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Los acahuales (i.e. selvas secundarias) de zonas tropicales secas o estacionales, suelen ser pobres en especies arbóreas y dominados por unas cuantas especies de arbustos y árboles pioneros, usualmente dispersados por viento, siendo notable la ausencia de plantas arbóreas del dosel cuyas semillas relativamente grandes dependen de vectores animales para su dispersión. Varios estudios han encontrado que la siembra directa de especies arbóreas zoócoras con semillas grandes, en pastizales abandonados puede ser una práctica exitosa para enriquecer y acelerar la sucesión secundaria. Sin embargo, todavía no se conocen cabalmente las condiciones de hábitat o etapa sucesional óptima para realizar la siembra directa de semillas de árboles de fases sucesionales tardías. En este estudio seleccionamos dos especies arbóreas con semillas zoócoras relativamente grandes, que suelen formar parte del dosel de las selvas sub-caducifolias del centro de Veracruz: Brosimum alicastrum y Enterolobium cyclocarpum. Las sembramos en siete hábitats; seis de ellos representando un gradiente de menor a mayor complejidad estructural o desarrollo sucesional, desde pastizal activo hasta acahual de 10 años y el hábitat restante fue selva mediana sub-caducifolia bien conservada. Evaluamos experimentalmente la importancia de la depredación de semillas, protegiendo la mitad de ellas sembradas dentro de jaulas diseñadas para excluir a vertebrados granívoros. Durante un año monitoreamos la emergencia, supervivencia y crecimiento de plántulas, marcando a las que sobrevivieron su primer año, para ser registradas cuatro años y medio después. Un porcentaje relativamente alto de plántulas emergió de las semillas sembradas (75% en Brosimum, 60% Enterolobium). No detectamos diferencias significativas en la emergencia de plántulas entre los siete hábitats, ni entre los dos tratamientos de exposición a granívoros (dentro vs. fuera de exclusorios). Ninguna de las semillas sembradas fue removida por granívoros. La supervivencia y crecimiento deEnterolobium durante el primer año fue mayor en hábitats abiertos sin cobertura de plantas leñosas (ca. 60%) que en los sombreados por arbustos y árboles (80%) que en hábitats abiertos (0%). Nuestros resultados muestran que los pastizales abandonados y los acahuales pobres en especies arbóreas, pueden ser enriquecidos mediante la siembra directa de árboles de fases sucesionales tardías con baja capacidad de dispersión, siempre y cuando se elija cuidadosamente el hábitat (o etapa sucesional) óptimo para la siembra de semillas, con base en la ecología del establecimiento de plántulas de las especies involucradas. En el centro de Veracruz se puede acelerar la recuperación de la selva, sembrando semillas de Enterolobium desde el momento del abandono del pastizal, siempre y cuando se controle el crecimiento de los pastos durante los primeros dos a tres años de crecimiento de las plántulas. A su vez las semillas de Brosimum deberán sembrarse hasta que los arbustos o árboles pioneros hayan colonizado el sitio y sombreado a los pastos.

This version of the article has been accepted for publication, after peer review and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at https://doi.org/10.1007/s13225-021-00493-7. Fungi are highly important biotic components of terrestrial ecosystems, but we still have a very limited understanding about their diversity and distribution. This data article releases a global soil fungal dataset of the Global Soil Mycobiome consortium (GSMc) to boost further research in fungal diversity, biogeography and macroecology. The dataset comprises 722,682 fungal operational taxonomic units (OTUs) derived from PacBio sequencing of full-length ITS and 18S-V9 variable regions from 3200 plots in 108 countries on all continents. The plots are supplied with geographical and edaphic metadata. The OTUs are taxonomically and functionally assigned to guilds and other functional groups. The entire dataset has been corrected by excluding chimeras, index-switch artefacts and potential contamination. The dataset is more inclusive in terms of geographical breadth and phylogenetic diversity of fungi than previously published data. The GSMc dataset is available over the PlutoF repository.

This work is aimed to bring insights on the potential sexual dimorphism differences on the venom composition of Bothrops asper and Crotalus simus to expand the knowledge of the venom variability that might improve the antivenom design. Biological characterization of venoms of each sex in both species did not show significant qualitative differences. Considerations on the sexual venom variations in these species are not relevant for choosing the snake donors for venom production.

Fasciolosis caused by the liver flukes Fasciola hepatica and Fasciola gigantica is one of the most important neglected parasitic diseases of humans and animals. The ability of the parasites to infect and multiply in their intermediate snail hosts, and their adaptation to a wide variety of mammalian definitive hosts contribute to their high transmissibility and distribution. Within the mammalian host, the trauma caused by the immature flukes burrowing through the liver parenchyma is associated with most of the pathogenesis. Similarly, the feeding activity and the physical presence of large flukes in the bile ducts can lead to anaemia, inflammation, obstruction and cholangitis. The high frequency of non-synonymous polymorphisms found in Fasciola spp. genes allows for adaptation and invasion of a broad range of hosts. This is also facilitated by parasite's excretory-secretory (ES) molecules that mediate physiological changes that allows their establishment within the host. ES contains cathepsin peptidases that aid parasite invasion by degrading collagen and fibronectin. In the bile ducts, cathepsin-L is critical to haemoglobin digestion during feeding activities. Other molecules (peroxiredoxin, cathepsin-L and Kunitz-type inhibitor) stimulate a strong immune response polarised towards a Treg/Th2 phenotype that favours fluke's survival. Helminth defence molecule, fatty acid binding proteins, Fasciola-specific glycans and miRNAs modulate host pro-inflammatory responses, while antioxidant scavenger enzymes work in an orchestrated way to deter host oxidant-mediated damage. Combining these strategies Fasciola spp. survive for decades within their mammalian host, where they reproduce and spread to become one of the most widespread zoonotic worm parasites in the world.

This is a multicenter prospective observational study which included a large cohort (n = 397) of allogeneic (allo-HSCT) (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3 to 6 weeks after complete SARS-CoV-2 vaccination from February 1st 2021 to July 20th 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia

La activación de BIM es esencial para la apoptosis desencadenada por el inhibidor de la tirosina quinasa (TKI) del receptor del factor de crecimiento epidérmico (EGFR) en el cáncer de pulmón de células no pequeñas (CPCNP) con mutación de EGFR. Una deleción en el intrón dos del gen BIM da como resultado la generación de isoformas empalmadas alternativamente que alteran su respuesta apoptótica a los TKI, lo que confiere a las células de NSCLC una resistencia intrínseca a estos medicamentos. Los pacientes con ambas alteraciones tienen mala evolución clínica. El estudio actual tuvo como objetivo investigar la eficacia clínica y la tolerabilidad de EGFR-TKI más bevacizumab (Bev) versus EGFR-TKI solos como tratamiento de primera línea en pacientes con NSCLC avanzado con mutaciones de EGFR y deleciones BIM (BIMdel). MATERIALES Y MÉTODOS Se realizó un análisis retrospectivo. BIMdel se detectó mediante análisis de reacción en cadena de la polimerasa y secuenciación directa de ADN. La expresión de la proteína BIM se investigó mediante inmunohistoquímica y los niveles de ARNm de BIM mediante la reacción en cadena de la polimerasa con transcriptasa inversa. Se compararon las características clínicas, la supervivencia general, la supervivencia libre de progresión (PFS), la tasa de respuesta general (ORR) y los eventos adversos relacionados con el tratamiento entre ambos grupos. RESULTADOS Se incluyeron 33 pacientes; 15 recibieron EGFR-TKI y 18 recibieron EGFR-TKI más Bev. La mediana de edad fue de 63 años, con una mayoría de pacientes mujeres reclutadas. Todos los individuos incluidos tenían una puntuación de rendimiento del Grupo Oncológico Cooperativo del Este de 2 o menos. La adición de Bev resultó en un ORR significativamente más alto (94,4 % versus 40 %, P > 0,001). La mediana de SLP fue más larga con el uso de la terapia combinada (11,12 frente a 7,87 meses; P = 0,001). La mediana de supervivencia general tendió a ser más prolongada en los inhibidores de la tirosina quinasa con EGFR más Bev (30,9 frente a 25,4 meses; P = 0,06), pero no alcanzó significación estadística. La respuesta en términos de PFS parcial y completa, así como en general, se vio afectada favorablemente. CONCLUSIÓN Los EGFR-TKI más Bev confirieron una ORR y una SLP significativamente más altas en pacientes con NSCLC avanzado con mutación de EGFR y BIMdel. Se necesitan más estudios prospectivos para validar estos hallazgos. BIM activation is essential for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)–triggered apoptosis in EGFR-mutant non–small-cell lung cancer (NSCLC). A deletion in the intron two of the BIM gene results in generation of alternatively spliced isoforms that impairs their apoptotic response to TKIs, conferring the NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel). MATERIALS AND METHODS A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction analysis and direct sequencing of DNA. BIM protein expression was investigated by immunohistochemistry, and BIM mRNA levels by reverse transcriptase-polymerase chain reaction. Clinical characteristics, overall survival, progression-free survival (PFS), overall response rate (ORR), and treatment-related adverse events were compared between both groups. RESULTS Thirty-three patients were included; 15 received EGFR-TKIs, and 18 received EGFR-TKIs plus Bev. The median age was 63 years, with a majority of recruited female patients. All included individuals had an Eastern Cooperative Oncology Group performance score of 2 or less. The addition of Bev resulted in a significantly higher ORR (94.4% v 40%, P > .001). Median PFS was longer with the use of the combination therapy (11.12 v 7.87 months; P = .001). Median overall survival tended to be longer in the EGFR-TKIs plus Bev (30.9 v 25.4 months; P = .06) but failed to reach statistical significance. Response in terms of both partial and complete as well as overall favorably affected PFS. CONCLUSION EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.

The modern cultivated common bean (Phaseolus vulgaris) has evolved from wild common beans distributed in Central America, Mexico and the Andean region of South America. It has been reported that wild common bean accessions have higher levels of protein content than the domesticated dry bean cultivars. However, there is limited proteomic analysis of wild or domesticated common beans. In this investigation, we reported a proteomic analysis of a wild bean from Mexico. We utilized the TCA/Acetone method for protein extraction, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) for protein separation, and subsequent mass spectrometry (MS) for protein identification. Proteins were separated in the first dimension using pH range from 4-7. A total of 237 protein spots from the second dimension were isolated, digested with trypsin, and analyzed by MALDI/TOF/TOF mass spectrometry. We identified 141 protein spots by searching NCBI non redundant databases using the Mascot search engine and found a total of 43 unique proteins. Gene Ontology (GO) analysis was employed to understand the molecular processes in which the identified common bean proteins are involved. The majority of proteins are involved in binding (41.5%) and catalytic activity (35.8%), followed by nutrient reservoir activity (7.5%), antioxidant activity (1.9%), transporter activity (3.8%), enzyme regulator activity (3.8%), structural molecule activity (1.9%), and electron carrier activity (3.8%). The results indicate that TCA/Acetone extraction and 2D-PAGE is efficient in separating common bean proteins. Further identification of these proteins by MS demonstrates the quality of this protein extraction method. These results will be useful for the development of value added common beans by alteration of protein components.

Bovine viral leukosis (BVL) is a disease with a high morbidity and low mortality. There are reports of natural infection in some bovine species, but it has been little studied in buffaloes. In Colombia, buffalo production is growing rapidly, and, so far, there are no reports of the disease. The objective of this study was to characterize buffalo production in the coffee-growing region and to determine, by PCR, the prevalence of BVL in buffaloes, as well as its presence in humans, cattle, and sheep near the coffee-growing region. Blood samples from 140 buffaloes and 10 buffalo milk samples were collected, and so were 58 samples from bovines, 35 samples from sheep, and 9 samples from humans that had been in contact with buffaloes. Hematological analyses were performed. Subsequently, DNA was extracted for PCR evaluation. Production information was gathered, and the results were processed and analyzed using the R software. The majority of animals were Mediterranean breed females, with a birth weight of 33.39 kg, a weaning weight of 202.93 kg, a calving interval of 491.77 d, a time to peak of 67.26 d, and 381.59 L of milk (adjusted to 305 d at two teats). A prevalence of 33.6 % and of 3.4 %, respectively, was detected in buffaloes and in bovines; no milk, sheep or human samples were positive. No risk factors associated with the infection were found; neither were significant alterations of the blood count or factors of production. These results constitute the first molecular report of the bovine leucosis virus (BLV) in the Americas and one of the first in the world.

Cnidarian jellyfish can be dominant players in the food webs of highly productive Eastern Boundary Currents (EBC). However, the trophic role of inconspicuous hydromedusae in EBCs has traditionally been overlooked. We collected mesozooplankton from five stations along two cross-shelf transects in the Northern California Current (NCC) during winter and summer of 2018–2019. We analyzed gut contents of 11 hydromedusan species and the prey community to (i) determine prey resource use by hydromedusae and (ii) determine temporal shifts in the trophic niche of hydromedusae, focusing on the two most collected species (Clytia gregaria and Eutonina indicans). Hydromedusae in the NCC fed mostly on copepods, appendicularians and invertebrate larvae. Nonmetric multidimensional scaling of hydromedusan diets showed seasonal shifts in prey resource driven by the abundant C. gregaria, which fed mostly on copepod eggs during winter and fed mostly on appendicularians and copepods during summer. Prey selectivity for copepod eggs increased during winter for C. gregaria and E. indicans. Intriguingly, theoretical ingestion rates show that both species acquire similar amounts of carbon during upwelling and nonupwelling conditions. Hydromedusae’s consistent presence and predation impact across seasons may lead to significant effects in carbon and energy transfer through the NCC food web.

Highlights • The identification of the KRAS G12C mutation in non-small cell lung cancer is relevant with new molecules being introduced for treatment. • The variation of mutation prevalence among different regions indicate that certain populations are more prone to develop KRAS G12C mutations among lung cancer than others. • Using genomic markers traditionally employed for the identification of individuals we managed to construct a model that was predictive for KRAS G12C mutational incidence, further indicating that appearance of KRAS G12C follows population substructures., Background The KRAS exon 2 p. G12C mutation in patients with lung adenocarcinoma has been increasing in relevance due to the development and effectiveness of new treatment medications. Studies around different populations indicate that regional variability between ethnic groups and ancestries could play an essential role in developing this molecular alteration within lung cancer. Methods In a prospective and retrospective cohort study on samples from lung adenocarcinoma from 1000 patients from different administrative regions in Colombia were tested for the KRAS p.G12C mutation. An analysis of STR populations markers was conducted to identify substructure contributions to mutation prevalence. Results Included were 979 patients with a national mean frequency for the KRAS exon 2 p.G12C mutation of 7.97% (95%CI 6.27–9.66%). Variation between regions was also identified with Antioquia reaching a positivity value of 12.7% (95%CI 9.1–16.3%) in contrast to other regions such as Bogota DC (Capital region) with 5.4% (2.7–8.2%) and Bolivar with 2.4% (95%CI 0–7.2%) (p-value = 0.00262). Furthermore, Short tandem repeat population substructures were found for eight markers that strongly yielded association with KRAS exon 2 p.G12C frequency reaching an adjusted R2 of 0.945 and a p-value of < 0.0001. Conclusions Widespread identification of KRAS exon 2 p.G12C mutations, especially in cases where NGS is not easily achieved is feasible at a population based level that can characterize regional and national patterns of mutation status. Furthermore, this type of mutation prevalence follows a population substructure pattern that can be easily determined by population and ancestral markers such as STR.

The genus Fusarium can be utilized to produce a great variety of secondary metabolites under specific culture conditions, including pigments of increasing biotechnological interest, such as bikaverin. Such pigments are important due to the biological properties they possess, including antitumor and antibiotic activities, among others. In Fusarium fujikuroi, bik1–bik6 have been identified as the genes that are responsible for the synthesis of bikaverin. Therefore, in this study, we screened for the presence of bik genes and examined changes in mRNA levels of the bik genes under the influence of NH4NO3 (0.024, 0.048, 0.50, 1.0, and 4.60 g L−1) and NH4Cl (0.50 and 1.0 g L−1) as nitrogen sources for the phytopathogen Fusarium oxysporum f. sp. lycopersici. Our results indicated the presence of at least six bik (bik1–bik6) genes and showed increased mRNA levels for bik4, bik5, and bik6 in conditions where NH4NO3 was used at pH 3.0. The characteristic coloration of bikaverin was obtained in 10 out of 16 culture conditions, except when the fungus was grown with higher concentrations of NH4NO3 (1.0 and 4.60 g L−1). The pigment was chloroform-extracted from the culture conditions of NH4NO3 (0.024, 0.048, and 0.50 g L−1) and NH4Cl (0.50 and 1.0 g L−1) with 3 and 9 days of incubation. Analysis via visible spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry were used for the identification of bikaverin.

espanolEl objetivo del presente estudio fue establecer la contaminacion bacteriologica de cuatro balnearios recreacionales cercanos a Valledupar (Colombia). Se tomaron 32 muestras durante los meses de octubre a diciembre del ano 2014 y en enero del ano 2015. La determinacion del grupo coliformes se realizo mediante la tecnica de filtracion por membrana combinada con el metodo de sustratos cromogenicos (Merck). A nivel espacial no se presentaron diferencias significativas para los coliformes totales; pero si para el indicador de Escherichia coli. A escala temporal se presentaron diferencias significativas para coliformes totales y E. coli. No hubo correlacion significativa entre las variables microbiologicas y fisicoquimicas. Las altas concentraciones de coliformes totales y E. coli se debe a la introduccion de residuos de origen antropogenico en las zonas examinadas. Se concluye que las concentraciones de coliformes totales y E. coli en las aguas de los balnearios sobrepasan lo estipulado en la normatividad ambiental vigente para uso recreativo mediante contacto primario. EnglishThe objective of the present research study was to examine the level of bacteriological contamination in four recreational river spas near Valledupar (Colombia). Thirty-two samples were collected from October to December 2014 and in January 2015. Quantification of coliforms was performed by the membrane filtration technique combined with the chromogenic substrates method (Merck). There were no significant differences for total coliforms counts at the spatial level, but differences were significant for Escherichia coli. On a temporal scale, there were significant differences for total coliforms and E. coli. In addition, there was no significant correlation between microbiological and physicochemical variables. Residues of anthropogenic origin in the study area most possibly caused the high concentrations of total coliforms and E. coli. In conclusion, the total coliform and E. coli concentrations observed in the recreational spas exceeded current environmental regulations for primary contact use.

Background Survivors of community-acquired pneumonia (CAP) are at increased risk of cardiovascular disease, cognitive and functional decline, and death, but the mechanisms remain unknown. Research Question Do CAP survivors have evidence of increased inflammatory activity in their lung parenchyma on 2-deoxy-2-[18F]fluoro- d -glucose (18FDG)-PET/CT imaging after clinical resolution of infection? Study Design and Methods We obtained 18FDG-PET/CT scans from 22 CAP survivors during their hospitalization with pneumonia (acute CAP) and 30 to 45 days after hospital discharge (post-CAP). In each set of scans, we assessed the lungs for foci of increased 18FDG uptake by visual interpretation and by total pulmonary glycolytic activity (tPGA), a background-corrected measure of total metabolic activity (as measured by 18FDG uptake). We also measured, post-CAP, the glycolytic activity of CAP survivor lung areas with volumes similar to the areas in 28 matched historical control subjects without pneumonia. Results Overall, 68% of CAP survivors (95% CI, 45%-85%) had distinct residual areas of increased 18FDG uptake in their post-CAP studies. tPGA decreased from 821.5 (SD, 1,140.2) in the acute CAP period to 80.0 (SD, 81.4) in the post-CAP period (P = .006). The tPGA post-CAP was significantly higher than that in lung areas of similar volume in control subjects (80.0 [SD, 81.4] vs –19.4 [SD, 5.9]; P Interpretation An important proportion of CAP survivors have persistent pulmonary foci of increased inflammatory activity beyond resolution of their infection. As inflammation contributes to cardiovascular disease, cognitive decline, functional waning, and mortality risk in the general population, this finding provides a plausible mechanism for the increased morbidity and mortality that have been observed post-CAP.

APR-246 (eprenetapopt) is in clinical development with a focus on hematologic malignancies and is promoted as a mutant-p53 reactivation therapy. Currently, the detection of at least one TP53 mutation is an inclusion criterion for patient selection into most APR-246 clinical trials. Preliminary results from our phase Ib/II clinical trial investigating APR-246 combined with doublet chemotherapy [cisplatin and 5-fluorouracil (5-FU)] in metastatic esophageal cancer, together with previous preclinical studies, indicate that TP53 mutation status alone may not be a sufficient biomarker for APR-246 response. This study aims to identify a robust biomarker for response to APR-246. Correlation analysis of the PRIMA-1 activity (lead compound to APR-246) with mutational status, gene expression, protein expression, and metabolite abundance across over 700 cancer cell lines (CCL) was performed. Functional validation and a boutique siRNA screen of over 850 redox-related genes were also conducted. TP53 mutation status was not consistently predictive of response to APR-246. The expression of SLC7A11, the cystine/glutamate transporter, was identified as a superior determinant of response to APR-246. Genetic regulators of SLC7A11, including ATF4, MDM2, wild-type p53, and c-Myc, were confirmed to also regulate cancer-cell sensitivity to APR-246. In conclusion, SLC7A11 expression is a broadly applicable determinant of sensitivity to APR-246 across cancer and should be utilized as the key predictive biomarker to stratify patients for future clinical investigation of APR-246.

Graphical abstract, We report a case of reinfection by SARS-CoV-2 with the second virus harboring amino acid changes in the Spike protein (141-143del, D215A, ins215AGY, L452R, D614 G), orf1a, helicase, orf3a, and Nucleocapside. The virus associated with the reinfection, from an endemic lineage containing the S:L452R immune escape mutation, was circulating in Panama at the time.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, and the number of worldwide cases continues to rise. The zoonotic origins of SARS-CoV-2 and its intermediate and potential spillback host reservoirs, besides humans, remain largely unknown. Because of ethical and experimental constraints and more important, to reduce and refine animal experimentation, we used our repository of well-differentiated airway epithelial cell (AEC) cultures from various domesticated and wildlife animal species to assess their susceptibility to SARS-CoV-2. We observed that SARS-CoV-2 replicated efficiently only in monkey and cat AEC culture models. Whole-genome sequencing of progeny viruses revealed no obvious signs of nucleotide transitions required for SARS-CoV-2 to productively infect monkey and cat AEC cultures. Our findings, together with previous reports of human-to-animal spillover events, warrant close surveillance to determine the potential role of cats, monkeys, and closely related species as spillback reservoirs for SARS-CoV-2.

Species of Russula are ubiquitous members of ectomycorrhizal fungal communities in tropical ecosystems. However, an important part of the total tropical diversity of this genus and its biogeographic patterns is unknown due to the lack of studies on Russula in tropical ecosystems. We combined molecular, morphological, ecological, and biogeographic data to elaborate concepts for two new subspecies of R. floriformis (subsection Substriatinae). Russula floriformis subsp. floriformis and R. floriformis subsp. symphoniae are described as new from montane forest dominated by Quercus and/or Oreomunnea (Fagales) from Colombia and Panama, respectively. Phylogenies were constructed using nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS), D1-D2 domains of nuc 28S rDNA (28S), and partial regions of the second largest subunit of RNA polymerase II (rpb2) and translation elongation factor 1-alpha (tef1). Similar environmental conditions, similar morphology, and an ITS sequence similarity higher than 99% with only three different positions indicate that these two subspecies are closely related. Detailed observations of microscopic structures and analyses of further DNA loci, however, revealed morphological and molecular characteristics that allow distinguishing the two subspecies of R. floriformis. Spatial distribution and phylogenetic proximity of the two Russula subspecies and their ectomycorrhizal hosts, i.e., species of Quercus, suggest that their diversification is a result of comigration, adaptation, and geographic isolation along the Isthmus of Panama during the Pliocene and Pleistocene.

Studies were undertaken across five field locations in Western Australia to determine the relative changes in disease severity and subsequent field pea yield from up to four foliar pathogens associated with a field pea foliar disease complex (viz. genera Didymella, Phoma, Peronospora, and Septoria) across four different pea varieties sown at three different times and at three different densities. Delaying sowing of field pea significantly (P < 0.05) reduced the severity of Ascochyta blight (all five locations) and Septoria blight (one location), increased the severity of downy mildew (four locations), but had no effect on seed yield. In relation to Ascochyta blight severity at 80 days after sowing, at all locations the early time of sowing had significantly (P < 0.05) more severe Ascochyta blight than the mid and late times of sowing. Increasing actual plant density from 20 to 25 plants m−2 to 58 to 78 plants m−2 significantly (P < 0.05) increased the severity of the Ascochyta blight (four locations) and downy mildew (one location), and it increased seed yield at four locations irrespective of sowing date and three locations irrespective of variety. Compared with varieties Dundale, Wirrega, and Pennant, variety Alma showed significantly (P < 0.05) less severe Ascochyta blight, downy mildew, and Septoria blight (one location each). Grain yield was highest for the early time of sowing at three locations. Varieties Alma, Dundale, and Wirrega significantly (P < 0.05) outyielded Pennant at four locations. The percentage of isolations of individual Ascochyta blight pathogens at 80 days after the first time of sowing varied greatly, with genus Didymella ranging from 25 to 93% and genus Phoma ranging from 6 to 23% across the five field locations. This fluctuating nature of individual pathogen types and proportions within the Ascochyta blight complex, along with variation in the occurrence of pathogens Peronospora and Septoria, highlights the challenges to understand and manage the complexities of co-occurring different foliar pathogens of field pea. While the search for more effective host resistance continues, there is a need for and opportunities from further exploring and exploiting cultural management approaches focusing on crop sequence diversification, intercropping, manipulating time of sowing and stand density, and application of improved seed sanitation and residue/inoculum management practices. We discuss the constraints and opportunities toward overcoming the challenges associated with managing foliar disease complexes in field pea.

During organ development, tubular organs often form from flat epithelial primordia. In the placodes of the forming tubes of the salivary glands in the Drosophila embryo, we previously identified spatially defined cell behaviors of cell wedging, tilting, and cell intercalation that are key to the initial stages of tube formation. Here, we address what the requirements are that ensure the continuous formation of a narrow symmetrical tube from an initially asymmetrical primordium whilst overall tissue geometry is constantly changing. We are using live-imaging and quantitative methods to compare wild-type placodes and mutants that either show disrupted cell behaviors or an initial symmetrical placode organization, with both resulting in severe impairment of the invagination. We find that early transcriptional patterning of key morphogenetic transcription factors drives the selective activation of downstream morphogenetic modules, such as GPCR signaling that activates apical-medial actomyosin activity to drive cell wedging at the future asymmetrically placed invagination point. Over time, transcription of key factors expands across the rest of the placode and cells switch their behavior from predominantly intercalating to predominantly apically constricting as their position approaches the invagination pit. Misplacement or enlargement of the initial invagination pit leads to early problems in cell behaviors that eventually result in a defective organ shape. Our work illustrates that the dynamic patterning of the expression of transcription factors and downstream morphogenetic effectors ensures positionally fixed areas of cell behavior with regards to the invagination point. This patterning in combination with the asymmetric geometrical setup ensures functional organ formation.

Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder caused by quantitative or qualitative defects of von Willebrand factor (VWF). This protein far from simplicity constitutes a very complex molecular model, remaining unravelled yet many aspects of it, even though the VWF gene (VWF) was cloned already in 1985 and the structure of VWF well defined. VWD diagnosis is difficult to achieve in a significant proportion of patients due to both disease heterogeneity and limitations in existing test processes. The cornerstone of diagnosis relies on interpretation of VWF test results, the presence of clinical manifestations of bleeding, especially mucocutaneous, and (in most cases) a positive family history. However, even with a significant bleeding history, a family history may not be positive due to factors of incomplete penetrance and variable expressivity that affect genetic changes. The laboratory diagnosis of VWD can be difficult, as the disease is heterogeneous and an array of assays is required to describe the phenotype. Basic classification of quantitative (type 1 and 3) and qualitative (type 2 variants) VWD requires determination of VWF antigenic (VWF:Ag) levels and assaying of VWF ristocetin cofactor (VWF:RCo) activity. The latter is required for identifying and subtyping VWD, but the assay is poorly standardized. For that reason, novel VWF activity assays have been developed awaiting more extensive comparison data between different methodologies and requiring validation on larger patient series. The qualitative type 2 VWF deficiency can be further divided into four different subtypes (A, B, M and N) using specific assays that measure other activities or the size distribution of VWF multimers. However, frequently, it may be difficult to correctly classify the VWD phenotype, and genetic analysis is through mutation identification may provide a tool to clarify the disorder.

There were errors in the name of author Laszlo G. Nagy and in affiliation no. 31 in the original publication. The original article has been corrected.

Fascioliasis is caused in Venezuela by the trematode Fasciola hepatica, affecting herbivorous and human. The Venezuelan Andean region is endemic for bovine fascioliasis and its presence in humans is not known. The objective of this work was to detected positive cases of bovine and human fascioliasis by coprological and immunological techniques and determine the possible risk factors, in eight cattle farms of a Venezuelan Andean rural area. We studied 143 samples of feces and sera of bovines, and 34 samples of feces and sera of humans. Feces were examined by several coprologic techniques, while sera were evaluated by ELISA using two antigens: crude extract (CE) and surface proteins (SP) of F. hepatica, which were previously standardized and validated. The frequency of fascioliasis in bovines was 21% by coprology, and 49.7% by SP-ELISA. The human detection was 0% by coprology, and 29.4% by SP-ELISA. There were statistical significative differences between cattle farms, regarding to the positive results by coprology and by SP-ELISA. About the possible risk factors, statistical association was found only with the presence of snails near or in the farms and consumption of non-channeled water (river, ditch or spring), both for cattle and for humans. The results showed that the studied area is endemic for bovine fascioliasis, the human has been in contact with F. hepatica and there are risk factors for the transmission of the parasite in the studied farms.

Longstanding industrial deposits of 1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (DDT) impose environmental threat in Salamanca city, located in central Mexico. Native bacteria from this location were isolated and identified, and their potential utility for DDT biodegradation was examined. Twenty-five isolates were obtained, and cell lysates were analyzed by matrix-assisted laser desorption/ionization–time of flight mass spectrometry (MALDI-TOF MS) with BiotyperTR; twenty-one organisms were identified at species level, and the other four were assigned to genus. The most abundant species corresponded to Bacillus (44%) and Pseudomonas genera (20%). Eight bacteria could grow in the presence of 200 mg/L of DDT. Two-week exposure of Lysinibacillus fusiformis, Bacillus mycoides, Bacillus pumilus, and Bacillus cereus to DDT 50 mg/L and 200 mg/L, caused percentage pesticide degradation in the range 41–48% and 26–31%, respectively. Other four bacteria presented lower degradation rates. Gas chromatography–mass spectrometry (GC-MS) analysis of the spent media revealed that eight isolates assisted the conversion of DDT, DDD (1,1-dichloro-2,2-bis-(4-chlorophenyl)ethane), and DDE (1,1-dichloro-2,2-bis-(4-chlorophenyl)ethylene) to DDMU (1,1-(2-chloro-1,1-ethenediyl)-bis-(4-chlorobenzene)); however, DDNU (2,2-bis(4-chlorophenyl)ethylene), DBP (4,4′-dichlorobenzophenone(bis(4-chlorophenyl)methanone)) and DBH (bis(4-chlorophenyl)methanol) were found only for L. fusiformis, B. mycoides, B. cereus, B. marisflavi, and B. megaterium. Within the context of DDT biodegradation, the first three were the most promising isolates and further studies will be aimed at setting the experimental conditions for efficient mineralization of DDT congeners.

SummaryThe preservation of Military MacawAra militarisin Mexico required the implementation of a nationwide assessment evaluating its vulnerability using IUCN criteria. With the combined effort of several institutions, the abundance, location, dispersion, habitat availability, and climatic conditions of areas occupied by the species were determined. Although the species’ extent of occurrence is extensive (263,919 km2) only 29% of this constitutes area of occupancy. Published estimates indicate a series of isolated populations containing from four macaws to 215. Macaws occurred in 35 populations in four regions of 16 states containing an estimated 1,563–3,263 macaws; lower than required for long-term viability. Within regions, neighbouring populations were separated by an average of 68 km. The extent of occurrence is heterogeneous, and macaws inhabit areas that differ in elevation, precipitation, temperature, and forest cover. Higher local abundances occur in landscapes where annual precipitation is ≥1,100 mm, and primary forest availability ≥1,800 km2. Although the existence of undetected macaw groups in Mexico is possible, these are likely to contain only small numbers of individuals, as most detected areas with macaws contain less than 40 individuals, and larger concentrations are more likely to be noticed due to their conspicuous behaviour. The species is threatened primarily by its low overall abundance, fragmented distribution, and forest loss around populations with the highest abundance. With the information generated, it is possible to design and implement specific management and conservation strategies at different geographic scales for the recovery and maintenance of the species in Mexico. It is necessary to strengthen collaborative programmes among conservation organizations, government agencies, and local communities in each region of the country to organize and finance community-based actions such as monitoring, habitat restoration, protection from poaching and the creation of a network of conservation corridors and macaw reserves focused on conservation.

Molecular cell 81(19), 3992 - 4007.e10 (2021). doi:10.1016/j.molcel.2021.09.004, ParB-like CTPases mediate the segregation of bacterial chromosomes and low-copy number plasmids. They act as DNA-sliding clamps that are loaded at parS motifs in the centromere of target DNA molecules and spread laterally to form large nucleoprotein complexes serving as docking points for the DNA segregation machinery. Here, we solve crystal structures of ParB in the pre- and post-hydrolysis state and illuminate the catalytic mechanism of nucleotide hydrolysis. Moreover, we identify conformational changes that underlie the CTP- and parS-dependent closure of ParB clamps. The study of CTPase-deficient ParB variants reveals that CTP hydrolysis serves to limit the sliding time of ParB clamps and thus drives the establishment of a well-defined ParB diffusion gradient across the centromere whose dynamics are critical for DNA segregation. These findings clarify the role of the ParB CTPase cycle in partition complex assembly and function and thus advance our understanding of this prototypic CTP-dependent molecular switch., Published by Elsevier, New York, NY

El estudio tuvo comparar dos frecuencias de aspiración folicular in vivo (OPU) en novillas Fleckvieh bajo condiciones tropicales, tomando como variables de respuesta las tasas de maduración, clivaje y producción de blastocistos in vitro. Para ello se emplearon 16 novillas, ocho fueron aspiradas a intervalos de una vez a la semana (T1); y ocho a intervalos de dos veces a la semana (T2); dos sesiones de aspiración por animal, 16 sesiones por tratamiento. Se realizó un análisis de comparación de proporciones (Chi cuadrado) para analizar las variables y se utilizó la dócima t de student para P

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays critical roles during the cellular response to hypoxia. Under normoxic conditions, its function is tightly regulated by the degradation of its alpha subunit (HIF-1α), which impairs the formation of an active heterodimer in the nucleus that otherwise regulates the expression of numerous genes. Importantly, HIF-1 participates in both cancer and infectious diseases unveiling new therapeutic targets for those ailments. Here, we discuss aspects related to the activation of HIF-1, the effects of this transcription factor over immune system components, as well as the involvement of HIF-1 activity in response to viral infections in humans. Although HIF-1 is currently being assessed in numerous clinical settings as a potential therapy for different diseases, up to date, there are no clinical studies evaluating the pharmacological modulation of this transcription factor as a possible new antiviral treatment. However, based on the available evidence, clinical trials targeting this molecule are likely to occur soon. In this review we discuss the role of HIF-1 in viral immunity, the modulation of HIF-1 by different types of viruses, as well as the effects of HIF-1 over their life cycle and the potential use of HIF-1 as a new target for the treatment of viral infections.

Purpose: The current study aimed to identify metabolites associated with age-related macular degeneration (AMD) by performing the largest metabolome association analysis in AMD to date, as well as aiming to determine the effect of AMD-associated genetic variants on metabolite levels and investigate associations between the identified metabolites and activity of the complement system, one of the main AMD-associated disease pathways. Design: Case-control association analysis of metabolomics data. Participants: Five European cohorts consisting of 2267 AMD patients and 4266 control participants. Methods: Metabolomics was performed using a high-throughput proton nuclear magnetic resonance metabolomics platform, which allows quantification of 146 metabolite measurements and 79 derivative values. Metabolome–AMD associations were studied using univariate logistic regression analyses. The effect of 52 AMD-associated genetic variants on the identified metabolites was investigated using linear regression. In addition, associations between the identified metabolites and activity of the complement pathway (defined by the C3d-to-C3 ratio) were investigated using linear regression. Main Outcome Measures: Metabolites associated with AMD. Results: We identified 60 metabolites that were associated significantly with AMD, including increased levels of large and extra-large high-density lipoprotein (HDL) subclasses and decreased levels of very low-density lipoprotein (VLDL), amino acids, and citrate. Of 52 AMD-associated genetic variants, 7 variants were associated significantly with 34 of the identified metabolites. The strongest associations were identified for genetic variants located in or near genes involved in lipid metabolism (ABCA1, CETP, APOE, and LIPC) with metabolites belonging to the large and extra-large HDL subclasses. Also, 57 of 60 metabolites were associated significantly with complement activation levels, independent of AMD status. Increased large and extra-large HDL levels and decreased VLDL and amino acid levels were associated with increased complement activation. Conclusions: Lipoprotein levels were associated with AMD-associated genetic variants, whereas decreased essential amino acids may point to nutritional deficiencies in AMD. We observed strong associations between the vast majority of the AMD-associated metabolites and systemic complement activation levels, independent of AMD status. This may indicate biological interactions between the main AMD disease pathways and suggests that multiple pathways may need to be targeted simultaneously for successful treatment of AMD.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an estimated heritability of around 70%. Although the largest genome-wide association study (GWAS) meta-analysis on ADHD identified independent loci conferring risk to the disorder, the molecular mechanisms underlying the genetic basis of the disorder remain to be elucidated. To explore ADHD biology, we ran a two-step transcriptome profiling in peripheral blood mononuclear cells (PBMCs) of 143 ADHD subjects and 169 healthy controls. Through this exploratory study we found eight differentially expressed genes in ADHD. These results highlight promising candidate genes and gene pathways for ADHD and support the use of peripheral tissues to assess gene expression signatures for ADHD. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The anthracnose disease caused by the fungal pathogen Colletotrichum lindemuthianum (Sacc & Magnus) Briosi & Cavara, is a disease that causes significant seed yield losses in common bean (Phaseolus vulgaris L.) worldwide. A germplasm collection of climbing beans from Guatemala was evaluated in the greenhouse for their reaction to race 73 of C. lindemuthianum that occurs in many growing areas worldwide. This germplasm mostly represents the so-called race Guatemala. Approximately 10% of 369 climbing bean accessions showed no symptoms (score of 1 on a 1–9 anthracnose severity visual score scale). Genome wide association study (GWAS) results using 78,754 SNP markers indicated that genomic regions with resistance to race 73 of C. lindemuthianum exist in Pv04 and Pv07, which have been previously reported. We also report four candidate genes located on Pv04 and Pv07 suspected to be responsible for anthracnose resistance, based on their proximity to significantly associated SNP markers.

1. Bivalve habitat restoration is growing in geographic extent and scale globally. While addressing the wide-scale loss of these biogenic habitats is still a key motivation behind restoration efforts, stakeholders and funders are increasingly drawn to shellfish restoration for the many ecosystem services these habitats provide. 2. There is clear evidence for the provision of ecosystem services from species targeted for restoration in the USA, in particular Crassostrea virginica. Ecosystem services, however, remain largely unquantified or even undescribed for the majority of other species targeted for restoration. 3. A structured review of the literature was undertaken and supplemented by expert knowledge to identify which ecosystem services are documented in the following other bivalve species targeted for restoration: Ostrea edulis, Ostrea angasi, Crassostrea rhizophorae, Perna canaliculus, Modiolus modiolus, Mytilus edulis, Mytilus platensis, Crassostrea gigas, Ostrea denselamellosa, Crassostrea ariakensis, and Crassostrea sikamea. 4. Key knowledge gaps in quantifying ecosystem services and the ecosystem engineering properties of habitat-building bivalves contributing to the provision of ecosystem services were identified. Ecosystem services with the potential to be widely applicable across bivalve habitat-building species were identified. 5. Though there is evidence that many of the ecosystem engineering properties that underpin the provision of ecosystem services are universal, the degree to which services are provided will vary between locations and species. Species-specific, in situ, studies are needed in order to avoid the inappropriate transfer of the ecosystem service delivery between locations, and to further build support and understanding for these emerging targets of restoration.

Linkage and genome-wide association analyses using high-throughput SNP genotyping revealed different loci controlling resistance to different isolates of race 65 of Colletotrichum lindemuthianum in common bean. Development of varieties with durable resistance to anthracnose is a major challenge in common bean breeding programs because of the extensive virulence diversity of Colletotrichum lindemuthianum fungus. We used linkage and genome-wide association analyses to tap the genomic regions associated with resistance to different isolates of race 65. Linkage mapping was done using an F2 population derived from the cross between the Mesoamerican common beans BRS Estilo x Ouro Vermelho, inoculated with two different isolates of race 65. Association genetics relied on a diversity common bean panel containing 189 common bean accessions inoculated with five different isolates of race 65 as an attempt to validate the linkage analysis findings and, eventually, identify other genomic regions associated with resistance to race 65. The F2 population and diversity panel were genotyped with the BARCBean6K_3 Illumina BeadChip containing 5398 SNP markers. Both linkage and genome-wide association analyses identified different loci controlling resistance to different isolates of race 65 on linkage group Pv04. Genome-wide association analysis also detected loci on Pv05, Pv10 and Pv11 associated with resistance to race 65. These findings indicate that resistance to race 65 can be overcome by the virulence diversity among different isolates of the same race and could lead to the loss of resistance after cultivar release. We identified 25 resistant common bean cultivars to all five isolates of race 65 in the diversity panel. The accessions should be useful to develop cultivars combining different resistance genes that favor durable resistance to anthracnose in common bean.

The invasion of Lehmann lovegrass (Eragrostis lehmanniana Nees) in rangelands of Chihuahua, Mexico, has resulted in a need for revegetation to recover lost forage productivity. Thus, new knowledge on generating alternatives to improve these invaded grasslands is of great importance. This study evaluated seedbeds prepared with unconventional tillage implements and seeded with a grass mixture to reduce the plant density of E. lehmanniana while increasing the productivity of an invaded semiarid grassland of Chihuahua. The unconventional tillage implements were: a Rangeland Harrow, which was used to prepare the Striped Harrowing and Full Harrowing seedbeds; Rangeland Rehabilitator, which was used to prepare the Deep-Stingray Subsoiler seedbed; and a Tandem-type Aerator Roller, which was used to prepare the Double-Digging Aeration seedbed. An area without tillage was left as a control. The seed mixture was composed of blue grama [Bouteloua gracilis (Willd. ex Kunth) Lag. ex Griffiths var. Hachita] (25%); sideoats grama [Bouteloua curtipendula (Michx.) Torr. ‘6107 Kansas’] (25%); green sprangletop [Leptochloa dubia (Kunth) Nees var. Van Horn] (5%); weeping lovegrass [Eragrostis curvula (Schrad.) Nees var. Ermelo] (40%), and Columbus grass [Sorghum almum Parodi] (5%). The experiment was conducted across 4 yr, and the evaluation started at the second year. Plant density and dry matter (DM) production were evaluated per species. In the control plot, the plant density of E. lehmanniana increased approximately 180% from the 2nd to the 4th year (18 to 50 plants m−2). The use of unconventional tillage implements for seedbed preparation and the inclusion of E. curvula in the seed mixture decreased E. lehmanniana density in more than 50% of plots and increased DM production in around 100% of plots. Considering the whole experimental period, in all the prepared seedbed treatments, E. curvula had the highest establishment and DM production of all the seeded species. The native species B. gracilis, B. curtipendula, and L. dubia had poor establishment in all the prepared seedbeds.

Coral cover is decreasing worldwide largely as a result of a rise in seawater temperatures that triggers coral bleaching and induces coral mortality. How coral reefs will respond to climate change will be a function of genetic variation and how it is partitioned within and among species. A critical initial step is to accurately delineate species and quantify their physiological potential to cope with heat stress. Cryptic species are morphologically similar but genetically distinct and may respond physiologically differently to climate change. A dominant Caribbean reef builder severely affected by climate change is the mountainous star coral, Orbicella faveolata. Recently in this journal, Dziedzic et al. reported quantitative genetic variation in the physiological response to thermal stress in a single population of this species, suggesting that variation within populations will allow these corals to adapt to rising ocean temperatures. We reanalysed their data and found multiple cryptic lineages rather than a single panmictic population, with one of the lineages being heat-intolerant. While different cryptic lineages co-occur in certain locations, there is at least one lineage that occurs only in a single location. Our finding of hidden lineages within a threatened species highlights the varying extinction risks faced by these independently evolving groups, especially when the prospects of survival under warmer oceans seem favourable for only some of them.

Mucor circinelloides is an opportunistic dimorphic pathogen, with the dimorphic process controlled in parts by fermentative and oxidative metabolisms, which lead to yeast or mycelial growth, respectively. Dimorphic transition is important for pathogenesis since the mycelium represents the virulent morphology. We previously reported that the deletion of arl1 or arl2 stimulate anaerobic germination in M. circinelloides, suggesting an augmented fermentative metabolism. In the present study, we demonstrate that the heterokaryon Δarl1(+)(−) and homokaryon Δarl2 strains contain low number of mitochondria, which possibly results in a dysfunctional oxidative metabolism, marked by a low oxygen consumption in glucose and poor growth in glycerol as the unique carbon source. This dysfunction is compensated for by an increase in the glycolysis and fermentation in aerobic conditions, demonstrating growth kinetics similar to that in the wild-type strain. Moreover, as a consequence a high fermentative activity, the Δarl1(+)(−) and Δarl2 strains possibly increased the yeast cell growth during low oxygen concentrations in presence of glucose. To the best of our knowledge, this is the first study to demonstrate the control of members of Arf family on the mitochondrial population in a Mucor species.

This study reports the salamander Oedipina complex (Dunn, 1924) in a tropical and relictual humid forest in the Magdalena Valley, Colombia. Previous records outline O. complex as a species associated with the pluvial forests of central and northern areas of the Chocó Biogeographic Region in Colombia, Ecuador, and Panama. Based on this new record, the geographic distribution of the species is expanded 257 km east.

Purpose Triple negative breast cancers (TNBCs) are enriched in cells bearing stem-like features, i.e., cancer stem cells (CSCs), which underlie cancer progression. Thus, targeting stemness may be an interesting treatment approach. The epigenetic machinery is crucial for maintaining the stemness phenotype. Bromodomain and extra-terminal domain (BET) epigenetic reader family members are emerging as novel targets for cancer therapy, and have already shown preclinical effects in breast cancer. Here, we aimed to evaluate the effect of the BET inhibitor JQ1 on stemness in TNBC. Methods Transcriptomic, functional annotation and qRT-PCR studies were performed on JQ1-exposed TNBC cells in culture. The results obtained were confirmed in spheroids and spheroid-derived tumours. In addition, limiting dilution, secondary and tertiary tumour sphere formation, matrigel invasion, immunofluorescence and flow cytometry assays were performed to evaluate the effect of JQ1 on CSC features. For clinical outcome analyses, the online tool Kaplan-Meier Plotter and an integrated response database were used. Results We found that JQ1 modified the expression of stemness-related genes in two TNBC-derived cell lines, MDA-MB-231 and BT549. Among these changes, the CD44 Antigen/CD24 Antigen (CD44/CD24) ratio and Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) expression level, i.e., both classical stemness markers, were found to be decreased by JQ1. Using a validated spheroid model to mimic the intrinsic characteristics of CSCs, we found that JQ1 decreased surface CD44 expression, inhibited self-renewal and invasion, and induced cell cycle arrest in G0/G1, thereby altering the stemness phenotype. We also found associations between four of the identified stemness genes, Gap Junction Protein Alpha 1 (GJA1), CD24, Epithelial Adhesion Molecule (EPCAM) and SRY-related HMG-box gene 9 (SOX9), and a worse TNBC patient outcome. The expression of another two of the stemness-related genes was found to be decreased by JQ1, i.e., ATP Binding Cassette Subfamily G Member 2 (ABCG2) and RUNX2, and predicted a low response to chemotherapy in TNBC patients, which supports a role for RUNX2 as a potential predictive marker for chemotherapy response in TNBC. Conclusions We identified a stemness-related gene panel associated with JQ1 and describe how this inhibitor modifies the stemness landscape in TNBC. Therefore, we propose a novel role for JQ1 as a stemness-targeting drug. Loss of the stem cell phenotype via JQ1 treatment could lead to less aggressive and more chemo-sensitive tumours, reflecting a better patient prognosis. Thus, the identified gene panel may be of interest for the clinical management of patients with aggressive TNBC.

In order to increase survival rates of greenhouse seedlings destined for restoration and conservation programs, successful mycorrhization of the seedlings is necessary. To reforest forest ecosystems, host trees must be inoculated with ectomycorrhizal fungi and, in order to guarantee a sufficient supply of ectomycorrhizal inoculum, it is necessary to develop technologies for the mass production of ectomycorrhizal fungi mycelia. We selected the ectomycorrhizal fungus Laccaria trichodermophora, due to its ecological traits and feasible mycelia production in asymbiotic conditions. Here, we report the field sampling of genetic resources, as well as the highly productive nutritional media and cultivation parameters in solid cultures. Furthermore, in order to achieve high mycelial production, we used strain screening and evaluated pH, carbon source concentration, and culture conditions of submerged cultures in normal and baffled shake flasks. The higher productivity culture conditions in shake flasks were selected for evaluation in a pneumatic bioreactor, using modified BAF media with a 10 g/L glucose, pH 5.5, 25 °C, and a volumetric oxygen transfer coefficient (KLa) of 36 h−1. Under those conditions less biomass (12–37 %) was produced in the pneumatic bioreactor compared with the baffled shake flasks. This approach shows that L. trichodermophora can generate a large biomass concentration and constitute the biotechnological foundation of its mycelia mass production.