101 research outputs found

    A rare case report of ruptured distal pica aneurysm and complications

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    Aneurysms of the distal PICA are rarely encountered and are challenging lesions prone for surgical rupture. PICA is the greatest of the branches of the vertebral artery, and is the causative vessel for aneurysm in the posterior cranial fossa. Common location of aneurysms of PICA is at its junction with vertebral artery. Aneurysms originating from more distant PICA segments are called distal aneurysms and are very rare, with a prevalence of 0.3%. Cerebral infarction and cranial nerve compression occur commonly with rupture of PICA aneurysm. CT angiography has been proposed superior to conventional angiography in patients with ruptured aneurysms presenting with SAH. Surgical treatment of PICA aneurysms depends on the sites of occurrence. Surgical aneurysm clipping and endovascular coiling are the available treatment options to prevent further complications. Here, we report a rare case of distal PICA aneurysm presenting with diffuse SAH and IVH

    Tsetse Salivary Gland Hypertrophy Virus: Hope or Hindrance for Tsetse Control?

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    Many species of tsetse flies (Diptera: Glossinidae) are infected with a virus that causes salivary gland hypertrophy (SGH), and flies with SGH symptoms have a reduced fecundity and fertility. The prevalence of SGH in wild tsetse populations is usually very low (0.2%–5%), but higher prevalence rates (15.2%) have been observed occasionally. The successful eradication of a Glossina austeni population from Unguja Island (Zanzibar) using an area-wide integrated pest management approach with a sterile insect technique (SIT) component (1994–1997) encouraged several African countries, including Ethiopia, to incorporate the SIT in their national tsetse control programs. A large facility to produce tsetse flies for SIT application in Ethiopia was inaugurated in 2007. To support this project, a Glossina pallidipes colony originating from Ethiopia was successfully established in 1996, but later up to 85% of adult flies displayed symptoms of SGH. As a result, the colony declined and became extinct by 2002. The difficulties experienced with the rearing of G. pallidipes, epitomized by the collapse of the G. pallidipes colony originating from Ethiopia, prompted the urgent need to develop management strategies for the salivary gland hypertrophy virus (SGHV) for this species. As a first step to identify suitable management strategies, the virus isolated from G. pallidipes (GpSGHV) was recently sequenced and research was initiated on virus transmission and pathology. Different approaches to prevent virus replication and its horizontal transmission during blood feeding have been proposed. These include the use of antiviral drugs such as acyclovir and valacyclovir added to the blood for feeding or the use of antibodies against SGHV virion proteins. In addition, preliminary attempts to silence the expression of an essential viral protein using RNA interference will be discussed

    ALADIN is Required for the Production of Fertile Mouse Oocytes

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    Asymmetric cell divisions depend on the precise placement of the spindle apparatus. In mammalian oocytes, spindles assemble close to the cell's center, but chromosome segregation takes place at the cell periphery where half of the chromosomes are expelled into small, nondeveloping polar bodies at anaphase. By dividing so asymmetrically, most of the cytoplasmic content within the oocyte is preserved, which is critical for successful fertilization and early development. Recently we determined that the nucleoporin ALADIN participates in spindle assembly in somatic cells, and we have also shown that female mice homozygously null for ALADIN are sterile. In this study we show that this protein is involved in specific meiotic stages, including meiotic resumption, spindle assembly, and spindle positioning. In the absence of ALADIN, polar body extrusion is compromised due to problems in spindle orientation and anchoring at the first meiotic anaphase. ALADIN null oocytes that mature far enough to be fertilized in vitro are unable to support embryonic development beyond the two-cell stage. Overall, we find that ALADIN is critical for oocyte maturation and appears to be far more essential for this process than for somatic cell divisions

    Lack of Wdr13 Gene in Mice Leads to Enhanced Pancreatic Beta Cell Proliferation, Hyperinsulinemia and Mild Obesity

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    WD-repeat proteins are very diverse, yet these are structurally related proteins that participate in a wide range of cellular functions. WDR13, a member of this family, is conserved from fishes to humans and localizes into the nucleus. To understand the in vivo function(s) of Wdr13 gene, we have created and characterized a mutant mouse strain lacking this gene. The mutant mice had higher serum insulin levels and increased pancreatic islet mass as a result of enhanced beta cell proliferation. While a known cell cycle inhibitor, p21, was downregulated in the mutant islets, over expression of WDR13 in the pancreatic beta cell line (MIN6) resulted in upregulation of p21, accompanied by retardation of cell proliferation. We suggest that WDR13 is a novel negative regulator of the pancreatic beta cell proliferation. Given the higher insulin levels and better glucose clearance in Wdr13 gene deficient mice, we propose that this protein may be a potential candidate drug target for ameliorating impaired glucose metabolism in diabetes

    Characterization of a Novel Binding Protein for Fortilin/TCTP β€” Component of a Defense Mechanism against Viral Infection in Penaeus monodon

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    The Fortilin (also known as TCTP) in Penaeus monodon (PmFortilin) and Fortilin Binding Protein 1 (FBP1) have recently been shown to interact and to offer protection against the widespread White Spot Syndrome Virus infection. However, the mechanism is yet unknown. We investigated this interaction in detail by a number of in silico and in vitro analyses, including prediction of a binding site between PmFortilin/FBP1 and docking simulations. The basis of the modeling analyses was well-conserved PmFortilin orthologs, containing a Ca2+-binding domain at residues 76–110 representing a section of the helical domain, the translationally controlled tumor protein signature 1 and 2 (TCTP_1, TCTP_2) at residues 45–55 and 123–145, respectively. We found the pairs Cys59 and Cys76 formed a disulfide bond in the C-terminus of FBP1, which is a common structural feature in many exported proteins and the β€œx–G–K–K” pattern of the amidation site at the end of the C-terminus. This coincided with our previous work, where we found the β€œx–P–P–x” patterns of an antiviral peptide also to be located in the C-terminus of FBP1. The combined bioinformatics and in vitro results indicate that FBP1 is a transmembrane protein and FBP1 interact with N-terminal region of PmFortilin

    Identifying New Therapeutic Targets via Modulation of Protein Corona Formation by Engineered Nanoparticles

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    We introduce a promising methodology to identify new therapeutic targets in cancer. Proteins bind to nanoparticles to form a protein corona. We modulate this corona by using surface-engineered nanoparticles, and identify protein composition to provide insight into disease development.Using a family of structurally homologous nanoparticles we have investigated the changes in the protein corona around surface-functionalized gold nanoparticles (AuNPs) from normal and malignant ovarian cell lysates. Proteomics analysis using mass spectrometry identified hepatoma-derived growth factor (HDGF) that is found exclusively on positively charged AuNPs ((+)AuNPs) after incubation with the lysates. We confirmed expression of HDGF in various ovarian cancer cells and validated binding selectivity to (+)AuNPs by Western blot analysis. Silencing of HDGF by siRNA resulted s inhibition in proliferation of ovarian cancer cells.We investigated the modulation of protein corona around surface-functionalized gold nanoparticles as a promising approach to identify new therapeutic targets. The potential of our method for identifying therapeutic targets was demonstrated through silencing of HDGF by siRNA, which inhibited proliferation of ovarian cancer cells. This integrated proteomics, bioinformatics, and nanotechnology strategy demonstrates that protein corona identification can be used to discover novel therapeutic targets in cancer

    The nature of economic development and the economic development of nature

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    Contemporary models of growth and development are founded on a category error: they ignore nature as a form of productive capital. Using as backdrop two recent books on the Indian economy that are representative of the prevailing orthodoxy, I review and in part extend an emerging literature that integrates development and environmental thinking. Contributors to the literature have reworked the economics of the household, communities, and other non-market institutions, reframed national accounting, reconstructed the theory of macro-economic development and public and trade policy, and revised the theory of collective action. In this paper I focus on a small part of the literature: economic evaluation. I develop the notion of sustainable development and construct a unified language for sustainability and policy analyses. I show that by economic growth we should mean growth in wealth - which is the social worth of an economy's entire set of capital assets - not growth in GDP nor the many ad hoc indicators of human development that have been proposed in recent years. The concept of wealth invites us to extend the notion of capital assets and the idea of investment well beyond conventional usage. I also show that by sustainable development we should mean development in which wealth (per head) adjusted for its distribution does not decline. This has radical implications for the way national accounts are prepared and interpreted. I then provide an account of a recent publication that has put the theory to work by studying the composition of wealth accumulation in contemporary India. Although much attention was given by the study's authors to the measurement of natural capital, due to a paucity of data the value of natural capital is acknowledged by them to be under-estimated, in all probability by a large margin. The study reveals that the entire architecture of contemporary development thinking is stacked against nature. These are still early days in the measurement of the wealth of nations, but both theory and the few empirical studies we now have at our disposal should substantially alter the way we interpret the progress and regress of nations
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