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The nature of endometrial morular metaplasia (MorM) is still unknown. The nuclear β-catenin accumulation and the not rare ghost cell keratinization suggest a similarity with hard keratin-producing odontogenic and hair matrix tumors rather than with squamous differentiation. We aimed to compare MorM to hard keratin-producing tumors. Forty-one hard keratin-producing tumors, including 26 hair matrix tumors (20 pilomatrixomas and 6 pilomatrix carcinomas) and 15 odontogenic tumors (adamantinomatous craniopharyngiomas), were compared to 15 endometrioid carcinomas with MorM with or without squamous/keratinizing features. Immunohistochemistry for β-catenin, CD10, CDX2, ki67, p63, CK5/6, CK7, CK8/18, CK19, and pan-hard keratin was performed; 10 cases of endometrioid carcinomas with conventional squamous differentiation were used as controls. In adamantinomatous craniopharyngiomas, the β-catenin-accumulating cell clusters (whorl-like structures) were morphologically similar to MorM (round syncytial aggregates of bland cells with round-to-spindled nuclei and profuse cytoplasm), with overlapping squamous/keratinizing features (clear cells with prominent membrane, rounded squamous formations, ghost cells). Both MorM and whorl-like structures consistently showed positivity for CD10 and CDX2, with low ki67; cytokeratins pattern was also overlapping, although more variable. Hard keratin was focally/multifocally positive in 8 MorM cases and focally in one conventional squamous differentiation case. Hair matrix tumors showed no morphological or immunophenotypical overlap with MorM. MorM shows wide morphological and immunophenotypical overlap with the whorl-like structures of adamantinomatous craniopharyngiomas, which are analogous to enamel knots of tooth development. This suggests that MorM might be an aberrant mimic of odontogenic differentiation. Supplementary Information The online version contains supplementary material available at 10.1007/s00428-021-03060-2.

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O 6-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in well-differentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.

BACKGROUND: Common COVID-19 vaccines side effects are pain at the injection site, muscle pain, fever, headaches, fatigue. Possible immune-related side effects in predisposed individuals have not been established so far. MATERIALS AND METHODS: We report three cases of recurrence of alopecia areata (AA) occurred after the first dose of COVID-19 vaccine. RESULTS: All patients had previous episodes of AA with total hair regrowth and stable remission during the months preceding the vaccination. Rapid hair loss occurred 2-3 weeks after BNT162b2 mRNA (patient 1) and AZD1222/ChAdOx1 vaccine (patient 2 and 3), with widespread hair loss in two cases and a single patch of the vertex in one case, with typical trichoscopic features of AA. DISCUSSION: Both BNT162b2 mRNA and AZD1222/ChAdOx1 vaccines share the same goal of inducing the immune system, with antibodies production and Th1 cells activation with release of pro-inflammatory cytokines. Thus, in patients with pre-existing inflammatory dysregulated pathways, the interaction between the immune system and vaccines may enhance other autoimmune mechanisms. In our cases, we speculate that vaccine may have induced the hair loss focusing on components having a key role in both COVID-19 vaccination and AA pathogenesis. CONCLUSION: This report may help to collect new data concerning possible immune-related effects of vaccines. Certainly, only three cases are not sufficient to draw conclusion, thus a large-scale study is necessary. Immune-mediated side effects remain a rare event, thus the benefits of COVID-19 vaccines outweigh the risk of disease flares and we strongly recommend it in all eligible patients with AA.

Contains fulltext : 244896.pdf (Publisher’s version ) (Closed access) BACKGROUND: Over the last decade, advances in genetic techniques have resulted in the identification of rare hereditary disorders of renal magnesium and salt handling. Nevertheless, approximately 20% of all patients with tubulopathy lack a genetic diagnosis. METHODS: We performed whole-exome and -genome sequencing of a patient cohort with a novel, inherited, salt-losing tubulopathy; hypomagnesemia; and dilated cardiomyopathy. We also conducted subsequent in vitro functional analyses of identified variants of RRAGD, a gene that encodes a small Rag guanosine triphosphatase (GTPase). RESULTS: In eight children from unrelated families with a tubulopathy characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis, we identified heterozygous missense variants in RRAGD that mostly occurred de novo. Six of these patients also had dilated cardiomyopathy and three underwent heart transplantation. We identified a heterozygous variant in RRAGD that segregated with the phenotype in eight members of a large family with similar kidney manifestations. The GTPase RagD, encoded by RRAGD, plays a role in mediating amino acid signaling to the mechanistic target of rapamycin complex 1 (mTORC1). RagD expression along the mammalian nephron included the thick ascending limb and the distal convoluted tubule. The identified RRAGD variants were shown to induce a constitutive activation of mTOR signaling in vitro. CONCLUSIONS: Our findings establish a novel disease, which we call autosomal dominant kidney hypomagnesemia (ADKH-RRAGD), that combines an electrolyte-losing tubulopathy and dilated cardiomyopathy. The condition is caused by variants in the RRAGD gene, which encodes Rag GTPase D; these variants lead to an activation of mTOR signaling, suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function. 01 november 2021

The cape gooseberry (Physalis peruviana) is a Solanaceae species with enormous economic importance in Colombia; it is the second most exported fruit, after bananas. Vascular wilt caused by Fusarium oxysporum f. sp. physali (Fox) is the most limiting factor of this crop, with losses of up to 80% of production. Biological control is a promising alternative for controlling this pathogen. Bacteria and fungi, originally isolated from potentially suppressive soils of cape gooseberry crops in Nariño, Colombia with different management (organic and conventional), were evaluated as biocontrol agents of Fox using a gnotobiotic model (seedlings cultured under axenic conditions with defined microbial strains). Of the 64 isolated microorganisms, 37.5% (15 bacteria and 9 fungi) were discarded because of toxicological risks and an unknow potential biological control. The remaining 62.5% of the microorganisms, 14 bacteria and 26 fungi, were evaluated to assess their potential as biological control agents against Fox. The gnotobiotic model system evaluated the protection and plant growth promotion characteristics. Response variables were used to group the microorganism using a principal component analysis (PCA), and five clusters were obtained. Cluster number four concentrated the 10 microorganisms (three bacteria and seven fungi) with the highest protection values against Fox, with a positive effect on growth. The isolates were identified as two Bacillus subtilis strains, Rhodococcus sp., Podospora setosa, Debaryomyces vindobonensis, Plectosphaerella plurivora, Acinetobacter rhizosphaerae, Umbelopsis sp. and two strains of Trichoderma koningiopsis. The gnobiotic system offered clear advantages for evaluating and selecting microorganisms with a biological control potential against Fusarium oxysporum f. sp. physalis. RESUMEN La uchuva (Physalis peruviana) es Solanaceae de enorme importancia económica en Colombia ya que es la segunda fruta más exportada después del banano. La marchitez vascular causada por Fusarium oxysporum f. sp. physali (Fox) es el factor más limitante de este cultivo, que ocasiona pérdidas de hasta el 80% de su producción. El control biológico se ha convertido en una alternativa prometedora para controlar este patógeno. Bacterias y hongos, originalmente aislados de suelos potencialmente supresores de cultivos de uchuva de Nariño, Colombia con diferente manejo (orgánico y convencional) fueron evaluados como agentes de control de Fox utilizando un modelo gnotobiótico (plántulas cultivadas en condiciones axiológicas con cepas microbianas definidas). A partir de los 64 microorganismos aislados, 37.5% (15 bacterias y nueve hongos) fueron descartados debido a su riesgo toxicológico y a un control biológico potencial desconocido, el 62.5% restante de microorganismos, 14 bacterias y 26 hongos, se evaluaron para evaluar su potencial como agentes de control biológico contra Fox. El sistema de modelos gnotobióticos nos permitió evaluar las características de protección y promoción del crecimiento vegetal, estas variables de respuesta se utilizaron para agrupar el microorganismo utilizando un análisis de componentes principales (PCA) y se obtuvieron cinco clústeres. El clúster número cuatro concentró 10 microorganismos (tres bacterias y siete hongos) con los valores de protección más altos contra Fox y con un efecto positivo en la promoción del crecimiento. Los aislados fueron identificados como dos cepas de Bacillus subtilis, Rhodococcus sp., Podospora setosa, Debaryomyces vindobonensis, Plectosphaerella plurivora, Acinetobacter rhizosphaerae, Umbelopsis sp. y dos cepas de Trichoderma koningiopsis. El sistema gnobiótico presentado ofrece claras ventajas para evaluar y seleccionar microorganismos con un potencial de control biológico contra Fusarium oxysporum f. sp. fisalis.

Comparative studies indicate that several mammalian clades obey Gloger’s rule in that they exhibit darker coloration in humid warm climates, although the mechanisms responsible for this association still are poorly understood. We surveyed external appearances of a single species, the feral pig (Sus scrofa), shot at 48 hunting lodges across North America and matched these to potential abiotic drivers, namely: relative humidity, temperature, precipitation, and ultraviolet (UV) radiation, and to biotic factors of habitat shade and predation pressure. We found that darker animals occupy locations of greater precipitation and warmer temperatures, as expected from Gloger’s rule. The recent range expansion of S. scrofa implies selection for pelage coloration has occurred very rapidly. Separating pelage coloration into eumelanin- and phaeomelanin-based pigmentation, we found more pronounced eumelanin-based pelage in areas of higher rainfall and temperatures and UV radiation, whereas pelage phaeomelanin is related to cool dry climates with lower UV radiation. This implies that humidity or UV protection but not crypsis are the mechanisms underlying Gloger’s rule in this species and the factors driving eumelanin and phaeomelanin expression in mammalian pelage are different, reinforcing new interpretations of this venerable rule.

Background Data regarding yeast microbiota in goat milk is scarce. Aims To isolate and identify species of the genus Candida in milk samples from clinically healthy goats, and evaluate their enzymatic activity and biofilm formation. Methods 1092 milk samples from clinically healthy goats were collected and processed. The yeast isolates were identified by phenotypic, methods and their enzymatic activity (phospholipase, hemolysin and protease) and biofilm formation evaluated. Results We obtained 221 Candida isolates belonging to six species: Candida kefyr (35.7%), Candida guilliermondii (33%), Candida famata (23.5%), Candida glabrata (5.9%), Candida albicans (1.35%) and Candida parapsilosis sensu lato (0.45%). Protease activity was detected in all Candida species while hemolysin activity was only present in C. kefyr, C. guilliermondii, C. famata and C. albicans. Only C. albicans showed phospholipase activity. With the exception of C. parapsilosis sensu lato, all Candida species formed biofilm, with 60.19% of the isolates being poor producers, 9.93% moderate producers, and 1.35% strong producers. Conclusions The milk of clinically healthy goats contains several species of the genus Candida that could play a role as opportunistic pathogens in mastitis.

The rapid and precise detection of diseases and plant disorders is the basis for the adequate and timely design of management strategies. Currently, there are several non-destructive alternatives that allow early detection, highlighting the use of spectral cameras attached to unmanned aerial vehicles (UAVs). The objective of this research was to evaluate the use of multispectral cameras on UAVs to discriminate vascular wilt caused by Verticillium spp., (VW), waterlogging stress (WL), and an unknown alteration (UA) in commercial potato (Solanum tuberosum) variety “Diacol Capiro” crops. Plots were monitored during the crop cycle, performing the visual characterization of the diseases and disorders present. Five spectral band images were acquired using a MicaSense RedEdge spectral camera attached to a Map-T680 hexacopter drone to extract the bands and calculate the vegetation indices that were calibrated and evaluated to determine their ability to discriminate between diseased and healthy plants based on a generalized linear model (GLM) and Kappa index. Additionally, the supervised random forest classification method was implemented, optimized, and evaluated using the accuracy, area under receiver operating characteristic curve (ROC-AUC), kappa index, and inference error based on k-fold cross-validation. After algorithms optimization our results show a classifier accuracy, kappa and ROC-AUC values to VW, WL and UA between 73.5–82.5%, 0.56–0.71, 0.97–0.98, and 35 37.5–51.9%, 0.07–0.06, and 0.88–0.94 for plots 1 and 2, respectively. This study reports an approach to the use of multispectral cameras attached to UAVs as a tool with potential for the detection of diseases and physiological disorders in commercial potato crops.

En este artículo se contrastan los resultados del proyecto de investigación, “Análisis de una muestra representativa de los relatos presentados al Concurso Nacional de Cuento Gabriel García Márquez (2007)”, con tres referentes importantes: La Revolución Educativa, que prevé las metas de desarrollo de la educación colombiana; los Lineamientos y Estándares del área de Lenguaje, que proporcionan el marco de trabajo para los docentes, y la evaluación masiva por competencias (pruebas SABER). Este ejercicio permite comprobar la distancia que existe entre lo deseable y el desempeño real de los estudiantes en la producción de textos escritos.

Background COVID‐19 convalescent plasma (CCP) ideally contains high titers of (neutralizing) anti‐SARS‐CoV‐2 antibodies. Several scalable immunoassays for CCP selection have been developed. We designed an enzyme‐linked immunosorbent assay (ELISA) that measures neutralizing antibodies (of all isotypes) in plasma by determining the level of competition between CCP and a mouse neutralizing antibody for binding to the receptor binding domain (RBD) of SARS‐CoV‐2. Methods Plasma was collected from 72 convalescent individuals and inhibition of viral infection was determined by plaque reduction neutralization (PRNT50). The level of neutralizing antibodies was measured in the novel competition ELISA and in a commercially available ELISA that measures inhibition of recombinant ACE2 binding to immobilized RBD. These results were compared with a high throughput chemiluminescent microparticle immunoassay (CMIA). Results The results from both ELISAs were correlating, in particular for high titer CCP (PRNT50 ≥ 1:160) (Spearman r = .73, p

Martina Spaziante,1 Carolina Venditti,2 Ornella Butera,2 Francesco Messina,2 Antonino Di Caro,2 Gilda Tonziello,1 Simone Lanini,1 Maria Adriana Cataldo,1 Vincenzo Puro1 1Emerging Infection Unit and Regional Service for Surveillance and Control of Infectious Diseases (SeRESMI), National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy; 2Laboratory of Microbiology, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, ItalyCorrespondence: Maria Adriana Cataldo Tel +39 0655170786Email adriana.cataldo@inmi.itIntroduction: New Delhi metallo-β-lactamase producing Klebsiella pneumoniae (NDM-Kpn) strains have been causing healthcare-associated infections worldwide. The aim of this study was to describe the molecular mechanisms of antimicrobial resistance and to analyze the clonality of NDM-Kpn isolates collected between January 2019 and June 2020 from patients admitted to hospitals from the Lazio region, Italy.Methods: We performed a retrospective cohort study. Whole-genome sequencing (WGS) was performed on all NDM-Kpn strains; clonality and genetic relationships were further investigated.Results: During the surveillance period, 17 NDM-Kpn isolates were obtained from 17 patients admitted to seven different hospitals. Eight different sequence types (STs) were detected: ST147 (n = 4), ST383 (n = 4), ST15 (n = 3), ST11 (n = 2), ST17 (n = 1), ST29 (n = 1), ST307 (n = 1) and the newly identified ST4853 (n = 1). Genetic relationships were further investigated by the WGS-based core genome MLST (cgMLST) scheme, and 5 cluster types (CTs) were identified. Whereas a substantial overall heterogeneity among isolates was detected (8 different STs were identified out of 17 isolates), the strains within each cluster showed a very high level of genome similarity.Discussion: Our study highlights the key role of surveillance, which allowed taking a picture of a part of the NDM-Kpn strains circulating in Italy, adding further insight into their molecular features.Keywords: carbapenem-resistant Klebsiella pneumoniae, New Delhi metallo-β-lactamase, surveillance, healthcare-associated infections

The objective was to determine the adequate dose of silicon foliar fertilization, to obtain a higher yield in pea crops. Regarding the methodology, the research is applied and experimental; Therefore, the Completely Random Block Design comprised of 4 blocks and 4 treatments was used, which were: T1 = 0, T2 = 0.50 L, T3 = 0.75 L and T4 = 1 L Silicon (Sil Trade) / 200 L of water Applied in four times, it is worth mentioning the chemical ingredient of silicon is orthosilicic acid. The physical characteristics from sowing to harvest were evaluated and the silicon concentrations in leaves were analyzed by treatment. Obtained data were processed by analysis of variance and Duncan. The results determined that T4 stood out in plant height with 89.74 cm, number of pods per plant with 37, weight of pods per plant with 234.43 g, yield with 4444.4 kg/ha and silicon concentration in leaves with 1.75 g/100 g of dry material. It is concluded that there were no silicon effects; that is, it did not statistically influence the physical characteristics. However, T4 with 1 L Silicon (Sil Trade) / 200 L of water increased 8.58% of the yield in relation to T1.

The macroinvertebrates associated with algae casts light on the possibility of coevolution in a specific environmental context. The understanding of how biological and environmental factors could favor, or limit such interactions and represent an important step for the comprehension of river socio-ecology dynamics. The aim of this study is to establish convergences and recurrent relationships between the most frequent algal groups and associated macroinvertebrates in temperate and tropical rivers from Mexico and Spain. We collected algal population from sixteen rivers, identifying that environmental factors and the algae characteristics that influence the biotic associations with macroinvertebrates and their implications in conservation from a biological and functional perspective. We found that habitat preference is guided by algae as a provider of food and shelter and that environmental factors were secondary. Paralemanea and Lemanea spp. (Rodophyta) recorded the greatest structural complexity, promoting more diverse but less specific associations, which could be a factor that limits co-evolution. Conversely, Phormidium and Nostoc (Cyanobacteria) recorded less diversity but greater specificity; in particular, Cricotopus (Chironomidae) was dominant, suggesting a recurrent association with the possibility of coupled life cycles. The algal structural complexity was the preponderant factor in determining the specificity of associated macroinvertebrates. The associations were in turn related to a river’s specific environmental context, for example, Nostoc and Cricotopus were characteristic of oligotrophic waters, while Paralemanea and Lemanea with Hydroptilidae and Hydrobiosidae (Trichoptera) were recurrent in meso-eutrophic waters. Changes in aquatic ecosystem quality can affect the establishment of populations of algae and insects, affecting species conservation and coexistence relationships mediated by evolutionary coupling events.

Objective This study aimed to determine the relation between titres of anti-Porphyromonas gingivalis (P. gingivalis) antibody and rheumatoid arthritis (RA) HLA-DRB1 susceptibility region associated with shared epitope (SE) using the Gregersen's and de Vries's classification methods. Material and methods In this cross-sectional study, results of immunoglobulin G1 (IgG1) and immunoglobulin G2 (IgG2) anti-P. gingivalis antibodies, anti-citrullinated protein antibodies (ACPA), diagnosis for RA, and periodontal disease (PD), and a genetic study of the HLA DRB1 region were obtained from 50 patients with RA and 50 control individuals. Results Anti-P. gingivalis antibody levels and PD parameters were similar in control and RA groups. Anti-P. gingivalis antibodies were not associated with SE or ACPA. There was no association between ACPA and SE. However, de Vries' classification in RA patients revealed an association between the HLA DRB1 neutral alleles and higher titres of anti-P. gingivalis antibodies as follows: IgG1 anti-P. gingivalis ≥ 1:400 (p = .039); IgG2 anti-P. gingivalis ≥ 1:400 with neutral/neutral genotype (N/N), being exclusive for RA (p = .008); and IgG2 anti-P. gingivalis ≥ 1:200 and N/N (p = .016). Conclusions Although no association was found between SE and anti-P. gingivalis antibodies; according to the de Vries' classification, there was an existing association between HLA DRB1 neutral alleles, with high titres of IgG anti-P.gingivalis antibodies for RA, focussing on novel associations between P.gingivalis and RA.

Summary Background The pathogenesis of infant colic is poorly defined. Gut microbiota seems to be involved, supporting the potential therapeutic role of probiotics. Aims To assess the rate of infants with a reduction of ≥50% of mean daily crying duration after 28 days of intervention with the probiotic Bifidobacterium animalis subsp. lactis BB‐12® (BB‐12). Secondary outcomes were daily number of crying episodes, sleeping time, number of bowel movements and stool consistency. Methods Randomized controlled trial (RCT) on otherwise healthy exclusively breastfed infants with infant colic randomly allocated to receive BB‐12 (1 × 109 CFU/day) or placebo for 28 days. Gut microbiota structure and butyrate, beta‐defensin‐2 (HBD‐2), cathelicidin (LL‐37), secretory IgA (sIgA) and faecal calprotectin levels were assessed. Results Eighty infants were randomised, 40/group. The rate of infants with reduction of ≥50% of mean daily crying duration was higher in infants treated with BB‐12, starting from the end of 2nd week. No infant relapsed when treatment was stopped. The mean number of crying episodes decreased in both groups, but with a higher effect in BB‐12 group (−4.7 ± 3.4 vs −2.3 ± 2.2, P

Acremonium strictum elicitor subtilisin (AsES) is a 34-kDa serine-protease secreted by the strawberry fungal pathogen A. strictum. On AsES perception, a set of defence reactions is induced, both locally and systemically, in a wide variety of plant species and against pathogens of alternative lifestyles. However, it is not clear whether AsES proteolytic activity is required for triggering a defence response or if the protein itself acts as an elicitor. To investigate the necessity of the protease activity to activate the defence response, AsES coding sequences of the wild-type gene and a mutant on the active site (S226A) were cloned and expressed in Escherichia coli. Our data show that pretreatment of Arabidopsis plants with inactive proteins, i.e. inhibited with phenylmethylsulphonyl fluoride (PMSF) and mutant, resulted in an increased systemic resistance to Botrytis cinerea and expression of defence-related genes in a temporal manner that mimics the effect already reported for the native AsES protein. The data presented in this study indicate that the defence-eliciting property exhibited by AsES is not associated with its proteolytic activity. Moreover, the enhanced expression of some immune marker genes, seedling growth inhibition and the involvement of the co-receptor BAK1 observed in plants treated with AsES suggests that AsES is being recognized as a pathogen-associated molecular pattern by a leucine-rich repeat receptor. The understanding of the mechanism of action of AsES will contribute to the development of new breeding strategies to confer durable resistance in plants. Fil: Caro, María del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; Argentina Fil: Holton, Nicholas. University of East Anglia; Reino Unido Fil: Conti, Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina Fil: Venturuzzi, Andrea Laura. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina Fil: Martinez Zamora, Martin Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; Argentina Fil: Zipfel, Cyril. University of East Anglia; Reino Unido. Universitat Zurich; Suiza Fil: Asurmendi, Sebastian. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina Fil: Diaz Ricci, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Biológica; Argentina

Sexually dimorphic development is responsible for some of the most remarkable phenotypic variation found in nature. Alternative splicing of the transcription factor gene doublesex (dsx) is a highly conserved developmental switch controlling the expression of sex-specific pathways. Here, we leverage sex-specific differences in butterfly wing color pattern to characterize the genetic basis of sexually dimorphic development. We use RNA-seq, immunolocalization, and motif binding site analysis to test specific predictions about the role of dsx in the development of structurally based ultraviolet (UV) wing patterns in Zerene cesonia (Southern Dogface). Unexpectedly, we discover a novel duplication of dsx that shows a sex-specific burst of expression associated with the sexually dimorphic UV coloration. The derived copy consists of a single exon that encodes a DNA binding but no protein-binding domain and has experienced rapid amino-acid divergence. We propose the novel dsx paralog may suppress UV scale differentiation in females, which is supported by an excess of Dsx-binding sites at cytoskeletal and chitin-related genes with sex-biased expression. These findings illustrate the molecular flexibility of the dsx gene in mediating the differentiation of secondary sexual characteristics.

Nematodes play an important role in agricultural soil in terms of their pest status and their contribution to soil quality, where they may serve as a valuable indicator of soil health. The aim of the study was to assess changes occurring in nematode community structure, as affected by soil tillage applied to high N-input and irrigated pastures in South Africa. Such practices were investigated by means of analysing diversity and ecosystem function indices, as well as the faunal profile, to enable analysis of their effect on soil quality. The pre-treatment soil analyses showed a low overall mean nematode density. No clear and predictable pattern was present in the nematode community structure in relation to tillage. The lack of indicative information leading from the nematode community structure to the tillage disturbance types might be linked to the fact that such systems were able to recover from soil disturbance within the relatively short period of less than a year.

Background In Tunisia a first SARS-CoV-2 confirmed case was reported in March 03, 2020. Since then, an increase of cases number was observed from either imported or local cases. The aim of this preliminary study was to better understand the molecular epidemiology and genetic variability of SARS-CoV-2 viruses circulating in Tunisia and worldwide. Methods Whole genome sequencing was performed using NGS approach on six SARS. CoV-2 highly positive samples detected during the early phase of the outbreak. Results Full genomes sequences of six Tunisian SARS-CoV-2 strains were obtained from imported and locally transmission cases during the COVID-19 outbreak. Reported sequences were non-identical with 0.1% nucleotide divergence rate and clustered into 6 different clades with worldwide sequences. SNPs results favor the distribution of the reported Tunisian sequences into 3 major genotypes. These SNP mutations are critical for diagnosis and vaccine development. Conclusions These results indicate multiple introductions of the virus in Tunisia and add new genomic data on SARS-CoV-2 at the international level.

Primates are noted for their varied and complex pelage and bare skin coloration but the significance of this diverse coloration remains opaque. Using new updated information, novel scoring of coat and skin coloration, and controlling for shared ancestry, we reexamined and extended findings from previous studies across the whole order and the five major clades within it. Across primates, we found (i) direct and indirect evidence for pelage coloration being driven by protective coloration strategies including background matching, countershading, disruptive coloration, and aposematism, (ii) diurnal primates being more colorful, and (iii) the possibility that pelage color diversity is negatively associated with female trichromatic vision; while (iv) reaffirming avoidance of hybridization driving head coloration in males, (v) darker species living in warm, humid conditions (Gloger’s rule), and (vi) advertising to multiple mating partners favoring red genitalia in females. Nonetheless, the importance of these drivers varies greatly across clades. In strepsirrhines and cercopithecoids, countershading is important; greater color diversity may be important for conspecific signaling in more diurnal and social strepsirrhines; lack of female color vision may be associated with colorful strepsirrhines and platyrrhines; whereas cercopithecoids obey Gloger’s rule. Haplorrhines show background matching, aposematism, character displacement, and red female genitalia where several mating partners are available. Our findings emphasize several evolutionary drivers of coloration in this extraordinarily colorful order. Throughout, we used coarse but rigorous measures of coloration, and our ability to replicate findings from earlier studies opens up opportunities for classifying coloration of large numbers of species at a macroevolutionary scale.

Unmitigated spread in Brazil Despite an extensive network of primary care availability, Brazil has suffered profoundly during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Using daily data from state health offices, Castro et al. analyzed the pattern of spread of COVID-19 cases and deaths in the country from February to October 2020. Clusters of deaths before cases became apparent indicated unmitigated spread. SARS-CoV-2 circulated undetected in Brazil for more than a month as it spread north from Sã o Paulo. In Manaus, transmission reached unprecedented levels after a momentary respite in mid-2020. Faria et al. tracked the evolution of a new, more aggressive lineage called P.1, which has 17 mutations, including three (K417T, E484K, and N501Y) in the spike protein. After a period of accelerated evolution, this variant emerged in Brazil during November 2020. Coupled with the emergence of P.1, disease spread was accelerated by stark local inequalities and political upheaval, which compromised a prompt federal response. Science , abh1558 and abh2644, this issue p. 821 and p. 815

An important aspect of plant-virus interaction is the way viruses dynamically move over long distances and how plant immunity modulates viral systemic movement. Salicylic acid (SA), a well-characterized hormone responsible for immune responses against virus, is activated through different transcription factors including TGA and WRKY. In tobamoviruses, evidence suggests that capsid protein (CP) is required for long-distance movement, although its precise role has not been fully characterized yet. Previously, we showed that the CP of Tobacco Mosaic Virus (TMV)-Cg negatively modulates the SA-mediated defense. In this study, we analyzed the impact of SA-defense mechanism on the long-distance transport of a truncated version of TMV (TMV ∆CP virus) that cannot move to systemic tissues. The study showed that the negative modulation of NPR1 and TGA10 factors allows the long-distance transport of TMV ∆CP virus. Moreover, we observed that the stabilization of DELLA proteins promotes TMV ∆CP systemic movement. We also characterized a group of genes, part of a network modulated by CP, involved in TMV ∆CP long-distance transport. Altogether, our results indicate that CP-mediated downregulation of SA signaling pathway is required for the virus systemic movement, and this role of CP may be linked to its ability to stabilize DELLA proteins.

Offspring across the animal kingdom have evolved a variety of vocalizations, postures and structural ornaments to help them solicit more food from their parents. These signals are typically assumed to convey information about offspring state that helps parents decide which offspring to feed, and the dominant framework holds that begging is a signal of need. However, species differ both in how they beg and how they respond to begging, and signalling theory has been unable to account for this variation. In this thesis, I use a combination of comparative, observational and theoretical data to explore how the degree of within-family conflict leads to differences in parent-offspring signalling systems both across and within bird species. I also explore the possibility that some signalling systems function differently because the information they transmit is not cryptic. Specifically: 1) I show that offspring signals of need are more likely to evolve in species living in predictable and/or unusually good environments, while signals or cues of quality are more likely to evolve in unpredictable and/or unusually poor environments, when conflict over food is greater because brood reduction is probable; 2) I show that the same patterns hold within-species, indicating that parents can facultatively adjust their responsiveness based on the risk of brood reduction; 3) I show that offspring signals of need are less honest when sibling competition is greater, due to offspring number and/or relatedness; 4) I argue, using a simple game, that signals of non-cryptic condition can be stable if signalling provides an efficiency benefit compared to parents’ using cues; and 5) I provide a potential example of such a signal in nature, gape size, and show that its honesty fluctuates based on local conditions.

Background Large woodpecker species with stable territories, specialized diets and narrow habitat choices, such as the Magellanic Woodpecker (Campephilus magellanicus), are expected to adjust their movements based on the distribution of available resources within territories. Thus, Magellanic Woodpeckers should concentrate foraging activity in areas of higher quality, a behavior consistent with the area-restricted search (ARS) behavior. Although previous studies have deepened the understanding of how Magellanic woodpeckers select habitats, the assessment of ARS behavior would contribute to the identification of feeding areas important for their conservation and habitats hindering their movement. Methods We addressed the independent effects of tree senescence, forest succession, stand composition and open habitats on the adoption of area-restricted search (ARS) behavior in Magellanic Woodpeckers in a heterogeneous landscape dominated by southern beech forest in southern South America. Using GPS relocations from 24 woodpeckers, we estimated the First-Passage Time (FPT), a measure of the time individuals remain in a given area, with longer FPT values indicating the adoption of an ARS behavior. We determined the effects of habitat variables on FPT using a methodological framework based on Linear Mixed Effect models and a randomization procedure intended to reduce spatial autocorrelation arising from consecutive circles whose areas tend to be overlapped along trajectories. Results Averaged model coefficients showed that woodpeckers spent less time in sites dominated by the Antarctic beech (Nothofagus antarctica) and partially covered by open habitats. Conversely, FPT increased in stands and home ranges where tree senescence was higher. Conclusions The adoption of the ARS behavior in Magellanic Woodpecker is explained by forest composition, avoidance of open habitats and tree senescence. Our results suggest the conservation of Magellanic Woodpeckers in heterogeneous landscapes involve retention of senescent trees and restoring open areas in order to reduce edge habitat.

This study aimed to determine the influence of sorghum ensiled with unsalable pumpkin at 20 or 40% dry matter (DM) basis on rumen fermentation characteristics and rumen microbial communities using the rumen simulation technique (RUSITEC). The experiment used a completely randomised design including silages comprising (1) 100% sorghum; (2) 80% sorghum + 20% DM pumpkin; or (3) 60% sorghum + 40% DM pumpkin. Each RUSITEC run (n = 2) was 15 d long, including 6 d of adaptation and 9 d of sampling. Dry matter digestibility (DMD) was measured on d 8 and 10-13. Gas production was measured daily, whereas methane and volatile fatty acids (VFA) production were measured from d 7-15. Solid-associated microbes (SAM) were collected on d 5, 10 and 15, whereas liquid-associated microbes (LAM) were collected after 15-d incubation. The V4 region of the 16S rRNA gene and the ITS1 region were sequenced to identify archaeal, bacterial and fungal communities. Ensiling 40% DM pumpkin with sorghum increased DMD and decreased the ratio of acetate to propionate (P ≤ 0.01). Both bacterial SAM and LAM communities were dominated by Megasphaera, and had the highest relative abundance (P = 0.03) with 40% DM pumpkin after 5 d incubation in the SAM community, while species of the Aspergillus genus dominated fungal SAM and LAM communities with 20 or 40% DM unsalable pumpkin. Therefore, ensiling up to 40% DM unsalable pumpkin with sorghum produces a high-quality ruminant feed with minimal influence on the rumen microbial population. KEY POINTS: • Including 40% DM unsalable pumpkin decreased acetate:propionate • Ensiling unsalable pumpkin with sorghum increases digestibility in a RUSITEC • Rumen microbial communities were slightly influenced by unsalable pumpkin inclusion.

This study revises the taxonomy and species limits of Chondrina taxa living in the Cantabrian mountain region of N Spain, based mainly on molecular data but supplemented with morphological data. On...

Similarly to HLA class I molecules, certain non-classical HLA class I genes and MHC class I polypeptide-related sequences A and B (MICA and MICB) act as ligands for KIR and NKG2D natural killer receptors. Although these genes are less polymorphic than HLA class I, few studies have analyzed their association with diseases. Information on allele frequencies in healthy donors is needed to map their distribution worldwide. This study is the first to analyze high-resolution HLA-G, HLA-F, MICA, and MICB allele frequencies using a novel high-throughput next generation-sequencing method. We analyzed DNA samples from 96 unrelated blood donors resident in Catalonia, Spain, and registered in the Barcelona Blood and Tissue Bank. Using the first two fields of the HLA nomenclature, we detected six HLA-G and two HLA-F alleles. The most frequent alleles were HLA-G*01:01 (77.08%) and HLA-F*01:01(84.90%). When the four fields were analyzed, we detected 16 and 10 alleles, respectively. Nineteen alleles were detected for MICA and 10 for MICB. The most frequent alleles in these cases were MICA*008:01 (16.15%) and MICB*005:02 (46.84%). All frequencies were in Hardy Weinberg equilibrium except MICA. We also estimated maximum-likelihood haplotype frequencies and calculated corresponding linkage disequilibrium (LD) values and found that few allele pairs were in disequilibrium. Strong LD between MICA and HLA-B (using data from a previous study) was observed. Our findings will be useful for guiding further research evaluating the functional role of these genes in different diseases and populations.

Aims Alterations in excitability represent an early hallmark in Amyotrophic Lateral Sclerosis (ALS). Therefore, deciphering the factors that impact motor neuron (MN) excitability offers an opportunity to uncover further aetiopathogenic mechanisms, neuroprotective agents, therapeutic targets, and/or biomarkers in ALS. Here, we hypothesized that the lipokine lysophosphatidic acid (lpa) regulates MN excitability via the G-protein-coupled receptor lpa1 . Then, modulating lpa1 -mediated signalling might affect disease progression in the ALS SOD1-G93A mouse model. Methods The influence of lpa-lpa1 signalling on the electrical properties, Ca2+ dynamic, and survival of MNs was tested in vitro. Expression of lpa1 in cultured MNs and in the spinal cord of SOD1-G93A mice was analysed. ALS mice were chronically treated with a small-interfering RNA against lpa1 (siRNAlpa1 ) or with the lpa1 inhibitor AM095. Motor skills, MN loss, and lifespan were evaluated. Results AM095 reduced MN excitability. Conversely, exogenous lpa increased MN excitability by modulating task1 "leak" potassium channels downstream of lpa1 . Lpa-lpa1 signalling evoked an excitotoxic response in MNs via voltage-sensitive calcium channels. Cultured SOD1-G93A MNs displayed lpa1 upregulation and heightened vulnerability to lpa. In transgenic mice, lpa1 was upregulated mostly in spinal cord MNs before cell loss. Chronic administration of either siRNAlpa1 or AM095 reduced lpa1 expression at least in MNs, delayed MN death, improved motor skills, and prolonged life expectancy of ALS mice. Conclusions These results suggest that stressed lpa-lpa1 signalling contributes to MN degeneration in SOD1-G93A mice. Consequently, disrupting lpa1 slows down disease progression. This highlights LPA1 signalling as a potential target and/or biomarker in ALS.

Most primates live in lowland ecosystems; however, some species have been particularly successful at colonizing higher altitudes, such as night monkeys (genus Aotus). Studies of the ecology of night monkeys in tropical forests are numerous, but behavioral data are limited due to the challenges associated with their nocturnal habits. Although Andean night monkeys (A. lemurinus) live in mountain forests >1000 m.a.s.l. and Caribbean night monkeys (A. griseimembra) live in rainforests

The rapid spread of SARS-CoV-2 and the resulting pandemic has led to a spasmodic search for approaches able to limit the diffusion of the disease. The epigenetic machinery has aroused considerable interest in the last decades, and much evidence has demonstrated that this type of modification could regulate the early stages of viral infection. Recently it was reported that N6-methyladenosine (m6A) influences SARS-CoV-2 replication, although its role remains to be further investigated. The knockdown of enzymes involved in the m6A pathway could represent an optimal strategy to deepen the epigenetic mechanism. In the present study, we blocked the catalytic activity of the fat mass and obesity-associated protein (FTO) by using the selective inhibitor rhein. We observed a strong broad-spectrum reduction of infectivity caused by various coronaviruses, including SARS-CoV-2. This effect could be due to the modulation of m6A levels and could allow identification of this modification as a new therapeutic target to treat SARS-CoV-2 infection.

Background Exhausted sugar beet pulp pellets (ESBPP) were used as raw material for lactic acid (LA) fermentation. The enzymatic hydrolysis of ESBPP was performed with the solid obtained after the fungal solid-state fermentation of ESBPP as a source of hydrolytic enzymes. Subsequently, a medium rich in glucose and arabinose was obtained, which was used to produce LA by fermentation. For LA production, two Lactobacillus strains were assayed and the effect of the supplementation of the hydrolysate with a nitrogen source and the mode of pH regulation of the fermentation were investigated. Moreover, a kinetic model for lactic acid fermentation by Lactobacillus plantarum on ESBPP hydrolysates was developed. Results L. plantarum produced a LA concentration 34 % higher than Lactobacillus casei. The highest LA concentration (30 g L-1 ) was obtained with L. plantarum when the hydrolysate was supplemented with 5 g L-1 of yeast extract and the pH was controlled with CaCO3 . The concentration of acetic acid differed depending on the concentration of CaCO3 added, producing its maximum value with 27 g L-1 of CaCO3 . The proposed kinetic model was able to predict the evolution of substrates and products depending on the variation of the pH in the hydrolysate, according to the amount of CaCO3 added. Conclusion ESBPP can be revalorized to produce lactic acid. A pure LA stream or a mixture of lactic and acetic acid, depending on the pH control method of the fermentation, can be produced. Thus, this control shows a great interest depending on the destination of the effluent. This article is protected by copyright. All rights reserved.

Rationale: We recently demonstrated that the Metabesity factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1-CoREST complex but its expression pattern and function in adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. Methods: HMG20A expression profile was assessed by quantitative PCR (QT-PCR), Western blotting and/or immunofluorescence in: 1) the hypothalamus of mice exposed or not to either a high-fat diet or a high-fat high-sucrose regimen, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals and 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-Treated astrocytes. The impact of ORY100. An Inhibitor Of The LSD1-CoREST Complex, On Hmg20a Expression, Reactive Astrogliosis And Glucose Metabolism Was Evaluated In Vitro And In Vivo In High-Fat High-Sucrose Fed Mice. Results: We Show That Hmg20a Is Predominantly Expressed In Hypothalamic Astrocytes, The Main Nutrient-Sensing Cell Type Of The Brain. Hmg20a Expression Was Upregulated In Diet-Induced Obesity And Glucose Intolerant Mice, Correlating With Increased Transcript Levels Of Gfap And Il1b Indicative Of Inflammation And Reactive Astrogliosis. Hmg20a Transcript Levels Were Also Increased In Adipose Tissue Of Obese Non-Diabetic Individuals As Compared To Obese Diabetic Patients. Hmg20a Silencing In Astrocytes Resulted In Repression Of Inflammatory, Cholesterol Biogenesis And Epithelial-To-Mesenchymal Transition Pathways Which Are Hallmarks Of Reactive Astrogliosis. Accordingly, Hmg20a Depleted Astrocytes Exhibited Reduced Mitochondrial Bioenergetics And Increased Susceptibility To Apoptosis. Neuron Viability Was Also Hindered In HMG20A-Depleted Astrocyte-Derived Conditioned Media. Ory1001 Treatment Rescued Expression Of Reactive Astrogliosis-Linked Genes In Hmg20a Ablated Astrocytes While Enhancing Cell Surface Area, Gfap Intensity And Stat3 Expression In Healthy Astrocytes, Mimicking The Effect Of Hmg20a. Furthermore, Ory1001 Treatment Protected Against Obesity-Associated Glucose Intolerance In Mice Correlating With A Regression Of Hypothalamic Hmg20a Expression, Indicative Of Reactive Astrogliosis Attenuation With Improved Health Status. Conclusion: Hmg20a Coordinates The Astrocyte Polarization State. Under Physiological Pressure Such As Obesity And Insulin Resistance That Induces Low Grade Inflammation, Hmg20a Expression Is Increased To Induce Reactive Astrogliosis In An Attempt To Preserve The Neuronal Network And Re-Establish Glucose Homeostasis. Nonetheless, A Chronic Metabesity State Or Functional Mutations Will Result In Lower Levels Of Hmg20a, Failure To Promote Reactive Astrogliosis And Increase Susceptibility Of Neurons To Stress-Induced Apoptosis. Such Effects Could Be Reversed By Ory1001 Treatment Both In Vitro And In Vivo, Paving The Way For A New Therapeutic Approach For Type 2 Diabetes Mellitus., The authors are supported by grants from the Consejería de Salud, Fundación Pública Andaluza Progreso y Salud, Junta de Andalucía (PI-0727-2010 and PI-0001-2020 to B.R.G.; PI-0085-2013 to P.I.L.; PI-0006-2016 to E.F.M.; PI-0574-2012 to S.Y.R.Z; PI-0247-2016 to F.J.B.S.), the Consejería de Economía, Innovación y Ciencia (P10.CTS.6359 to B.R.G.; CTS.8081 to E.G.F.), the Ministerio de Economía y Competitividad co-funded by Fondos FEDER (PI10/00871, PI13/00593 and BFU2017-83588-P to B.R.G.; PRE2018-084907 to M.E.M.V.G.; PI13/00309; PI17/01004 to F.J.B.S.; BFU2014-5343-P to J.C.R.; and AGL2017-86927-R to F.M.), Vencer el Cancer (B.R.G), DiabetesCero (B.R.G.) and the Juvenile Diabetes Research Foundation (17-2013-372 and 2-SRA-2019-837-S-B to B.R.G.). E.F.M. was a recipient of a Juan de la Cierva Incorporación Fellowship from the Ministerio de Economía y Competitividad (IJCI-2015-26238). S.Y.R.Z is a recipient of a postdoctoral fellowship from Consejería de Salud, Junta de Andalucía (RH-0070-2013). L.L.N. is supported by a Consejeria de Economia, Conocimiento, Empresas y Universidad postdoctoral fellowship (DOC_00652). F.J.B.S. and E.G.F. are recipients of "Nicolás Monardes" research contracts from Consejería de Salud Junta de Andalucía, (C-0070-2012 and C-0031-2016). A.M.M. is supported by CPII19/00023 and PI18/01590 from the Instituto de Salud Carlos III co-funded by Fondos FEDER. CIBERDEM is an initiative of the Instituto de Salud Carlos III. V.C. is supported by a AECC investigator award.

DNA analysis can have great practical application in the management and successful operation of the farm. The application of DNA technology is becoming a tremendous challenge for farm breeding of domestic animals. In recent years, traditional selection methods have been supplement by the results of molecular analysis of the genome. Determining the genetic distance of sheep and goat breeds had practical and multiple significance. Microsatellites are used widely in the selection, and genomic selection is becoming an increasing challenge for breeders. The development of SNP chips brings an immense advanced for rapid and comprehensive analysis of the genome, which is of great importance for the successful selection and Genomic selection in sheep concentrated on all aspects of genetic and production directions. However, it should be noted that genomic selections in sheep breeding, and especially in goat breeding, take place at a slower pace compared to cattle breeding.

Convergence of virulence and antibiotic-resistance has been reported in Klebsiella pneumoniae, but not in Klebsiella variicola. We, hereby, report the detection and genomic characterization of hypervirulent and hypermucoviscous K. pneumoniae and K.variicola recovered in Chile from health-care associated infections, which displayed resistance to broad-spectrum cephalosporins. One hundred forty-six K. pneumoniae complex isolates were screened by hypermucoviscosity by the “string test.” Two hypermucoid isolates, one hypermucoviscous K. pneumoniae (hmKp) and one K. variicola (hmKv), were further investigated by whole-genome sequencing. In vivo virulence was analyzed by the Galleria mellonella killing assay. In silico analysis of hmKp UCO-494 and hmKv UCO-495 revealed the presence of multiple antibiotic-resistance genes, such as blaCTX-M-1, blaDHA-1 and blaLEN-25 among others clinically relevant resistance determinants, including mutations in a two-component regulatory system related to colistin resistance. These genetic features confer a multidrug-resistant (MDR) phenotype in both strains. Moreover, virulome in silico analysis confirmed the presence of the aerobactin gene iutA, in addition to yersiniabactin and/or colicin V encoding genes, which are normally associated to high virulence in humans. Furthermore, both isolates were able to kill G. mellonella and displayed higher virulence in comparison with the control strain. In summary, the convergence of virulence and the MDR-phenotype in K. pneumoniae complex members is reported for the first time in Chile, denoting a clinical problem that deserves special attention and continuous surveillance in South America.

Adesmia trijuga es un arbusto espinoso, micrófilo, nativo, perenne; crece entre 1100-3000 m snm, en regiones montañosas de quebradas húmedas o zonas áridas y rocosas; vulgarmente es conocida como “cuerno de cabra”, “añagua” o “suncho”. A. trijuga es polimórfica de hojas pinnadas con 3-5 pares de folíolos, forrajera, utilizada como leña y de amplia distribución en Argentina y Chile. Los antecedentes se refieren únicamente a la citogenética de poblaciones de la Región de Cuyo. El objetivo fue caracterizar los parámetros micrográficos vegetativos, histoquímica y citogenética de A. trijuga en poblaciones del NOA. Se recolectaron, al azar, 5 individuos en poblaciones ubicadas en Jujuy, Salta y Tucumán. El material fue fijado en FAA y herborizado; se aplicaron técnicas anatómicas, histoquímicas y citogenéticas convencionales. Los resultados evidenciaron hojas paripinadas, micrófilas, con folíolos de lámina entera, simétrica, obovada y venación pinnada-camptódroma-eucamptódroma. Foliolos anfistomáticos, pubescentes en ambas epidermis, con tricomas eglandulares y glandulares de 3 tipos; células epidérmicas isodiamétricas a rectangulares de paredes rectas a curvas con cutícula estriada; estomas anomocíticos, hemibraquiparacítico, braquiparacítico, anfibraquiparacítico, hemianfibraquiparacítico y hemianficiclocítico; mesofilo equilateral; haces vasculares colaterales con casquete de esclerénquina hacia floema y vaina parenquimática. Pecíolo subcircular, con tricomas eglandulares y glandulares idénticos a los de la lámina; 2-3 estratos de clorénquima en empalizada subepidermico; 5 haces vasculares colaterales. Espinas circulares con tricomas idénticos a los de la lámina y el pecíolo, crecimiento secundario con abundante esclerénquima. Tubos e idioblastos con fenoles se presentan en el mesofilo de la hoja, médula del pecíolo y en la espina. El número cromosómico fue de 2n=20 cromosomas. Los elementos de valor diagnóstico son: tipo de tricomas, cantidad y posición del tejido de sostén, idioblastos y tubos productores de fenoles y el número cromosómico.

Los cromosomas holocinéticos carecen de una constricción primaria y se encuentra mayormente en insectos, entre ellos el orden Dermaptera, comúnmente conocido como “tijeretas”. Los integrantes del género Doru son depredadores de plagas en cultivos de maíz, caña de azúcar y algodón, que se distribuyen ampliamente en Sudamérica. En Argentina se encuentran dos especies: D. lineare (Eschs.) y D. luteipes (Scudder). El material se recolectó en la provincia de Tucumán (Argentina). Para teñir los cromosomas se aplicaron técnicas citogenéticas clásicas, así como el método fluorescente DAPI. El análisis comparativo entre D. luteipes y D. lineare reveló que ambos taxones tienen fórmula haploide n = 10 (9A + XY) y 2n = 20. Además, se encontraron numerosas irregularidades meióticas y se observaron cromosomas holocinéticos sin constricción primaria que varían gradualmente en tamaño. Se presenta por primera vez información citogenética para D. luteipes, se realizan las primeras descripciones de los cariotipos para ambas especies y se discute el posible origen poliploide del género.

Objectives Progression-free survival (PFS) and response rate to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) varies in patients with non-small-cell lung cancer (NSCLC) driven byEGFR mutations, suggesting that other genetic alterations may influence oncogene addiction. Low BRCA1 mRNA levels correlate with longer PFS in erlotinib-treated EGFR-mutant NSCLC patients. Since the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, may attenuate and/or prevent BRCA1 expression, the addition of olaparib to gefitinib could improve outcome in EGFR-mutant advanced NSCLC. Materials and methods GOAL was a multicenter, randomized phase IB/II study performed in two countries, Spain and Mexico. Eligible patients were 18 years or older, treatment-naive, pathologically confirmed stage IV NSCLC, with centrally confirmed EGFR mutations and measurable disease. Patients were randomly allocated (1:1) to receive gefitinib 250 mg daily or gefitinib 250 mg daily plus olaparib 200 mg three times daily in 28-day cycles. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), response rate, safety and tolerability. Results Between September 2013, and July 2016, 182 patients underwent randomization, 91 received gefitinib and 91 received gefitinib plus olaparib. There were no differences in gender, age, smoking status, performance status, presence of bone and brain metastases or type ofEGFR mutation. Median PFS was 10.9 months (95 % CI 9.3–13.3) in the gefitinib arm and 12.8 months (95 % CI 9.1–14.7) in the gefitinib plus olaparib arm (HR 1.38, 95 % CI 1.00–1.92; p = 0.124). The most common adverse events were anemia, 78 % in gefitinib plus olaparib group, 38 % in gefitinib arm, diarrhea, 65 % and 60 %, and fatigue, 40 % and 32 %, respectively. Conclusions The gefitinib plus olaparib combination did not provide significant benefit over gefitinib alone. The combination’s safety profile showed an increase in hematological and gastrointestinal toxicity, compared to gefitinib alone, however, no relevant adverse events were noted.

Using seeds to restore natural ecosystems has a greater chance of success if the seeds used are ready to germinate given appropriate environmental conditions. For Australian native Poaceae species, seed quality and dormancy can impose constraints on restoration success. In this study, germination biology of three Australian native Poaceae species, such asCymbopogon refractus,Capillipedium spicigerumandBothriochloa bladhii, was investigated. The seeds were exposed to different germination-enhancing chemicals (GECs, namely smoke water (SW), potassium nitrate (KNO3) or a combination (SW + KNO3)) and treated with three different seed enhancement technologies (SETs, namely seed priming, seed coating or seed cookies) then sown into two contrasting soil types (sodosol or black vertisol). Laboratory germination percentages achieved were C. refractusandC. spicigerum, priming and/or coating with KNO3+ SW had the highest cumulative emergence. ForB. bladhii, total seedling emergence was the highest (36% in both soils) for primed seeds with KNO3. Seedling emergence from seed cookies was low in all three species (

RESUMEN Con el objetivo de describir las características genómicas relacionadas con la resistencia antimicrobiana y genómica comparativa de Escherichia coli diarreogénica (DEC), se sometieron a secuenciamiento genómico catorce aislamientos de DEC del banco de cepas del Instituto Nacional de Salud (INS). Las secuencias obtenidas se analizaron mediante procedimientos bioinformáticos a fin de buscar genes de resistencia microbiana y regiones genéticas relacionadas con patotipos y filogrupos. Se detectaron diversos determinantes de resistencia antimicrobiana, se destaca la producción de betalactamasas y mutaciones asociadas a la resistencia a quinolonas. Además, se observaron aislamientos de un mismo patotipo agrupados en distintos filogrupos. El análisis de genómica comparativa mostró un mayor número de genes ortólogos en aislamientos que pertenecían al mismo patotipo y filogrupo. Sobre la base de lo estudiado, los aislamientos de DEC en Lima, Perú, presentan resistencia a múltiples fármacos, y se detectaron varios patotipos y filogrupos con diversidad molecular y filogenética. ABSTRACT In order to describe the genomic characteristics related to antimicrobial resistance and comparative genomics of diarrheagenic Escherichia coli (DEC), 14 DEC isolates from the strain collection of the Instituto Nacional de Salud (INS) were subjected to genome sequencing. We used bioinformatic procedures to analyze the obtained sequences in order to look for microbial resistance genes and genetic regions related to pathotypes and phylogroups. Several antimicrobial resistance determinants were detected, but the production of beta-lactamases and mutations associated to quinolone resistance were the most relevant. Additionally, we observed isolates of the same pathotype grouped in different phylogroups. The comparative genomics analysis showed a greater number of orthologous genes in isolates from the same pathotype and phylogroup. In conclusion, DEC isolates from Lima, Peru, showed resistance to multiple drugs; likewise, molecular and phylogenetic diversity was observed in several pathotypes and phylogroups.

The coconut crab Birgus latro, the largest terrestrial decapod, is under threat in most parts of its geographical range. Its life cycle involves two biomes (restricted terrestrial habitats near the coast, and salt water currents of the tropical Indian and Pacific Oceans). Its dependence on coastal habitat means it is highly vulnerable to the habitat destruction that typically accompanies human population expansion along coastlines. Additionally, it has a slow reproductive rate and can reach large adult body sizes that, together with its slow movement when on land, make it highly susceptible to overharvesting. We studied the distribution and population changes of coconut crabs at 15 island sites in coastal Tanzania on the western edge of the species' geographical range. Our aim was to provide the data required for reassessment of the extinction risk status of this species, which, despite indications of sharp declines in many places, is currently categorized on the IUCN Red List as Data Deficient. Pemba Island, Zanzibar, in Tanzania, is an important refuge for B. latro but subpopulations are fragmented and exploited by children and fishers. We discovered that larger subpopulations are found in the presence of crops and farther away from people, whereas the largest adult coconut crabs are found on more remote island reserves and where crabs are not exploited. Remoteness and protection still offer hope for this species but there are also opportunities for protection through local communities capitalizing on tourist revenue, a conservation solution that could be applied more generally across the species' range.

In Western countries, Cryptosporidium parvum infection is considered a rare opportunistic parasitic disease, most commonly seen in immunocompromised patients. Although most cases have been described in Acquired ImmunoDeficiency Syndrome (AIDS) patients, an increase of cases in other immunocompromised patients has been noted. We hereby describe the case of two patients from our institution in Northern France with heavily pre-treated multiple myeloma, both of whom underwent allogeneic stem cell transplants, who presented late Cryptosporidium infections while treated on novel agents. These cases illustrate novel examples of infection in multiple myeloma as survival improves and novel treatment approaches are being applied.

Biologists usually pursue the adaptationist paradigm in trying to explain the functional significance of animal coloration. Here I collate instances in which coloration may be a poor match in the context of background matching, Batesian mimicry, aposematism, and colour polymorphisms. This can occur because of trade-offs with other functions, relaxed selection from predation, or colour trait neutrality. Also, mechanistic, pleiotropic and chance genetic effects can all result in a poor match to the background environment or to signaling efficiently. While biologists implicitly recognise these constraints placed on adaptive coloration, they rarely explicitly acknowledge the heterodox notion that coloration might be under weak selection or no selection at all. Unfortunately, it is difficult to show this definitively, as illustrated in an investigation into the function of colour polymorphisms in coconut crabs.