Epigenetic Signatures Associated with Different Levels of Differentiation Potential in Human Stem Cells

BACKGROUND: The therapeutic use of multipotent stem cells depends on their differentiation potential, which has been shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic profiles. METHODOLOGY/PRINCIPAL FINDINGS: to address this issue, we have investigated the levels of epigenetic regulation in well characterized populations of pluripotent embryonic stem cells (ESC) and multipotent adult stem cells (ASC) at the trancriptome, methylome, histone modification and microRNA levels. Differences in gene expression profiles allowed classification of stem cells into three separate populations including ESC, multipotent adult progenitor cells (MAPC) and mesenchymal stromal cells (MSC). The analysis of the PcG repressive marks, histone modifications and gene promoter methylation of differentiation and pluripotency genes demonstrated that stem cell populations with a wider differentiation potential (ESC and MAPC) showed stronger representation of epigenetic repressive marks in differentiation genes and that this epigenetic signature was progressively lost with restriction of stem cell potential. Our analysis of microRNA established specific microRNA signatures suggesting specific microRNAs involved in regulation of pluripotent and differentiation genes. CONCLUSIONS/SIGNIFICANCE: Our study leads us to propose a model where the level of epigenetic regulation, as a combination of DNA methylation and histone modification marks, at differentiation genes defines degrees of differentiation potential from progenitor and multipotent stem cells to pluripotent stem cells

A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary

BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease

The Eighteenth Data Release of the Sloan Digital Sky Surveys: Targeting and First Spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Comment: Accepted to ApJ

The eighteenth data release of the Sloan Digital Sky Surveys : targeting and first spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Publisher PDFPeer reviewe

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Propiedades de rehidratación de frijol entero precocido (Phaseolus vulgaris) deshidratado a temperatura ambiente

The aim of this research was to study the rehydration behavior of precooked whole beans (Phaseolus vulgaris) dehydrated at room temperature (258C) and soaked in water at three temperatures (40, 60, and 808C). The water absorption of the beans was determined by the gain in weight. The dehydration kinetic at room temperature of the beans was adequately described by the Logarithmic model (R2 ¼ 0.9989) with a dehydration rate constant (kd) value of 1.96 6 1073 min71 . A semi-empirical first-order differential equation adequately described the rehydration characteristics of precooked whole bean under the experimental conditions (R2 ¼ 0.9934–0.9976). The rehydration rate constant (kr) increased from 6.10 6 1072 to 12.14 6 1072 min71 with an increase in the temperature from 40 to 808C. The temperature dependence of kr was well described by Arrhenius-type equation (R2 ¼ 0.8785), with estimated activation energy of 16.03 kJ mol71 K71.El propo´sito de este trabajo fue estudiar el comportamiento de rehidratacio´n de frijol (Phaseolus vulgaris) entero precocido deshidratado a temperatura ambiente (258C) y remojado en agua a tres temperaturas (40, 60 y 808C). La absorcio´n de agua del frijol se determino´ por la ganancia de peso. La cine´tica de deshidratacio´n a temperatura ambiente del frijol fue descrita adecuadamente por el modelo Logarı´tmico (R2 ¼ 0,9986) con un valor de la constante de velocidad de deshidratacio´n (kd) de 1,96 6 1073 min71 . Una ecuacio´n diferencial empı´rica de primer orden describio´ adecuadamente las caracterı´sticas de rehidratacio´n del frijol entero precocido bajo las condiciones experimentales (R2 ¼ 0,9933 a 0,9976). La constante de velocidad de rehidratacio´n (kr) se incremento´ de 6,10 6 1072 a 12,14 6 1072 con el aumento de temperatura de 40 a 808C. La dependencia de temperatura de kr fue descrita por la ecuacio´n de Arrhenius (R2 ¼ 0,8785), con una energı´a de activacio´n estimada de 16,03 kJ mol71 K71

Oleoresins from chili pepper and turmeric could substitute for salinomycin in broilers

Background: Coccidiosis is the infectious disease with the greatest economic impact in poultry production. Additionally, chemotherapeutic growth promoters are being substituted for safer alternative strategies. Objective: To evaluate the effect of feeding oleoresins from chili pepper (Capsicum annuum) and turmeric (Curcuma longa L.) on the performance, survival rate, and the Productive Efficiency Index of broilers from 1 to 21d challenged by Eimeria sp. Methods: A total of 700 male 1-dayold chicks (Cobb 500) challenged with Eimeria sp, were assigned to a completely randomized design with four treatments: (1) negative control diet, without anticoccidial agent or growth promoters; (2) control diet+0.05% salinomycin; (3) negative control diet+100g/ton; and (4) negative control diet +140g/ton of test product (Curcuma longa L. plus Capsicum annuum oleoresins). Results: Body weight, weight gain, feed conversion and Productive Efficiency Index did not differ between broilers fed anticoccidial chemotherapeutics and oleoresins. In addition, there was no difference in feed intake and survival rate between dietary treatments. Conclusion: Broilers supplemented with chili pepper and turmeric oleoresins from 1 to 21d present similar body weight, weight gain, feed conversion, and Productive Efficiency Index compared to broilers supplemented with chemotherapeutic anticoccidials without affecting feed intake or survival rate.Antecedentes: O impacto econômico da coccidiose é o maior quando comparado a outras doenças na produção avícola. Além disso, promotores de crescimento quimioterápicos tem sido substituídos por estratégias alternativas. Objetivo: Avaliar o efeito das oleoresinas da pimenta Chilli (Capsicum annuum) e açafrão-da-terra (Curcuma longa L.) no desempenho zootécnico, taxa de sobrevivência e Índice de Eficiência Produtiva de frangos de corte de 1 a 21d desafiados por Eimeria sp. Métodos: Foram utilizados 700 pintos de 1d, machos (Cobb500) distribuídos em delineamento inteiramente casualizado, em quatro tratamentos: (1) dieta controle negativo, sem agente anticoccidiano ou promotores de crescimento; (2) dieta controle+0,05% de salinomicina; (3) dieta controle negativa+100g/ton; e (4)+140g/ton de produto teste (oleoresina de Curcuma longa L. mais Capsicum annuum) e desafiados por Eimeria sp. Resultados: Houve resultados similares para peso, ganho de peso, conversão alimentar e Índice de Eficiência Produtiva entre frangos alimentados com dietas contendo anticocidiano quimioterápico e dietas contendo oleoresinas. Além disso, não houve diferença para consumo de ração e a taxa de sobrevivência entre os tratamentos dietéticos. Conclusão: Frangos de corte alimentados com dietas suplementadas com oleorresinas de pimenta chili e açafrãoda-terra apresentaram resultados similares para peso, ganho de peso, conversão alimentar e Índice de Eficiência Produtiva que frangos de corte alimentados com dietas suplementadas com anticoccidianos quimioterápicos de 1 a 21d, sem afetar o consumo de ração e a taxa de sobrevivência dos animais.Antecedentes: El impacto económico generado por la coccidiosis en el sector avícola es el mayor en relación con otras enfermedades. Adicionalmente, los promotores de crecimiento quimioterapéuticos se han venido reemplazando por estrategias alternativas. Objetivo: Evaluar el efecto de oleorresinas de pimiento (Capsicum annuum) y cúrcuma (Curcuma longa L.) sobre el desempeño zootécnico, tasa de supervivencia y el Índice de Eficiencia Productiva en pollos de engorde de 1 a 21 dias desafiados con Eimeria sp. Métodos: Se utilizaron 700 pollos machos (Cobb500) de 1 día de edad, distribuidos en un diseño completamente al azar con cuatro tratamientos: (1) dieta control negativo sin agentes anticoccidianos ni promotores de crecimiento; (2) dieta control+0,05% de salinomicina; (3) dieta control negativa+100g/ton; y (4) dieta control negativa +140g/ton del producto a evaluar (oleorresina de Curcuma longa L. y Capsicum annuum). Resultados: Se obtuvieron resultados similares repecto a peso corporal, ganancia de peso, conversión alimenticia e Índice de Eficiencia Productiva en los tratamientos que contenían anticoccidiano quimioterapéutico y los que contenian oleorresinas. Además, no se observaron diferencias en el consumo de alimento ni en la tasa de supervivencia entre los tratamientos dietarios. Conclusión: Los pollos de engorde suplementados entre 1 y 21 d con oleorresinas de pimiento y cúrcuma presentan similar peso corporal, ganancia de peso, conversión alimenticia e Índice de Eficiencia Productiva en comparación con los suplementados con anticoccidianos quimioterapéuticos, sin afectar el consumo de alimento ni la viabilidad

Exploring the biomechanical properties of brain malignancies and their pathologic determinants in vivo with magnetic resonance elastography

Malignant tumors are typically associated with altered rigidity relative to normal host tissue. Magnetic resonance elastography (MRE) enables the noninvasive quantitation of the mechanical properties of deep-seated tissue following application of an external vibrational mechanical stress to that tissue. In this preclinical study, we used MRE to quantify (kPa) the elasticity modulus G(d) and viscosity modulus G(l) of three intracranially implanted glioma and breast metastatic tumor models. In all these brain tumors, we found a notable softness characterized by lower elasticity and viscosity than normal brain parenchyma, enabling their detection on G(d) and G(l) parametric maps. The most circumscribed tumor (U-87 glioma) was the stiffest whereas the most infiltrative tumor (MDA-MB-231 metastatic breast carcinoma) was the softest. Tumor cell density and microvessel density correlated positively with elasticity and viscosity significantly, whereas there was no association with the extent of collagen deposition or myelin fiber entrapment. In conclusion, while malignant tumors tend to exhibit increased rigidity, intracranial tumors presented as remarkably softer than normal brain parenchyma. Our findings reinforce the case for MRE use in diagnosing and staging brain malignancies, based on the association of different tumor phenotypes with different mechanical properties

Dietary utilisation of protein and energy from fresh and ensiled coffee pulp by the Nile tilapia, Oreochromis niloticus

Dietary protein and energy utilisation of diets containing fresh and ensiled coffee pulp were studied on 3.2 ± 0.2 g Nile tilapia for 28 days. Diets formulation and feeding were designed on the basis of daily dietary protein and energy allowance. A control diet A (100 % protein and 100 % energy allowance) corresponding to 15 g CP kg-1 day-1 and 750 kJ kg-1 day-1, a low protein control diet B (80 % protein and 100 % energy allowance), two diets C and E (100 % protein and 100 % energy allowance) where 20 % of protein were supplied by coffee pulp, and two diets D and F with the same amount of coffee pulp than in C and E and supplementation in non-protein energy. Inclusion of coffee pulp in the diet strongly impaired growth and feed utilisation. Silage process improved overall feed utilisation comparing to fresh coffee pulp. Results showed that fresh or ensiled coffee pulp was not a suitable feedstuff for Nile tilapia. However, better knowledge on modification occurring during silage process could allow finding the way to significantly improve nutritive value of coffee pulp by-products.<br>Polpa de café ensilada foi utilizada na dieta calórica-protéica de Tilápia do Nilo na razão de 3.2 g ± 0,2 durante um período de 28 dias. As dietas calórico-protéica foram formuladas com base na ingestão diária permitida. Uma dieta A controle (100% de proteína e 100% da energia) que corresponde a g PC/kg/dia e 750 Kj/Kg/dia, uma dieta B baixa em proteína (80% de proteína e 100% da energia), duas dietas C e E (100% de proteína e 100% da energia) onde 20% da proteína foi suplementada com polpa de café e duas dietas D e F com a mesma concentração de polpa de café é prejudicial a dieta de crescimento. O processo de ensilagem melhorou sua utilização como alimento em comparação com a polpa de café fresca. Os resultados demonstraram que a polpa fresca ou ensilada não é para ser usada como alimentação de Tilápia do Nilo. Entretanto, uma melhor conhecimento do processo de ensilagem da polpa de café pode ser uma via importante para aumentar o valor nutritivo da polpa de café