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Diffuse large B-cell lymphoma (DLBCL) with aberrant coexpression of CD10+BCL6+MUM1+ (DLBCL-AE), classified as germinal center B cell (GCB) type by the Hans algorithm (HA), was genetically characterized. To capture the complexity of DLBCL-AE, we used an integrated approach that included gene expression profiling (GEP), fluorescence in situ hybridization, targeted gene sequencing, and copy number (CN) arrays. According to GEP, 32/54 (59%) cases were classified as GCB-DLBCL, 16/54 (30%) as activated B-cell (ABC) DLBCL, and 6/54 (11%) as unclassifiable. The discrepancy between HA and GEP was 41%. Three genetic subgroups were identified. Group 1 included 13/50 (26%) cases without translocations and mainly showing and ABC/MCD molecular profile. Group 2 comprised 11/50 (22%) cases with IRF4 alterations (DLBCL-IRF4), frequent mutations in IRF4 (82%) and NF-κB pathway genes (MYD88, CARD11, and CD79B), and losses of 17p13.2. Five cases each were classified as GCB- or ABC-type. Group 3 included 26/50 (52%) cases with 1 or several translocations in BCL2/BCL6/MYC/IGH, and GCB/EZB molecular profile predominated. Two cases in this latter group showed complex BCL2/BCL6/IRF4 translocations. DLBCL-IRF4 in adults showed a similar copy number profile and shared recurrent CARD11 and CD79B mutations when compared with LBCL-IRF4 in the pediatric population. However, adult cases showed higher genetic complexity, higher mutational load with frequent MYD88 and KMT2D mutations, and more ABC GEP. IRF4 mutations were identified only in IRF4-rearranged cases, indicating its potential use in the diagnostic setting. In conclusion, DLBCL-AE is genetically heterogeneous and enriched in cases with IRF4 alterations. DLBCL-IRF4 in adults has many similarities to the pediatric counterpart.

Aims Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that, in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four such cases, two of which regressed spontaneously. Methods and results All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein-Barr virus (EBV)-positive with type I latency. Investigation of the TME showed similar features in all four cases. The analysis revealed a proinflammatory response triggered by Th1 lymphocytes and M1 polarised macrophages encircling the neoplastic cells with a peculiar topographic distribution. Conclusions Our data provide an in-vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights into new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy.

16 Pág. Departamento de ​Mejora Genética Animal, ROHs are long stretches of DNA homozygous at each polymorphic position. The proportion of genome covered by ROHs and their length are indicators of the level and origin of inbreeding. Frequent common ROHs within the same population define ROH islands and indicate hotspots of selection. In this work, we investigated ROHs in a total of 1131 pigs from 20 European local pig breeds and in three cosmopolitan breeds, genotyped with the GGP Porcine HD Genomic Profiler. plink software was used to identify ROHs. Size classes and genomic inbreeding parameters were evaluated. ROH islands were defined by evaluating different thresholds of homozygous SNP frequency. A functional overview of breed-specific ROH islands was obtained via over-representation analyses of GO biological processes. Mora Romagnola and Turopolje breeds had the largest proportions of genome covered with ROH (~1003 and ~955 Mb respectively), whereas Nero Siciliano and Sarda breeds had the lowest proportions (~207 and 247 Mb respectively). The highest proportion of long ROH (>16 Mb) was in Apulo-Calabrese, Mora Romagnola and Casertana. The largest number of ROH islands was identified in the Italian Landrace (n = 32), Cinta Senese (n = 26) and Lithuanian White Old Type (n = 22) breeds. Several ROH islands were in regions encompassing genes known to affect morphological traits. Comparative ROH structure analysis among breeds indicated the similar genetic structure of local breeds across Europe. This study contributed to understanding of the genetic history of the investigated pig breeds and provided information to manage these pig genetic resources., This work has been funded by University of Bologna RFO 2016-2019 programs and by the European Union’s Horizon 2020 research and innovation programme (TREASURE project – grant agreement no. 634476). The content of this work reflects only the authors’ view and the European Union Agency is not responsible for any use that may be made of the information it contains.

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm with a heterogeneous clinical and biological behavior. SOX11 oncogenic expression contributes to the aggressiveness of these tumors by different mechanisms, including tumor and stromal cell interactions. However, the precise composition of the immune cell microenvironment of MCL, its possible relationship to SOX11 expression, and how it may contribute to tumor behavior is not well known. Here, we performed an integrative transcriptome analysis of 730 immune-related genes combined with the immune cell phenotype analysis by immunohistochemistry in SOX11+ and SOX11− primary nodal MCL cases and non-neoplastic reactive lymph nodes. SOX11+ MCL had a significant lower T-cell intratumoral infiltration compared with negative cases. A reduced expression of MHCI/II-like and T-cell costimulation and signaling activation related transcripts was significantly associated with poor clinical outcome. Moreover, we identified CD70 as a SOX11 direct target gene, whose overexpression was induced in SOX11+, but not SOX11− tumor cells by CD40L in vitro. CD70 was overexpressed in primary SOX11+ MCL and it was associated with an immune unbalance of the tumor microenvironment characterized by increased number of effector regulatory T (Treg) cell infiltration, higher proliferation, and aggressive clinical course. CD27 was expressed with moderate to strong intensity in 76% of cases. Overall, our results suggest that SOX11 expression in MCL is associated with an immunosuppressive microenvironment characterized by CD70 overexpression in tumor cells, increased Treg cell infiltration and downmodulation of antigen processing, and presentation and T-cell activation that could promote MCL progression and represent a potential target for tailored therapies.

Anemia is a common complication of chronic kidney disease, affecting the quality of life of patients. Among various factors, such as iron and erythropoietin deficiency, reduced red blood cell (RBC) lifespan has been implicated in the pathogenesis of anemia. However, mechanistic data on in vivo RBC dysfunction in kidney disease are lacking. Herein, we describe the development of chronic kidney disease-associated anemia in mice with proteinuric kidney disease resulting from either administration of doxorubicin or an inducible podocin deficiency. In both experimental models, anemia manifested at day 10 and progressed at day 30 despite increased circulating erythropoietin levels and erythropoiesis in the bone marrow and spleen. Circulating RBCs in both mouse models displayed altered morphology and diminished osmotic-sensitive deformability together with increased phosphatidylserine externalization on the outer plasma membrane, a hallmark of RBC death. Fluorescence-labelling of RBCs at day 20 of mice with doxorubicin-induced kidney disease revealed premature clearance from the circulation. Metabolomic analyses of RBCs from both mouse models demonstrated temporal changes in redox recycling pathways and Lands’ cycle, a membrane lipid remodeling process. Anemic patients with proteinuric kidney disease had an increased proportion of circulating phosphatidylserine-positive RBCs. Thus, our observations suggest that reduced RBC lifespan, mediated by altered RBC metabolism, reduced RBC deformability, and enhanced cell death contribute to the development of anemia in proteinuric kidney disease.

One of the main health problems in cattle farming is infestations caused by ticks. The most important species is Rhipicephalus microplus, which affects 80% of bovine population worldwide. Its control is mainly based on the use of ixodicides. However, excessive and inappropriate use has generated multi-resistant strains of ticks. Alternatively, immune control has been proposed as an important method to reduce tick populations. The recombinant Bm86 vaccine is the only commercially available and reports variations in its efficacy due to polymorphisms in the gene's coding sequence. Therefore, this work aimed to characterize an immunogenic region of Bm86 strain R. microplus "Media Joya" to propose a vaccine candidate that is conserved and with minimal variability in its efficacy. Computational tools, molecular biology techniques, and phylogenetic analysis were used. As a result, an immunogenic region consisting of 178 amino acids and 98-100% identity/similarity were obtained concerning strains of R. microplus ticks from the Americas. Furthermore, is necessary to evaluate the immunoprotective potential of the Bm86 region characterized in this work as an anti-tick vaccine.

BACKGROUND In situ follicular neoplasia (ISFN) is a t(14;18)(q32;q21)+ precursor lesion of follicular lymphoma (FL), which in turn can transform into diffuse large B‑cell lymphoma (DLBCL). For DLBCL that arise de novo, no precursor lesion is known. Given the high frequency of the t(14;18) translocation in de novo DLBCL as well, we investigated whether they can also arise from ISFN without FL as an intermediate step. OBJECTIVES To investigate the clonal evolution of ISFN to DLBCL - transformed from FL and de novo. MATERIALS AND METHODS Identification of ISFN lesions in patients with DLBCL was performed by BCL2 staining of reactive lymphoid tissues. ISFN and DLBCL were subsequently analyzed by fluorescence in situ hybridization, clonality analyses, sequencing of the t(14;18) breakpoint, and targeted next-generation sequencing. RESULTS 10 cases with paired ISFN and DLBCL samples were identified, 6 of which were de novo DLBCL and 4 transformed from FL. 3 DLBCL carried MYC-rearrangements in addition to the t(14;18) and were classified as high-grade B‑cell lymphoma (HGBL). The clonal relationship of ISFN and DLBCL/HGBL was confirmed for all cases. CREBBP, KMT2D, EZH2, TNFRSF14, and BCL2 were the genes most frequently mutated, with the distribution of private and shared mutations pointing to 2 different scenarios of clonal evolution. In most cases, DLBCL/HGBL, ISFN, and, if also present, FL had evolved divergently from a common progenitor, whereas linear evolution was less frequent. CONCLUSION We show for the first time that t(14;18)+ DLBCL/HGBL can arise directly from ISFN without FL as an intermediate step and that during this progression, divergent evolution is common.

Background The gut microbiota influences host performance playing a relevant role in homeostasis and function of the immune system. The aim of the present work was to identify microbial signatures linked to immunity traits and to characterize the contribution of host-genome and gut microbiota to the immunocompetence in healthy pigs. Results To achieve this goal, we undertook a combination of network, mixed model and microbial-wide association studies (MWAS) for 21 immunity traits and the relative abundance of gut bacterial communities in 389 pigs genotyped for 70K SNPs. The heritability (h2; proportion of phenotypic variance explained by the host genetics) and microbiability (m2; proportion of variance explained by the microbial composition) showed similar values for most of the analyzed immunity traits, except for both IgM and IgG in plasma that was dominated by the host genetics, and the haptoglobin in serum which was the trait with larger m2 (0.275) compared to h2 (0.138). Results from the MWAS suggested a polymicrobial nature of the immunocompetence in pigs and revealed associations between pigs gut microbiota composition and 15 of the analyzed traits. The lymphocytes phagocytic capacity (quantified as mean fluorescence) and the total number of monocytes in blood were the traits associated with the largest number of taxa (6 taxa). Among the associations identified by MWAS, 30% were confirmed by an information theory network approach. The strongest confirmed associations were between Fibrobacter and phagocytic capacity of lymphocytes (r = 0.37), followed by correlations between Streptococcus and the percentage of phagocytic lymphocytes (r = -0.34) and between Megasphaera and serum concentration of haptoglobin (r = 0.26). In the interaction network, Streptococcus and percentage of phagocytic lymphocytes were the keystone bacterial and immune-trait, respectively. Conclusions Overall, our findings reveal an important connection between gut microbiota composition and immunity traits in pigs, and highlight the need to consider both sources of information, host genome and microbial levels, to accurately characterize immunocompetence in pigs.

El objetivo fue establecer un protocolo para la desinfección y el establecimiento de microesquejes de café Coffea arabica Var. Caturra Rojo provenientes de campo, como etapa previa para la multiplicación in vitro. El diseño utilizado fue el diseño en bloques completos al azar (DBCA), los tratamientos para desinfección fueron t1, t2 y t3; mientras que, en la fase de establecimiento fueron t1, t2, t3, t4 y t5. Se encontró que el protocolo de desinfección que mejor funcionó fue t3 que utilizó benomilo y gentamicina por 10 minutos, luego el uso de hipoclorito de sodio, lejía, a 1,3 % por 30 minutos, en base a que favoreció una mayor sobrevivencia y menor fenolización de los explantes. El mejor medio de establecimiento fue el t5 que tuvo como ingredientes MS más BAP a 0,5 mg l-1.

Benzo[a]pyrene (BaP) is a highly toxic and carcinogenic polycyclic aromatic hydrocarbon (PAH) whose toxicological effects in the gut microbiota of aquatic organisms have not yet been fully revealed. Therefore, in this study, we used high-throughput 16S rRNA gene sequencing to evaluate the effects of BaP in the gut microbiome of Oreochromis niloticus, including its possible participation in the process of detoxification and its ability to recover. The fish were injected with a single intraperitoneal dose of 20 mg kg−1 of BaP, and the effects in the microbiome were evaluated at 24, 72, and 120 h post-injection. The results indicate a clear dysbiosis (in composition, relative abundance, diversity, and interaction networks) of the gut microbiota during 24 h post-injection, dominated by Fusobacteria and Bacteroidetes and a decrease in Proteobacteria and Spirochaetae. Interestingly, a slight recovery of the microbiome begins at 72 h and stabilises at 120 h post-injection. Pathway analysis revealed the participation of the gut microbiome in PAH degradation mainly at 24 h post-injection. This study provides new insights in the toxicology of BaP in O. niloticus and the first evidence of the ability of the gut microbiome to recovery after a chemical disturbance. • Benzo[a]pyrene caused a dysbiosis in the gut microbiota of Oreochromis niloticus. • We observed an enrichment of bacteria involved in the metabolism of xenobiotics. • The gut microbiota was recovered after exposure to benzo[a]pyrene.

Temephos is an organophosphorus pesticide used in control campaigns against vectors that transmit diseases, including dengue, a public health concern. The WHO classifies temephos in category III and its safe concentration (low-observable-adverse-effect level) in male rats is 100 mg/kg/day for up to 44 days. Temephos inhibits acetylcholinesterase (AChE) and is metabolized in different tissues, probably by mixed-function oxidases; one of its metabolites is bisphenol S (BPS), which is considered an endocrine disruptor. The aim of this study was to evaluate the effects of temephos on sperm function and its biotransformation in the testis, epididymis, and other tissues to explore its toxicity in rats treated with 100 mg/kg/day/5 or 7 days (gavage). AChE activity was inhibited 70% starting on day 3 and 13 or 41% mortality was observed at 5 or 7 days, respectively. After 7 days, temephos significantly decreased sperm motility (30%) and viability (10%) and increased (10%) lipoperoxidation, and the sperm DNA exhibited no damage. Temephos was distributed and metabolized in all tissues, with the highest levels observed in the adipose tissue and temephos levels were 16-fold higher in the epididymis than in the testis. Notably, BPS was observed in the testis. At 5 days, decreased sperm motility (12.5%) and viability (5.7%) were observed and sperm fertilization decreased (30%). These results suggest that temephos decreases sperm quality and fertilization capacity at recommended safe concentrations and that it is metabolized in male reproductive tissues. This pesticide places the reproductive health of exposed people at risk, suggesting the need to reevaluate its toxicity.

Introduction: Candida albicans is a ubiquitous commensal organism that commonly colonizes the oral mucosa. In fact, up to 80% of the general population are carriers. Objective: To analyze the literature about C. albicans, its epidemiology, diagnosis, clinical manifestations, antimicrobial resistance and treatment in relation to endodontics. Methodology: Using the keywords Candida albicans in conjunction with epidemiology, diagnosis, clinical manifestations, antimicrobial resistance and treatment, the main public databases were searched, with emphasis on the last 5 years. It was evaluated with the PRISMA and AMSTAR-2 guidelines. Results: C. albicans is the fungus most frequently isolated in root canal infections, it binds to the dentin to form biofilms within the dentin tubules. C. albicans can be detected by different diagnostic methods, the most used is cultivation. This microorganism is increasingly found in the oral cavity, it is responsible for endodontic failure, its biofilms are inherently resistant to antifungal drugs, the host's immune system, environmental stresses and biomechanical treatment. The most favourable method to eliminate is using QmiX irritant and EndoVac as a suction system, together with chemo mechanical debridement. Conclusions: C. albicans is a pathogen which has been presenting itself more frequently in the oral cavity, in the endodontic area, it is the fungus that is most frequently found in the root canals, either due to primary or secondary infection.

Introducción: La halterofilia al requerir levantar el mayor peso posible necesita optimizar diversas variables del rendimiento deportivo, incluyendo la técnica deportiva como componente determinante en el proceso de dirección del entrenamiento deportivo aplicado. Objetivo: comparar biomecánicamente el clin olímpico en halterofilia, teniendo presente las diferencias entre deportistas de alto nivel y novatos de la Federación Deportiva Provincial de Orellana. Métodos: investigación descriptiva-correlativa de orden transversal, estudiado dos grupos independientes de 5 deportistas de halterofilia de alto nivel, y 6 de nivel novato. Se investigan los resultados en tres variables (AFR: articulación femorotibial rotuliana, ACF: articulación coxofemoral y TE: tiempo de ejecución), calificando el movimiento motriz cualitativamente, y realizando una comparación en cada variable de análisis. Resultados: Las medias registradas fueron superiores en los atletas de alto rendimiento (AFR: 118.4°; ACF: 85° y TE: 3.18s) que en los atletas de nivel novato (AFR: 111.17°; ACF: 81.17° y TE: 3.67s), no existiendo diferencias significativas entre grupos independientes, obteniendo la evaluación cualitativa de la trayectoria de la barra un nivel superior en atletas de alto rendimiento (media de 2.8 puntos: Bueno-Muy Bueno) que los atletas novatos (media de 1.5 puntos: Malo-Bueno). Conclusiones: El estudio realizado reafirma que las medias alcanzadas en las variables ángulos de las rodillas, ángulo de la articulación coxofemoral y tiempo de ejecución fueron mayormente positivas en los atletas de altos rendimientos que, en atletas novatos, requiriendo ampliar los estudios con muestras mayores a las investigadas.

Aims: Habanero pepper (Capsicum annuum L.) cultivation is growing worldwide, mainly as a result of its high demand and nutritive contribution to human society. The presence of endogenous gibberellins and cytokinins in seeds of various vegetable crops has been related to a good germination; however, little is known on habanero pepper. The aim of this study was to search for the presence, identification and amount of gibberellins and cytokinins in seeds of habanero pepper cv “Jaguar”. Study design: Laboratory analysis for gibberellins and cytokinins were organized in solvent solutions groups with three technical replicates using a complete randomized design and results when applicable were analyzed using the statistical program 'RStudio' (version 10) and data obtained subjected to a comparison of means with the Tukey (P≤0.05) test. Place and duration of study: The experiment was conducted at the Department of Horticulture in Universidad Autónoma Agraria Antonio Narro, Saltillo, Mexico, during 2020-2021. Methodology: Lots of 50 grams dry weight of “Jaguar” habanero pepper seed samples were freeze dried and prepared with several organic solvents for the extraction, purification and identification of gibberellins and cytokinins using the techniques of GC-MS and GCMS-SIM respectively. Results: Gibberellins A1, A4, A7, A9, A15, A17 and A44 were found in habanero seed tissue. The cytokinins zeatin and zeatin-riboside were also detected in analyzed habanero samples. Conclusion: The endogenous gibberellins A1, A4, A7, A9, A15, A17, A44, and the cytokinins zeatin and zeatin-riboside are present in habanero pepper cv “Jaguar” contributing to an improve seed viability, ensuring health and overall plant yield.

This is the first published case report of a child with acute lymphatic leukemia developing a fatal mucormycosis during blinatumomab treatment. The patient showed multiple, systemic thromboembolic lesions with ischemia, bleeding and infarction in almost all organs. The child succumbed to increased brain pressure resulting in cerebral herniation. This case particularly illustrates the fulminant progression and huge challenges of diagnosing and treating mucormycosis in children with hemato-oncological diseases during treatment with targeted therapeutic antibodies (blinatumomab).

Aims: Tomato (SolanumlycopersicumL.) is one of the most important vegetable crops worldwide, mainly as a result of its economic and nutritive contribution to human society. The presence of endogenous gibberellins and cytokinins in seeds of several crops has been related to a good germination; however, little is known in tomato. Therefore, the aim of this study was to analyze and identify the presence of gibberellins and cytokinins in saladette tomato seeds. Study Design: Laboratory analysis for gibberellins and cytokinins were conducted in solvent solutions groups with three technical replicates using a complete randomized design and results when applicable were analyzed using the statistical program 'RStudio' (version 10) and data obtained subjected to a comparison of means with the Tukey (P≤0.05) test. Place and Duration of Study: The experiment was conducted at the Department of Horticulture in Universidad AutónomaAgraria Antonio Narro, Saltillo, Mexico, during 2020-2021. Methodology: Lots of 50 grams dry weight of saladette “SVTE8832” tomato seed samples were freeze dried and prepared with several organic solvents for the extraction, purification and identification of gibberellins and cytokinins using the techniques of gas chromatography mass spectrometry(GC-MS) and gas chromatography mass spectrometry with selection ion monitoring(GCMS-SIM) respectively. Results: Gibberellins A1, A4, A7, A9, A12, A15, A17, A20, A44 and A53 were found in tomato seed tissue. The cytokininszeatin and zeatin-ribozide were also detected in analyzed tomato samples. Conclusion:The endogenous gibberellins A1, A4, A7, A9, A12, A15, A17, A20, A44, A53 and the cytokininszeatin and zeatin-riboside are present in saladette“SVTE8832” tomato seeds.

In this study, we report molecular and metabolic responses of Sciaenops ocellatus during an acute oil exposure bioassay (100, 800 and 8000 mg 1–1 of crude oil). The global DNA methylation and expression profiles of key genes of the xenobiotic biotransformation system (cytochrome P450 1A [cyp1a] and glutathione S-tranferase [gst]), oxidative stress system (glutathione peroxidase [gpx], catalase [cat], aldehyde dehydrogenase [aldh]) and reproductive system (vitellogenin [vtg]) were evaluated. At the metabolic level, we evaluated the concentration of four polycyclic aromatic hydrocarbon (PAH) metabolites -hydroxybenzo[a]pyrene, hydroxypyrene, hydroxynaphthalene and hydroxyphenanthrene- in fish bile. The results of this study revealed that fish exposed to crude oil exhibited hypomethylation of DNA, up-regulation of cyp1a and gst and down-regulation of gpx, cat, aldh and vtg and high concentrations of PAH metabolites with respect to the control.

We report the chemical characterisation and toxic effects of municipal solid waste landfill leachates on the embryonic development of Danio rerio. The results of the Fourier transform infrared spectroscopy (FTIR) revealed the presence of nitrogen-containing groups and aromatic functional groups associated with highly toxic pollutants such as ammonia and heavy metal–humic complexes. Mortalities of up to 93 and 100% were observed in 1:64 and 1:32 landfill leachate dilutions, v/v, respectively. The hatching percentages of the fish were also severely affected, with very low percentages ranging from 0 to 33.3% for 1:32, 1:64 and 1:128 dilutions, v/v. Morphologically, a developmental arrest was evident for all treatments. This study reveals the high toxicity of landfill leachates that could contaminate the aquifer of the Yucatan Peninsula and threaten the health of living organisms.

14 Pág. Departamento de ​Mejora Genética Animal, Coronaviruses silently circulate in human and animal populations, causing mild to severe diseases. Therefore, livestock are important components of a "One Health" perspective aimed to control these viral infections. However, at present there is no example that considers pig genetic resources in this context. In this study, we investigated the variability of four genes (ACE2, ANPEP and DPP4 encoding for host receptors of the viral spike proteins and TMPRSS2 encoding for a host proteinase) in 23 European (19 autochthonous and three commercial breeds and one wild boar population) and two Asian Sus scrofa populations. A total of 2229 variants were identified in the four candidate genes: 26% of them were not previously described; 29 variants affected the protein sequence and might potentially interact with the infection mechanisms. The results coming from this work are a first step towards a "One Health" perspective that should consider conservation programs of pig genetic resources with twofold objectives: (i) genetic resources could be reservoirs of host gene variability useful to design selection programs to increase resistance to coronaviruses; (ii) the described variability in genes involved in coronavirus infections across many different pig populations might be part of a risk assessment including pig genetic resources., This work has received funding from the University of Bologna RFO 2016-2019 programmes, the Italian MIUR 2017 PigPhenomics project, from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 634476 for the project with acronym TREASURE, from the European Open Science Cloud (EOSC) Secretariat, project “Application of animal genomics and data mining to predict and monitor novel coronavirus potential infections (VirAnimalOne)”, the EGI call for COVID-19 research projects (AnGen1H project) and from the Por Fesr Emilia-Romagna 2014-2020 (actions 1.1.4 and 1.2.2—Bando per sostenere progetti di ricerca ed innovazione per lo sviluppo di soluzioni finalizzate al contrasto dell’epidemia da COVID-19—Project LIVESTOCK-STOP-COVI). The content of this article reflects only the authors' view and the European Union Agency is not responsible for any use that may be made of the information it contains.

Piscirickettsia salmonis is the aetiological agent of piscirickettsiosis, a bacterial disease that affects farmed salmonids, causing high mortalities and significant economic losses in the Chilean salmon farm industry. Given the Chilean native fish species Patagonian blenny, Eleginops maclovinus, lives in the vicinity of salmon farms, it is relevant to clarify the epidemiological role that this species could play in the transmission and/or dissemination of this pathogen. This study aimed to evaluate the bidirectional transmission of P. salmonis between the Patagonian blenny and Oncorhynchus mykiss (rainbow trout), via a cohabitation challenge model. The results of this study demonstrated the transmission of the bacteria from Patagonian blennies to rainbow trout, considering the specific mortality in cohabitant rainbow trout, reaching 46%: the necropsy of these specimens, evidencing the characteristic pathological lesions of the disease and the positive results of the qPCR analysis for P. salmonis, in the same individuals. In contrast, no mortalities of Patagonian blenny specimens were recorded in the challenged experimental groups. This study is the first report showing the horizontal transmission of P. salmonis from a native non-salmonid species, such as the Patagonian blenny, to a salmonid species, generating the disease and specific mortality in rainbow trout, using a cohabitation challenge.

Objectives The 2019 Workshop of the Society for Hematopathology/European Association for Haematopathology received and reviewed cases covering the spectrum of mastocytosis and related diseases, including morphologic mimics, focusing on recent updates and relevant findings for pathologists. Methods The workshop panel reviewed 99 cases of cutaneous and systemic mastocytosis (SM) and SM and associated hematologic neoplasms (SM-AHN). Results Despite a common theme of KIT mutation (particularly D816V), mastocytosis is a heterogeneous neoplasm with a wide variety of presentations. This spectrum, including rare subtypes and extramedullary organ involvement, is discussed and illustrated by representative cases. Conclusions In the age of targeted treatment aimed at KIT, the accurate diagnosis and classification of mastocytosis has major implications for therapy and further interventions. Understanding the clinical, pathologic, and genetic findings of mastocytosis is crucial for selecting the proper tests to perform and subsequent arrival at a correct diagnosis in this rare disease.

Continuing with the study of the Astragalus of Mexico and based on the measurement of 30 morphological characters and applying multivariate statistics, the two varieties of Astragalus radicans: A. radicans var. radicans and A. radicans var. harshbergeri were ranked at the species level and have their nomenclature updated. The results of the analysis allow the two infraspecific constitute isolated groups without overlapping between their individuals; therefore, they are raised from varieties to species, Astragalus radicans and Astragalus harshbergeri. A map with the updated distribution was included, and a dichotomous key is provided to identify the species. Both species are placed under the category of Threatened.

[Background] The European Syncope Guidelines (ESG) recommend the use of Head-up tilt test (HUT) in case of suspicion of vasovagal syncope (VVS) or orthostatic hypotensive syncope (OHS) after an adequate initial inconclusive evaluation. We report a single center experience in the scenario of suspected VVS or OHS, who underwent HUT in patients referred to a Syncope Clinic after ruling out high-risk causes., [Methods] We prospectively and consecutively included all syncopal patients that were referred for HUT, by their attending physician after performing a series of diagnostic tests to rule out cardiac etiology. The clinical history and diagnostic tests performed were reviewed prior to HUT. Patients were pre-classified according to the recommendations from the ESG as; VVS, OHS or Syncope of Unknown Etiology (SUE)., [Results] We studied 1058 patients, 558 (52.7%) males, mean age 46.5 ± 20.1 yr. There were no gender differences in age, risk factors, previous heart diseases, ECG findings or number of previous tests. Based on the ESG criteria a significant number of diagnostic tests were probably unnecessarily performed. HUT was positive in 609 patients (57.5%). The rate of positive HUT according to pre-classification was significantly different among groups: 60% VVS, 46.1% OHS and 54.3% SUE (p = 0.037). Combining ESG recommendations and HUT results of the 1058 resulted in 762 (72%) diagnosed as VVS, 89 (8.4%) as OHS and 207 (19.5%) as SUE., [Conclusions] Appropriate application of ESG recommendations combined with HUT, identified 81% of patients with non-cardiogenic syncope, potentially avoiding a significant number of unnecessary diagnostic tests.

We present the first record of leucism of Molossus nigricans a chromatic disorder rarely documented in mammals of Honduras, as well as species’ biological and ecological information. In addition, we present the currently known distribution and altitudinal range of M. nigricans in Honduras, based on acoustic records, opportunistic findings and previous records. We confirm the presence of M. nigricans in sixteen departments of which four are new departmental records.

The use of medicinal plants in Mexico has a diverse and deeply-rooted tradition concerning. Plants play an important role in traditional medicine among the inhabitants of Güémez, Tamaulipas in northeastern Mexico. With the aim of obtaining quantitative information on the plants and their uses as medicinal sources, semi-structured interviews with 113 local residents were taken. In addition, Informant Consensus Factor (ICF) and Use Value (UV) were calculated. A total of 85 species of medicinal plants belonging to 44 families were identified. The most common families were Asteraceae, Lamiaceae and Euphorbiaceae. The most used part of the plant was the leaf and the most frequent preparation method was boiling, preparing as an infusion. A total of 50 medicinal uses were registered. Fever had highest ICF (0.93), whereas, according to UV, the most important plants were Artemisia ludoviciana Nutt., Mentha spicata L., Matricaria recutita L. and Achillea millefolium L. The information generated strengthens traditional knowledge, bringing new species and uses to the country´s records for future phytochemical studies that could lead to new medicines.

Climate change poses several challenges to biological communities including changes in the frequency of encounters between closely related congeners as a result of range shifts. When climate change leads to increased hybridization, hybrid dysfunction or genetic swamping may increase extinction risk—particularly in range‐restricted species with low vagility. The Peaks of Otter Salamander, Plethodon hubrichti, is a fully terrestrial woodland salamander that is restricted to ~18 km of ridgeline in the mountains of southwestern Virginia, and its range is surrounded by the abundant and widespread Eastern Red‐backed Salamander, Plethodon cinereus. In order to determine whether these two species are hybridizing and how their range limits may be shifting, we assessed variation at eight microsatellite loci and a 1,008 bp region of Cytochrome B in both species at allopatric reference sites and within a contact zone. Our results show that hybridization between P. hubrichti and P. cinereus either does not occur or is very rare. However, we find that diversity and differentiation are substantially higher in the mountaintop endemic P. hubrichti than in the widespread P. cinereus, despite similar movement ability for the two species as assessed by a homing experiment. Furthermore, estimation of divergence times between reference and contact zone populations via approximate Bayesian computation is consistent with the idea that P. cinereus has expanded into the range of P. hubrichti. Given the apparent recent colonization of the contact zone by P. cinereus, future monitoring of P. cinereus range limits should be a priority for the management of P. hubrichti populations., This study uses population genetic approaches to assess whether hybridization between a severely range‐restricted mountaintop endemic salamander and a closely related widespread congener is contributing to the extinction risk of the former. While we find little to no evidence of hybridization, we do present evidence that the more common species is expanding into the range of the mountaintop endemic species. We discuss the conservation implications of this finding.

Summary Nematode parasitism is a yield limiting factor in many cropping systems, including potato production, which can translate into substantial economic losses. These impacted financial returns are simply calculated by subtracting the cost of production from total revenue (yield times the price per yield of potatoes). The production costs can include, but are not limited to, chemical and biological control agents. To assess economic returns associated with different nematode management strategies, we evaluated complete cost estimations for a representative commercial potato farm in central Michigan, USA. Economic returns were calculated using stochastic parameters for two biological control agents (MeloCon and Majestene), six chemical controls (Mocap, Movento, Nimitz, Velum and Vydate), and two soil amendments (poultry and dairy manure). Evaluated costs included stochastic estimations for price per unit weight of potatoes, fuel, labour and production land rent. Yield data from three field trials were used to create empirical distributions. Using yield data and stochastic cost estimations, we generated 500 simulations of net returns per treatment. The top three average returns were obtained from the use of Mocap, Nimitz and poultry manure. Velum, Movento, dairy manure and Vydate also gave returns significantly higher than no treatment at all; however, the biological nematicide, Majestene, showed negative returns. This simple financial model is a crucial layer of analysis on the performance of nematicides that can be adapted to advise growers through Agricultural Extension activities and needs to include the evaluation of biological control agents.

Aims: The apricot (Prunus armeniaca L.), is a drought-sensitive deciduous fruit. This concept arises from the fact that soil moisture stress can: Decrease the number and quality of flower buds differentiated; delay the time of flower differentiation and decrease the number of flower buds per shoot. The objectives of this investigation were to determine: The extent to which drought influences water status in the leaves; its effect on flower buds development and on bloom in apricot cv. “Royal”. Study Design: Trees were divided into 6 groups of six replicate each under a random block design. Results were analyzed using the statistical program 'RStudio' for Windows version 10 and data obtained subjected to a comparison of means with the Tukey (P≤0.05) test. Place and Duration of Study: The experiment was conducted at the Department of Horticulture in Universidad Autónoma Agraria Antonio Narro, Saltillo, Mexico, during 2018-2019. Methodology: Seven-year-old apricot trees growing in containers were subjected to a 4 to 5week period of water stress at different times during the growing season. Leaf water potential was periodically measured and flower bud development was followed from early differentiation up to full bloom. Results: Leaf water potential in water stressed trees was constantly low. Water stress early in the season induced a delay in bud development during late summer and fall. Water stress late in the season did not appreciably affect the rate of bud development. Full bloom was delayed when water stress was applied in late summer and fall. Water stress at flower bud initiation and differentiation, together with high temperatures, may have induced flowers with double pistils. Water stress from April through October did not induce flower drop. Conclusion: Soil water stress severely affect leaf water potential; delays flower bud development and may induce flowers with double pistils without flower drop.

The role of glycoprotein VI (GPVI) in platelets was investigated in 3 families bearing an insertion within the GP6 gene that introduces a premature stop codon prior to the transmembrane domain, leading to expression of a truncated protein in the cytoplasm devoid of the transmembrane region. Western blotting and flow cytometry of GP6hom (homozygous) platelets confirmed loss of the full protein. The level of the Fc receptor γ-chain, which associates with GPVI in the membrane, was partially reduced, but expression of other receptors and signaling proteins was not altered. Spreading of platelets on collagen and von Willebrand factor (which supports partial spreading) was abolished in GP6hom platelets, and spreading on uncoated glass was reduced. Anticoagulated whole blood flowed over immobilized collagen or a mixture of von Willebrand factor, laminin, and rhodocytin (noncollagen surface) generated stable platelet aggregates that express phosphatidylserine (PS). Both responses were blocked on the 2 surfaces in GP6hom individuals, but adhesion was not altered. Thrombin generation was partially reduced in GP6hom blood. The frequency of the GP6het (heterozygous) variant in a representative sample of the Chilean population (1212 donors) is 2.9%, indicating that there are ∼4000 GP6hom individuals in Chile. These results demonstrate that GPVI supports aggregation and PS exposure under flow on collagen and noncollagen surfaces, but not adhesion. The retention of adhesion may contribute to the mild bleeding diathesis of GP6hom patients and account for why so few of the estimated 4000 GP6hom individuals in Chile have been identified.

The cattle tick Rhipicephalus microplus has a large impact on cattle production due to its bloodsucking habit and transmission of pathogens that cause babesiosis and anaplasmosis. Application of acaricides constitutes the major control method but is often accompanied by serious drawbacks, including environmental contamination and an increase in acaricide resistance by ticks. The recent development of anti-tick vaccines has provided positive results in the post-genomic era, owing to the rise of reverse vaccinological and bioinformatics approaches to analyze and identify candidate protective antigens for use against ticks. The ATAQ protein is considered a novel antigen for the control of the cattle tick R. microplus; it is expressed in midguts and Malpighian tubules of all ticks from the Rhipicephalus genus. However, genetic diversity studies are required. Here, the ATAQ gene was sequenced of seven R. microplus tick isolates from different regions in Mexico to understand the genetic diversity. The results showed that sequence identity among the Mexican isolates ranged between 98 and 100% and 97.8–100% at the nucleotide and protein levels, respectively. Alignments of deduced amino acid sequences from different R. microplus ATAQ isolates in Mexico revealed a high degree of conservation. However, the Mexican isolates differed from the R. microplus “Mozambique” strain, at 20 amino acid residues. Finally, the analysis of more R. microplus isolates, and possibly of other Rhipicephalus species, to determine the genetic diversity in the ATAQ locus is essential to suggest this antigen as a vaccine candidate that might control tick infestations.

The interaction of the root lesion nematode Pratylenchus penetrans and the fungal plant pathogen Verticillium dahliae causes potato early die (PED) complex, which induces premature vine senescence and dramatically reduces yield in potatoes. Management of PED is often achieved through the use of soil fumigants and nematicides, but their adverse effects on soil, human and environmental health, and strict regulations worldwide require alternative control tactics. In this study, we investigated the effects of multiple composts and manures on nematode mortality and PED. In lab assays, root lesion nematodes were exposed to poultry manure, layer ash blend, Dairy Doo, or wood ash for 7 days at rates of 0, 0.1, 1, 10, and 20% by volume of product and assessed for nematode survivorship. Additionally, these products were evaluated for volatile fatty acid content to determine if fatty acid content affects nematode control. In a field trial, the composts and manures were evaluated at two different rates, high (11.2 t/ha) or low (2.8 t/ha), and populations of P. penetrans and V. dahliae were quantified. Our results show that a 1% application rate of poultry manure and layer ash blend provided the greatest nematode control in lab assays with 24.5 and 38.2% reduction, respectively, with greater control at higher rates. In the field, plots treated with poultry manure had significantly higher potato yields and significantly fewer nematodes than control plots. Taken together, our results suggest that poultry manure could be a promising amendment to control PED.

There is evidence that cannabis use during adolescence leads to memory and cognitive problems in young adulthood but little is known about effects of early life cannabis exposure on synaptic operations that are critical for encoding and organizing information. We report here that a 14-day course of daily Δ9-tetrahydrocannabinol treatments administered to adolescent rats and mice (aTHC) leads to profound but selective deficits in synaptic plasticity in two axonal systems in female, and to lesser extent male, hippocampus as assessed in adulthood. Adolescent-THC exposure did not alter basic synaptic transmission (input/output curves) and had only modest effects on frequency facilitation. Nevertheless, aTHC severely impaired the endocannabinoid-dependent long-term potentiation in the lateral perforant path in females of both species, and in male mice; this was reliably associated with impaired acquisition of a component of episodic memory that depends on lateral perforant path function. Potentiation in the Schaffer-commissural (S-C) projection to field CA1 was disrupted by aTHC treatment in females only and this was associated with both a deficit in estrogen effects on S-C synaptic responses and impairments to CA1-dependent spatial (object location) memory. In all the results demonstrate sexually dimorphic and projection system-specific effects of aTHC exposure that could underlie discrete effects of early life cannabinoid usage on adult cognitive function. Moreover they suggest that some of the enduring, sexually dimorphic effects of cannabis use reflect changes in synaptic estrogen action.

Bacteriophages are ubiquitous in nature and their use is a current promising alternative in biological control. Multidrug resistant (MDR) bacterial strains are present in the livestock industry and phages are attractive candidates to eliminate them and their biofilms. This alternative therapy also reduces the non-desirable effects produced by chemicals on food. The World Health Organization (WHO) estimates that around 420,000 people die due to a foodborne illness annually, suggesting that an improvement in food biocontrol is desirable. This review summarizes relevant studies of phage use in biocontrol focusing on treatments in live animals, plants, surfaces, foods, wastewaters and bioremediation. España , Instituto de Salud Carlos III Project PI20/00261 España Ministerio de Ciencia e Innovación (CP19/00104)

12 pages, 9 figures, 1 table, Alcyonium coralloides is an epibiotic soft coral overgrowing living colonies of Mediterranean gorgonians. The main features of the sexual reproductive cycle of this soft coral species are described and quantified for the first time, in a population found at 18 to 22 m depth off the Medes Islands (NW Mediterranean). A. coralloides is a gonochoric internal brooder. The sexual cycle showed a single reproductive event per year. Gametogenesis took 5 to 6 mo, which is the shortest known gametogenesis in littoral octocorals (especially for oogenesis). The maximum mean ± SD diameter was 365 ± 86 µm for spermatic cysts and 632 ± 125 µm for mature oocytes. Sperm was released in spring (late May). Average male and female fecundity in this last phase of the cycle was 15 ± 9 spermatic cysts and 7 ± 4 oocytes per polyp, respectively. Larvae of about 1000 µm in length were observed in the gastrovascular cavities of female colonies in May, before they were released in June. We suggest that the remarkable short gametogenesis and timing shown by A. coralloides is an adaptation to optimize the colonization of its host (in this case the gorgonian octocoral Paramuricea clavata). We conclude that A. coralloides larvae could be ready to settle in early summer when the host P. clavata is probably more vulnerable as a result of its own reproductive cycle coming to an end, We are especially grateful to J. Pascual for environmental data collection, E. Rodriguez from the American Museum of Natural History, NY, for reviewing the text and the reviewers who critically read the manuscript and helped to improve the document with their comments. This work was partially funded by the program LIFE+INDEMARES (LIFE07 NAT/E/000732- ‘Inventariación y designación de la red Natura 2000 en áreas marinas del estado español’). Partial support was provided to T.M. by a JAEDoc (Consejo Superior de Investigaciones Científicas, SPAIN) grant; S.R. was funded by a Ramón y Cajal contract (RYC-2007-01327)

Cementum is a bone connective tissue that provides a flexible attachment for the tooth to the alveolar bone in many mammalian species. It does not undergo continuous remodelling, unlike non-dental bone, which combined with its growth pattern of seasonal layering makes this tissue uniquely suitable as a proxy for tracking changes in body repair investment throughout an animal´s life. We tested functional and sexual selection hypotheses on the rate of cementum deposition related to the highly polygynous mating strategy of red deer. We used a sample of 156 first lower molars from wild Scottish red deer of known age between 1 and 17 years old, approximately balanced by sex and age class. Cementum deposition on the inter-radicular pad increased with age at a constant average rate of 0.26 mm per year, with no significant differences between sexes. Cementum deposition was independent of (i) tooth wear, other than that associated with age, and (ii) enamel and dentine micro-hardness. The results partially supported the hypothesis that the main function of cementum is the repositioning of the tooth to maintain opposing teeth in occlusion. However, teeth that had more wear or males´ teeth that had faster rates of tooth wear than those of females did not present the expected higher rates of cementum deposition., The study was supported by projects Ministerio de Economia, Industria y Competitividad, Gobierno de España RTC-2016-5327-2 (Dr. T Landete-Castillejos); Junta de Comunidades de Castilla-La Mancha SBPLY/19/180501/000115 (Dr. MP Serrano). The red deer study on the Isle of Rum National Nature Reserve takes place with the support of the UK Natural Environment Research Council and Scottish Natural Heritage. The European Union Lifelong learning programme (Leonardo da Vinci) for supporting the postgraduate students who collaborated in this study.

In recent years, the increase in awareness of antimicrobial resistance together with the societal demand of healthier meat products have driven attention to health-related traits in livestock production. Previous studies have reported medium to high heritabilities for these traits and described genomic regions associated with them. Despite its genetic component, health- and immunity-related traits are complex and its study by association analysis with genomic markers may be missing some information. To analyse multiple phenotypes and gene-by-gene interactions, systems biology approaches, such as the association weight matrix (AWM), allows combining genome wide association study results with network inference algorithms. The present study aimed to identify gene networks, key regulators and candidate genes associated to immunocompetence in pigs by integrating multiple health-related traits, enriched for innate immune phenotypes, using the AWM approach. The co-association network analysis unveiled a network comprised of 3,636 nodes (genes) and 451,407 edges (interactions), including a total of 246 regulators. From these, five genes (ARNT2,BRMS1L,MED12L,SUPT3HandTRIM25) were selected as key regulators as they were associated with the maximum number of genes with the minimum overlapping (1,827 genes in total). The five regulators were involved in pathways related to immunity such as lymphocyte differentiation and activation, platelet activation and degranulation, megakaryocyte differentiation, FcγR-mediated phagocytosis and response to nitric oxide, among others, but also in immunometabolism. Furthermore, we identified genes co-associated with the key regulators previously reported as candidate genes (e.g.,ANGPT1, CD4, CD36, DOCK1,PDE4B, PRKCE, PTPRCandSH2B3) for immunity traits in humans and pigs, but also new candidate ones (e.g.,ACSL3,CXADR,HBB,MMP12,PTPN6,WLS) that were not previously described. The co-association analysis revealed new regulators associated with health-related traits in pigs. This approach also identified gene-by-gene interactions and candidate genes involved in pathways related to cell fate and metabolic and immune functions. Our results shed new light in the regulatory mechanisms involved in pig immunity and reinforce the use of the pig as biomedical model.

Alcoholic fermentation is known to be a key stage in the winemaking process that directly impacts the composition and quality of the final product. Twelve wines were obtained from fermentations of Chardonnay must made with twelve different commercial wine yeast strains of Saccharomyces cerevisiae. In our study, FT-ICR-MS, GC-MS, and sensory analysis were combined with multivariate analysis. Ultra-high-resolution mass spectrometry (uHRMS) was able to highlight hundreds of metabolites specific to each strain from the same species, although they are characterized by the same technological performances. Furthermore, the significant involvement of nitrogen metabolism in this differentiation was considered. The modulation of primary metabolism was also noted at the volatilome and sensory levels. Sensory analysis allowed us to classify wines into three groups based on descriptors associated with white wine. Thirty-five of the volatile compounds analyzed, including esters, medium-chain fatty acids, superior alcohols, and terpenes discriminate and give details about differences between wines. Therefore, phenotypic differences within the same species revealed metabolic differences that resulted in the diversity of the volatile fraction that participates in the palette of the sensory pattern. This original combination of metabolomics with the volatilome and sensory approaches provides an integrative vision of the characteristics of a given strain. Metabolomics shine the new light on intraspecific discrimination in the Saccharomyces cerevisiae species Keywords: yeast; Saccharomyces cerevisiae; Chardonnay wine; metabolomic; volatile compounds; sensory analysis

This article belongs to the Section Animal Welfare., Agonistic behavioural interactions play a decisive role in the competition for food, space, mating opportunities, and establishing social rank. We used pelt biting (number of bites on an animal’s body) as a proxy for assessing the intensity of agonistic animal interactions and how it responded to social, population, and heat stress factors. We modelled a 14-year time series of pelt biting records and observational data of agonistic interactions on a population of captive Iberian red deer (Cervus elaphus). We found that (i) the higher the social rank of deer, the lower the number of pelt bites received; (ii) increasing heat stress conditions caused deer to suffer more pelt bites; (iii) males received more bites than females; (iv) the heavier the deer, the lower the number of bites on their bodies; (v) the bigger the group, the more bites exhibited on its members; (vi) deer 5–6 years old suffered greater rate of pelt biting than younger or older deer; and (vii) hinds that gave birth earlier in the parturition period suffered less pelt biting than those that gave birth around the peak of the parturition season (p < 0.01 for all effects). Pelt biting is useful to predict management situations in which deer welfare could be at stake., The authors are grateful to Junta de Comunidades de Castilla-La Mancha (research project SBPLY/19/180501/000115) and programme Beatriz Galindo 2020 (Plan Estatal de Política Científica y Técnica y de Innovación CNU/692/2019) for financial support.

Plant roots interact with many bacteria, fungi, and microscopic organisms within the soil that can impact how well the plants grow. Some of these microscopic organisms are animals called nematodes, and they are an especially important part of the life in the soil. Nematodes can be good, bad, and neutral for plants. Some scientists called nematologists study nematodes and how to prevent the bad ones from damaging important crops, like carrots. Nematologists and other scientists partner up to help farmers manage these pests and grow healthy crops.

Elastin polypeptides based on -VPGVG- repeated motifs are widely used in the production of biomaterials because they are stimuli-responsive systems. On the other hand, glycine-rich sequences, mainly present in tropoelastin terminal domains, are responsible for the elastin self-assembly. In a previous study, we have recombinantly expressed a chimeric polypeptide, named resilin, elastin, and collagen (REC), inspired by glycine-rich motifs of elastin and containing resilin and collagen sequences as well. Herein, a three-block polypeptide, named (REC)3, was expressed starting from the previous monomer gene by introducing key modifications in the sequence. The choice was mandatory because the uneven distribution of the cross-linking sites in the monomer precluded the hydrogel production. In this work, the cross-linked polypeptide appeared as a soft hydrogel, as assessed by rheology, and the linear un-cross-linked trimer self-aggregated more rapidly than the REC monomer. The absence of cell-adhesive sequences did not affect cell viability, while it was functional to the production of a material presenting antiadhesive properties useful in the integration of synthetic devices in the body and preventing the invasion of cells.

We examined the association between habitat variables and the relative impacts of topographic microclimates as a valuable tool for restoration and conservation of Abies pinsapo in southern Spain. We used presence–absence data from A. pinsapo and 79 environmental variables and biomod species distribution models to describe the current and future species habitat across the Sierra de las Nieves Natural Park (southern Spain). A. pinsapo habitat was most strongly associated with microtopographic (solar incidence) and temperature variables, indicating climate-driven changes in microhabitat use. Most of the temperature variation among the study site was attributable to topographic microclimates rather than regional temperature differences, such that differences in microhabitat associations occurred principally between north- and south-facing slopes within the same region. The current potential distribution suggests that around 8.7% (56.44 km2) of the study area is highly suitable for A. pinsapo, with 9.7% (62.84 km2) being moderately suitable. Under different global circulation models and climate change scenarios, the net decrease in suitable habitat is predicted to be 93% of the current distribution by 2040, disappearing altogether by 2099. Our findings also show a sharp reduction of potential restoration areas (1.8% of the current areas). Microclimatic variation generated by the topography offers the microclimate-driven locations of habitat suitability which could shape species’ distribution restoration actions and their responses to environmental change. The approach presented here can provide a rapid assessment of the future conservation status of other important forest tree species in Spain, improving our understanding of the vulnerability of endangered species under climate change, and can be an effective tool for biodiversity conservation, restoration, and management.

Pediatric large B-cell lymphomas (LBCLs) share morphological and phenotypic features with adult types but have better prognosis. The higher frequency of some subtypes such as LBCL with IRF4 rearrangement (LBCL-IRF4) in children suggests that some age-related biological differences may exist. To characterize the genetic and molecular heterogeneity of these tumors, we studied 31 diffuse LBCLs (DLBCLs), not otherwise specified (NOS); 20 LBCL-IRF4 cases; and 12 cases of high-grade B-cell lymphoma (HGBCL), NOS in patients ≤25 years using an integrated approach, including targeted gene sequencing, copy-number arrays, and gene expression profiling. Each subgroup displayed different molecular profiles. LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B, and MYD88), losses of 17p13 and gains of chromosome 7, 11q12.3-q25, whereas DLBCL, NOS was predominantly of germinal center B-cell (GCB) subtype and carried gene mutations similar to the adult counterpart (eg, SOCS1 and KMT2D), gains of 2p16/REL, and losses of 19p13/CD70. A subset of HGBCL, NOS displayed recurrent alterations of Burkitt lymphoma–related genes such as MYC, ID3, and DDX3X and homozygous deletions of 9p21/CDKN2A, whereas other cases were genetically closer to GCB DLBCL. Factors related to unfavorable outcome were age >18 years; activated B-cell (ABC) DLBCL profile, HGBCL, NOS, high genetic complexity, 1q21-q44 gains, 2p16/REL gains/amplifications, 19p13/CD70 homozygous deletions, and TP53 and MYC mutations. In conclusion, these findings further unravel the molecular heterogeneity of pediatric and young adult LBCL, improve the classification of this group of tumors, and provide new parameters for risk stratification.

Inhibitors of the tyrosine kinase Btk have been proposed as novel antiplatelet agents. In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCγ2 in human platelets. Activation is also blocked in patients with X-linked agammaglobulinemia (XLA) caused by a deficiency or absence of Btk. In contrast, the response to GPVI is delayed in the presence of low concentrations of ibrutinib or in patients with XLA, and tyrosine phosphorylation of Syk is preserved. A similar set of results is seen with the second-generation inhibitor, acalabrutinib. The differential effect of Btk inhibition in CLEC-2 relative to GPVI signalling is explained by the positive feedback role involving Btk itself, as well as ADP and thromboxane A2 mediated activation of P2Y12 and TP receptors, respectively. This feedback role is not seen in mouse platelets and, consistent with this, CLEC-2-mediated activation is blocked by high but not by low concentrations of ibrutinib. Nevertheless, thrombosis was absent in 8 out of 13 mice treated with ibrutinib. These results show that Btk inhibitors selectively block activation of human platelets by CLEC-2 relative to GPVI suggesting that they can be used at 'low dose' in patients to target CLEC-2 in thrombo-inflammatory disease.

We describe and illustrate Astragalus sagitticarpus A.E. Estrada, Villarreal & Encina (Fabaceae) as a new species from south-central Mexico. Its annual habit, free stipules, few leaves, small calyx teeth, and pendulous, persistent, stipitate, dorsoventrally compressed pod characterize this species. Added to other characteristics related to the other sections, but not in the same combination of them, such as habit, flower size, and union of the stipules allow recognizing a new section also.

The goal of this study was to determine the effect of the carrier material, drying technology and dissolution media during the passage of L. fermentum K73 through a dynamic in vitro digestion system (IViDiS). The carrier materials were (i) culture medium with growing micro-organisms and (ii) culture medium with maltodextrin : sweet whey [0.6 : 0.4]. The carrier materials were dried by spray-drying and freeze-drying to obtain four types of powders. The dissolution media consisted of water and 1% fat milk. The powders were tested using an in vitro dynamic digestion system (IViDiS). The results showed that powders derived from culture medium had the highest protective effect on the viability of L. fermentum K73 in both dissolution media and that survival increased when the powders were tested in milk. The modified Gompertz model was used to model L. fermentum K73 behaviour during the digestion process. The model showed that cells entrapped in culture medium had the longest lag phase and the slowest inactivation rate when evaluated in milk.

An intimate link exists between circadian clocks and metabolism with nearly every metabolic pathway in the mammalian liver under circadian control. Circadian regulation of metabolism is largely driven by rhythmic transcriptional activation of clock-controlled genes. Among these output genes, Nocturnin ( Noct ) has one of the highest amplitude rhythms at the mRNA level. The Noct gene encodes a protein (NOC) that is highly conserved with the endonuclease/exonuclease/phosphatase (EEP) domain-containing CCR4 family of deadenylases, but highly purified NOC possesses little or no ribonuclease activity. Here, we show that NOC utilizes the dinucleotide NADP(H) as a substrate, removing the 2′ phosphate to generate NAD(H), and is a direct regulator of oxidative stress response through its NADPH 2′ phosphatase activity. Furthermore, we describe two isoforms of NOC in the mouse liver. The cytoplasmic form of NOC is constitutively expressed and associates externally with membranes of other organelles, including the endoplasmic reticulum, via N-terminal glycine myristoylation. In contrast, the mitochondrial form of NOC possesses high-amplitude circadian rhythmicity with peak expression level during the early dark phase. These findings suggest that NOC regulates local intracellular concentrations of NADP(H) in a manner that changes over the course of the day.

Targeted expression of transgenes is essential for the accurate representation of human disease in in vivo models. Current approaches to generate conditional transgenic mouse models are cumbersome and not amenable to high-throughput analysis since they require de novo generation and characterization of genetically modified mice. Here we describe a new system for lineage-restricted expression of transgenes based on a retroviral vector incorporating a translational stop cassette flanked by loxP recombination sites. Conditional transgene expression in chimeric mice is achieved by retroviral infection and transplantation of hematopoietic stem cells (HSC) derived from transgenic mice expressing Cre-recombinase from a lineage-specific promoter. For validation, we directed expression of NPM-ALK, the fusion oncogene driving a subset of anaplastic large cell lymphoma (ALCL), to T-cells by infecting hematopoietic stem cells from Lck-Cre-transgenic mice with a retroviral construct containing the NPM-ALK cDNA preceded by a translational stop cassette. These mice developed T-cell lymphomas within 12-16 weeks, featuring increased expression of the ALCL hallmark antigen CD30 as well as other cytotoxic T-cell markers, similar to the human disease. The new model represents a versatile tool for the rapid analysis of gene function in a defined lineage or in a developmental stage in vivo.

The parthenogenetic marbled crayfish, or Marmorkrebs (Procambarus virginalis Lyko 2017), is an emerging model organism. We describe a method to isolate cells from early-stage embryos and culture them in vitro. The identity of the cells was confirmed by sequencing the cytochrome c oxidase subunit I (COI) gene. This technique can be applied for use in the manipulation of embryonic parthenogenetic crayfish cells.