The Institute of Medical science

Foresterhill, United Kingdom

The Institute of Medical science

Foresterhill, United Kingdom
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Tamaki F.K.,University of Sao Paulo | Tamaki F.K.,The Institute of Medical science | Araujo E.M.,University of Sao Paulo | Rozenberg R.,University of Sao Paulo | Marana S.R.,University of Sao Paulo
Biochemistry and Biophysics Reports | Year: 2016

The enzymatic hydrolysis of cellulose and lignocellulosic materials is marked by a rate decrease along the reaction time. Cellobiohydrolase slow dissociation from the substrate and its inhibition by the cellobiose produced are relevant factors associated to the rate decrease. In that sense, addition of β-glucosidases to the enzyme cocktails employed in cellulose enzymatic hydrolysis not only produces glucose as final product but also reduces the cellobiohydrolase inhibition by cellobiose. The digestive β-glucosidase GH1 from the fall armyworm Spodoptera frugiperda, hereafter called Sfβgly, containing the mutation L428V showed an increased kcat for cellobiose hydrolysis. In comparison to assays conducted with the wild-type Sfβgly and cellobiohydrolase TrCel7A, the presence of the mutant L428V increased in 5 fold the initial rate of crystalline cellulose hydrolysis and reduced to one quarter the time needed to TrCel7A produce the maximum glucose yield. As our results show that mutant L428V complement the action of TrCel7A, the introduction of the equivalent replacement in β-glucosidases is a promising strategy to reduce costs in the enzymatic hydrolysis of lignocellulosic materials. © 2016 The Authors.


PubMed | University of New South Wales, The Institute of Medical science, University of Bristol, Flinders University and 7 more.
Type: | Journal: Autoimmunity reviews | Year: 2017

To outline recommendations from an expert committee on the assessment and investigation of patients with severe inflammatory eye disease commencing immunosuppressive and/or biologic therapy.The approach to assessment is based on the clinical experience of an expert committee and a review of the literature with regard to corticosteroids, immunosuppressive drug and biologic therapy and other adjunct therapy in the management of patients with severe sight-threatening inflammatory eye disease.We recommend a careful assessment and consultative approach by ophthalmologists or physicians experienced in the use of immunosuppressive agents for all patients commencing immunosuppressive and/or biologic therapy for sight threatening inflammatory eye disease with the aim of preventing infection, cardiovascular, metabolic and bone disease and reducing iatrogenic side effects.


Wilson D.,Hans Knoell Institute | Wilson D.,The Institute of Medical science | Mayer F.L.,Hans Knoell Institute | Mayer F.L.,Michael Smith Laboratories | And 8 more authors.
Eukaryotic Cell | Year: 2014

Human fungal pathogens are distributed throughout their kingdom, suggesting that pathogenic potential evolved independently. Candida albicans is the most virulent member of the CUG clade of yeasts and a common cause of both superficial and invasive infections. We therefore hypothesized that C. albicans possesses distinct pathogenicity mechanisms. In silico genome subtraction and comparative transcriptional analysis identified a total of 65 C. albicans-specific genes (ASGs) expressed during infection. Phenotypic characterization of six ASG-null mutants demonstrated that these genes are dispensable for in vitro growth but play defined roles in host-pathogen interactions. Based on these analyses, we investigated two ASGs in greater detail. An orf19.6688Δ mutant was found to be fully virulent in a mouse model of disseminated candidiasis and to induce higher levels of the proinflammatory cytokine interleukin-1β (IL-1β) following incubation with murine macrophages. A pga16Δ mutant, on the other hand, exhibited attenuated virulence. Moreover, we provide evidence that secondary filamentation events (multiple hyphae emerging from a mother cell and hyphal branching) contribute to pathogenicity: PGA16 deletion did not influence primary hypha formation or extension following contact with epithelial cells; however, multiple hyphae and hyphal branching were strongly reduced. Significantly, these hyphae failed to damage host cells as effectively as the multiple hypha structures formed by wild-type C. albicans cells. Together, our data show that species-specific genes of a eukaryotic pathogen can play important roles in pathogenicity. © 2014, American Society for Microbiology. All Rights Reserved.


Kikuchi T.,Advanced Clinical Research Center | Iwatsuki-Horimoto K.,The Institute of Medical Science | Adachi E.,Advanced Clinical Research Center | Koga M.,Advanced Clinical Research Center | And 10 more authors.
Vaccine | Year: 2012

Neutralizing antibody titers were determined before and after a single dose of pandemic (H1N1) 2009 influenza vaccine in HIV-1-positive Japanese adults in the first season of the pandemic and in those in the second season who had already received the vaccine in the first season. The antibody response rate at 2-month post-vaccination increased significantly from 49.0% (50/102, 95%CI: 39.0-59.1%) in the 2009/2010 season to 66.7% (42/63, 95%CI: 53.7-78.1%) in the 2010/2011 season. Geometric mean antibody titers (fold dilution) at baseline, at 2 months, and at 4 months also increased significantly from 4.4 (95%CI: 3.3-5.7), 19.0 (95%CI: 13.4-26.8) and 13.7 (95%CI: 9.3-20.2), respectively, in the 2009/2010 season to 8.3 (95%CI: 5.8-11.7), 47.0 (95%CI: 32.2-68.6) and 38.2 (95%CI: 23.8-61.4), respectively, in the 2010/2011 season. Although the vaccine response was low in the first season, it was improved in the second season. © 2012 Elsevier Ltd.


Paspala S.A.B.,PAN Research Foundation | Paspala S.A.B.,The Institute of Medical science | Vishwakarma S.K.,PAN Research Foundation | Murthy T.V.R.K.,The Institute of Medical science | And 2 more authors.
Stem Cells and Cloning: Advances and Applications | Year: 2012

Stem cell transplantation for spinal cord injury (SCI) along with new pharmacotherapy research offers the potential to restore function and ease the associated social and economic burden in the years ahead. Various sources of stem cells have been used in the treatment of SCI, but the most convincing results have been obtained with neural progenitor cells in preclinical models. Although the use of cell-based transplantation strategies for the repair of chronic SCI remains the long sought after holy grail, these approaches have been to date the most successful when applied in the subacute phase of injury. Application of cell-based strategies for the repair and regeneration of the chronically injured spinal cord will require a combinational strategy that may need to include approaches to overcome the effects of the glial scar, inhibitory molecules, and use of tissue engineering strategies to bridge the lesion. Nonetheless, cell transplantation strategies are promising, and it is anticipated that the Phase I clinical trials of some form of neural stem cell-based approach in SCI will commence very soon. © 2012 Paspala et al, publisher and licensee Dove Medical Press Ltd.


PubMed | The Institute of Medical science
Type: | Journal: Stem cells and cloning : advances and applications | Year: 2013

Stem cell transplantation for spinal cord injury (SCI) along with new pharmacotherapy research offers the potential to restore function and ease the associated social and economic burden in the years ahead. Various sources of stem cells have been used in the treatment of SCI, but the most convincing results have been obtained with neural progenitor cells in preclinical models. Although the use of cell-based transplantation strategies for the repair of chronic SCI remains the long sought after holy grail, these approaches have been to date the most successful when applied in the subacute phase of injury. Application of cell-based strategies for the repair and regeneration of the chronically injured spinal cord will require a combinational strategy that may need to include approaches to overcome the effects of the glial scar, inhibitory molecules, and use of tissue engineering strategies to bridge the lesion. Nonetheless, cell transplantation strategies are promising, and it is anticipated that the Phase I clinical trials of some form of neural stem cell-based approach in SCI will commence very soon.

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