Hypoxia coordinates the spatial landscape of myeloid cells within glioblastoma to affect survival.

Myeloid cells are highly prevalent in glioblastoma (GBM), existing in a spectrum of phenotypic and activation states. We now have limited knowledge of the tumor microenvironment (TME) determinants that influence the localization and the functions of the diverse myeloid cell populations in GBM. Here, we have utilized orthogonal imaging mass cytometry with single-cell and spatial transcriptomic approaches to identify and map the various myeloid populations in the human GBM tumor microenvironment (TME). Our results show that different myeloid populations have distinct and reproducible compartmentalization patterns in the GBM TME that is driven by tissue hypoxia, regional chemokine signaling, and varied homotypic and heterotypic cellular interactions. We subsequently identified specific tumor subregions in GBM, based on composition of identified myeloid cell populations, that were linked to patient survival. Our results provide insight into the spatial organization of myeloid cell subpopulations in GBM, and how this is predictive of clinical outcome.

¿Cómo mejoramos la participación comunitaria en salud? Análisis de las acciones propuestas tras la aplicación de una herramienta de evaluación / How to improve community engagement in health: Analysis of proposed actions following the implementation of a community engagement assessment tool

Objetivo Analizar las líneas de acción propuestas por los proyectos de promoción de la salud participantes en el proyecto de investigación EvaluAGPS, y su relación con las puntuaciones obtenidas con EvalGuía, una herramienta para evaluar la participación comunitaria basada en la evidencia. Diseño Estudio multicéntrico cuali-cuantitativo. Emplazamiento Proyectos de atención primaria o de red intersectorial de atención primaria y municipalidades de 5 comunidades autónomas en España. Participantes Personas que trabajan en 10 proyectos de promoción de la salud, seleccionados con muestreo intencional según criterios de inclusión (proyectos con un mínimo de participación comunitaria centrados en la salud comunitaria). Método Se recogieron los datos mediante cuestionarios (herramienta EvalGuía) y talleres participativos. Los datos cuantitativos se analizaron con estadística descriptiva, los datos cualitativos se analizaron utilizando el análisis de matriz. Resultados Tras pasar la herramienta EvalGuía, las puntuaciones más bajas estaban en la evaluación de resultados, conocimiento de leyes relacionadas con participación comunitaria, diversidad en el grupo motor, medidas de conciliación, recursos financieros y devolución de resultados. Las líneas de acción planteadas eran heterogéneas y no siempre coinciden con las priorizadas. Las líneas priorizadas giraban en torno a la organización del proyecto y a la comunicación. Conclusiones La herramienta EvalGuía puede ser útil para diseñar planes de acción en proyectos de promoción de la salud. La implementación de medidas en 12 meses para aumentar la diversidad del grupo motor, incorporar medidas de conciliación o mejorar la evaluación es difícil. Se requiere más tiempo para implementar este tipo de medidas. (AU)

Objective To analyse the lines of action identified in the health promotion projects participating in the EvaluA GPS research, and their relationship with the scores assigned in EvalGuia, a tool for evaluating evidence-based community participation. Design Qualitative-quantitative multicentre study. Setting Primary care or intersectoral network of primary care and municipalities in five autonomous communities in Spain. Participants Participants of 10 health promotion projects, selected with convenience sampling, following inclusion criteria (projects with a minimum of community engagement and centred on community health). Method Data were collected through questionnaires (EvalGuía tool) and participatory workshops. Quantitative data were analysed with descriptive statistics, qualitative data were analysed using matrix analysis. Results After implementing the EvalGuide tool, the lowest scores were assigned in outcome evaluation, knowledge of policies related to community participation, diversity in the core working group, inclusivity policies, financial resources and diffusion of results. The lines of action proposed were heterogeneous and did not always match with those prioritised as lower score. The prioritised lines revolved around project organisation and communication. Conclusions The EvalGuide tool can be helpful to design action plans in Health Promotion projects. The implementation of measures in 12 months to increase the diversity of the core working group, to incorporate work–life balance measures or to improve evaluation is difficult. More time is needed to implement such measures. (AU)

The Impact of Children's and Parents' Perceptions of Parenting Styles on Attention, Hyperactivity, Anxiety, and Emotional Regulation.

Attention-deficit/hyperactivity disorder (ADHD) symptomatology can be studied by examining the associated neurobiological factors or by looking at the environmental factors involved, such as parenting styles. Negative parenting styles have been associated with ADHD symptoms in childhood and adolescence. The present study aimed to analyze the predictive power of two parenting style dimensions (warmth-communication and criticism-rejection) and three factors about rule-setting and compliance (inductive, strict, and indulgent styles) in the explanation of ADHD symptoms (attention and hyperactivity) and associated emotional factors (anxiety and emotional regulation) considering parents' and children's perspectives. The results indicate that from the parents' perspective, the criticism-rejection variable was the most important in explaining attention difficulties, anxiety and emotional regulation. From the children's perspective, the strict parenting style was the most important variable in explaining hyperactivity and emotional regulation. In addition, for children, warmth-communication was significant in predicting fewer emotional regulation difficulties. Our results highlight the importance of considering family dynamics when assessing ADHD in order to implement comprehensive interventions that consider parental training in positive parenting styles.

The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease.

The differentiation of resident intestinal macrophages from blood monocytes depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). Analysis of genome-wide association studies (GWAS) indicates that dysregulation of macrophage differentiation and response to microorganisms contributes to susceptibility to chronic inflammatory bowel disease (IBD). Here, we analyzed transcriptomic variation in monocyte-derived macrophages (MDM) from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls. Transcriptional network analysis of the data revealed no overall or inter-sib distinction between affected and unaffected individuals in basal gene expression or the temporal response to lipopolysaccharide (LPS). However, the basal or LPS-inducible expression of individual genes varied independently by as much as 100-fold between subjects. Extreme independent variation in the expression of pairs of HLA-associated transcripts (HLA-B/C, HLA-A/F and HLA-DRB1/DRB5) in macrophages was associated with HLA genotype. Correlation analysis indicated the downstream impacts of variation in the immediate early response to LPS. For example, variation in early expression of IL1B was significantly associated with local SNV genotype and with subsequent peak expression of target genes including IL23A, CXCL1, CXCL3, CXCL8 and NLRP3. Similarly, variation in early IFNB1 expression was correlated with subsequent expression of IFN target genes. Our results support the view that gene-specific dysregulation in macrophage adaptation to the intestinal milieu is associated with genetic susceptibility to IBD.

[How to improve community engagement in health: Analysis of proposed actions following the implementation of a community engagement assessment tool]. / ¿Cómo mejoramos la participación comunitaria en salud? Análisis de las acciones propuestas tras la aplicación de una herramienta de evaluación.

OBJECTIVE: To analyse the lines of action identified in the health promotion projects participating in the EvaluA GPS research, and their relationship with the scores assigned in EvalGuia, a tool for evaluating evidence-based community participation. DESIGN: Qualitative-quantitative multicentre study. SETTING: Primary care or intersectoral network of primary care and municipalities in five autonomous communities in Spain. PARTICIPANTS: Participants of 10 health promotion projects, selected with convenience sampling, following inclusion criteria (projects with a minimum of community engagement and centred on community health). METHOD: Data were collected through questionnaires (EvalGuía tool) and participatory workshops. Quantitative data were analysed with descriptive statistics, qualitative data were analysed using matrix analysis. RESULTS: After implementing the EvalGuide tool, the lowest scores were assigned in outcome evaluation, knowledge of policies related to community participation, diversity in the core working group, inclusivity policies, financial resources and diffusion of results. The lines of action proposed were heterogeneous and did not always match with those prioritised as lower score. The prioritised lines revolved around project organisation and communication. CONCLUSIONS: The EvalGuide tool can be helpful to design action plans in Health Promotion projects. The implementation of measures in 12 months to increase the diversity of the core working group, to incorporate work-life balance measures or to improve evaluation is difficult. More time is needed to implement such measures.

Preschool Children's Loose Parts Play and the Relationship to Cognitive Development: A Review of the Literature.

Play is an integrative process, and the skills acquired in it-overcoming impulses, behavior control, exploration and discovery, problem-solving, reasoning, drawing conclusions, and attention to processes and outcomes are foundational cognitive structures that drive learning and motivation. Loose parts play is a prominent form of play that many scholars and educators explicitly endorse for cognitive development (e.g., divergent thinking, problem-solving). It is unique among play types because children can combine different play types and natural or manufactured materials in one occurrence. While educators and policymakers promote the benefits of loose parts play, no previous research has explored the direct relationship between preschool-age children's indoor loose parts play experiences and cognitive development. We address this gap by bringing together the relevant literature and synthesizing the empirical studies on common play types with loose parts, namely object and exploratory, symbolic and pretend, and constructive play. We also focus on studies that examine children's experiences through loose parts, highlighting the impact of different play types on learning through the reinforcement of cognitive skills, such as executive function, cognitive self-regulation, reasoning, and problem-solving. By examining the existing literature and synthesizing empirical evidence, we aim to deepen our understanding of the relationship between children's play with loose parts and its impact on cognitive development. Ultimately, pointing out the gaps in the literature that would add to the body of knowledge surrounding the benefits of play for cognitive development and inform educators, policymakers, and researchers about the significance of incorporating loose parts play into early childhood education.

Newspaper Coverage and Framing of Bats, and Their Impact on Readership Engagement.

The media is a valuable pathway for transforming people's attitudes towards conservation issues. Understanding how bats are framed in the media is hence essential for bat conservation, particularly considering the recent fearmongering and misinformation about the risks posed by bats. We reviewed bat-related articles published online no later than 2019 (before the recent COVID19 pandemic), in 15 newspapers from the five most populated countries in Western Europe. We examined the extent to which bats were presented as a threat to human health and the assumed general attitudes towards bats that such articles supported. We quantified press coverage on bat conservation values and evaluated whether the country and political stance had any information bias. Finally, we assessed their terminology and, for the first time, modelled the active response from the readership based on the number of online comments. Out of 1095 articles sampled, 17% focused on bats and diseases, 53% on a range of ecological and conservation topics, and 30% only mention bats anecdotally. While most of the ecological articles did not present bats as a threat (97%), most articles focusing on diseases did so (80%). Ecosystem services were mentioned on very few occasions in both types (< 30%), and references to the economic benefits they provide were meagre (< 4%). Disease-related concepts were recurrent, and those articles that framed bats as a threat were the ones that garnered the highest number of comments. Therefore, we encourage the media to play a more proactive role in reinforcing positive conservation messaging by presenting the myriad ways in which bats contribute to safeguarding human well-being and ecosystem functioning.

Gastrointestinal manifestations of COVID-19 in a Colombian population. A cross-sectional study

Introduction: gastrointestinal involvement in COVID-19 occurs in approximately 20% of patients and may include nausea, vomiting, abdominal pain, diarrhea or abnormal liver function tests. In our country, the characteristics of gastrointestinal involvement in COVID-19 patients have not been studied. Objectives: to determine the prevalence of gastrointestinal and liver involvement in patients with COVID-19 treated at two hospitals in Bogotá, Colombia. To determine the association between COVID-19 gastrointestinal involvement and length of hospital stay, severity and mortality. Design and methodology: a cross-sectional study carried out at two hospitals in a hospital subnetwork in Bogotá, Colombia from February 2020 to March 2021. Results: a total of 1,176 patients with a positive reverse transcription polymerase chain reaction (RT-PCR) were included. Gastrointestinal manifestations occurred in 50% (95%CI 47-52%), with the most frequent being diarrhea in 18.4%, odynophagia in 17.6%, anorexia in 14.7% and abdominal pain in 8.8%. An association was found between diarrhea during hospitalization and prolonged hospitalization (OR 1.93 95%CI 1.19-3.13), and between gastrointestinal bleeding on admission and death (OR 3.13, 95%CI 1.1-9.1), among others. Abnormal liver function tests occurred in 46% (95%CI 43-49%) and were more frequent in patients with severe disease and those who died. Conclusions: the prevalence of gastrointestinal manifestations in patients with COVID-19 was 50%. Diarrhea was associated with a longer hospital stay, and gastrointestinal bleeding was associated with respiratory failure and death. Forty-six percent of patients had abnormal liver function tests, with elevated transaminases being the most frequent. Elevated aspartate transaminase (AST) on admission was associated with greater mortality. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2729).

Entrega de malas noticias: emociones experimentadas por internos de obstetricia en un escenario clínico simulado / Breaking bad news: emotions experienced by midwifery students in a simulated clinical scenario

Objetivo: Identificar y analizar la respuesta emocional de un grupo de internos de Obstetricia durante el desarrollo de un escenario clínico simulado de entrega de malas noticias en salud. Métodos: Estudio cualitativo con enfoque fenomenológico en el que participaron 21 estudiantes de último año de la carrera de Obstetricia de la Universidad Mayor de Santiago de Chile durante el año 2019. Posteriormente a la simulación clínica con paciente estandarizado se realizaron cuestionarios y entrevistas semiestructuradas, que fueron analizados mediante Análisis Temático Cualitativo. Resultados: Emergieron una categoría central (Emociones experimentadas durante el proceso) y cuatro subcategorías (Autopercepción de emociones en el ejercicio simulado; Emociones y malestar ante la entrega de malas noticias en salud; Sentimientos encontrados y su afección en el desempeño de la actividad; y Gestión y estrategias para la entrega de malas noticias en salud). El miedo y la ansiedad fueron las emociones más referidas, vinculadas principalmente al desconocimiento sobre la posible respuesta del paciente. La tristeza y la empatía se relacionaron con experiencias propias. Las manifestaciones físicas de la emoción pueden tornarse intensas, pudiendo desorganizar y/o bloquear el desempeño. Por último, la principal estrategia de respuesta utilizada por los estudiantes fue la represión de sus propias emociones. Conclusiones: La simulación clínica de alta fidelidad con paciente estandarizado es una herramienta muy útil para el desarrollo de competencias de entrega de malas noticias en salud. Abogamos por incorporar la educación emocional en la formación de matronas y matrones. (AU)

Objective: To identify and analyze the emotional response of a group of Obstetrics interns during the development of a simulated clinical scenario of delivering bad health news. Methods: Qualitative study with a phenomenological approach in which 21 senior students of the Obstetrics career of the Universidad Mayor de Santiago de Chile participated during the year 2019. Questionnaires and semi-structured interviews were carried out after the clinical simulation with a standardized patient, the that were analyzed through Qualitative Thematic Analysis. Results: A central category emerged (Emotions experienced during the process) and four subcategories (Self-perception of emotions in the simulated exercise; Emotions and discomfort when delivering bad health news; Mixed feelings and their effect on the performance of the activity; and Management and strategies for the delivery of bad health news). Fear and anxiety were the most frequently reported emotions, mainly linked to ignorance about the patient's possible response. Sadness and empathy were related to their own experiences. Physical manifestations of emotion can become intense, disorganizing and/or blocking performance. Finally, the main response strategy used by the students was the repression of their own emotions. Conclusions: High-fidelity clinical simulation with a standardized patient is a very useful tool for developing skills in delivering bad news in health. We advocate incorporating emotional education in the training of midwives and midwives. (AU)

Atomic Layer Grown Zinc-Tin Oxide as an Alternative Buffer Layer for Cu2ZnSnS4-Based Thin Film Solar Cells: Influence of Absorber Surface Treatment on Buffer Layer Growth.

Zn1-x Sn x O y (ZTO) deposited by atomic layer deposition has shown promising results as a buffer layer material for kesterite Cu2ZnSnS4 (CZTS) thin film solar cells. Increased performance was observed when a ZTO buffer layer was used as compared to the traditional CdS buffer, and the performance was further increased after an air annealing treatment of the absorber. In this work, we study how CZTS absorber surface treatments may influence the chemical and electronic properties at the ZTO/CZTS interface and the reactions that may occur at the absorber surface prior to atomic layer deposition of the buffer layer. For this, we have used a combination of microscopy and synchrotron-based spectroscopies with variable information depths (X-ray photoelectron spectroscopy, high-energy X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy), allowing for an in-depth analysis of the CZTS near-surface regions and bulk material properties. No significant ZTO buffer thickness variation is observed for the differently treated CZTS absorbers, and no differences are observed when comparing the bulk properties of the samples. However, the formation of SnO x and compositional changes observed toward the CZTS surface upon an air annealing treatment may be linked to the modified buffer layer growth. Further, the results indicate that the initial N2 annealing step integrated in the buffer layer growth by atomic layer deposition, which removes Na-CO x species from the CZTS surface, may be useful for the ZTO/CZTS device performance.

Implementación de un protocolo de recomendación formal de activos para la salud en los equipos de atención primaria aragoneses / Implementation of a social prescribing protocol in Aragon's primary care teams

Objetivo: Analizar la implementación de la «Guía de recomendación de activos para la salud en atención primaria Aragón». Diseño: Estudio observacional, descriptivo, transversal. Emplazamiento: Ciento veintitrés equipos de atención primaria aragoneses. Participantes: Recomendaciones de Activos para la Salud realizadas con el protocolo «Recomendación Activos-AP» de historia clínica electrónica de atención primaria Aragón desde septiembre de 2018 a marzo de 2021. Mediciones principales: Se describieron las variables más relevantes del protocolo: edad, sexo, provincia, sector sanitario, zona básica de salud, problema de salud, aspecto a potenciar, activo para la salud recomendado, tipo de profesional, grado de asistencia, satisfacción y mejoría. Resultados: El protocolo fue utilizado 2.109 veces y se realizaron 1.482 recomendaciones y 428 seguimientos. El uso del protocolo fue aumentando progresivamente hasta marzo de 2020. A 1.431 personas se les realizó una recomendación y a 51 más de una. La edad media de las personas beneficiarias fue de 67,9años. El 74,8% de recomendaciones se dirigieron a mujeres. Diagnósticos relacionados con problemas sociales y psicológicos fueron los más vinculados a recomendaciones, y la esfera física fue el aspecto más potenciado. Los activos más recomendados se vinculaban con actividad física y recursos de promoción de la autonomía personal. Más del 90% de las personas asistieron con regularidad al activo. La satisfacción media fue de 4,8 (0/5) y el grado de mejoría de 4,3 (0/5). Conclusiones: La implementación de recomendación de activos para la salud dentro la Estrategia de Atención Comunitaria Aragón está funcionando. Sin embargo, es necesario revisar algunos aspectos. Es preciso continuar generando evidencia para poder adecuar y hacer más eficiente este proceso.(AU)

Objective: To analyze the implementation of social prescribing guideline in primary care Aragón. Design: Observational, descriptive, cross-sectional study. Location: One hundred twenty-three primary care teams of Aragón. Participants: Social prescribing made with the protocol «Recomendación Activos - AP» of electronic health record of primary care Aragón from September 2018 to March 2021. Main measurements: The most relevant variables of the protocol were described: age, sex, province, health sector, basic health area, health problem, aspect to be enhanced, asset for health recommended, type of professional, degree of assistance, satisfaction and improvement. Results: The protocol was used 2109 times, 1482 recommendations were made and 428 follow-ups were performed. The use of the protocol increased progressively until March 2020. A total of 1431 people received one recommendation and 51 received more than one recommendation. The average age of the beneficiaries was 67.9years. 74.8% of recommendations were addressed to women. Diagnoses related to social and psychological problems were the most frequently recommended, and the physical sphere was the aspect most promoted. Most social prescribing was linked to physical activity and resources for the promotion of personal autonomy. More than 90% of the people regularly attended the activity, the average satisfaction was 4.8 (0/5) and the degree of improvement 4.3 (0/5). Conclusions: The implementation of asset for health recommended within the Aragon community care strategy is working, however, some aspects need to be reviewed. It is necessary to continue generating evidence to be able to adapt and make this process more efficient.(AU)

[Implementation of a social prescribing protocol in Aragon's primary care teams]. / Implementación de un protocolo de recomendación formal de activos para la salud en los equipos de atención primaria aragoneses.

OBJECTIVE: To analyze the implementation of social prescribing guideline in primary care Aragón. DESIGN: Observational, descriptive, cross-sectional study. LOCATION: One hundred twenty-three primary care teams of Aragón. PARTICIPANTS: Social prescribing made with the protocol «Recomendación Activos - AP¼ of electronic health record of primary care Aragón from September 2018 to March 2021. MAIN MEASUREMENTS: The most relevant variables of the protocol were described: age, sex, province, health sector, basic health area, health problem, aspect to be enhanced, asset for health recommended, type of professional, degree of assistance, satisfaction and improvement. RESULTS: The protocol was used 2109 times, 1482 recommendations were made and 428 follow-ups were performed. The use of the protocol increased progressively until March 2020. A total of 1431 people received one recommendation and 51 received more than one recommendation. The average age of the beneficiaries was 67.9years. 74.8% of recommendations were addressed to women. Diagnoses related to social and psychological problems were the most frequently recommended, and the physical sphere was the aspect most promoted. Most social prescribing was linked to physical activity and resources for the promotion of personal autonomy. More than 90% of the people regularly attended the activity, the average satisfaction was 4.8 (0/5) and the degree of improvement 4.3 (0/5). CONCLUSIONS: The implementation of asset for health recommended within the Aragon community care strategy is working, however, some aspects need to be reviewed. It is necessary to continue generating evidence to be able to adapt and make this process more efficient.

A Graph Based Neural Network Approach to Immune Profiling of Multiplexed Tissue Samples.

Multiplexed immunofluorescence provides an un-precedented opportunity for studying specific cell-to-cell and cell microenvironment interactions. We employ graph neural networks to combine features obtained from tissue morphology with measurements of protein expression to profile the tumour microenvironment associated with different tumour stages. Our framework presents a new approach to analysing and processing these complex multi-dimensional datasets that overcomes some of the key challenges in analysing these data and opens up the opportunity to abstract biologically meaningful interactions.

Ultrathin wide band gap kesterites.

Kesterite Cu2ZnSnS4 (CZTS), used for thin film solar cells, has a band gap energy around 1.5-1.6 eV with possibilities for further increase through alloying. In some applications for wide band gap solar cells, reduced absorber thickness can be beneficial, to allow partial light transmission. Reduced thickness can also be beneficial to reduce bulk recombination, and so called ultrathin solar cells (<700 nm thick) have been studied for several materials systems. Here, we report performance for CZTS devices down to 250 nm thickness and show that performance loss from thickness reduction is relatively small, partly due to short minority carrier diffusion length. Insertion of thin passivation layers (Al2O3, SiO2 or HfO2) at the Mo/CZTS interface gives improved performance of ultrathin devices, from 4.7% to 5.6% efficiency for best performing cells having 250 nm thick CZTS with Mo as compared to Mo/Al2O3 back contact. The approach of NaF post deposition for making isolating passivation layers conductive is tested for the first time for CZTS and is shown to work. For fabrication of CZTS devices on transparent ITO back contact, the insertion of passivation layers can reduce diffusion of indium into CZTS, but device performance is lower than on Mo back contacts.

High SOX9 Maintains Glioma Stem Cell Activity through a Regulatory Loop Involving STAT3 and PML.

Glioma stem cells (GSCs) are critical targets for glioma therapy. SOX9 is a transcription factor with critical roles during neurodevelopment, particularly within neural stem cells. Previous studies showed that high levels of SOX9 are associated with poor glioma patient survival. SOX9 knockdown impairs GSCs proliferation, confirming its potential as a target for glioma therapy. In this study, we characterized the function of SOX9 directly in patient-derived glioma stem cells. Notably, transcriptome analysis of GSCs with SOX9 knockdown revealed STAT3 and PML as downstream targets. Functional studies demonstrated that SOX9, STAT3, and PML form a regulatory loop that is key for GSC activity and self-renewal. Analysis of glioma clinical biopsies confirmed a positive correlation between SOX9/STAT3/PML and poor patient survival among the cases with the highest SOX9 expression levels. Importantly, direct STAT3 or PML inhibitors reduced the expression of SOX9, STAT3, and PML proteins, which significantly reduced GSCs tumorigenicity. In summary, our study reveals a novel role for SOX9 upstream of STAT3, as a GSC pathway regulator, and presents pharmacological inhibitors of the signaling cascade.

Meat quality of beef-cross-dairy cattle from Angus or Hereford sires: A case study in a pasture-based system in New Zealand.

Meat quality of beef-cross-dairy cattle born in the dairy industry and finished on hill-country pastures is not well characterised. This experiment aimed to objectively evaluate meat quality traits of 15 Angus and 18 Hereford sires via progeny testing of their 326 beef-cross-dairy offspring, and to compare the intramuscular fat (IMF) percentage with the AUS-MEAT marble scores. Beef-breed sires had similar and overall good objective meat quality characteristics. Ultimate pH was not affected by sire (P > 0.05). The differences among sires in meat quality (fat yellowness b*, meat redness a*, yellowness b* and chroma C*, cook loss and shear force, P < 0.05) were small and all values were within the normal range for beef. Marble scores could capture the variation of IMF at marbling score 1-3, but was not effective to distinguish between 0 and 1. In conclusion, the effect of sire on the meat quality of the beef-cross-dairy progeny in this study was of minor importance.

Angiocrine polyamine production regulates adiposity.

Reciprocal interactions between endothelial cells (ECs) and adipocytes are fundamental to maintain white adipose tissue (WAT) homeostasis, as illustrated by the activation of angiogenesis upon WAT expansion, a process that is impaired in obesity. However, the molecular mechanisms underlying the crosstalk between ECs and adipocytes remain poorly understood. Here, we show that local production of polyamines in ECs stimulates adipocyte lipolysis and regulates WAT homeostasis in mice. We promote enhanced cell-autonomous angiogenesis by deleting Pten in the murine endothelium. Endothelial Pten loss leads to a WAT-selective phenotype, characterized by reduced body weight and adiposity in pathophysiological conditions. This phenotype stems from enhanced fatty acid ß-oxidation in ECs concomitant with a paracrine lipolytic action on adipocytes, accounting for reduced adiposity. Combined analysis of murine models, isolated ECs and human specimens reveals that WAT lipolysis is mediated by mTORC1-dependent production of polyamines by ECs. Our results indicate that angiocrine metabolic signals are important for WAT homeostasis and organismal metabolism.

PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer.

Glycine N-Methyltransferase (GNMT) is a metabolic enzyme that integrates metabolism and epigenetic regulation. The product of GNMT, sarcosine, has been proposed as a prostate cancer biomarker. This enzyme is predominantly expressed in the liver, brain, pancreas, and prostate tissue, where it exhibits distinct regulation. Whereas genetic alterations in GNMT have been associated to prostate cancer risk, its causal contribution to the development of this disease is limited to cell line-based studies and correlative human analyses. Here we integrate human studies, genetic mouse modeling, and cellular systems to characterize the regulation and function of GNMT in prostate cancer. We report that this enzyme is repressed upon activation of the oncogenic Phosphoinositide-3-kinase (PI3K) pathway, which adds complexity to its reported dependency on androgen signaling. Importantly, we demonstrate that expression of GNMT is required for the onset of invasive prostate cancer in a genetic mouse model. Altogether, our results provide further support of the heavy oncogenic signal-dependent regulation of GNMT in prostate cancer.

Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment.

The tumor microenvironment (TME) is reprogrammed by cancer cells and participates in all stages of tumor progression. The contribution of stromal cells to the reprogramming of the TME is not well understood. Here, we provide evidence of the role of the cytokine oncostatin M (OSM) as central node for multicellular interactions between immune and nonimmune stromal cells and the epithelial cancer cell compartment. OSM receptor (OSMR) deletion in a multistage breast cancer model halted tumor progression. We ascribed causality to the stromal function of the OSM axis by demonstrating reduced tumor burden of syngeneic tumors implanted in mice lacking OSMR. Single-cell and bioinformatic analysis of murine and human breast tumors revealed that OSM expression was restricted to myeloid cells, whereas OSMR was detected predominantly in fibroblasts and, to a lower extent, cancer cells. Myeloid-derived OSM reprogrammed fibroblasts to a more contractile and tumorigenic phenotype and elicited the secretion of VEGF and proinflammatory chemokines CXCL1 and CXCL16, leading to increased myeloid cell recruitment. Collectively, our data support the notion that the stromal OSM/OSMR axis reprograms the immune and nonimmune microenvironment and plays a key role in breast cancer progression.