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Abstract Defining the trajectory of cells during differentiation and disease is key for uncovering the mechanisms driving cell fate and identity. However, trajectories of human cells remain largely unexplored due to the challenges of studying them with human samples. In this study, we investigate the proteome trajectory of iPSCs differentiation to hepatic stellate cells (diHSCs) and identify RORA as a key transcription factor governing the metabolic reprogramming of HSCs necessary for diHSCs’ commitment, identity, and activation. Using RORA deficient iPSCs and pharmacologic interventions, we show that RORA is required for early differentiation and prevents diHSCs activation by reducing the high energetic state of the cells. While RORA knockout mice have enhanced fibrosis, RORA agonists rescue multi-organ fibrosis in in vivo models. Notably, RORA expression correlates negatively with liver fibrosis and HSCs activation markers in patients with liver disease. This study reveals that RORA regulates cell metabolic plasticity, important for mesoderm differentiation, pericyte quiescence, and fibrosis, influencing cell commitment and disease.

Germline SAMD9 mutations are one of the most common alterations that predispose to pediatric myelodysplastic syndrome (MDS), a clonal disorder characterized by ineffective hematopoiesis, increasing the risk of developing acute myeloid leukemia (AML). Up to date, a disease model to study the role of SAMD9 mutation in MDS is still lacking. Here, we have generated a human induced pluripotent stem cell (hiPSC) line carrying SAMD9mut (p.I1567M), taking advantage of CRISPR/Cas9 system. As a result, the genetic engineered hiPSC line represent a new in vitro disease model to understand the impact of SAMD9 mutation at molecular and cellular level during hematopoiesis.

Objetivo: Comparar los costes de los tratamientos más establecidos para el cáncer de próstata localizado según grupos de riesgo, edad y comorbilidad, desde la perspectiva del proveedor asistencial. Métodos: Comparación de costes en pacientes reclutados consecutivamente entre 2003 y 2005 en una unidad funcional de tratamiento del cáncer de próstata. La utilización de servicios hasta 6 meses después del inicio del tratamiento se obtuvo de las bases de datos hospitalarias, y los costes directos se estimaron mediante cálculo microcoste. La información sobre las características clínicas de los pacientes y los tratamientos recogió prospectivamente. Los costes se compararon mediante tests no paramétricos de comparación de medianas (Kruskall-Wallis) y un modelo semilogarítmico de regresión múltiple. Resultados: La diferencia de costes fue estadísticamente significativa: medianas de 3229.10 €, 5369.00 € y 6265.60 € para los pacientes tratados con radioterapia conformacional externa 3D, braquiterapia, y prostatectomía radical retropública, respectivamente (pObjective: To compare the initial costs of the three most established treatments for clinically localized prostate cancer according to risk, age and comorbidity groups, from the healthcare provider's perspective. Methods: We carried out a cost comparison study in a sample of patients consecutively recruited between 2003 and 2005 from a functional unit for prostate cancer treatment in Catalonia (Spain). The use of services up to 6 months after the treatment start date was obtained from hospital databases and direct costs were estimated by micro-cost calculation. Information on the clinical characteristics of patients and treatments was collected prospectively. Costs were compared by using nonparametric tests comparing medians (Kruskall-Wallis) and a semi-logarithmic multiple regression model. Results: Among the 398 patients included, the cost difference among treatments was statistically significant: medians were €3,229.10, €5,369.00 and €6,265.60, respectively, for the groups of patients treated with external 3D conformal radiotherapy, brachytherapy and radical retropublic prostatectomy, (p

Purpose: Lip cancer can be treated by surgery, external radiotherapy, and/or brachytherapy (BT). In recent years,BT has become increasingly favored for this type of cancer. The aim of the present study was to analyze local control and survival of patients treated at our institution between July 1989 and June 2008.Material and methods: We performed a retrospective study of 121 patients (109 males and 12 females) who underwent lip cancer brachytherapy from July 1989 to June 2008. Median age was 67 years and median follow-up was 31.8 months (range 20-188 months). Out of 121 patients, 100 (82.6%) were treated with low dose rate (LDR) BT while the remaining 21 patients (17.4%) received high dose rate (HDR) BT.Results: The most common cell type was squamous cell carcinoma (115 cases; 95%) and most tumors were located on the lower lip (107 patients; 88.4%). Most cases were either stage T1 (62 patients; 51.2%), or T2 (44 cases; 36.4%). After 15 years of follow-up, overall survival was 89.5%, cause-specific survival 97.8%, and disease-free survival 86.6%. Local, regional, and distant control at 15 years were 90%, 92%, and 98.8%, respectively. Grade 3 mucosal toxicity was observed in 23% of patients treated with LDR compared to 33% of HDR patients, and grade 4 mucosal toxicity in 9% versus 0%in the HDR group.Conclusions: Our findings confirm that brachytherapy is an effective treatment for lip cancer. The results from our series are in line with those published elsewhere. Based on our limited data, HDR appears to be equally as good as LDR, although this needs to be confirmed by further studies.

Abstract   Pinus pinea plants were inoculated with different strains of the edible ectomycorrhizal fungus Lactarius deliciosus. The inoculated plants were established in six experimental plantations in two sites located in the Mediterranean area to determine the effect of the initial colonization level and the inoculated strain on fungal persistence in the field. Ectomycorrhizal root colonization was determined at transplantation time and monitored at different times from uprooted plants. Extraradical soil mycelium biomass was determined from soil samples by TaqMan® real-time polymerase chain reaction (PCR). The results obtained indicate that the field site played a decisive role in the persistence of L. deliciosus after outplanting. The initial colonization level and the selection of the suitable strain were also significant factors but their effect on the persistence and spread of L. deliciosus was conditioned by the physical–chemical and biotic characteristics of the plantation soil and, possibly, by their influence in root growth. Molecular techniques based on real-time PCR allowed a precise quantification of extraradical mycelium of L. deliciosus in the field. The technique is promising for non-destructive assessment of fungal persistence since soil mycelium may be a good indicator of root colonization. However, the accuracy of the technique will ultimately depend on the development of appropriate soil sampling methods because of the high variability observed. [ABSTRACT FROM AUTHOR]

Abstract  Ectomycorrhizas of Boletus aereus, Boletus edulis, and Boletus reticulatus were synthesized with Cistus sp. under laboratory conditions using synthesis tubes filled with a mixture of sterilized peat-vermiculite and nutrient solution. The fungal strains isolated from sporocarps were identified by molecular techniques. The inoculated seedlings were grown for 4–5 months. The ectomycorrhizas formed were described based on standard morphological and anatomical characters. The three ectomycorrhizas described were very similar, with white monopodial-pinnate morphology, a three-layered plectenchymatous mantle on plan view and boletoid rhizomorphs. [ABSTRACT FROM AUTHOR]

Abstract  The objective of this study is to evaluate the field persistence of the edible ectomycorrhizal fungus Lactarius deliciosus in competition with two ubiquitous soil fungi. Couples of plants inoculated with either L. deliciosus, Rhizopogon roseolus, or R. luteolus were transplanted, 10 cm apart, in two different sites at the following combinations: L. deliciosus–R. roseolus, L. deliciosus–R. luteolus, L. deliciosus–control (non-inoculated), control–R. roseolus, control–R. luteolus, and control–control. Eight months after transplantation, root colonization and extraradical soil mycelium for each fungal species were quantified. For mycelium quantification, soil cores equidistant to the two plants in each couple were taken, and total deoxyribonucleic acid (DNA) was extracted. Real-time polymerase chain reaction analysis was performed using specific primers and TaqMan® Minor groove binding (MGB) probes designed in the ribosomal DNA internal transcribed spacer region of each fungal species. Field site significantly influenced persistence of both mycorrhizas and extraradical mycelium of L. deliciosus. Extraradical mycelium quantity was positively correlated with the final percentage of ectomycorrhizas for the three fungal species. Different competitive pressure between the two Rhizopogon species on L. deliciosus persistence was observed, with R. luteolus having no effect on L. deliciosus survival. Negative correlation between the final percentage of mycorrhizas of L. deliciosus and R. roseolus was observed. However, no relationship was determined between extraradical mycelia of both fungal species. The results obtained suggest that competition between L. deliciosus and R. roseolus takes place in the root system, for ectomycorrhiza formation in available roots, rather than in the extraradical phase. [ABSTRACT FROM AUTHOR]

The influence of the fertilisation method: soluble (SF) vs. slow-release fertiliser (SRF) and of inoculation with Laccaria laccata (Scop.) Fr., Pisolithus tinctorius (Pers.) Coker & Couch and Melanogaster ambiguus (Vittad.) Tul & C. Tul. on ectomycorrhizal colonization and growth of Pinus pinea L. and Pinus pinaster Ait. was evaluated. For both pines, mycorrhization with L. laccata was not affected by the fertilisation method. Percentages of ectomycorrhizas (ECM) formed by P.?tinctorius were dependent on the fertilisation method, the inoculum type (vegetative or spores) and the pine species involved. ECM formed by M. ambiguus were increased with fertilisation in both pines. Inoculation significantly improved P.?pinea biomass when seedlings were fertilised with SRF whereas no effect was found in non-fertilised ones. For non-fertilised P.?pinaster, inoculation with L. laccata and both inocula of P.?tinctorius increased seedling biomass whereas fertilisation neutralised the fungal effect. Fertilisation increased P.?pinea and P.?pinaster biomass, independently of the inoculation treatment. Influence de la m?thode de fertilisation sur la mycorhization contr?l?e de deux esp?ces de Pins m?diterran?ens. L''impact sur le degr? de mycorhization et la croissance de jeunes plants de Pinus pinea L. et de Pinus pinaster Ait., de deux m?thodes de fertilisation?(fertilisant soluble (FS) et fertilisant ? lib?ration lente) et d''une inoculation contr?l?e avec Laccaria laccata (Sco.) Fr., Pisolithus tinctorius (Pers.) Coker et Couch et Melanogaster ambiguus (Vittad.) Tul et C. Tul. Pour les deux pins, la mycorhization avec Laccaria laccata n''a pas ?t? modifi?e par la m?thode de fertilisation. Le pourcentage d''ectomycorrhizes (ECM) form? by P.?tinctorius d?pendait de la m?thode de fertilisation, su type d''inoculum (spores ou inoculum v?g?tatif) et de l''esp?ce de pin. La fertilisation a augment? les ECM produites par Melanogaster ambiguus chez les deux pins. L''inoculation a augment? significativement la biomasse des semis de Pinus pinea lorsqu''ils ont ?t? fertilis?s avec SRF tandis qu''aucun effet n''a ?t? trouv? pour les traitements non fertilis?s. Pour les semis non fertilis?s de Pinus pinaster, l''inoculation avec Laccaria laccata et avec les deux inoculums de Pisolithus tinctorius a augment? la biomasse des semis tandis que la fertilisation a neutralis? l''effet de l''inoculation. La fertilisation a augment? la biomasse de Pinus pinaster et de Pinus pinea ind?pendamment du traitement d''inoculation utilis?. [ABSTRACT FROM AUTHOR]

Different methods to inoculate seedlings of Pinus pinaster and P. sylvestris with edible Lactarius species under standard greenhouse conditions were evaluated. Fungal inoculations were performed both under pure culture synthesis in vitro, followed by transplantation of acclimatized seedlings, and directly in the greenhouse using different techniques for inocula production (mycelial slurries, vegetative inoculum grown in peat-vermiculite and alginate-entrapped mycelium). In vitro inoculations with L. deliciosus produced thoroughly colonized seedlings. However, a sharp decrease in mycorrhizal colonization was detected on transplanted seedlings after 4 month's growth in the greenhouse. On the other hand, all the inocula applied directly in the greenhouse, except the alginate-entrapped mycelium, produced a variable number of mycorrhizal seedlings and colonization rates after the first growing season, depending on the plant-fungal combination and the inoculation method. Inoculations with vegetative inocula of the strain 178 of L. deliciosus were the most effective in producing mycorrhizal seedlings. All the seedlings inoculated with this strain were colonized although the colonization rates were relatively low. The commercial feasibility of the different inoculation methods for the production of seedlings colonized with edible Lactarius species is discussed. [ABSTRACT FROM AUTHOR]

Purpose: Lip cancer can be treated by surgery, external radiotherapy, and/or brachytherapy (BT). In recent years, BT has become increasingly favored for this type of cancer. The aim of the present study was to analyze local control and survival of patients treated at our institution between July 1989 and June 2008., Material and Methods: We performed a retrospective study of 121 patients (109 males and 12 females) who underwent lip cancer brachytherapy from July 1989 to June 2008. Median age was 67 years and median follow-up was 31.8 months (range 20-188 months). Out of 121 patients, 100 (82.6%) were treated with low dose rate (LDR) BT while the remaining 21 patients (17.4%) received high dose rate (HDR) BT., Results: The most common cell type was squamous cell carcinoma (115 cases; 95%) and most tumors were located on the lower lip (107 patients; 88.4%). Most cases were either stage T1 (62 patients; 51.2%), or T2 (44 cases; 36.4%). After 15 years of follow-up, overall survival was 89.5%, cause-specific survival 97.8%, and disease-free survival 86.6%. Local, regional, and distant control at 15 years were 90%, 92%, and 98.8%, respectively. Grade 3 mucosal toxicity was observed in 23% of patients treated with LDR compared to 33% of HDR patients, and grade 4 mucosal toxicity in 9% versus 0% in the HDR group., Conclusions: Our findings confirm that brachytherapy is an effective treatment for lip cancer. The results from our series are in line with those published elsewhere. Based on our limited data, HDR appears to be equally as good as LDR, although this needs to be confirmed by further studies.