DNA barcoding and morphology reveal European and western Asian Arctiavillica (Linnaeus, 1758) as a complex of species (Lepidoptera, Erebidae, Arctiinae).

Currently, the genus Arctia Schrank, 1802 includes approximately 16 species in the Palaearctic region, depending on the taxonomic interpretation. Here, populations of the Arctiavillica (Linnaeus, 1758) morphospecies complex were studied from Europe to the Middle East (Turkey, northern Iran) by molecular methods. Morphological treatment has traditionally revealed the presence of five nominal taxa: A.villica (Linnaeus, 1758), A.angelica (Boisduval, 1829), A.konewkaii (Freyer, 1831), A.marchandi de Freina, 1983, and A.confluens Romanoff, 1884. The molecular approach tests whether they represent well-delimited species. Subsequently, this study corroborates the suitability of the mitochondrial cytochrome c oxidase subunit 1 (COI) marker sequence for species delimitation. In total, 55 barcodes of the Arctiavillica complex were compared, and two molecular species delimitation algorithms were applied to reveal the potential Molecular Operational Taxonomic Units (MOTUs), namely the distance-based Barcode Index Number (BIN) System, and the hierarchical clustering algorithm based on a pairwise genetic distances approach using the Assemble Species by Automatic Partitioning (ASAP). The applied ASAP distance-based species delimitation method for the analysed dataset revealed an interspecific threshold of 2.0-3.5% K2P distance as suitable for species identification purposes of the Iberian A.angelica and the Sicilian A.konewkaii and less than 2% for the three taxa of the A.villica clade: A.villica, A.confluens, and A.marchandi. This study contributes to a better understanding of the taxonomy of the genus Arctia and challenges future revision of this genus in Turkey, the Caucasus, Transcaucasia as well as northern Iran using standard molecular markers.

Down-Regulation-Resistant STAT4 Risk Haplotype Contributes to Lupus Nephritis Through CD4+ T Cell Interferon-γ Production.

OBJECTIVE: Variants in STAT4 are associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. We undertook this study to investigate how disease-associated variants affect STAT4 expression, in particular in CD4+ T cells where STAT4 plays an essential role. METHODS: We compared Th1 differentiation between naive CD4+ T cells from healthy donors homozygous for the risk (R/R) or nonrisk (NR/NR) alleles. We analyzed epigenetic marks in STAT4 and evaluated the relevance of its third intron, assessed the consequences of Stat4 overexpression in vivo in mice, and analyzed the effects of the STAT4 genotype in patients with lupus nephritis. RESULTS: Naive CD4+ T cells from NR/NR healthy donors down-regulated STAT4 in response to interleukin-12 (IL-12). In contrast, cells from R/R healthy donors maintained high levels. R/R cells exhibited a higher abundance of transcriptionally active STAT4 and increased interferon-γ production. Accordingly, R/R healthy donors exhibited a stronger induction of local active enhancer marks. Genetic editing confirmed the presence of a negative regulatory region in the STAT4 third intron, where most of the SLE-associated STAT4 single-nucleotide polymorphisms (SNPs) are located. In vivo forced expression demonstrated that increases in Stat4 levels in T cells enhanced glomerulonephritis in mice. Accordingly, the R/R genotype was associated with suboptimal response to treatment and with worse clinical outcomes in patients with proliferative lupus nephritis. CONCLUSION: The SLE-associated STAT4 haplotype correlates with an abnormal IL-12-mediated STAT4 transcriptional regulation. Carriers of the risk variant exhibit exaggerated CD4+ proinflammatory capacities that, in the context of SLE, contribute to more severe disease. R/R patients may benefit from blockade of the IL-12/STAT4 pathway.

Significaciones del malestar psíquico en espacios de apoyo mutuo y activismo: Una historia de vida / Meanings for mental distress in mutual support spaces and activism: A life story

Nuestra experiencia y el saber derivado de ella es habitualmente segregado de las prácticas para tratarnos en el ámbito de la salud mental. En este trabajo exploramos qué significados son construidos para la experiencia del malestar psíquico cuando participamos en espacios de apoyo mutuo y activismo. Realizamos una investigación cualitativa, de carácter exploratoria, dentro del marco de los Mad Studies (Estudios Locos) y la Survivor Research (Investigación guiada por sobrevivientes), utilizando como método la historia vida de una activista en salud mental. Analizamos la historia según recomendaciones de la Survivor Research y el análisis narrativo comprensivo. La participante entiende su malestar psíquico como un viaje hacia la recuperación, camino que cursa con esperanza y optimismo. Discutimos estos hallazgos y concluimos que se requiere más investigación para desafiar el modelo biomédico predominante y su hegemonía en la definición de nuestras experiencias de malestar psíquico y/o diversidad psicosocial. (AU)

In mental health our experience and the knowledge derived from it is usually omitted from the practices that are used to treat us. In this work, we explore what meanings are built for the experience of mental distress when we participate in mutual support spaces and activism. We carried out a qualitative and exploratory research following the Mad Studies and the Survivor Research framework. The life story of a mental health activist was used as a method. We considered the Survivor Research recommendations and the comprehensive narrative analysis for the analysis. The participant understands her mental distress as a journey to recovery in which she walks with hope and optimism. We discussed these findings and concluded that more research is required to challenge the prevailing biomedical model and its hegemony in defining our experiences of mental distress and /or psychosocial diversity. (AU)

An annotated checklist of the Pyralidae of the region of Murcia (Spain) with new records, distribution and biological data (Lepidoptera, Pyraloidea, Pyralidae).

Background: The Murcia Region (south-eastern Iberian Peninsula) has a great diversity of Lepidopteran fauna, as a zoogeographical crossroads and biodiversity hotspot with more than 850 butterflies and moth species recorded. New information: In the present paper, based on an examination of museum specimens, published records and new samples, a comprehensive and critical species list of Pyralidae moths (Lepidoptera, Pyraloidea) is synthesised. In total, three subfamilies, 67 genera and 142 species have been recorded and these are listed, along with their collection, literature references and biological data, including chorotype, voltinism and the flight period in the study area. The subfamilies are Galleriinae, Phycitinae and Pyralinae. Seventy-three species are newly recorded, sixty-two species are confirmed from literature and only seven species have not been observed for the Murcia Region.

Molecular Characterization of Imported and Autochthonous Dengue in Northeastern Spain.

Dengue is the most significant arbovirus worldwide and a public health threat to non-endemic areas in which Aedes vectors are present. Autochthonous dengue transmission has been reported in several European countries in the last decade. Infected travelers from endemic regions arriving to areas colonized by Aedes albopictus in Europe need to be monitored in surveillance and control programs. We aimed to perform molecular characterization of RT-PCR-positive dengue cases detected in Catalonia, northeastern Spain, from 2013 to 2018. The basic demographic information and the geographical regions of importation were also analyzed. One-hundred four dengue cases were studied (103 imported infections and the first autochthonous case in our region). The dengue virus strains detected were serotyped and genotyped using molecular methods, and phylogenetic analyses were conducted. All four dengue serotypes were detected in travelers, including up to 10 different genotypes, reflecting the global circulation of dengue in endemic areas. The primary travel-related case of the 2018 autochthonous transmission was not identified, but the molecular analysis revealed dengue serotype 1, genotype I of Asian origin. Our results highlight the diversity of imported dengue virus strains and the role of molecular epidemiology in supporting arbovirus surveillance programs.

An annotated checklist of the Crambidae of the region of Murcia (Spain) with new records, distribution and biological data (Lepidoptera: Pyraloidea, Crambidae).

BACKGROUND: The Murcia Region (osouth-eastern Iberian Peninsula) has a great diversity of Lepidopteran fauna, as a zoogeographical crossroads and biodiversity hotspot with more than 850 butterflies and moth species recorded. NEW INFORMATION: In the present paper, based on an examination of museum specimens, published records and new samples, a comprehensive and critical species list of Crambidae moths (Lepidoptera: Pyraloidea) is synthesised. In total, 8 subfamilies, 50 genera and 106 species have been recorded and these are listed along with their collection, literature references and biological data including chorotype, voltinism and the flight period in the study area. The subfamilies are as follows: Acentropinae, Crambinae, Glaphyriinae, Lathrotelinae, Odontiinae, Pyraustinae, Scopariinae and Spilomelinae. Forty nine species are here newly recorded for the Murcia Region.

Fas/FasL Signaling Regulates CD8 Expression During Exposure to Self-Antigens.

Activation of self-reactive CD8+ T cells induces a peripheral tolerance mechanism that involves loss of CD8 expression. Because genetic deficiency of Fas and Fasl causes the accumulation of double-negative (DN; CD3+ TCR-αß+ CD4- CD8-) T cells that have been proposed to derive from CD8+ cells, we decided to explore the role of Fas and FasL in self-antigen-induced CD8 downregulation. To this end, we quantified Fas and FasL induction by different stimuli and analyzed the effects of Fas/FasL deficiency during a protective immune response and after exposure to self-antigens. Our data describes how Fas and FasL upregulation differs depending on the setting of CD8 T cell activation and demonstrates that Fas/FasL signaling maintains CD8 expression during repetitive antigen stimulation and following self-antigen encounter. Together, our results reveal an unexpected role of Fas/FasL signaling and offer a new insight into the role of these molecules in the regulation of immune tolerance.

Unilateral Orbital Emphysema Secondary to Vitreoretinal Surgery.

PURPOSE: To describe preoperative, intraoperative, and postoperative characteristics, imaging findings, and clinical evolution of patients who developed orbital emphysema after vitreoretinal surgery. DESIGN: Retrospective, descriptive, observational case series. PARTICIPANTS: Patients with orbital emphysema after vitreoretinal surgery who were diagnosed and treated between January 2006 and October 2018 at a single ophthalmology referral center. METHODS: Medical records and orbital computed tomography images were reviewed and analyzed. A minimum follow-up of 3 months was required. MAIN OUTCOME MEASURES: Final best-corrected visual acuity (BCVA). RESULTS: This study included 16 patients with a mean age of 47.9 ± 14.7 years, 50% were women, and 25% had a history of previous ocular trauma. A diagnosis of rhegmatogenous retinal detachment was established in 75% of patients. Twenty-five percent of patients underwent pars plana vitrectomy (PPV), 50% underwent encircling scleral buckling plus PPV, 18.8% underwent repeat PPV, and 6.2% underwent scleral buckling plus repeat PPV. Additionally, 62.5% received silicone oil endotamponade. The median time between vitreoretinal surgery and orbital emphysema was 8 days (interquartile range [IQR] 5-15 days). Mean proptosis was 6.7 ± 4.6 mm. Orbital cellulitis was considered as a differential diagnosis in 31.2% of patients, and tomographic evidence of fracture was observed in 25% of patients. Treatment with compressive patching was prescribed for 87.5% of patients, transpalpebral drainage was prescribed for 75% of patients, hyperbaric oxygen therapy was prescribed for 43.8% of patients, and surgical management was prescribed for 31.2% of patients. The comparison between BCVA before vitreoretinal surgery (median, 1.8 logarithm of the minimum angle of resolution [logMAR]; IQR, 1.33-2.3 logMAR) and at the last follow-up (median, 2.3 logMAR; IQR, 1.42-2.8 logMAR) was not statistically significant (P = 0.125, Wilcoxon matched-pairs signed-rank test). No association was found between surgeon experience and lower final BCVA (P = 0.604, Fisher exact test); however, development of ocular hypertension was associated with worse final BCVA (P = 0.0101; relative risk, 7; 95% confidence interval, 1.01-44.63). CONCLUSIONS: Although orbital emphysema constitutes a very unusual complication of vitreoretinal surgery, it is important to identify this condition promptly and treat patients efficiently to avoid potential vision loss.

Inhibition of ULK1 and Beclin1 by an α-herpesvirus Akt-like Ser/Thr kinase limits autophagy to stimulate virus replication.

Autophagy is a powerful host defense that restricts herpes simplex virus-1 (HSV-1) pathogenesis in neurons. As a countermeasure, the viral ICP34.5 polypeptide, which is exclusively encoded by HSV, antagonizes autophagy in part through binding Beclin1. However, whether autophagy is a cell-type-specific antiviral defense or broadly restricts HSV-1 reproduction in nonneuronal cells is unknown. Here, we establish that autophagy limits HSV-1 productive growth in nonneuronal cells and is repressed by the Us3 gene product. Phosphorylation of the autophagy regulators ULK1 and Beclin1 in virus-infected cells was dependent upon the HSV-1 Us3 Ser/Thr kinase. Furthermore, Beclin1 was unexpectedly identified as a direct Us3 kinase substrate. Although disabling autophagy did not impact replication of an ICP34.5-deficient virus in primary human fibroblasts, depleting Beclin1 and ULK1 partially rescued Us3-deficient HSV-1 replication. This shows that autophagy restricts HSV-1 reproduction in a cell-intrinsic manner in nonneuronal cells and is suppressed by multiple, independent viral functions targeting Beclin1 and ULK1. Moreover, it defines a surprising role regulating autophagy for the Us3 kinase, which unlike ICP34.5 is widely encoded by alpha-herpesvirus subfamily members.

RNA m6 A modification enzymes shape innate responses to DNA by regulating interferon ß.

Modification of mRNA by N6-adenosine methylation (m6A) on internal bases influences gene expression in eukaryotes. How the dynamic genome-wide landscape of m6A-modified mRNAs impacts virus infection and host immune responses remains poorly understood. Here, we show that type I interferon (IFN) production triggered by dsDNA or human cytomegalovirus (HCMV) is controlled by the cellular m6A methyltrasferase subunit METTL14 and ALKBH5 demethylase. While METTL14 depletion reduced virus reproduction and stimulated dsDNA- or HCMV-induced IFNB1 mRNA accumulation, ALKBH5 depletion had the opposite effect. Depleting METTL14 increased both nascent IFNB1 mRNA production and stability in response to dsDNA. In contrast, ALKBH5 depletion reduced nascent IFNB1 mRNA production without detectably influencing IFN1B mRNA decay. Genome-wide transcriptome profiling following ALKBH5 depletion identified differentially expressed genes regulating antiviral immune responses, while METTL14 depletion altered pathways impacting metabolic reprogramming, stress responses, and aging. Finally, we determined that IFNB1 mRNA was m6A-modified within both the coding sequence and the 3' untranslated region (UTR). This establishes that the host m6A modification machinery controls IFNß production triggered by HCMV or dsDNA. Moreover, it demonstrates that responses to nonmicrobial dsDNA in uninfected cells, which shape host immunity and contribute to autoimmune disease, are regulated by enzymes controlling m6A epitranscriptomic changes.

Evolution of the Pseudomonas aeruginosa Aminoglycoside Mutational Resistome In Vitro and in the Cystic Fibrosis Setting.

Inhaled administration of high doses of aminoglycosides is a key maintenance treatment of Pseudomonas aeruginosa chronic respiratory infections in cystic fibrosis (CF). We analyzed the dynamics and mechanisms of stepwise high-level tobramycin resistance development in vitro and compared the results with those of isogenic pairs of susceptible and resistant clinical isolates. Resistance development correlated with fusA1 mutations in vitro and in vivo. pmrB mutations, conferring polymyxin resistance, were also frequently selected in vitro In contrast, mutational overexpression of MexXY, a hallmark of aminoglycoside resistance in CF, was not observed in in vitro evolution experiments.

Close congruence between Barcode Index Numbers (bins) and species boundaries in the Erebidae (Lepidoptera: Noctuoidea) of the Iberian Peninsula.

The DNA barcode reference library for Lepidoptera holds much promise as a tool for taxonomic research and for providing the reliable identifications needed for conservation assessment programs. We gathered sequences for the barcode region of the mitochondrial cytochrome c oxidase subunit I gene from 160 of the 176 nominal species of Erebidae moths (Insecta: Lepidoptera) known from the Iberian Peninsula. These results arise from a research project which constructing a DNA barcode library for the insect species of Spain. New records for 271 specimens (122 species) are coupled with preexisting data for 38 species from the Iberian fauna. Mean interspecific distance was 12.1%, while the mean nearest neighbour divergence was 6.4%. All 160 species possessed diagnostic barcode sequences, but one pair of congeneric taxa (Eublemma rosea and Eublemma rietzi) were assigned to the same BIN. As well, intraspecific sequence divergences higher than 1.5% were detected in four species which likely represent species complexes. This study reinforces the effectiveness of DNA barcoding as a tool for monitoring biodiversity in particular geographical areas and the strong correspondence between sequence clusters delineated by BINs and species recognized through detailed taxonomic analysis.

Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone.

Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators. The extraordinary capacity of P. aeruginosa to develop resistance was evidenced by the emergence of mutations in >100 genes related to antibiotic resistance during the evolution of CC274, catalyzed by mutator phenotypes. While the presence of classical mutational resistance mechanisms was confirmed and correlated with resistance phenotypes, results also showed a major role of unexpected mutations. Among them, PBP3 mutations, shaping up ß-lactam resistance, were noteworthy. A high selective pressure for mexZ mutations was evidenced, but we showed for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa.

Sequential Treatment of Biofilms with Aztreonam and Tobramycin Is a Novel Strategy for Combating Pseudomonas aeruginosa Chronic Respiratory Infections.

Traditional therapeutic strategies to control chronic colonization in cystic fibrosis (CF) patients are based on the use of a single nebulized antibiotic. In this study, we evaluated the therapeutic efficacy and dynamics of antibiotic resistance in Pseudomonas aeruginosa biofilms under sequential therapy with inhaled aztreonam (ATM) and tobramycin (TOB). Laboratory strains PAO1, PAOMS (hypermutable), PAOMA (mucoid), and PAOMSA (mucoid and hypermutable) and two hypermutable CF strains, 146-HSE (Liverpool epidemic strain [LES-1]) and 1089-HSE (ST1089), were used. Biofilms were developed using the flow cell system. Mature biofilms were challenged with peak and 1/10-peak concentrations of ATM (700 mg/liter and 70 mg/liter), TOB (1,000 mg/liter and 100 mg/liter), and their alternations (ATM/TOB/ATM and TOB/ATM/TOB) for 2 (t = 2), 4 (t = 4), and 6 days (t = 6). The numbers of viable cells (CFU) and resistant mutants were determined. Biofilm structural dynamics were monitored by confocal laser scanning microscopy and processed with COMSTAT and IMARIS software programs. TOB monotherapy produced an intense decrease in CFU that was not always correlated with a reduction in biomass and/or a bactericidal effect on biofilms, particularly for the CF strains. The ATM monotherapy bactericidal effect was lower, but effects on biofilm biomass and/or structure, including intense filamentation, were documented. The alternation of TOB and ATM led to an enhancement of the antibiofilm activity against laboratory and CF strains compared to that with the individual regimens, potentiating the bactericidal effect and/or the reduction in biomass, particularly at peak concentrations. Resistant mutants were not documented in any of the regimens at the peak concentrations and only anecdotally at the 1/10-peak concentrations. These results support the clinical evaluation of sequential regimens with inhaled antibiotics in CF, as opposed to the current maintenance treatments with just one antibiotic in monotherapy.

Congenital Upper Eyelid Coloboma: Clinical and Surgical Management.

Purpose. The goal was to describe our experience in the surgical management and treatment of four patients with congenital upper eyelid colobomas. Methods. A descriptive, observational, retrospective study was performed including patients with congenital eyelid colobomas referred to Asociación para Evitar la Ceguera en México I.A.P. "Dr. Luis Sánchez Bulnes" between 2004 and 2014 and assessed by the Oculoplastics and Orbit Service. Results. The four cases required surgical treatment of the eyelid defects before one year of age and their evolution was monitored from the time of referral to the present day. One of the patients needed a second surgical procedure to repair the eyelid defect and correct the strabismus. Conclusions. Eyelid colobomas are a potential threat to vision at an early age, which requires close monitoring of the visual development of patients.

Rotavirus prevents the expression of host responses by blocking the nucleocytoplasmic transport of polyadenylated mRNAs.

Rotaviruses are the most important agent of severe gastroenteritis in young children. Early in infection, these viruses take over the host translation machinery, causing a severe shutoff of cell protein synthesis while viral proteins are efficiently synthesized. In infected cells, there is an accumulation of the cytoplasmic poly(A)-binding protein in the nucleus, induced by the viral protein NSP3. Here we found that poly(A)-containing mRNAs also accumulate and become hyperadenylated in the nuclei of infected cells. Using reporter genes bearing the untranslated regions (UTRs) of cellular or viral genes, we found that the viral UTRs do not determine the efficiency of translation of mRNAs in rotavirus-infected cells. Furthermore, we showed that while a polyadenylated reporter mRNA directly delivered into the cytoplasm of infected cells was efficiently translated, the same reporter introduced as a plasmid that needs to be transcribed and exported to the cytoplasm was poorly translated. Altogether, these results suggest that nuclear retention of poly(A)-containing mRNAs is one of the main strategies of rotavirus to control cell translation and therefore the host antiviral and stress responses.

Congenital smooth muscle hamartoma of the palpebral conjunctiva.

Smooth muscle hamartoma is defined as a disorganized focus or an overgrowth of mature smooth muscle, generally with low capacity of autonomous growth and benign behavior. The implicated tissues are mature and proliferate in a disorganized fashion. A healthy 5-day-old Mexican boy was referred to the authors' hospital in México city for evaluation of a "cystic" lesion of the right eye that had been noted since birth. The pregnancy and delivery were unremarkable. On physical examination, there was a reddish-pink soft lesion with a tender "cystic" appearance, which was probably emerging from the upper eyelid conjunctiva, which measured 2.7 cm in its widest diameter and transilluminated. Ultrasound imaging revealed an anterior "cystic" lesion with normally formed phakic eye. An excisional biopsy was performed, and the lesion was dissected from the upper tarsal subconjunctival space. Subsequent histologic and immunohistochemical findings were consistent with the diagnosis of congenital smooth muscle hamartoma (CSMH) of the tarsal conjunctiva. The authors' research revealed that only one case of CSMH localized in the conjunctiva (Roper GJ, Smith MS, Lueder GT. Congenital smooth muscle hamartoma of the conjunctival fornix. Am J Ophthalmol. 1999;128:643-4) has been reported to date in the literature. To the best of the authors' knowledge, this current case would be the second case reported of CSMH in this anatomic location. Therefore, the authors' recommendation is to include CSMH in the differential diagnosis of a cystic mass that presents in the fornix and palpebral conjunctiva.

Effect of inoculation with Penicillium albidum, a phosphate-solubilizing fungus, on the growth of Trifolium pratense cropped in a volcanic soil.

Volcanic soils in the south of Chile have an elevated quantity of total P, which is scarcely available due to its high P fixation capacity. One strategy for increasing the availability of P for the vegetables that grow there would be to use phosphate-solubilizing microorganisms. In one assay conducted in a greenhouse on a volcanic soil, the effect of inoculation with Penicillium albidum, a phosphate-solubilizing fungus, was studied on the growth of red clover (Trifolium pratense L). Some chemical and biological properties of the soil were also evaluated. There were three treatments: a) active inoculum [In(+)], b) inactive inoculum (autoclaved) [In(-)] and c) without inoculum [In(0)], each one done in three replicates. The In(+) significantly (P < 0.050) increased the growth of the plants, contributing particularly to root development. The P mobilized to the shoot with In(+) was higher than twofold related to In(0) and In(-) treatments; however, the In(+) plants had similar concentration of shoot P. In the soil, available-P was not statistically different (P < 0.050) among the treatments but phosphatase activity in In(+) was higher (P < 0.050) in comparison to In(0). The results suggest that Penicillium albidum contributed to growth and nutrition of the red clover through the induction of root development and enhancing phosphate mobilization from the soil and into the plant. It is concluded that Penicillium albidum, under greenhouse conditions, in soils deficient in available P can increase the inoculation potential for volcanic soils in Chile. Anyway further studies are required, especially in organic farming where the use of soluble P fertilizer is avoided.