Seed bank Synamics of Paspalum quadrifarium Lam. in the Flooding Pampa

Paspaium quadrifarium, ("paja colorada”) puede ser considerada una maleza y un recurso forrajero valioso de los pastizales naturales de la Pampa Deprimida. Las quemas inverno-primaverales de las comunidades dominadas por esta especie ("pajonales”) posibilitan rápidos incrementos de su receptividad ganadera. A fin de contribuir al conocimiento de la demografía de esta especie, se analizó la dinámica del banco de cariopsis. llamadas "semillas" bajo distintas condiciones de fuego y pastoreo. Los resultados indican que: a) Las semillas de paja colorada carecen de mecanismos de dormición; b) El pastoreo sobre pajonales no quemados no afecta la producción de cariopsis de paja colorada; c) El fuego al actuar aisladamente o en combinación con pastoreo, redujo la producción de semillas durante el primer ciclo de crecimiento pos-quema. No obstante, durante el ciclo siguiente, se registró una respuesta compensatoria, en términos de proporción de semillas viables.Paspalum quadrifarium can be considerad a weed or an useful forage resource of the Flooding Pampa. When bumed during the winter-spring period, the communities dominated by this specles ("pajonales”) show fast increments in stocking capacity for cattle. To contribute at the demographic knowledge of Paspalum quadrifarium, the dynamics of the seed bank was studied under different conditions of buming and grazing. The results suggesit that: a) Paspalum quadrifarium fiack dormition mechanisms; b) grazing didn’t affect seed ipmductlon; c) buming foilowed by grazing or buming wjthout grazing, ireduce ¡seed production during the first post-bum growing cyde. However, during the following eyeie, a compensatory responso of viable seeds was found since they had an increase.Universidad Nacional de La Plata (UNLP) - Facultad de Ciencias Agrarias y Forestale

Seed bank Synamics of Paspalum quadrifarium Lam. in the Flooding Pampa

Paspaium quadrifarium, ("paja colorada”) puede ser considerada una maleza y un recurso forrajero valioso de los pastizales naturales de la Pampa Deprimida. Las quemas inverno-primaverales de las comunidades dominadas por esta especie ("pajonales”) posibilitan rápidos incrementos de su receptividad ganadera. A fin de contribuir al conocimiento de la demografía de esta especie, se analizó la dinámica del banco de cariopsis. llamadas "semillas" bajo distintas condiciones de fuego y pastoreo. Los resultados indican que: a) Las semillas de paja colorada carecen de mecanismos de dormición; b) El pastoreo sobre pajonales no quemados no afecta la producción de cariopsis de paja colorada; c) El fuego al actuar aisladamente o en combinación con pastoreo, redujo la producción de semillas durante el primer ciclo de crecimiento pos-quema. No obstante, durante el ciclo siguiente, se registró una respuesta compensatoria, en términos de proporción de semillas viables.Paspalum quadrifarium can be considerad a weed or an useful forage resource of the Flooding Pampa. When bumed during the winter-spring period, the communities dominated by this specles ("pajonales”) show fast increments in stocking capacity for cattle. To contribute at the demographic knowledge of Paspalum quadrifarium, the dynamics of the seed bank was studied under different conditions of buming and grazing. The results suggesit that: a) Paspalum quadrifarium fiack dormition mechanisms; b) grazing didn’t affect seed ipmductlon; c) buming foilowed by grazing or buming wjthout grazing, ireduce ¡seed production during the first post-bum growing cyde. However, during the following eyeie, a compensatory responso of viable seeds was found since they had an increase.Universidad Nacional de La Plata (UNLP) - Facultad de Ciencias Agrarias y Forestale

Hepatocyte growth factor enhances death receptor-induced apoptosis by up-regulating DR5

<p>Abstract</p> <p>Background</p> <p>Hepatocyte growth factor (HGF) and its receptor c-MET are commonly expressed in malignant gliomas and embryonic neuroectodermal tumors including medulloblastoma and appear to play an important role in the growth and dissemination of these malignancies. Dependent on cell context and the involvement of specific downstream effectors, both pro- and anti-apoptotic effects of HGF have been reported.</p> <p>Methods</p> <p>Human medulloblastoma cells were treated with HGF for 24–72 hours followed by death receptor ligand TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) for 24 hours. Cell death was measured by MTT and Annexin-V/PI flow cytometric analysis. Changes in expression levels of targets of interest were measured by Northern blot analysis, quantitative reverse transcription-PCR, Western blot analysis as well as immunoprecipitation.</p> <p>Results</p> <p>In this study, we show that HGF promotes medulloblastoma cell death induced by TRAIL. TRAIL alone triggered apoptosis in DAOY cells and death was enhanced by pre-treating the cells with HGF for 24–72 h prior to the addition of TRAIL. HGF (100 ng/ml) enhanced TRAIL (10 ng/ml) induced cell death by 36% (<it>P </it>< 0.001). No cell death was associated with HGF alone. Treating cells with PHA-665752, a specific c-Met receptor tyrosine kinase inhibitor, significantly abrogated the enhancement of TRAIL-induced cell death by HGF, indicating that its death promoting effect requires activation of its canonical receptor tyrosine kinase. Cell death induced by TRAIL+HGF was predominately apoptotic involving both extrinsic and intrinsic pathways as evidenced by the increased activation of caspase-3, 8, 9. Promotion of apoptosis by HGF occurred via the increased expression of the death receptor DR5 and enhanced formation of death-inducing signal complexes (DISC).</p> <p>Conclusion</p> <p>Taken together, these and previous findings indicate that HGF:c-Met pathway either promotes or inhibits medulloblastoma cell death via pathway and context specific mechanisms.</p

DNER, an epigenetically modulated gene, regulates glioblastoma-derived neurosphere cell differentiation and tumor propagation

Neurospheres derived from glioblastoma (GBM) and other solid malignancies contain neoplastic stem-like cells that efficiently propagate tumor growth and resist cytotoxic therapeutics. The primary objective of this study was to use histone-modifying agents to elucidate mechanisms by which the phenotype and tumor-promoting capacity of GBM-derived neoplastic stem-like cells are regulated. Using established GBM-derived neurosphere lines and low passage primary GBM-derived neurospheres, we show that histone deacetylase (HDAC) inhibitors inhibit growth, induce differentiation, and induce apoptosis of neoplastic neurosphere cells. A specific gene product induced by HDAC inhibition, Delta/Notch-like epidermal growth factor-related receptor (DNER), inhibited the growth of GBM-derived neurospheres, induced their differentiation in vivo and in vitro, and inhibited their engraftment and growth as tumor xenografts. The differentiating and tumor suppressive effects of DNER, a noncanonical Notch ligand, contrast with the previously established tumor-promoting effects of canonical Notch signaling in brain cancer stem-like cells. Our findings are the first to implicate noncanonical Notch signaling in the regulation of neoplastic stem-like cells and suggest novel neoplastic stem cell targeting treatment strategies for GBM and potentially other solid malignancies

Molecular clarification of brainstem astroblastoma with EWSR1-BEND2 fusion in a 38-year-old man

The majority of astroblastoma occur in a cerebral location in children and young adults. Here we describe the unusual case of a 38-year-old man found to have a rapidly growing cystic enhancing circumscribed brainstem tumor with high grade histopathology classified as astroblastoma, MN1-altered by methylome profiling. He was treated with chemoradiation and temozolomide followed by adjuvant temozolomide without progression to date over one year from treatment initiation. Astroblastoma most frequently contain a MN1-BEND2 fusion, while in this case a rare EWSR1-BEND2 fusion was identified. Only a few such fusions have been reported, mostly in the brainstem and spinal cord, and they suggest that BEND2, rather than MN1, may have a more critical functional role, at least in these regions. This unusual clinical scenario exemplifies the utility of methylome profiling and assessment of gene fusions in tumors of the central nervous system

Methods to Quantify Nanomaterial Association with, and Distribution across, the Blood-Brain Barrier in Vivo

The role and functional anatomy of the blood-brain barrier (BBB) is summarized to enable the investigator to appropriately address evaluation of nanomaterial interaction with, and distribution across, it into brain tissue (parenchyma). Transport mechanisms across the BBB are presented, in relation to nanomaterial physicochemical properties. Measures and test substances to assess BBB integrity/disruption/permeation are introduced, along with how they are used to interpret the results obtained with the presented methods. Experimental pitfalls and misinterpretation of results of studies of brain nanomaterial uptake are briefly summarized, that can be avoided with the methods presented in this chapter. Two methods are presented. The in situ brain perfusion technique is used to determine rate and extent of nanomaterial distribution into the brain. The capillary depletion method separates brain parenchymal tissue from the endothelial cells that contribute to the BBB. It is used to verify nanomaterial brain tissue entry. These methods are best used together, the latter refining the results obtained with the former. Details of the materials and equipment needed to conduct these methods, and description of the procedures and data interpretation, are provided

A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II

Approximately two-thirds of patients with the lysosomal storage disease mucopolysaccharidosis II have progressive cognitive impairment. Intravenous (i.v.) enzyme replacement therapy does not affect cognitive impairment because recombinant iduronate-2-sulfatase (idursulfase) does not penetrate the blood-brain barrier at therapeutic concentrations. We examined the safety of idursulfase formulated for intrathecal administration (idursulfase-IT) via intrathecal drug delivery device (IDDD). A secondary endpoint was change in concentration of glycosaminoglycans in cerebrospinal fluid. Sixteen cognitively impaired males with mucopolysaccharidosis II who were previously treated with weekly i.v. idursulfase 0.5 mg/kg for ≥6 months were enrolled. Patients were randomized to no treatment or 10-mg, 30-mg, or 1-mg idursulfase-IT monthly for 6 months (four patients per group) while continuing i.v. idursulfase weekly. No serious adverse events related to idursulfase-IT were observed. Surgical revision/removal of the IDDD was required in 6 of 12 patients. Twelve total doses were administrated by lumbar puncture. Mean cerebrospinal fluid glycosaminoglycan concentration was reduced by approximately 90% in the 10-mg and 30-mg groups and approximately 80% in the 1-mg group after 6 months. These preliminary data support further development of investigational idursulfase-IT in MPS II patients with the severe phenotype who have progressed only to a mild-to-moderate level of cognitive impairment.Genet Med advance online publication 02 April 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.36

CNS Penetration of Intrathecal-Lumbar Idursulfase in the Monkey, Dog and Mouse: Implications for Neurological Outcomes of Lysosomal Storage Disorder

A major challenge for the treatment of many central nervous system (CNS) disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome) is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S). I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a) warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b) may have broader implications for CNS treatment with biopharmaceuticals