Propriedades dos solos em três sucessões de floresta tropical seca.

O aumento da qualidade da cobertura vegetal pode ter ligação direta com as propriedades químicas e físicas do solo. Esse trabalho objetivou estudar como alguns atributos do solo modificam de acordo com a mudança da complexidade da cobertura vegetal, em três estágios de sucessão (inicial, intermediário e tardio), em Floresta Tropical Seca, no Parque Estadual da Mata Seca, Minas Gerais. Com a finalidade de monitorar os solos, dos estágios sucessionais estudados, instalou-se em cada estágio um tratamento, com três replicadas em cada, totalizando nove parcelas de monitoramento. Realizaram-se coletas de solos em três profundidades, 0-10 cm, 10-20 cm e 20-40 cm. Os tratamentos nos estádios inicial e tardio apresentaram teor de carbono orgânico (C) mais elevado do que o tratamento no estágio intermediário. Os resultados apontam para associação da capacidade de troca catiônica (CTC) com a capacidade de fixar carbono, onde a CTC elevada esteve associada ao alto teor de C, nos estágios inicial e tardio

Regulation of a progenitor gene program by SOX4 is essential for mammary tumor proliferation

In breast cancer the transcription factor SOX4 has been shown to be associated with poor survival, increased tumor size and metastasis formation. This has mostly been attributed to the ability of SOX4 to regulate Epithelial-to-Mesenchymal-Transition (EMT). However, SOX4 regulates target gene transcription in a context-dependent manner that is determined by the cellular and epigenetic state. In this study we have investigated the loss of SOX4 in mammary tumor development utilizing organoids derived from a PyMT genetic mouse model of breast cancer. Using CRISPR/Cas9 to abrogate SOX4 expression, we found that SOX4 is required for inhibiting differentiation by regulating a subset of genes that are highly activated in fetal mammary stem cells (fMaSC). In this way, SOX4 re-activates an oncogenic transcriptional program that is regulated in many progenitor cell-types during embryonic development. SOX4-knockout organoids are characterized by the presence of more differentiated cells that exhibit luminal or basal gene expression patterns, but lower expression of cell cycle genes. In agreement, primary tumor growth and metastatic outgrowth in the lungs are impaired in SOX4KO tumors. Finally, SOX4KO tumors show a severe loss in competitive capacity to grow out compared to SOX4-proficient cells in primary tumors. Our study identifies a novel role for SOX4 in maintaining mammary tumors in an undifferentiated and proliferative state. Therapeutic manipulation of SOX4 function could provide a novel strategy for cancer differentiation therapy, which would promote differentiation and inhibit cycling of tumor cells

Plasticity of Lgr5-Negative Cancer Cells Drives Metastasis in Colorectal Cancer

Colorectal cancer stem cells (CSCs) express Lgr5 and display extensive stem cell-like multipotency and self-renewal and are thought to seed metastatic disease. Here, we used a mouse model of colorectal cancer (CRC) and human tumor xenografts to investigate the cell of origin of metastases. We found that most disseminated CRC cells in circulation were Lgr5- and formed distant metastases in which Lgr5+ CSCs appeared. This p

FGF2 Translationally Induced by Hypoxia Is Involved in Negative and Positive Feedback Loops with HIF-1α

BACKGROUND: Fibroblast growth factor 2 (FGF2) is a major angiogenic factor involved in angiogenesis and arteriogenesis, however the regulation of its expression during these processes is poorly documented. FGF2 mRNA contains an internal ribosome entry site (IRES), a translational regulator expected to allow mRNA expression during cellular stress. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we have developed a skin ischemia model in transgenic mice expressing a reporter transgene under the control of the FGF2 IRES. The results reveal that FGF2 is induced at the protein level during ischemia, concomitant with HIF-1alpha induction and a decrease in FGF2 mRNA. In addition, the FGF2 IRES is strongly activated under these ischemic conditions associated with hypoxia, whereas cap-dependent translation is repressed by 4E-BP hypophosphorylation. We also show that up-regulation of FGF2 protein expression in response to hypoxia correlates with the increase of FGF2 IRES activity in vitro, in human retinoblasts 911. The use of siRNAs targeting HIF or FGF2 indicates that FGF2 and HIF-1alpha reciprocally regulate their expression/accumulation, by a negative feedback loop in early hypoxia, followed by a positive feedback loop in late hypoxia. CONCLUSION/SIGNIFICANCE: FGF2 expression is up-regulated in vivo and in vitro in response to hypoxia. Strikingly, this up-regulation is not transcriptional. It seems to occur by an IRES-dependent mechanism, revealing new mechanistic aspects of the hypoxic response. In addition, our data show that FGF2 interacts with HIF-1alpha in a unique crosstalk, with distinct stages in early and late hypoxia. These data reveal the physiological importance of IRES-dependent translation during hypoxic stress and underline the complexity of the cellular response to hypoxia, suggesting a novel role of FGF2 in the regulation of HIF-1alpha during the induction of angiogenesis

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place

The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives

This is the final version. Available on open access from Oxford University Press via the DOI in this recordCandida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients

In vivo study of the biological properties of cheese fraction.

International audienc

Surgical Outcomes of Dual-Plate Fixation for Periprosthetic Femur Fractures Around a Stable Hip Arthroplasty Stem

INTRODUCTION: The incidence of periprosthetic femur fractures is increasing. Multiple treatment methods exist to treat fractures surrounding stable hip arthroplasty implants including locking plate fixation, cable fixation, allograft augmentation, and revision arthroplasty. No consensus regarding optimal treatment has been reached, and significant complications remain. Recently, biomechanical studies have demonstrated the benefits of orthogonal dual-plate fixation, but little clinical data exist. The purpose of the current study was to investigate the clinical and radiographic outcomes of dual-plated periprosthetic femur fractures around stable hip stems. MATERIALS AND METHODS: Patients with periprosthetic femur fractures following hip arthroplasty with a stable femoral stem treated with dual-plate fixation were identified through chart review at a single institution. Fracture classification, fixation characteristics, radiographic outcomes, clinical outcomes and complications including re-operation were recorded. RESULTS: Over a 12-year period, 31 patients (mean age 77 years at surgery, range 48-94) underwent dual plating by three traumatologists for implant-stable periprosthetic femur fractures surrounding a hip arthroplasty stem. There were 27 Vancouver B1-type and 9 inter-prosthetic fractures. Average follow-up was 2 years. Of the 26 patients with minimum 6-month follow-up, 24 (92%) united after index surgery (mean time to union 6.0 months, range 1.5-14.0). Mean time to full weight-bearing post-operatively was 2.6 months (range 1.5-4.0 months). Two patients required secondary surgery to address nonunion. CONCLUSIONS: Dual-plating achieved high union rates with an acceptable complication profile for the treatment of periprosthetic femur fractures surrounding a stable hip arthroplasty stem. Our preferred fixation construct involves a lateral plate spanning the entire femur secured with non-locking bicortical screws supplemented with an anteriorly based reconstruction plate. Additional prospective research is required to confirm the results of this study