172 research outputs found
Tillering Dynamics of \u3ci\u3ePanicum maximum\u3c/i\u3e Jacq. cv. Tanzania-1 After Grazing
Tillering dynamics and tiller dry matter weight from Tanzania grass (Panicum maximum cv. Tanzania-1) were evaluated in two post-grazing stubbles (High Post-grazing Stubble – HPS-3.6 t of DM/ha and Low Post-grazing Stubble – LPS-2.3 t of DM/ha). There was no difference between post-grazing stubbles for decapitated axillary and basal remainder and new axillary tillers. The LPS presented greater number of new basal tillers. The rate of appearance of new basal and axillary tillers decreased with time after grazing. There were differences between the treatments on tiller dry matter weight, and greater values were found in the high post-graze stubble
The mitochondrial tRNA-derived fragment, mt-tRF-Leu<sup>TAA</sup>, couples mitochondrial metabolism to insulin secretion.
The contribution of the mitochondrial electron transfer system to insulin secretion involves more than just energy provision. We identified a small RNA fragment (mt-tRF-Leu <sup>TAA</sup> ) derived from the cleavage of a mitochondrially-encoded tRNA that is conserved between mice and humans. The role of mitochondrially-encoded tRNA-derived fragments remains unknown. This study aimed to characterize the impact of mt-tRF-Leu <sup>TAA</sup> , on mitochondrial metabolism and pancreatic islet functions.
We used antisense oligonucleotides to reduce mt-tRF-Leu <sup>TAA</sup> levels in primary rat and human islet cells, as well as in insulin-secreting cell lines. We performed a joint transcriptome and proteome analysis upon mt-tRF-Leu <sup>TAA</sup> inhibition. Additionally, we employed pull-down assays followed by mass spectrometry to identify direct interactors of the fragment. Finally, we characterized the impact of mt-tRF-Leu <sup>TAA</sup> silencing on the coupling between mitochondrial metabolism and insulin secretion using high-resolution respirometry and insulin secretion assays.
Our study unveils a modulation of mt-tRF-Leu <sup>TAA</sup> levels in pancreatic islets in different Type 2 diabetes models and in response to changes in nutritional status. The level of the fragment is finely tuned by the mechanistic target of rapamycin complex 1. Located within mitochondria, mt-tRF-Leu <sup>TAA</sup> interacts with core subunits and assembly factors of respiratory complexes of the electron transfer system. Silencing of mt-tRF-Leu <sup>TAA</sup> in islet cells limits the inner mitochondrial membrane potential and impairs mitochondrial oxidative phosphorylation, predominantly by affecting the Succinate (via Complex II)-linked electron transfer pathway. Lowering mt-tRF-Leu <sup>TAA</sup> impairs insulin secretion of rat and human pancreatic β-cells.
Our findings indicate that mt-tRF-Leu <sup>TAA</sup> interacts with electron transfer system complexes and is a pivotal regulator of mitochondrial oxidative phosphorylation and its coupling to insulin secretion
Restructuring and formalizing: Scholarly communication as a sustainable growth opportunity in information agencies?
Emerging technologies are revolutionizing the field of scholarly communication. Because of this, scholars increasingly need specialized support during all stages of the research process. With the academic library as the unit of analysis, two concepts from Rogers’ Diffusion of Innovation theory and organizational innovation literature are drawn upon to assess the sustainability of scholarly communication work in libraries. These concepts are organizational restructuring and formalization. Data on Association of Research Libraries (ARL) employees with relevant job titles and three digital curation competencies documents are analysed. Study findings suggest that ARL information agencies have restructured to provide added research support and that skills associated with scholarly communication positions are becoming more uniform. We conclude that scholarly communication information professionals are part of a sustainable area of practice within ARL information agencies, that has matured over the past decade, and this trend is likely to continue in at least the short term.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147770/1/pra214505501041.pd
A circular RNA generated from an intron of the insulin gene controls insulin secretion
Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of β-cells, resulting in impaired glucose- or KCl-induced insulin release and calcium signaling. The effect of the circular RNA is exerted at the transcriptional level and involves an interaction with the RNA-binding protein TAR DNA-binding protein 43 kDa (TDP-43). The level of this circularized intron is reduced in the islets of rodent diabetes models and of type 2 diabetic patients, possibly explaining their impaired secretory capacity. The study of this and other circular RNAs helps understanding β-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder
Use of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with hydroxyurea as post-transplant therapy in chronic myelogenous leukemia patients autografted with unmanipulated hematopoietic cells
Background and Objective. Allogeneic bone marrow transplantation remains the only potentially curative treatment for CML, but more than 70% of patients will be ineligible for allogeneic marrow transplant either because they do not have a suitable HLA-matched related or unrelated donor or because they are more than 50 years old. Several experimental and clinical findings support a role for autologous stem cell transplantation (ASCT) in CML. It has been suggested that in the early phase following autografting the Ph-negative clone has a proliferative advantage over the Ph-positive clone. We hypothesized that post-transplant GM-CSF administration could reactivate the functional activity of quiescent normal progenitors and prolong the duration of the post-transplant proliferative advantage of Ph-negative over Ph- positive progenitors. In order to evaluate the effect of post-transplant GM- CSF administration, a pilot clinical study was performed in which CML patients resistant to IFN-α therapy were autografted with unmanipulated marrow or blood cells and given prolonged GM-CSF therapy post-transplant. Methods. Five adult CML patients conditioned with the BAVC regimen were reinfused with either marrow (n=2) or blood (n=3) cells and given granulocyte-macrophage colony-stimulating factor (GM-CSF). Recombinant GM- CSF was initially administered at standard dosage (5 pg/kg/day) until a white blood cell count ≤2x109/L was achieved on two consecutive examinations, and thereafter at a low dose (1 μg/kg/day) for 5 to 9 months. On a weekly basis, GM-CSF was discontinued and hydroxyurea (1,000 mg/d) was given for two days. Results. Evidence of trilineage engraftment was observed in all cases. At autografting, 3 out of the 5 patients revealed 8-9% Ph-negative metaphases. During the initial phase of hematopoietic regeneration, direct cytogenetic analysis revealed 81% and 100% Ph-negative metaphases in two cases; nonleukemic hematopoiesis progressively decreased and was no longer detectable at +9 months. One patient showed cyclic Ph-negative hematopoiesis that appeared 3 months following autografting and peaked at +4 and +8 months. The fourth patient showed a low percentage (20%) of Ph-negative metaphases 1 month after ASCT, followed by a significant expansion of nonleukemic hematopoiesis, which could be detected up to month +13. No evidence of Ph- negative hematopoiesis could be detected in one patient. Three patients are in chronic phase 28, 30 and 31 months after autografting, respectively, and two patients evolved into blast crisis. Interpretation and Conclusions. This pilot study demonstrates that combined GM-CSF and hydroxyurea therapy seems to be effective in inducing and/or prolonging a transient period of Ph- negative hematopoiesis. The late appearance of Ph-negative hematopoiesis detected in two patients suggests an antileukemic activity of the combined GM-CSF/hydroxyurea therapy rather than an antileukemic effect of the conditioning regimen
Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience
Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue
In vitro and in vivo effects of easily administered, low-toxic retinoid and phenylacetate compounds on human neuroblastoma cells
Essential Role of the Small GTPase Ran in Postnatal Pancreatic Islet Development
The small GTPase Ran orchestrates pleiotropic cellular responses of nucleo-cytoplasmic shuttling, mitosis and subcellular trafficking, but whether deregulation of these pathways contributes to disease pathogenesis has remained elusive. Here, we generated transgenic mice expressing wild type (WT) Ran, loss-of-function Ran T24N mutant or constitutively active Ran G19V mutant in pancreatic islet β cells under the control of the rat insulin promoter. Embryonic pancreas and islet development, including emergence of insulin+ β cells, was indistinguishable in control or transgenic mice. However, by one month after birth, transgenic mice expressing any of the three Ran variants exhibited overt diabetes, with hyperglycemia, reduced insulin production, and nearly complete loss of islet number and islet mass, in vivo. Deregulated Ran signaling in transgenic mice, adenoviral over-expression of WT or mutant Ran in isolated islets, or short hairpin RNA (shRNA) silencing of endogenous Ran in model insulinoma INS-1 cells, all resulted in decreased expression of the pancreatic and duodenal homeobox transcription factor, PDX-1, and reduced β cell proliferation, in vivo. These data demonstrate that a finely-tuned balance of Ran GTPase signaling is essential for postnatal pancreatic islet development and glucose homeostasis, in vivo
Intracellular Serotonin Modulates Insulin Secretion from Pancreatic β-Cells by Protein Serotonylation
Non-neuronal, peripheral serotonin deficiency causes diabetes mellitus and identifies an intracellular role for serotonin in the regulation of insulin secretion
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