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Effective circularization of mRNA molecules is a key step for the efficient initiation of translation. Research has shown that the intrinsic separation of the ends of mRNA molecules is rather small, suggesting that intramolecular arrangements could provide this effective circularization. Considering that the innate proximity of RNA ends might have important unknown biological implications, we aimed to determine whether the close proximity of the ends of mRNA molecules is a conserved feature across organisms and gain further insights into the functional effects of the proximity of RNA ends. To do so, we studied the secondary structure of 274 full native mRNA molecules from 17 different organisms to calculate the contour length (CL) of the external loop as an index of their end‐to‐end separation. Our computational predictions show bigger variations (from 0.59 to 31.8 nm) than previously reported and also than those observed in random sequences. Our results suggest that separations larger than 18.5 nm are not favored, whereas short separations could be related to phenotypical stability. Overall, our work implies the existence of a biological mechanism responsible for the increase in the observed variability, suggesting that the CL features of the exterior loop could be relevant for the initiation of translation and that a short CL could contribute to the stability of phenotypes.

Antibodies directed against DNA in systemic lupus erythematosus are functionally diverse. This study demonstrates that DNAse1L3 is the primary target of a subset of autoantibodies previously considered specific for double-stranded DNA.

The origin and mechanisms of autoantigen generation in systemic lupus erythematosus (SLE) are poorly understood. Here, we identified SLE neutrophils activated in vivo by IFN as a prominent source of Ro52, also known as tripartite motif–containing protein 21 (TRIM21), a critical autoantigen historically thought to be primarily generated by keratinocytes in SLE. Different from mononuclear cells and keratinocytes, SLE neutrophils are enriched in several unique Ro52 species containing a core sequence encoded by exon 4 (Ro52Ex4) in TRIM21. Ro52Ex4 is the main target of anti-Ro52 antibodies and is found in 2 Ro52 variants (Ro52α and an isoform termed Ro52γ) upregulated in SLE neutrophils. Further analysis of Ro52γ revealed a subset of autoantibodies against a unique C-terminal domain (Ro52γCT) generated from a frameshift due to the lack of exon 6 in Ro52γ. Antibodies to Ro52Ex4 and Ro52γCT distinguish SLE patient subsets characterized by distinct clinical, laboratory, treatment, and transcriptional profiles that are not discerned by the “classical” anti-Ro52 antibodies. These studies uncover IFN-activated neutrophils as a key source of unique immunogenic forms of Ro52 in SLE. Moreover, the finding of Ro52Ex4 and Ro52γCT as core targets of anti-Ro52 antibodies focus interest on Ro52γ as the potential isoform toward which immunological tolerance is initially lost in SLE.

Bacillus subtilis has been documented in the past years as an effective probiotic for different aquacultured species, with recognized beneficial effects on water quality, fish growth and immune status. Furthermore, its potential as a vaccine adjuvant has also been explored in different species. In the current work, we have used B. subtilis spores as delivery vehicles for the presentation of the VP2 protein from infectious pancreatic necrosis virus (IPNV). For this, the VP2 gene was amplified and translationally fused to the crust protein CotY. The successful expression of VP2 on the spores was confirmed by Western blot. We then compared the immunostimulatory potential of this VP2-expressing strain (CRS208) to that of the original B. subtilis strain (168) on rainbow trout (Oncorhynchus mykiss) leukocytes obtained from spleen, head kidney and the peritoneal cavity. Our results demonstrated that both strains significantly increased the percentage of IgM+ B cells and the number of IgM-secreting cells in all leukocyte cultures. Both strains also induced the transcription of a wide range of immune genes in these cultures, with small differences between them. Importantly, specific anti-IPNV antibodies were detected in fish intraperitoneally or orally vaccinated with the CRS208 strain. Altogether, our results demonstrate B. subtilis spores expressing foreign viral proteins retain their immunomodulatory potential while inducing a significant antibody response, thus constituting a promising vaccination strategy.

Introducción: El Síndrome de Pseudoexfoliación (PEX) es un trastorno genético-hereditario, consiste en el depósito de microfibras de elastina en tejido intra y extraocular. El PEX es una de las causas secundarias identificables más comunes del glaucoma. Varios estudios han asociado el PEX con afecciones sistémicas y se ha descripto el hallazgo de material fibrilar en las estructuras del oído interno, similares al de pseudoexfoliación detectado en el ojo. Objetivo: comparar los niveles de audiométricos en pacientes con y sin PEX ocular. Materiales y Métodos: Estudio retrospectivo de casos y controles. Se seleccionaron 48 historias clínicas de pacientes que asistieron al servicio de oftalmología del Hospital Privado de Córdoba, entre enero del 2015 y diciembre de 2017, de entre 59 y 75 años. Se los dividió en grupos: controles (n=22): sin PEX y casos (n=26): con PEX. Se analizaron las historias clínicas de pacientes a los que se les realizaron estudios oftalmológicos y audiométricos. Para el análisis estadístico se utilizó el test T de Student para muestras independientes y apareadas; en todos los casos se consideró un nivel de significación ≤ 0.05. Resultados: El porcentaje de pérdida auditiva fue del 56,8% en el grupo control y un 82,7% en el grupo PEX. La incapacidad porcentual en el grupo con PEX fue mayor en la audición monoaural (p=0,0008) y biaural (p=0,0307) con respecto a los pacientes sin PEX. Conclusión: Los pacientes con PEX ocular mostraron un porcentaje mayor de hipoacusia, en comparación con aquellos pacientes sin evidencia oftalmológica de PEX.

One of the main known effects of cholesterol is to rigidify the cell membrane throughout the so-called condensing effect. Although many studies have been done in mixtures of cholesterol with different membrane lipids, there are not many studies in a wide concentration range of cholesterol or at physiological conditions. In this work, we studied mixtures of DMPC/Cholesterol monolayers to determine the effect of cholesterol, from very low to physiological concentrations and two pHs. We use a Langmuir balance and Brewster angle microscopy to study their thermodynamic behavior at 37.0 ± 0.1°C at the air/solution interface. From the analysis of the (π−A) isotherms, we determined the excess area and the compressibility elastic modulus to determine the monolayers mechanical properties. Surprisingly, we found three main effects of cholesterol: The first one is a fluidization effect of the monolayer at all cholesterol concentrations. The second effect is the so-called condensing effect that appears due to the non-ideality of the mixture. The third effect is a stiffness of the monolayer as the cholesterol concentration increases. These effects are stronger in pure water, pH ≈ 6.6, than on buffer at physiological pH = 7.4. We also found that all mixtures are thermodynamically stable at all concentrations at a surface pressure of 30.1 ± 1.6 and 27.4 ± 3.2 mN/m in pure water and buffer, respectively. Furthermore, we compared this stability with a fatty acid monolayer that shows a much lower surface pressure equilibrium value that DMPC or its mixtures with cholesterol, indicating a possibly reason why double chain lipids are better than single chain lipids to made up the cell membrane.

Abstract Background Pharyngeal and anorectal reservoirs of gonorrhea (GC) and chlamydia (CT) are increasingly recognized among heterosexual women. While a number of studies performed at sexually transmitted disease (STD) clinics have found a high prevalence of extragenital GC/CT infection, such screening is typically not offered during routine primary care visits for women. We sought to define the prevalence of and factors associated with extragenital GC/CT among women in the U.S. Navy. Methods We recruited servicewomen stationed in San Diego, California, between the ages of 18 and 25 who presented for an annual physical exam between January and September, 2017. Nucleic acid amplification testing was performed on swabs collected at endocervical, oropharyngeal and anorectal sites to assess the presence of GC/CT. An anonymous behavioral questionnaire was also administered to characterize sexual risk. Descriptive statistics were used to compare women with and without a prior history of any sexually transmitted infection (STI) (self-report) along with a current GC/CT diagnosis. This study was approved by the Institutional Review Board of the Uniformed Services University of Health Sciences. Results Of the 75 patients who were approached, 60 subjects were enrolled in the study, including white 20 (33.3%), black/African American 18 (31.0%), Hispanic/Latina 13 (21.7%) and Asian/Pacific Islander 9 (15.5%) women. Among all the women, six (10.0%) were diagnosed with CT infection, all via endocervical exam. Of these, five (8.3%) had concurrent anorectal infection, including two cases (3.3%) accompanied by pharyngeal infection. Of the subjects, 15 (25.0%) reported anal intercourse in their most recent sexual encounter, most of which was condomless (13/15, 86.7%). A high number of women who reported sex with a casual male partner (19/45, 42.2%) reported rarely or never using condoms; last, 41.7% consuming at least 3 drinks on a typical drinking day, and one-third of the reported drinking more than once per week. Conclusions We found a high prevalence of anorectal CT infection, although no infections were detected without concurrent endocervical involvement. Nonetheless, the high prevalence of condomless anal intercourse reported by participants argues for further study and ongoing consideration of extragenital screening among high-risk patients. Behavioral interventions are also warranted given the high prevalence of sexual and related risk factors.

This article assesses the impact on the Power Quality produced by the interconnection of a microgrid to a transmission system, real-time simulation have been used to carry out the study, applying national and international power quality standards, IEEE 1547 of 2018, IEEE 519 of 2014 and NTC 5001 of 2008. The phenomena of voltage harmonics, current harmonics, flicker and DC injection were evaluated on a microgrid case study. The results show that the interconnection of the microgrid produces a high impact on the current harmonics and the DC injection of the local transmission system, while the flicker phenomena and voltage harmonics have a smaller impact.

As coffee consumption is on the rise, and the global coffee production creates an excess of 23 million tons of waste per year, a revolutionary transition towards a circular economy via the transformation and valorization of the main by-products from its cultivation and preparation (Coffee Husk (CH), Coffee Pulp (CP), Coffee Silverskin (CS), and Spent Coffee Grounds (SCG)) is inspiring researchers around the world. The recent growth of scholarly publications in the field and the emerging applications of coffee by-products published in these scientific papers encourages a systematic review to identify the knowledge structure, research hotspots, and to discuss the challenges and future directions. This paper displays a comprehensive scientometric analysis based on 108 articles with a high level of influence in the field of coffee by-products and their applications. According to our analysis, the research in this field shows an explosive growth since 2017, clustered in five core applications: bioactive compounds, microbial transformation, environmental applications, biofuels from thermochemical processes, and construction materials.

Introduction: Cardiovascular parameters disruption can be found in patients at early stages of rheumatoid arthritis (RA). The primary endpoint of this study was the reduction of arterial stiffness in RA patients without traditional cardiovascular risk factors or previous comorbidities, measured by cardio-ankle vascular index (CAVI) through the enalapril intervention. The secondary endpoints were the enalapril influence on carotid femoral pulse wave velocity (cfPWV), carotid intima media thickness (cIMT), carotid artery distensibility (cDistensibility), Young's incremental elastic modulus (Einc)].Materials and Methods: Fifty-three patients were enrolled in a clinical, randomized, closed-label trial. The subjects were randomly assigned into two groups: One receiving 5 mg of enalapril (27) or placebo (26), both twice a day. The drug was acquired at Victory Enterprises®. The placebo was kindly provided by the Universidad de Guadalajara (UdeG), as well as the blinding into two groups: A and B. Enalapril and placebo were packed into bottles without labeling. Clinical assessment included a structured questionnaire to gather demographic and clinical variables as well as determination of CAVI, cfPWV, cIMT, carotid artery distensibility and Einc. The whole set of evaluations were analyzed at the baseline and at the end of 12 weeks of intervention.Results: The CAVI measurement at baseline was 7.1 ± 1.4 and increased up to 7.5 ± 1.2 at the end of 12 weeks. Meanwhile, the enalapril group was as follows: 7.4 ± 1.2 and at the of intervention, reduced to 7.1 ± 0.9. A reduction in delta CAVI of 0.21 in the enalapril intervention group was found. In contrast, an increase of 0.39 was observed in the placebo group. The delta CAVI reduction was not influenced by age or peripheral systolic blood pressure (pSBP).Discussion: Enalapril seems to be effective in CAVI reduction in RA patients. The effect of enalapril intervention on arterial stiffness translated to the clinical context might be interpreted as a reduction of 6.4 years of arterial aging.Trial Registration: The protocol was approved by the Institutional Review Board with the register CI-0117 from UdeG, and 0211/18 from Hospital Civil “Dr. Juan I. Menchaca”, Secretaría de Salud Jalisco: DGSP/DDI/D.INV.28/18 and retrospectively registered at ClinicalTrials.gov Protocol Registration and Results System: NCT03667131.

It is well known that cardiovascular diseases (CVD) are a major contributor of death in systemic lupus erythematosus (SLE) as well in other rheumatic illness. In the last decades, there has been a growing development of different methodologies with the purpose of early detection of CVD.ObjectiveThe aim of this study is to correlate the usefulness of subclinical parameters of vascular aging and QRISK 3-2017 score for early detection of CVD in SLE.MethodsClinical assessment including systemic lupus erythematosus disease activity index (SLEDAI) and systemic lupus international collaborating clinics / american college of rheumatology damage index (SLICC/ACR DI), laboratory measurements, carotid ultrasound examination, carotid intima media thickness (cIMT) measurement, carotid distention and diameter analysis, arterial stiffness measurement measured by tonometry and QRISK 3-2017 were done. All results were analyzed by SPSS 24 software.ResultsWe observed correlation between QRISK3 and mean cIMT (rs = 0.534, P < 0.001), PWV (rs = 0.474, P < 0.001), cfPWV (rs = 0.569, P < 0.001) and distensibility (rs = -0.420, P = 0.006). Consistent with above, SLE patients in middle and high risk QRISK 3-2017 showed increased arterial stiffness versus low risk group.ConclusionsWe encourage to the rheumatology community to assess cardiovascular risk in SLE patients with QRISK 3-2017 risk calculator as an alternative method at the outpatient clinic along a complete cardiovascular evaluation when appropriate.

The following article presents the results obtained in experiences that use the Impulse Frequency Response Analysis (IFRA) method with a transformer in service. The IFRA method has been implemented in order to transform the transient signals to the frequency domain using Discrete Fourier Transform (DFT). However, it can be considered that the DFT is not the most suitable tool for this type of analysis, since, by definition, this tool is useful for processing stationary signals. Taking that into consideration, the analysis of transient signals could be hypothetically improved by using continuous wavelet transform (CWT), given their variable time/frequency resolution. The analysis of transient signals in Wavelet domain has improved the repeatability of the frequency response curves, as it has been ob-served in experimental results. The proposed on-line IFRA method, based on Wavelet transform, was validated under load and no-load conditions on a 150 kVA three-phase transformer 13200/225 Volts, in the Campus of the Universidad del Valle, Cali, Colombia.

Viral haemorrhagic septicaemia virus (VHSV) is one of the worst viral threats to fish farming. Non-virion (NV) gene-deleted VHSV (dNV-VHSV) has been postulated as an attenuated virus, because the absence of the NV gene leads to lower induced pathogenicity. However, little is known about the immune responses driven by dNV-VHSV and the wild-type (wt)-VHSV in the context of infection. Here, we obtained the immune transcriptome profiling in trout infected with dNV-VHSV and wt-VHSV and the pathways involved in immune responses. As general results, dNV-VHSV upregulated more trout immune genes than wt-VHSV (65.6% vs 45.7%, respectively), whereas wt-VHSV maintained more non-regulated genes than dNV-VHSV (45.7% vs 14.6%, respectively). The modulated pathways analysis (Gene-Set Enrichment Analysis, GSEA) showed that, when compared to wt-VHSV infected trout, the dNV-VHSV infected trout upregulated signalling pathways (n = 19) such as RIG-I (retinoic acid-inducible gene-I) like receptor signalling, Toll-like receptor signalling, type II interferon signalling, and nuclear factor kappa B (NF-kappa B) signalling, among others. The results from individual genes and GSEA demonstrated that wt-VHSV impaired the activation at short stages of infection of pro-inflammatory, antiviral, proliferation, and apoptosis pathways, delaying innate humoral response and cellular crosstalk, whereas dNV-VHSV promoted the opposite effects. Therefore, these results might support future studies on using dNV-VHSV as a potential live vaccine.

Kurds from Iraq (Dohuk and Erbil Area, North Iraq) have been analyzed for HLA genes. Their HLA genetic profile has been compared with that of other Kurd groups from Iran and Tbilisi (Georgia, Caucasus) and also Worldwide populations. A total of 7,746 HLA chromosomes have been used. Genetic distances, NJ dendrograms and correspondence analyses have been carried out. Haplotype HLA-B*52-DRB1*15 is present in all three analyzed Kurd populations. HLA-A*02-B*51-DRB1*11 is present in Iraq and Georgia Kurds. Haplotypes common to Iran and Iraq Kurds are HLA DRB1*11-DQB1*03, HLA DRB1*03-DQB1*02 and others in a lower frequency. Our HLA study conclusions are that Kurds most probably belong to an ancient Mediterranean / Middle East / Caucasian genetic substratum and that present results and those previously obtained by us in Kurds may be useful for Medicine in future Kurd transplantation programs, HLA Epidemiology (HLA linked diseases) and Pharmacogenomics (HLA-associated drug side effects) and also for Anthropology. It is discussed that one of the most ancient Kurd ancestor groups is in Hurrians (2,000 years BC).

There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis.The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN).In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN.We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02). Instead, leptin was not associated with LN.These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

Spring viremia carp virus (SVCV) is a rhabdovirus seasonally affecting warm-water cyprinid fish farming causing high impacts in worldwide economy. Because of the lack of effective preventive treatments, the identification of multipath genes involved in SVCV infection might be an alternative to explore the possibilities of using drugs for seasonal prevention of this fish disease. Because the zebrafish (Danio rerio) is a cyprinid susceptible to SVCV and their genetics and genome sequence are well advanced, it has been chosen as a model for SVCV infections. We have used newly designed pathway-targeted microarrays 3-4-fold enriched for immune/infection functional-relevant probes by using zebrafish orthologous to human genes from selected pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG). The comparative analysis of differential expression of genes through 20 pathways in 2-day exposed or 30-day survivors of SVCV infection allowed the identification of 16 multipath genes common to more than 6 pathways. In addition, receptors (Toll-like, B-cell, T-cell, RIG1-like) as well as viral RNA infection pathways were identified as the most important human-like pathways targeted by SVCV infection. Furthermore, by using bioinformatic tools to compare the promoter sequences corresponding to up and downregulated multipath gene groups, we identified putative common transcription factors which might be controlling such responses in a coordinated manner. Possible drug candidates to be tested in fish, can be identified now through search of data bases among those associated with the human orthologous to the zebrafish multipath genes. With the use of pathway-targeted microarrays, we identified some of the most important genes and transcription factors which might be implicated in viral shutoff and/or host survival responses after SVCV infection. These results could contribute to develop novel drug-based prevention methods and consolidate the zebrafish/SVCV as a model for vertebrate viral diseases.

Flagellins evoke strong innate and adaptive immune responses. These proteins may play a key role as radioprotectors, exert antitumoral activity in certain types of tumor and reduce graft-versus-host disease in allogeneic hematopoietic stem cell transplant recipients. Notwithstanding, flagellins are highly immunogenic, and repeated use leads to their neutralization by systemic antibodies. This neutralization is not prevented by using functional deleted flagellins. These observations led us to explore the possibility of preventing initial neutralization by means of another functional flagellin that does not belong to common pathogenic bacteria but that has the capacity to activate TLR5. Here we characterized the functional capacity of the two-phase Marinobacter algicola (MA)-derived flagellins (F and FR) as systemic and mucosal adjuvants and compared their performance with that of Salmonella typhimurium (STF) flagellins (FljB and FliC). We also report for the first time on the in vitro and in vivo capacity of various flagellins to trigger TLR5 activation in the presence of species-specific anti-flagellin antibodies, the cross-neutralization mediated by these antibodies, and the sequential use of these flagellins for TLR5 activation. Our results showed that MA flagellins behave in a similar way to STF ones, inducing pro-inflammatory cytokines (IL8, CCL20, CCL2) and evoking a strong in vivo antibody response against a model epitope. More importantly, MA flagellins were fully functional, in vitro or in vivo, in the presence of a high concentration of neutralizing anti-flagellin STF antibodies, and STF flagellin was not inhibited by neutralizing anti-flagellin MA antibodies. The use of active flagellins from distinct bacteria could be a useful approach to prevent systemic neutralization of this group of adjuvants and to facilitate the rational design of flagellin-based vaccines and/or other therapeutic treatments (against ischemia, acute renal failure, tumors, ionizing radiations and also to improve the outcome of bone marrow transplants).

Control of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age children living in endemic areas. There is limited data on the effectiveness of long-term periodic anthelmintic treatment on the prevalence of STHs, particularly from operational programmes. The current study investigated the impact of 15 to 17 years of treatment with the broad-spectrum anthelmintic ivermectin, used for the control of onchocerciasis, on STH prevalence and intensity in school-age and pre-school children.A cross-sectional study was conducted in communities that had received annual or twice-annual ivermectin treatments and geographically adjacent communities that had not received treatment in two districts of Esmeraldas Province in Ecuador. Stool samples were collected from school-age children and examined for STH infection using the Kato-Katz and formol-ether concentration methods. Samples were collected also from pre-school children and examined by the formol-ether concentration method. Data on risk factors for STH infection were collected by parental questionnaire. We sampled a total of 3,705 school-age children (6-16 years) from 31 treated and 27 non-treated communities, and 1,701 pre-school children aged 0-5 years from 18 treated and 18 non-treated communities. Among school-age children, ivermectin treatment had significant effects on the prevalence (adjusted OR = 0.06, 95% CI 0.03-0.14) and intensity of Trichuris trichiura infection (adjusted RR = 0.28, 95% CI 0.11-0.70), but appeared to have no impact on Ascaris lumbricoides or hookworm infection. Reduced prevalence and intensities of T. trichiura infection were observed among children not eligible to receive ivermectina, providing some evidence of reduced transmission of T. trichiura infection in communities receiving mass ivermectin treatments.Annual and twice-annual treatments with ivermectin over a period of up to 17 years may have had a significant impact on T. trichiura infection. The present data indicate that the long-term control of onchocerciasis with ivermectin may provide additional health benefits by reducing infections with trichuriasis. The addition of a second anthelmintic drug such as albendazole may be useful for a long-term effect on A. lumbricoides infection.