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.

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.

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.

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.

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.