Lixiviação de nutrientes em substrato enriquecido com biochar.

Resumo

Levantamento de reconhecimento dos solos do Noroeste do Estado do Paraná: (informe preliminar).

A execucao do levantamento dos solos vem sendo realizada de maneira a atender as necessidades do estado e ao plano basico da EPFS, que visa ao inventario dos recursos potenciais dos solos do territorio nacional, consistindo na identificacao, classificacao, distribuicao e determinacao da area das diversas unidades de solos, de modo a proporcionar elementos basicos essenciais para planejamentos, principalmente os referntes a futuros trabalhos de levantamentos detalhados e ao estabelecimento racional de projetos de experimentacao e pesquisa, com possibilidades de aplicacao dos resultados em areas representativas de cada unidade que apresente expressao geografica importante, permitindo a extrapolacao dos resultados para solos semelhantes. O objetivo e o estudo dosdiferentes solos do Parana, atraves do reconhecimento da sua distribuicao geografica, delimitacao das areas por eles ocupadas e investigacao das suas caracteristicas morfologicas, fisicas e quimicas. O carater generalizado do mapeamento limita a precisao de detalhes cartograficos e nao pode ter por finalidade responder questoes de utilizacao de terras, problemas de fertilidade e produtividade em areas especificas. Procurou-se, tanto quanto possivel, elaborar a presente publicacao em forma simples, evitando ao maximo o excessivo emprego de termos tecnicos, a fim de poder atingir um maior numero de pessoas que dela possam fazer uso. Far-se-a, em seguida, a publicacao do levantamento do Noroeste e, finalmente, de todo o estado, abrangendo as suas varias regioes.bitstream/item/212067/1/EPFS-BT-14-1970.pdf; bitstream/item/125769/1/Levantamento-de-Reconhecimento-dos-Solos-do-Noroeste-do-Estado-do-Parana.pdfAcompanha 1 mapa, color. Escala 1:300.000

Hirnorganoide – Modellsysteme des menschlichen Gehirns

This is the final version. Available from Deutsche Akademie der Naturforscher Leopoldina via the DOI in this record. Hirnorganoide sind Gewebestrukturen aus dem Labor, die Teile der Hirnfunktion imitieren. Sie eröffnen als vereinfachtes Modellsystem einen experimentellen Zugang zu Fragen rund um die Entwicklung und die Funktion des menschlichen Gehirns. Während die Forschung an menschlichen lebenden Gehirnen aus ethischen Gründen enge Grenzen hat und Tiermodelle viele Fragen nur bedingt beantworten können, bieten Hirnorganoide neue Forschungsmöglichkeiten. In der Stellungnahme „Hirnorganoide ‒ Modellsysteme des menschlichen Gehirns“ der Nationalen Akademie der Wissenschaften Leopoldina beschreiben Wissenschaftlerinnen und Wissenschaftler die Möglichkeiten dieses Forschungsgebietes und erörtern, ob es aus ethischen oder juristischen Gründen stärker reguliert werden sollte

The Teacher, the Physician and the Person: How Faculty's Teaching Performance Influences Their Role Modelling

OBJECTIVE: Previous studies identified different typologies of role models (as teacher/supervisor, physician and person) and explored which of faculty's characteristics could distinguish good role models. The aim of this study was to explore how and to which extent clinical faculty's teaching performance influences residents' evaluations of faculty's different role modelling statuses, especially across different specialties. METHODS: In a prospective multicenter multispecialty study of faculty's teaching performance, we used web-based questionnaires to gather empirical data from residents. The main outcome measures were the different typologies of role modelling. The predictors were faculty's overall teaching performance and faculty's teaching performance on specific domains of teaching. The data were analyzed using multilevel regression equations. RESULTS: In total 219 (69% response rate) residents filled out 2111 questionnaires about 423 (96% response rate) faculty. Faculty's overall teaching performance influenced all role model typologies (OR: from 8.0 to 166.2). For the specific domains of teaching, overall, all three role model typologies were strongly associated with "professional attitude towards residents" (OR: 3.28 for teacher/supervisor, 2.72 for physician and 7.20 for the person role). Further, the teacher/supervisor role was strongly associated with "feedback" and "learning climate" (OR: 3.23 and 2.70). However, the associations of the specific domains of teaching with faculty's role modelling varied widely across specialties. CONCLUSION: This study suggests that faculty can substantially enhance their role modelling by improving their teaching performance. The amount of influence that the specific domains of teaching have on role modelling differs across specialties

Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R0-resected gastric adenocarcinomas and non-cancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n=175), whereas only 56% of gastric cancer specimens showed CAR positivity (P<0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor

A meta-analysis of GFR slope as a surrogate endpoint for kidney failure

Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min−1 per 1.73 m2 or kidney failure with replacement therapy). We used a Bayesian mixed-effects meta-regression model to relate treatment effects on GFR slope with those on the clinical endpoint across all studies and by disease groups (diabetes, glomerular diseases, CKD or cardiovascular diseases). Treatment effects on the clinical endpoint were strongly associated with treatment effects on total slope (median coefficient of determination (R2) = 0.97 (95% Bayesian credible interval (BCI) 0.82–1.00)) and moderately associated with those on chronic slope (R2 = 0.55 (95% BCI 0.25–0.77)). There was no evidence of heterogeneity across disease. Our results support the use of total slope as a primary endpoint for clinical trials of CKD progression

Mutation Analysis of BRAF, MEK1 and MEK2 in 15 Ovarian Cancer Cell Lines: Implications for Therapy

Among gynecologic cancers, ovarian cancer is the second most common and has the highest death rate. Cancer is a genetic disorder and arises due to the accumulation of somatic mutations in critical genes. An understanding of the genetic basis of ovarian cancer has implications both for early detection and for therapeutic intervention in this population of patients.Fifteen ovarian cancer cell lines, commonly used for in vitro experiments, were screened for mutations using bidirectional direct sequencing in all coding regions of BRAF, MEK1 and MEK2. BRAF mutations were identified in four of the fifteen ovarian cancer cell lines studied. Together, these four cell lines contained four different BRAF mutations, two of which were novel. ES-2 had the common B-Raf p.V600E mutation in exon 15 and Hey contained an exon 11 missense mutation, p.G464E. The two novel B-Raf mutants identified were a 5 amino acid heterozygous deletion p.N486-P490del in OV90, and an exon 4 missense substitution p.Q201H in OVCAR 10. One of the cell lines, ES-2, contained a mutation in MEK1, specifically, a novel heterozygous missense substitution, p.D67N which resulted from a nt 199 G-->A transition. None of the cell lines contained coding region mutations in MEK2. Functional characterization of the MEK1 mutant p.D67N by transient transfection with subsequent Western blot analysis demonstrated increased ERK phosphorylation as compared to controls.In this study, we report novel BRAF mutations in exon 4 and exon 12 and also report the first mutation in MEK1 associated with human cancer. Functional data indicate the MEK1 mutation may confer alteration of activation through the MAPK pathway. The significance of these findings is that BRAF and MEK1/2 mutations may be more common than anticipated in ovarian cancer which could have important implications for treatment of patients with this disease and suggests potential new therapeutic avenues

iPSC-Derived Microglia as a Model to Study Inflammation in Idiopathic Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease with unknown cause in the majority of patients, who are therefore considered "idiopathic" (IPD). PD predominantly affects dopaminergic neurons in the substantia nigra pars compacta (SNpc), yet the pathology is not limited to this cell type. Advancing age is considered the main risk factor for the development of IPD and greatly influences the function of microglia, the immune cells of the brain. With increasing age, microglia become dysfunctional and release pro-inflammatory factors into the extracellular space, which promote neuronal cell death. Accordingly, neuroinflammation has also been described as a feature of PD. So far, studies exploring inflammatory pathways in IPD patient samples have primarily focused on blood-derived immune cells or brain sections, but rarely investigated patient microglia in vitro. Accordingly, we decided to explore the contribution of microglia to IPD in a comparative manner using, both, iPSC-derived cultures and postmortem tissue. Our meta-analysis of published RNAseq datasets indicated an upregulation of IL10 and IL1B in nigral tissue from IPD patients. We observed increased expression levels of these cytokines in microglia compared to neurons using our single-cell midbrain atlas. Moreover, IL10 and IL1B were upregulated in IPD compared to control microglia. Next, to validate these findings in vitro, we generated IPD patient microglia from iPSCs using an established differentiation protocol. IPD microglia were more readily primed as indicated by elevated IL1B and IL10 gene expression and higher mRNA and protein levels of NLRP3 after LPS treatment. In addition, IPD microglia had higher phagocytic capacity under basal conditions-a phenotype that was further exacerbated upon stimulation with LPS, suggesting an aberrant microglial function. Our results demonstrate the significance of microglia as the key player in the neuroinflammation process in IPD. While our study highlights the importance of microglia-mediated inflammatory signaling in IPD, further investigations will be needed to explore particular disease mechanisms in these cells

Expression of coxsackie and adenovirus receptor distinguishes transitional cancer states in therapy-induced cellular senescence

Therapy-induced cellular senescence describes the phenomenon of cell cycle arrest that can be invoked in cancer cells in response to chemotherapy. Sustained proliferative arrest is often overcome as a contingent of senescent tumor cells can bypass this cell cycle restriction. The mechanism regulating cell cycle re-entry of senescent cancer cells remains poorly understood. This is the first report of the isolation and characterization of two distinct transitional states in chemotherapy-induced senescent cells that share indistinguishable morphological senescence phenotypes and are functionally classified by their ability to escape cell cycle arrest. It has been observed that cell surface expression of coxsackie and adenovirus receptor (CAR) is downregulated in cancer cells treated with chemotherapy. We show the novel use of surface CAR expression and adenoviral transduction to differentiate senescent states and also show in vivo evidence of CAR downregulation in colorectal cancer patients treated with neoadjuvant chemoradiation. This study suggests that CAR is a candidate biomarker for senescence response to antitumor therapy, and CAR expression can be used to distinguish transitional states in early senescence to study fundamental regulatory events in therapy-induced senescence

Serotonin and Dopamine Protect from Hypothermia/Rewarming Damage through the CBS/ H2S Pathway

Biogenic amines have been demonstrated to protect cells from apoptotic cell death. Herein we show for the first time that serotonin and dopamine increase H2S production by the endogenous enzyme cystathionine-β-synthase (CBS) and protect cells against hypothermia/rewarming induced reactive oxygen species (ROS) formation and apoptosis. Treatment with both compounds doubled CBS expression through mammalian target of rapamycin (mTOR) and increased H2S production in cultured rat smooth muscle cells. In addition, serotonin and dopamine treatment significantly reduced ROS formation. The beneficial effect of both compounds was minimized by inhibition of their re-uptake and by pharmacological inhibition of CBS or its down-regulation by siRNA. Exogenous administration of H2S and activation of CBS by Prydoxal 5′-phosphate also protected cells from hypothermic damage. Finally, serotonin and dopamine pretreatment of rat lung, kidney, liver and heart prior to 24 h of hypothermia at 3°C followed by 30 min of rewarming at 37°C upregulated the expression of CBS, strongly reduced caspase activity and maintained the physiological pH compared to untreated tissues. Thus, dopamine and serotonin protect cells against hypothermia/rewarming induced damage by increasing H2S production mediated through CBS. Our data identify a novel molecular link between biogenic amines and the H2S pathway, which may profoundly affect our understanding of the biological effects of monoamine neurotransmitters