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In 2018 the Organisation for Economic Co-operation and Development (OECD) launched its International Early Learning Child Well-being Study (IELS), also known as Baby PISA. In the first round of data collection, the IELS focused on three OECD countries: England, Estonia and the United States. In this article we show that a similar study of pre-schoolers to IELS took place in Mexico – EXCALE for Pre-school – and argue there is much the research community can learn from an empirical study of this initiative. Our novel comparative study draws on data from policy documents and interviews with sub-national and municipal education officials in Mexico. We reveal how EXCALE for Pre-school led to a narrowing of teaching practices and standardising student assessment aimed at 5-year-olds. We argue that the Mexican case shows how large-scale assessments bring early years learners into the orbit of official state governing, and that assessment now drives those pedagogical practices that limit the diversity of learning experiences of pre-schoolers. [ABSTRACT FROM AUTHOR]

Cotija and Bola de Ocosingo are artisanal ripened cheeses produced in Mexico. Both are made with raw bovine milk from free-grazing cows and with no starter cultures. Unlike culture-based techniques, molecular methods for pathogen detection in food allow a shorter turnaround time, higher detection specificity, and represent a lower microbiological risk for the analyst. In the present investigation, we analyzed 111 cheese samples (95 Cotija and 16 Bola de Ocosingo) by qPCR (TaqMan®) after an enrichment-culture step specific to each foodborne bacterium. The results showed that 100% of the samples were free of DNA from Listeria monocytogenes, Brucella spp., Escherichia coli enterotoxigenic (ETEC), and O157:H7; 9% amplified Salmonella spp. DNA; and 11.7%, Staphylococcus aureus DNA. However, the threshold cycle (Ct) values of the amplified targets ranged between 23 and 30, indicating DNA from non-viable microorganisms. Plate counts supported this assumption. In conclusion, 100% of the cheeses analyzed were safe to consume, and the enrichment step before DNA extraction proved essential to discern between viable and non-viable microorganisms. Hygienic milking, milk handling, cheese manufacturing, and ripening are crucial to achieve an adequate microbiological quality of cheeses made with raw milk. [ABSTRACT FROM AUTHOR]

Sodium tungstate (Na2WO4) normalizes glucose metabolism in the liver and muscle, activating the Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Because this pathway controls neuronal survival and differentiation, we investigated the effects of Na2WO4 in mouse Neuro2a and human SH-SY5Y neuroblastoma monolayer cell cultures. Na2WO4 promotes differentiation to cholinergic neurites via an increased G1/G0 cell cycle in response to the synergic activation of the Phosphatidylinositol 3-kinase (PI3K/Akt) and ERK1/2 signaling pathways. In Neuro2a cells, Na2WO4 increases protein synthesis by activating the mechanistic target of rapamycin (mTOR) and S6K kinases and GLUT3-mediated glucose uptake, providing the energy and protein synthesis needed for neurite outgrowth. Furthermore, Na2WO4 increased the expression of myocyte enhancer factor 2D (MEF2D), a member of a family of transcription factors involved in neuronal survival and plasticity, through a post-translational mechanism that increases its half-life. Site-directed mutations of residues involved in the sumoylation of the protein abrogated the positive effects of Na2WO4 on the MEF2D-dependent transcriptional activity. In addition, the neuroprotective effects of Na2WO4 were evaluated in the presence of advanced glycation end products (AGEs). AGEs diminished neurite differentiation owing to a reduction in the G1/G0 cell cycle, concomitant with lower expression of MEF2D and the GLUT3 transporter. These negative effects were corrected in both cell lines after incubation with Na2WO4. These findings support the role of Na2WO4 in neuronal plasticity, albeit further experiments using 3D cultures, and animal models will be needed to validate the therapeutic potential of the compound. [ABSTRACT FROM AUTHOR]

RNA degradation is an essential process that allows bacteria to regulate gene expression and has emerged as an important mechanism for controlling virulence. However, the individual contributions of RNases in this process are mostly unknown. Here, we tested the influence of 11 potential RNases in the intestinal pathogen Yersinia pseudotuberculosis on the expression of its type III secretion system (T3SS) and associated effectors (Yops) that are encoded on the Yersinia virulence plasmid. We found that exoribonuclease PNPase and endoribonuclease RNase III inhibit T3SS and yop gene transcription by repressing the synthesis of LcrF, the master activator of Yop-T3SS. Loss of both RNases led to an increase in lcrF mRNA levels. Our work indicates that PNPase exerts its influence via YopD, which accelerates lcrF mRNA degradation. Loss of RNase III, on the other hand, results in the downregulation of the CsrB and CsrC RNAs, thereby increasing the availability of active CsrA, which has been shown previously to enhance lcrF mRNA translation and stability. This CsrA-promoted increase of lcrF mRNA translation could be supported by other factors promoting the protein translation efficiency (e.g. IF-3, RimM, RsmG) that were also found to be repressed by RNase III. Transcriptomic profiling further revealed that Ysc-T3SS-mediated Yop secretion leads to global reprogramming of the Yersinia transcriptome with a massive shift of the expression from chromosomal to virulence plasmid-encoded genes. A similar reprogramming was also observed in the RNase III-deficient mutant under non-secretion conditions. Overall, our work revealed a complex control system where RNases orchestrate the expression of the T3SS/Yop machinery on multiple levels to antagonize phagocytic uptake and elimination by innate immune cells. Author summary: Bacterial pathogens need to quickly adapt the expression of virulence- and fitness-relevant traits in response to host defenses. Pathogenic Yersinia species rapidly upregulate a type III secretion system (T3SS) to inject antiphagocytic and cell toxic effector proteins, named Yersinia outer proteins (Yops), into attacking immune cells. For this purpose, they display complex and resilient regulatory mechanisms. At the post-transcriptional level, this is mediated by different RNA-binding regulators including YopD and CsrA, while the fate of mRNAs is balanced by ribonucleases. Here, we demonstrate that out of 11 tested putative RNases of Yersinia, two major RNases, the endoribonuclease RNase III, and the exonuclease and degradosome component PNPase play a crucial role in the activation of the Ysc-T3SS/Yop machinery. We show that they promote the decay of the lcrF mRNA encoding the common transcriptional activator LcrF of the Ysc-T3SS/Yop components. PNPase seems to act through the control of the effector YopD, known to promote the decay of the lcrF transcript. In contrast, RNase III triggers processes that reduce lcrF mRNA translation and stability, and involve CsrA. A transcriptome analysis further revealed that RNase III controls a series of events that include rapid and massive genetic reprogramming from mainly chromosomal-encoded genes to virulence-plasmid-encoded ysc-T3SS/yop genes. This control process ensures immediate counter-measures during an immune attack but could also help to overcome the associated energetic burdens of defense reactions and allow a rapid readjustment of the genetic program after a successful defense. [ABSTRACT FROM AUTHOR]

Neltuma alba (algarrobo blanco) is a commercially valuable native in Argentina that is of interest for the restoration of degraded soils. Incorporation of arbuscular mycorrhizal fungi (AMF) has been suggested to benefit plants during field establishment. The aim of this study was to evaluate the edaphic properties and growth of N. alba plantations inoculated with AMF isolated from the Chaco Region of Argentina six years after field establishment. The treatments consisted of plants inoculated with AMF isolated from two sites: Colonia Benitez (CB, Chaco Province, humid site) and Padre Lozano (PL, Salta Province, semi-arid site). The uninoculated control (TE) group was maintained. Survival, collar diameter, and total plant height were measured. Additionally, composite soil samples were collected per treatment to determine physical, chemical, and biological variables. Regardless of inoculation, the incorporation of trees had positive effects on the evaluated edaphic properties. Soil samples from plants inoculated with CB showed higher values of total biological activity, electrical conductivity, pH, exchangeable calcium, and soil respiration. In contrast, soil samples from plants inoculated with PL showed higher organic matter content. N. alba plants inoculated with AMF from CB exhibited the lowest growth rates under the environmental conditions evaluated. [ABSTRACT FROM AUTHOR]

Abstract Neuroscience has studied deductive reasoning over the last 20 years under the assumption that deductive inferences are not only de jure but also de facto distinct from other forms of inference. The objective of this research is to verify if logically valid deductions leave any cerebral electrical trait that is distinct from the trait left by non-valid deductions. 23 subjects with an average age of 20.35 years were registered with MEG and placed into a two conditions paradigm (100 trials for each condition) which each presented the exact same relational complexity (same variables and content) but had distinct logical complexity. Both conditions show the same electromagnetic components (P3, N4) in the early temporal window (250–525 ms) and P6 in the late temporal window (500–775 ms). The significant activity in both valid and invalid conditions is found in sensors from medial prefrontal regions, probably corresponding to the ACC or to the medial prefrontal cortex. The amplitude and intensity of valid deductions is significantly lower in both temporal windows (p = 0.0003). The reaction time was 54.37% slower in the valid condition. Validity leaves a minimal but measurable hypoactive electrical trait in brain processing. The minor electrical demand is attributable to the recursive and automatable character of valid deductions, suggesting a physical indicator of computational deductive properties. It is hypothesized that all valid deductions are recursive and hypoactive.

BackgroundInfertile men with non-obstructive azoospermia (NOA) have impaired spermatogenesis. Dilated and un-dilated atrophic seminiferous tubules are often present in the testes of these patients, with the highest likelihood of active spermatogenesis in the dilated tubules. Little is known about the un-dilated tubules, which in NOA patients constitute the majority. To advance therapeutic strategies for men with NOA who fail surgical sperm retrieval we aimed to characterize the spermatogonial stem cell microenvironment in atrophic un-dilated tubules.MethodsTestis biopsies approximately 3x3x3 mm3 were obtained from un-dilated areas from 34 patients. They were classified as hypospermatogenesis (HS) (n=5), maturation arrest (MA) (n=14), and Sertoli cell only (SCO) (n= 15). Testis samples from five fertile men were included as controls. Biopsies were used for histological analysis, RT-PCR analysis and immunofluorescence of germ and Sertoli cell markers.ResultsAnti-Müllerian hormone mRNA and protein expression was increased in un-dilated tubules in all three NOA subtypes, compared to the control, showing an immature state of Sertoli cells (p

Living in an industrialized era, we are exposed to man-made chemicals including persistent organic pollutants (POPs). Previous studies have shown associations of POP exposure with adverse outcomes in humans, wildlife, and the environment, making it a global concern. Exposure during sensitive windows of susceptibility such as fetal development is of particular concern because of the potential increased risk of developing diseases in childhood and adulthood. However, there are limited studies on the sexual dimorphism of POP accumulation during the prenatal period. In this mini-review, we focus on differences in POP concentrations in the placenta and fetal tissues between males and females. We also show the sexually dimorphic adverse outcomes of prenatal exposure to POPs. Overall, our summary shows that males may accumulate higher concentrations of POPs in the placenta and fetal tissues compared to females, although studies are sparse and inconsistent. In addition, there are differences in adverse health outcomes associated to prenatal POP exposure according to sex. Hence, we highly urge researchers investigating the health effects of POP exposure to consider sexual dimorphism in their studies.

La evaluación por organismos externos se ha convertido en un mecanismo tendiente a promover la mejora continua en la educación superior. El objetivo de esta investigación fue describir las experiencias que guardan los profesores universitarios de una institución pública del noroeste de México, respecto a los procesos de evaluación y acreditación de programas educativos por parte de organismos externos. Se realizó un estudio de tipo cualitativo que empleó un diseño de estudio de caso, y entrevista como técnica para recolección de datos. Los principales hallazgos indican que el ejercicio de evaluación externa ha traído beneficios relacionados con la mejora de los programas educativos, pero también se han identificado consecuencias no deseadas ligadas a la dinámica de trabajo que en cierta forma inhibe la mejora continua institucional. También se observa que la falta de estudios empíricos respecto a las voces de los diferentes actores de las universidades, representa una importante limitación para la mejora de estos procesos. En conclusión, es importante tomar en cuenta las fortalezas y áreas de oportunidad que han traído los procesos de evaluación externa, así como desarrollar nuevos estudios que permitan argumentar estrategias que conlleven a la mejora continua de la institución.

Currently, there is a varied production of knowledge that has enriched what is known about the conquest of the Wallmapubetween 1879 and 1885. A subject that, at least in the primary and secondary schools of the Alto Valle de Rio Negro and Neuquén (Argentina), forms part of the prescribed and taught curriculum; it has a classic presence in school editorial proposals and inteaching practices at these educational levels in the region. The purpose of this article is to communicate a material that contributes to its teaching, initially distinguishing some aspects of what is known about the subject, then identifying some problems and challenges in its teaching and raising the perspectives and didactic foundations that guided its development. Finally, the material is presented and some aspects of it are highlighted in concrete experiences in teacher training and in its use with primary school students.

Multiplex immunofluorescence is a powerful tool for the simultaneous detection of tissue‐based biomarkers, revolutionising traditional immunohistochemistry. The Opal methodology allows up to eight biomarkers to be measured concomitantly without cross‐reactivity, permitting identification of different cell populations within the tumour microenvironment. In this study, we aimed to validate a multiplex immunofluorescence workflow in two complementary multiplex panels and evaluate the tumour immune microenvironment in colorectal cancer (CRC) formalin‐fixed paraffin‐embedded tissue. We stained CRC and tonsil samples using Opal multiplex immunofluorescence on a Leica BOND RX immunostainer. We then acquired images on an Akoya Vectra Polaris and performed multispectral unmixing using inform. Antibody panels were validated on tissue microarray sections containing cores from six normal tissue types, using qupath for image analysis. Comparisons between chromogenic immunohistochemistry and multiplex immunofluorescence on consecutive sections from the same tissue microarray showed significant correlation (rs > 0.9, P‐value

La acción de nulidad en contra de los laudos arbitrales surge en el Ecuador como mecanismo de control judicial al arbitraje al ser este un método alternativo de resolución de controversias con potestades jurisdiccionales. Ante interpretaciones amplias de las causales existentes de la acción de nulidad previstas en la Ley de Arbitraje y Mediación, la Corte Constitucional emitió en el 2019 dos sentencias que limitan la aplicación de las causales, ratificando la taxatividad de las mismas. Por esta razón, el presente artículo busca realizar un análisis del régimen jurídico de la acción de nulidad en el Ecuador y establecer si las causales deberían ser taxativas o no. En este sentido, en primer lugar, se expondrá la acción de nulidad y su rol en el arbitraje. A continuación, se analizarán diversas decisiones que reflejan la interpretación, el alcance y la aplicación de las causales de anulación. Una vez establecidas las diversas posiciones que ha tomado la jurisprudencia ecuatoriana, se ratificará la taxatividad de las causales de anulación de laudos al ser una característica intrínseca de la excepcionalidad de dicha acción. Finalmente, se pondrán en consideración causales no previstas en el ordenamiento jurídico ecuatoriano, pero que deben ser tomadas en cuenta por el rol del Estado a nivel internacional.

Abstract Background Limited studies examine the immune landscape in Esophageal Adenocarcinoma (EAC). We aim to identify novel associations, which may inform immunotherapy treatment stratification. Methods Three hundred twenty-nine EAC cases were available in Tissue Microarrays (TMA) format. A discovery cohort of 166 EAC cases were stained immunohistochemically for range of adaptive immune (CD3, CD4, CD8 and CD45RO) and immune checkpoint biomarkers (ICOS, IDO-1, PD-L1, PD-1). A validation cohort of 163 EAC cases was also accessed. A digital pathology analysis approach was used to quantify biomarker density. Results CD3, CD4, CD8, CD45RO, ICOS and PD-1 were individually predictive of better overall survival (OS) (Log rank p =

Insulin-like peptide 3 (INSL3) is a small peptide hormone of the insulin-relaxin family which is produced and secreted by the fetal Leydig cells in the testes only. It appears to be undetectable in female fetuses. In the human fetus INSL3 synthesis begins immediately following gonadal sex determination at weeks 7 to 8 post coitum and the peptide can be detected in amniotic fluid 1 to 2 weeks later. INSL3 acts through a unique G-protein-coupled receptor, called RelaXin-like Family Peptide receptor 2 (RXFP2), which is expressed by the mesenchymal cells of the gubernacular ligament linking the testes to the inguinal wall. The role of INSL3 in the male fetus is to cause a thickening of the gubernaculum which then retains the testes in the inguinal region, while the remainder of the abdominal organs grow away in an antero-dorsal direction. This represents the first phase of testis descent and is followed later in pregnancy by the second inguino-scrotal phase whereby the testes pass into the scrotum through the inguinal canal. INSL3 acts as a significant biomarker for Leydig cell differentiation in the fetus and may be reduced by maternal exposure to endocrine disrupting chemicals, such as xenoestrogens or phthalates, leading to cryptorchidism. INSL3 may have other roles within the fetus, but as a Leydig cell biomarker its reduction acts also as a surrogate for anti-androgen action.

BackgroundCryopreservation of prepubertal testicular tissue preserves spermatogonial stem cells (SSCs) that may be used to restore fertility in men at risk of infertility due to gonadotoxic treatments for either a malignant or non-malignant disease. Spermatogonial stem cell-based transplantation is a promising fertility restoration technique. Previously, we performed xenotransplantation of propagated SSCs from prepubertal testis and found human SSCs colonies within the recipient testes six weeks post-transplantation. In order to avoid the propagation step of SSCs in vitro that may cause genetic and epigenetic changes, we performed direct injection of single cell suspension in this study, which potentially may be safer and easier to be applied in future clinical applications.MethodsTestis biopsies were obtained from 11 infant boys (median age 1.3 years, range 0.5-3.5) with cryptorchidism. Following enzymatic digestion, dissociated single-cell suspensions were prelabeled with green fluorescent dye and directly transplanted into seminiferous tubules of busulfan-treated mice. Six to nine weeks post-transplantation, the presence of gonocytes and SSCs was determined by whole-mount immunofluorescence for a number of germ cell markers (MAGEA, GAGE, UCHL1, SALL4, UTF1, and LIN28), somatic cell markers (SOX9, CYP17A1).ResultsFollowing xenotransplantation human infant germ cells, consisting of gonocytes and SSCs, were shown to settle on the basal membrane of the recipient seminiferous tubules and form SSC colonies with expression of MAGEA, GAGE, UCHL1, SALL4, UTF1, and LIN28. The colonization efficiency was approximately 6%. No human Sertoli cells were detected in the recipient mouse testes.ConclusionXenotransplantation, without in vitro propagation, of testicular cell suspensions from infant boys with cryptorchidism resulted in colonization of mouse seminiferous tubules six to nine weeks post-transplantation. Spermatogonial stem cell-based transplantation could be a therapeutic treatment for infertility of prepubertal boys with cryptorchidism and boys diagnosed with cancer. However, more studies are required to investigate whether the low number of the transplanted SSC is sufficient to secure the presence of sperm in the ejaculate of those patients over time.

Childhood obesity prevention is important to avoid obesity and its comorbidities into adulthood. Although the energy density of food has been considered a main obesogenic factor, a focus on food quality rather that the quantity of the different macronutrients is needed. Therefore, this study investigates the effects of changing the quality of carbohydrates from rapidly to slowly digestible carbohydrates on metabolic abnormalities and its impact on obesity in growing rats fed a high-fat diet (HFD). Growing rats were fed on HFD containing carbohydrates with different digestion rates: a HFD containing rapid-digesting carbohydrates (OBE group) or slow-digesting carbohydrates (ISR group), for 4 weeks and the effect on the metabolism and signaling pathways were analyzed in different tissues. Animals from OBE group presented an overweight/obese phenotype with a higher body weight gain and greater accumulation of fat in adipose tissue and liver. This state was associated with an increase of HOMA index, serum diacylglycerols and triacylglycerides, insulin, leptin, and pro-inflammatory cytokines. In contrast, the change of carbohydrate profile in the diet to one based on slow digestible prevented the obesity-related adverse effects. In adipose tissue, GLUT4 was increased and UCPs and PPARγ were decreased in ISR group respect to OBE group. In liver, GLUT2, FAS, and SRBP1 were lower in ISR group than OBE group. In muscle, an increase of glycogen, GLUT4, AMPK, and Akt were observed in comparison to OBE group. In conclusion, this study demonstrates that the replacement of rapidly digestible carbohydrates for slowly digestible carbohydrates within a high-fat diet promoted a protective effect against the development of obesity and its associated comorbidities.

Glioblastoma (GBM) is the most prevalent and aggressive adult brain tumor. Despite multi-modal therapies, GBM recurs, and patients have poor survival (~14 months). Resistance to therapy may originate from a subpopulation of tumor cells identified as glioma-stem cells (GSC), and new treatments are urgently needed to target these. The biology underpinning GBM recurrence was investigated using whole transcriptome profiling of patient-matched initial and recurrent GBM (recGBM). Differential expression analysis identified 147 significant probes. In total, 24 genes were validated using expression data from four public cohorts and the literature. Functional analyses revealed that transcriptional changes to recGBM were dominated by angiogenesis and immune-related processes. The role of MHC class II proteins in antigen presentation and the differentiation, proliferation, and infiltration of immune cells was enriched. These results suggest recGBM would benefit from immunotherapies. The altered gene signature was further analyzed in a connectivity mapping analysis with QUADrATiC software to identify FDA-approved repurposing drugs. Top-ranking target compounds that may be effective against GSC and GBM recurrence were rosiglitazone, nizatidine, pantoprazole, and tolmetin. Our translational bioinformatics pipeline provides an approach to identify target compounds for repurposing that may add clinical benefit in addition to standard therapies against resistant cancers such as GBM.

The biomass of crops in rotation, such as that generated by the banana plant, is an interesting source of lignocellulose due to its composition and availability. This research aimed to compare the amount of glucose obtained from different parts of the banana plant (leaves, rachis, and pseudostem) by hydrolysis with sulfuric acid at 100 °C. This reaction was analyzed to determine the amount of water and reagents consumed versus the glucose obtained. The optimal time and acid concentration were studied between 0–30 min and 3–5% v/v, respectively. The best results were obtained with the pseudostem of 13.02 gL−1 of glucose in a reaction time of 20 min and an acid concentration of 5%. In addition, the kinetic study of hydrolysis was carried out. The adjustment to the Saeman model was R2 0.96, which represents a first-order reaction and kinetic constants K1 = 0.5 and K2 = 0.3 min−1. This study has shown that these residues can be used as raw materials to generate value-added products due to their high glucose content.