural and therapeutic applications requires the use of systems with high expression yields. Escherichia coli is considered the workhorse for this purpose, given its fast growth rate and feasible manipulation. However, bacterial inclusion body formation remains a challenge for further protein purification. We analyzed and optimized the expression conditions for three different proteins: an anti-MICA scFv, MICA, and p19 subunit of IL-23. We used a response surface methodology based on a three-level Box-Behnken design, which included three factors: post-induction temperature, post-induction time and IPTG concentration. Comparing this information with soluble protein data in a principal component analysis revealed that insoluble and soluble proteins have different optimal conditions for post-induction temperature, post-induction time, IPTG concentration and in amino acid sequence features. Finally, we optimized the refolding conditions of the least expressed protein, anti-MICA scFv, using a fast dilution protocol with different additives, obtaining soluble and active scFv for binding assays. These results allowed us to obtain higher yields of proteins expressed in inclusion bodies. Further studies using the system proposed in this study may lead to the identification of optimal environmental factors for a given protein sequence, favoring the acceleration of bioprocess development and structural studies.

Background and Aims: In order to re-establish lichen symbiosis, fungal spores must first germinate and then associate with a compatible photobiont. To detect possible establishment limitations in a sexually reproducing cyanolichen species, we studied ascospore germination, photobiont growth and photobiont association patterns in Pectenia plumbea., Methods: Germination tests were made with ascospores from 500 apothecia under different treatments, and photobiont growth was analysed in 192 isolates obtained from 24 thalli. We determined the genotype identity [tRNALeu (UAA) intron] of the Nostoc cyanobionts from 30 P. plumbea thalli from one population. We also sequenced cyanobionts of 41 specimens of other cyanolichen species and 58 Nostoc free-living colonies cultured from the bark substrate., Key Results: Not a single fungal ascospore germinated and none of the photobiont isolates produced motile hormogonia. Genetic analyses revealed that P. plumbea shares Nostoc genotypes with two other cyanolichen species of the same habitat, but these photobionts were hardly present in the bark substrate., Conclusions: Due to the inability of both symbionts to thrive independently, the establishment of P. plumbea seems to depend on Dendriscocaulon umhausense, the only cyanolichen species in the same habitat that reproduces asexually and acts as a source of appropriate cyanobionts. This provides support to the hypothesis about facilitation among lichens., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Transcription activator-like effectors (TALEs) are important effectors of Xanthomonas spp. that manipulate the transcriptome of the host plant, conferring susceptibility or resistance to bacterial infection. Xanthomonas citri ssp. citri variant A T (X. citri A T ) triggers a host-specific hypersensitive response (HR) that suppresses citrus canker development. However, the bacterial effector that elicits this process is unknown. In this study, we show that a 7.5-repeat TALE is responsible for triggering the HR. PthA4 AT was identified within the pthA repertoire of X. citri A T followed by assay of the effects on different hosts. The mode of action of PthA4 AT was characterized using protein-binding microarrays and testing the effects of deletion of the nuclear localization signals and activation domain on plant responses. PthA4 AT is able to bind DNA and activate transcription in an effector binding element-dependent manner. Moreover, HR requires PthA4 AT nuclear localization, suggesting the activation of executor resistance (R) genes in host and non-host plants. This is the first case where a TALE of unusually short length performs a biological function by means of its repeat domain, indicating that the action of these effectors to reprogramme the host transcriptome following nuclear localization is not limited to 'classical' TALEs., (© 2019 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

The electronics era is flourishing and morphing itself into Internet of Everything, IoE. At the same time, questions arise on the issue of electronic materials employed: especially their natural availability and low-cost fabrication, their functional stability in devices, and finally their desired biodegradation at the end of their life cycle. Hydrogen bonded pigments and natural dyes like indigo, anthraquinone and acridone are not only biodegradable and of bio-origin but also have functionality robustness and offer versatility in designing electronics and sensors components. With this Perspective, we intend to coalesce all the scattered reports on the above-mentioned classes of hydrogen bonded semiconductors, spanning across several disciplines and many active research groups. The article will comprise both published and unpublished results, on stability during aging, upon electrical, chemical and thermal stress, and will finish with an outlook section related to biological degradation and biological stability of selected hydrogen bonded molecules employed as semiconductors in organic electronic devices. We demonstrate that when the purity, the long-range order and the strength of chemical bonds, are considered, then the Hydrogen bonded organic semiconductors are the privileged class of materials having the potential to compete with inorganic semiconductors. As an experimental historical study of stability, we fabricated and characterized organic transistors from a material batch synthesized in 1932 and compared the results to a fresh material batch., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

The continuous increase of approved biopharmaceutical products drives the development of more efficient recombinant protein expression systems. Chinese hamster ovary (CHO) cells are the mainstay for this purpose but have some drawbacks, such as low levels of expression. Several strategies have been applied to increase the productivity of CHO cells with different outcomes. Transcription factor (TF) engineering has emerged as an interesting and successful approach, as these proteins can act as master regulators; the expression and function of a TF can be controlled by small molecules, and it is possible to design tailored TFs and promoters with desired features. To date, the majority of studies have focused on the use of TFs with growth, metabolic, cell cycle or endoplasmic reticulum functions, although there is a trend to develop new, synthetic TFs. Moreover, new synthetic biological approaches are showing promising advances for the development of specific TFs, even with tailored ligand sensitivity. In this article, we summarize the strategies to increase recombinant protein expression by modulating and designing TFs and with advancements in synthetic biology. We also illustrate how this class of proteins can be used to develop more robust expression systems.

Background: The production of recombinant proteins in mammalian cell lines is one of the most important areas in biopharmaceutical industry. Viral transcriptional promoters are widely used to express recombinant proteins in mammalian cell lines. However, these promoters are susceptible to silencing, thus limiting protein productivity. Some CpG islands can avoid the silencing of housekeeping genes; for that reason, they have been used to increase the production of recombinant genes in cells of animal origin. In this study, we evaluated the CpG island of the promoter region of the β-actin gene of Cricetulus griseous (Chinese hamster), associated to the Cytomegalovirus (CMV) promoter, to increase recombinant antibodies production in Chinese Hamster Ovary (CHO) cells., Results: We focused on the non-coding region of CpG island, which we called RegCG. RegCG behaved as a promoter, whose transcriptional activity was mainly commanded by the CAAT and CArG boxes of the proximal promoter. However, the transcription started mainly at the intronic region before the proximal transcription start site. While the CMV promoter was initially more powerful than RegCG, the latter promoter was more resistant to silencing than the CMV promoter in stable cell lines, and its activity was improved when combined with the CMV promoter. Thereby, the chimeric promoter was able to maintain the expression of recombinant antibodies in stable clones for 40 days at an average level 4 times higher than the CMV promoter. Finally, the chimeric promoter showed compatibility with a genetic amplification system by induction with methotrexate in cells deficient in the dihydrofolate reductase gene., Conclusions: We have generated an efficient synthetic hybrid transcription promoter through the combination of RegCG with CMV, which, in stable cell lines, shows greater activity than when both promoters are used separately. Our chimeric promoter is compatible with a genetic amplification system in CHO DG44 cells and makes possible the generation of stable cell lines with high production of recombinant antibodies. We propose that this promoter can be a good alternative for the generation of clones expressing high amount of recombinant proteins, essential for industrial applications., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

The potential of tolerogenic dendritic cells (tolDCs) to shape immune responses and restore tolerance has turn them into a promising therapeutic tool for cellular therapies directed toward immune regulation in autoimmunity. Although the cellular mechanisms by which these cells can exert their regulatory function are well-known, the mechanisms driving their differentiation and function are still poorly known, and the variety of stimuli and protocols applied to differentiate DCs toward a tolerogenic phenotype makes it even more complex to underpin the molecular features involved in their function. Through transcriptional profiling analysis of monocyte-derived tolDCs modulated with dexamethasone (Dex) and activated with monophosphoryl lipid A (MPLA), known as DM-DCs, we were able to identify MYC as one of the transcriptional regulators of several genes differentially expressed on DM-DCs compared to MPLA-matured DCs (M-DCs) and untreated/immature DCs (DCs) as revealed by Ingenuity Pathway Analysis (IPA) upstream regulators evaluation. Additionally, MYC was also amidst the most upregulated genes in DM-DCs, finding that was confirmed at a transcriptional as well as at a protein level. Blockade of transactivation of MYC target genes led to the downregulation of tolerance-related markers IDO1 and JAG1. MYC blockade also led to downregulation of PLZF and STAT3, transcription factors associated with immune regulation and inhibition of DC maturation, further supporting a role of MYC as an upstream regulator contributing to the regulatory phenotype of DM-DCs. On the other hand, we had previously shown that fatty acid oxidation, oxidative metabolism and zinc homeostasis are amongst the main biological functions represented in DM-DCs, and here we show that DM-DCs exhibit higher intracellular expression of ROS and Zinc compared to mature M-DCs and DCs. Taken together, these findings suggest that the regulatory profile of DM-DCs is partly shaped by the effect of the transcriptional regulation of tolerance-inducing genes by MYC and the modulation of oxidative metabolic processes and signaling mediators such as Zinc and ROS.

Introduction: Population ageing requires that health and social systems focus their attention on identifying frailty in the elderly. In the Canary Islands, there are no studies to determine the prevalence of frailty among its population. The objective of this study is to determine the prevalence and profile of frailty in the island of La Palma, Canary Islands, Spain., Material and Method: A cross-sectional study was conducted to estimate the prevalence and the profile of frailty. The sample were residents over 70 years old, valued by the Fried criteria, and taking into account other related factors. The prevalence is offered with a confidence interval of 95% and is compared with that of other Spanish populations. To determine the profile, a simple comparison of variables was made, followed by using them in logistic regression models. All the tests were bilateral at a P≤0.05 level., Results: The prevalence of frailty in people over 70 years was estimated at 20% (17-23%). This prevalence shows differences with those of other Spanish populations. The factors that showed a relationship with frailty were, being female, widowed, living alone, low physical activity, cognitive impairment, depression, polymedication, and adverse clinical history. Multivariate analysis identifies factors associated with the frailty variables related to marital status, co-existence, polypharmacy, depressive states, and lack of physical exercise., Conclusions: The elderly population of La Palma have greater frailty compared to that described in other regions of Spain, with their profile being that of a widowed person, with depression, polymedicated, living alone, and not exercising., (Copyright © 2018 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Multidrug resistant bacteria are a serious worldwide problem, especially carbapenem-resistant Enterobacteriaceae (such as Klebsiella pneumoniae and Escherichia coli ), Acinetobacter baumannii and Pseudomonas aeruginosa . Since the emergence of extensive and pan-drug resistant bacteria there are few antibiotics left to treat patients, thus novel RNA-based strategies are being considered. Here, we examine the current situation of different non-coding RNAs found in bacteria as well as their function and potential application as antimicrobial agents. Furthermore, we discuss the factors that may contribute in the efficient development of RNA-based drugs, the limitations for their implementation and the use of nanocarriers for delivery.

Objective: We implemented and evaluated the Parenting Skills Program for families in Spain 1) to examine differences in parenting skills, social support, children's behaviours and parental stress pre, immediately post and six months post intervention and 2) to identify mechanisms by which the intervention is related to changes in the four outcomes examined., Methods: Quasi-experimental study design with pre (T0), post (T1), a follow-up (T2) and no control group, complemented by a qualitative study was used. The outcome variables were social support, parenting skills, parental stress and children's behaviours. 216 parents completed pre and post questionnaire and 130 parents the follow-up questionnaire. 39 professionals and 34 parents participated in 17 interviews and 5 discussion groups., Results: Compared with T0, all four outcomes improved significantly at T1. 76% of the participants improved parenting skills and 61% social support. 56% reduced children's negative behaviours and 66% parental stress. All outcomes maintained this significant improvement at T2. Parents and professionals describe different changes in parents' parenting skills, stress and social support after participation in the PSP, and in their children's behaviours. Some subcategories emerged after analysing parents' and professionals' discourses., Conclusions: This study describes positive parenting effects on participants of a parent-training program in Spain, which is a country where implementation and evaluation of these kind of interventions is an incipient issue., (Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims: To investigate multiple tolerance of Saccharomyces cerevisiae obtained through a laboratory strategy of adaptive evolution in acetic acid, its relation with enzymatic ROS detoxification and bioethanol 2G production., Methods and Results: After adaptive evolution in acetic acid, a clone (Y8A) was selected for its tolerance to high acetic acid concentrations (13 g l -1 ) in batch cultures. Y8A was resistant to multiple stresses: osmotic, thermic, oxidative, saline, ethanol, organic acid, phenolic compounds and slow freeze-thawing cycles. Also, Y8A was able to maintain redox homeostasis under oxidative stress, whereas the isogenic parental strain (Y8) could not, indicating higher basal activity levels of antioxidative enzyme Catalase (CAT) and Gluthatione S-transferase (GST) in Y8A. Y8A reached higher bioethanol levels in a fermentation medium containing up to 8 g l -1 of acetic acid when compared to parental strain Y8., Conclusions: A multiple-stress-tolerant clone was obtained using adaptive evolution in acetic acid. Stress cross-tolerance could be explained by its enzymatic antioxidative capacity, namely CAT and GST., Significance and Impact of the Study: We demonstrate that adaptive evolution used in S. cerevisiae was a useful strategy to obtain a yeast clone tolerant to multiple stresses. At the same time, our findings support the idea that tolerance to oxidative stress is the common basis for stress cotolerance, which is related to an increase in the specific enzymes CAT and GST but not in Superoxide dismutase, emphasizing the fact that detoxification of H 2 O 2 and not O 2 ˙ is a key condition for multiple stress tolerance in S. cerevisiae., (© 2018 The Society for Applied Microbiology.)

This study investigated metal accumulation and oxidative effects in mantle, gill and digestive gland of the ribbed mussel Aulacomya atra from the Argentinean North Patagonian coastline. Mussels were transplanted over an 18-month period from a site with low anthropogenic impact to a harbor site with higher seawater concentration of aluminum, chromium, copper, manganese, nickel and zinc. Total trace metal concentration in seawater did not change throughout the 18-month transplant in either site. A. atra bioaccumulated metals in digestive gland, gills and mantle at different levels. Digestive gland had the highest concentration of metals, especially towards the end of the transplant experiment in the harbor area. Mussels transplanted to the harbor site experienced an upregulation in their antioxidant system, which likely explains the lack of oxidative damage to lipids despite higher metal accumulation. These results demonstrate that A. atra selectively accumulates metals from the water column and their prooxidant effects depend on the tissue antioxidant defenses and the exposure time., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Chinese hamster ovary (CHO) cells are the most frequently used host for commercial production of therapeutic proteins. However, their low protein productivity in culture is the main hurdle to overcome. Mild hypothermia has been established as an effective strategy to enhance protein specific productivity, although the causes of such improvement still remain unclear. The self-regulation of global transcriptional regulatory factors, such as Myc and XBP1s, seems to be involved in increased the recombinant protein production at low temperature. This study evaluated the impact of low temperature in CHO cell cultures on myc and xbp1s expression and their effects on culture performance and cell metabolism. Two anti-TNFα producing CHO cell lines were selected considering two distinct phenotypes: i.e. maximum cell growth, (CN1) and maximum specific anti-TNFα production (CN2), and cultured at 37, 33 and 31°C in a batch system. Low temperature led to an increase in the cell viability, the expression of the recombinant anti-TNFα and the production of anti-TNFα both in CN1 and CN2. The higher production of anti-TNFα in CN2 was mainly associated with the large expression of anti-TNFα. Under mild hypothermia myc and xbp1s expression levels were directly correlated to the maximal viable cell density and the specific anti-TNFα productivity, respectively. Moreover, cells showed a simultaneous metabolic shift from production to consumption of lactate and from consumption to production of glutamine, which were exacerbated by reducing culture temperature and coincided with the increased anti-TNFα production. Our current results provide new insights of the regulation of myc and xbp1s in CHO cells at low temperature, and suggest that the presence and magnitude of the metabolic shift might be a relevant metabolic marker of productive cell line.

There is growing interest in the use of tolerogenic dendritic cells (tolDCs) as a potential target for immunotherapy. However, the molecular bases that drive the differentiation of monocyte-derived DCs (moDCs) toward a tolerogenic state are still poorly understood. Here, we studied the transcriptional profile of moDCs from healthy subjects, modulated with dexamethasone (Dex) and activated with monophosphoryl lipid A (MPLA), referred to as Dex-modulated and MPLA-activated DCs (DM-DCs), as an approach to identify molecular regulators and pathways associated with the induction of tolerogenic properties in tolDCs. We found that DM-DCs exhibit a distinctive transcriptional profile compared to untreated (DCs) and MPLA-matured DCs. Differentially expressed genes downregulated by DM included MMP12, CD1c, IL-1B, and FCER1A involved in DC maturation/inflammation and genes upregulated by DM included JAG1, MERTK, IL-10, and IDO1 involved in tolerance. Genes related to chemotactic responses, cell-to-cell signaling and interaction, fatty acid oxidation, metal homeostasis, and free radical scavenging were strongly enriched, predicting the activation of alternative metabolic processes than those driven by counterpart DCs. Furthermore, we identified a set of genes that were regulated exclusively by the combined action of Dex and MPLA, which are mainly involved in the control of zinc homeostasis and reactive oxygen species production. These data further support the important role of metabolic processes on the control of the DC-driven regulatory immune response. Thus, Dex and MPLA treatments modify gene expression in moDCs by inducing a particular transcriptional profile characterized by the activation of tolerance-associated genes and suppression of the expression of inflammatory genes, conferring the potential to exert regulatory functions and immune response modulation.

Triatoma infestans is an important hematophagous vector of Chagas disease, a neglected chronic illness affecting approximately 6 million people in Latin America. Hematophagous insects possess several molecules in their saliva that counteract host defensive responses. Calreticulin (CRT), a multifunctional protein secreted in saliva, contributes to the feeding process in some insects. Human CRT (HuCRT) and Trypanosoma cruzi CRT (TcCRT) inhibit the classical pathway of complement activation, mainly by interacting through their central S domain with complement component C1. In previous studies, we have detected CRT in salivary gland extracts from T. infestans We have called this molecule TiCRT. Given that the S domain is responsible for C1 binding, we have tested its role in the classical pathway of complement activation in vertebrate blood. We have cloned and characterized the complete nucleotide sequence of CRT from T. infestans , and expressed its S domain. As expected, this S domain binds to human C1 and, as a consequence, it inhibits the classical pathway of complement, at its earliest stage of activation, namely the generation of C4b. Possibly, the presence of TiCRT in the salivary gland represents an evolutionary adaptation in hematophagous insects to control a potential activation of complement proteins, present in the massive blood meal that they ingest, with deleterious consequences at least on the anterior digestive tract of these insects., (© The American Society of Tropical Medicine and Hygiene.)

The Mediterranean region, comprising the Mediterranean Basin and the Macaronesian Islands, represents a center of diversification for many organisms. The genetic structure and connectivity of mainland and island microbial populations has been poorly explored, in particular in the case of symbiotic fungi. Here we investigated genetic diversity and spatial structure of the obligate outcrossing lichen-forming fungus Parmelina carporrhizans in the Mediterranean region. Using eight microsatellite and mating-type markers we showed that fungal populations are highly diverse but lack spatial structure. This is likely due to high connectivity and long distance dispersal of fungal spores. Consistent with low levels of linkage disequilibrium and lack of clonality, we detected both mating-type idiomorphs in all populations. Furthermore we showed that the Macaronesian Islands are the result of colonization from the Mediterranean Basin. The unidirectional gene flow, though, seemed not to be sufficient to counterbalance the effects of drift, resulting in comparatively allelic poor peripheral populations. Our study is the first to shed light on the high connectivity and lack of population structure in natural populations of a strictly sexual lichen fungus. Our data further support the view of the Macaronesian Islands as the end of the colonization road for this symbiotic ascomycete.

Tolerogenic dendritic cells (TolDCs) are promising tools for therapy of autoimmune diseases, such as rheumatoid arthritis (RA). Here, we characterize monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated with monophosphoryl lipid A (MPLA), referred to as MPLA-tDCs, in terms of gene expression, phenotype, cytokine profile, migratory properties, and T cell-stimulatory capacity in order to explore their suitability for cellular therapy. MPLA-tDCs derived from RA patients displayed an anti-inflammatory profile with reduced expression of co-stimulatory molecules and high IL-10/IL-12 ratio, but were capable of migrating toward the lymphoid chemokines CXCL12 and CCL19. These MPLA-tDCs induced hyporesponsiveness of autologous CD4+ T cells specific for synovial antigens in vitro . Global transcriptome analysis confirmed a unique transcriptional profile of MPLA-tDCs and revealed that RA-associated genes, which were upregulated in untreated DCs from RA patients, returned to expression levels of healthy donor-derived DCs after treatment with dexamethasone and MPLA. Thus, monocyte-derived DCs from RA patients have the capacity to develop tolerogenic features at transcriptional as well as at translational level, when modulated with dexamethasone and MPLA, overcoming disease-related effects. Furthermore, the ability of MPLA-tDCs to impair T cell responses to synovial antigens validates their potential as cellular treatment for RA.

Sterols are essential for several physiological processes in most eukaryotes. Sterols regulate membrane homeostasis and participate in different signalling pathways not only as precursors of steroid hormones and vitamins, but also through its role in the formation of lipid rafts. Two major types of sterols, cholesterol and ergosterol, have been described so far in the opisthokonts, the clade that comprise animals, fungi and their unicellular relatives. Cholesterol predominates in derived bilaterians, whereas ergosterol is what generally defines fungi. We here characterize, by a combination of bioinformatic and biochemical analyses, the sterol metabolism in the filasterean Capsaspora owczarzaki, a close unicellular relative of animals that is becoming a model organism. We found that C. owczarzaki sterol metabolism combines enzymatic activities that are usually considered either characteristic of fungi or exclusive to metazoans. Moreover, we observe a differential transcriptional regulation of this metabolism across its life cycle. Thus, C. owczarzaki alternates between synthesizing 7-dehydrocholesterol de novo, which happens at the cystic stage, and the partial conversion-via a novel pathway-of incorporated cholesterol into ergosterol, the characteristic fungal sterol, in the filopodial and aggregative stages., (© 2016 The Authors.)

Background: Biofumigation with defatted seed meal of Brassicaceae in the form of pellets has several advantages over the incorporation of fresh Brassicaceae crops to control soil-borne diseases. Two field experiments were established to evaluate the effect of biofumigation with brassica pellets on the survival and infectivity of Phytophthora nicotianae Breda de Haan inoculum introduced before treatments. In the spring experiment the incorporation of additional Brassicaceae cover crop (Brassica nigra L. and Sinapis alba L.) was tested, and in the summer experiment two brassica pellet doses were applied., Results: Biofumigation with brassica pellets in spring (3000 kg ha(-1) with and without plastic) or in summer (3000 kg ha(-1) with or without plastic; 6000 kg ha(-1) without plastic) had no significant effect on the survival of P. nicotianae, regardless of the incorporation of additional Brassicaceae cover crop in spring. Reduction in infectivity in spring was related to the application of plastic, especially when combined with brassica pellets and Brassicaceae crop. In summer, soil temperature was the main factor in the inactivation of the inoculum, especially when plastic was applied, and no additional inactivation was achieved with brassica pellets., Conclusion: In spring and summer, biofumigation with brassica pellets had no effect on the survival of P. nicotianae. Application of plastic in spring may reduce infectivity. Soil temperature is the main factor in the inactivation of inoculum in summer, especially when plastic is applied. © 2015 Society of Chemical Industry., (© 2015 Society of Chemical Industry.)

Background and Objectives: Dyslipidemia is a pivotal risk factor for coronary heart disease (CHD). The purpose of this study was to identify the profile of dyslipidemia in a Brazilian population, according to high low-density lipoprotein (LDL-C) levels. We used the classification of the 2004 update of National Cholesterol Education Program Adult Treatment Panel III (ATP-III)., Methods: Of the 15,105 men and women aged 35 to 74 years enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we included 14,648 subjects (97%). They had data to categorize them according to the NCEP-ATP-III criteria. We compared 4 categories: "0-1" risk factors, "2 or more risk factors", "CHD or CHD risk equivalent", and "CHD at very high risk". The sociodemographic determinants used were sex, age, ethnicity, income, education, and health insurance. Poisson regression was used to estimate the prevalence ratios for cholesterol (LDL-C), frequency, awareness, treatment, and control of high LDL-C., Results: The frequencies of high LDL-C, awareness, treatment, and control were 45.5%, 58.1%, 42.3%, and 58.3%, respectively. After adjustment for sociodemographic determinants, the prevalence ratios for high LDL-C were significantly higher for men, blacks, older subjects, and subjects with lower levels of education. Low frequency of awareness, treatment, and uncontrolled values of LDL-C was observed among men, mixed race and blacks, poorer, less educated, and those who did not have private health insurance., Conclusions: The prevalence of high LDL-C was elevated in this Brazilian population, with low rates of awareness, treatment and control, and remarkable socioeconomic disparity., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)