91 research outputs found
Genomic and genetic insights into a cosmopolitan fungus, Paecilomyces variotii (Eurotiales)
Species in the genus Paecilomyces, a member of the fungal order Eurotiales, are ubiquitous in nature and impact a variety of human endeavors. Here, the biology of one common species, Paecilomyces variotii, was explored using genomics and functional genetics. Sequencing the genome of two isolates revealed key genome and gene features in this species. A striking feature of the genome was the two-part nature, featuring large stretches of DNA with normal GC content separated by AT-rich regions, a hallmark of many plant-pathogenic fungal genomes. These AT-rich regions appeared to have been mutated by repeat-induced point (RIP) mutations. We developed methods for genetic transformation of P. variotii, including forward and reverse genetics as well as crossing techniques. Using transformation and crossing, RIP activity was identified, demonstrating for the first time that RIP is an active process within the order Eurotiales. A consequence of RIP is likely reflected by a reduction in numbers of genes within gene families, such as in cell wall degradation, and reflected by growth limitations on P. variotii on diverse carbon sources. Furthermore, using these transformation tools we characterized a conserved protein containing a domain of unknown function (DUF1212) and discovered it is involved in pigmentation.Peer reviewe
Realising the right to data portability for the domestic Internet of Things
There is an increasing role for the IT design community to play in regulation
of emerging IT. Article 25 of the EU General Data Protection Regulation (GDPR)
2016 puts this on a strict legal basis by establishing the need for information
privacy by design and default (PbD) for personal data-driven technologies.
Against this backdrop, we examine legal, commercial and technical perspectives
around the newly created legal right to data portability (RTDP) in GDPR. We are
motivated by a pressing need to address regulatory challenges stemming from the
Internet of Things (IoT). We need to find channels to support the protection of
these new legal rights for users in practice. In Part I we introduce the
internet of things and information PbD in more detail. We briefly consider
regulatory challenges posed by the IoT and the nature and practical challenges
surrounding the regulatory response of information privacy by design. In Part
II, we look in depth at the legal nature of the RTDP, determining what it
requires from IT designers in practice but also limitations on the right and
how it relates to IoT. In Part III we focus on technical approaches that can
support the realisation of the right. We consider the state of the art in data
management architectures, tools and platforms that can provide portability,
increased transparency and user control over the data flows. In Part IV, we
bring our perspectives together to reflect on the technical, legal and business
barriers and opportunities that will shape the implementation of the RTDP in
practice, and how the relationships may shape emerging IoT innovation and
business models. We finish with brief conclusions about the future for the RTDP
and PbD in the IoT
Surgical procedures in the treatment of 784 infected THAs reported to the Norwegian Arthroplasty Register: Best survival with 2-stage exchange revision, but also good results with debridement and retention of the fixed implant
Synthetic Plasmodium-Like Hemozoin Activates the Immune Response: A Morphology - Function Study
Increasing evidence points to an important role for hemozoin (HZ), the malaria pigment, in the immunopathology related to this infection. However, there is no consensus as to whether HZ exerts its immunostimulatory activity in absence of other parasite or host components. Contamination of native HZ preparations and the lack of a unified protocol to produce crystals that mimic those of Plasmodium HZ (PHZ) are major technical limitants when performing functional studies with HZ. In fact, the most commonly used methods generate a heterogeneous nanocrystalline material. Thus, it is likely that such aggregates do not resemble to PHZ and differ in their inflammatory properties. To address this issue, the present study was designed to establish whether synthetic HZ (sHZ) crystals produced by different methods vary in their morphology and in their ability to activate immune responses. We report a new method of HZ synthesis (the precise aqueous acid-catalyzed method) that yields homogeneous sHZ crystals (Plasmodium-like HZ) which are very similar to PHZ in their size and physicochemical properties. Importantly, these crystals are devoid of protein and DNA contamination. Of interest, structure-function studies revealed that the size and shape of the synthetic crystals influences their ability to activate inflammatory responses (e.g. nitric oxide, chemokine and cytokine mRNA) in vitro and in vivo. In summary, our data confirm that sHZ possesses immunostimulatory properties and underline the importance of verifying by electron microscopy both the morphology and homogeneity of the synthetic crystals to ensure that they closely resemble those of the parasite. Periodic quality control experiments and unification of the method of HZ synthesis are key steps to unravel the role of HZ in malaria immunopathology
Early cartilage abnormalities at the hip are associated with obesity and body composition measures – a 3.0T MRI community-based study
Exploring the interpersonal-, organization-, and system-level factors that influence the implementation and use of an innovation-synoptic reporting-in cancer care
<p>Abstract</p> <p>Background</p> <p>The dominant method of reporting findings from diagnostic and surgical procedures is the narrative report. In cancer care, this report inconsistently provides the information required to understand the cancer and make informed patient care decisions. Another method of reporting, the synoptic report, captures specific data items in a structured manner and contains only items critical for patient care. Research demonstrates that synoptic reports vastly improve the quality of reporting. However, synoptic reporting represents a complex innovation in cancer care, with implementation and use requiring fundamental shifts in physician behaviour and practice, and support from the organization and larger system. The objective of this study is to examine the key interpersonal, organizational, and system-level factors that influence the implementation and use of synoptic reporting in cancer care.</p> <p>Methods</p> <p>This study involves three initiatives in Nova Scotia, Canada, that have implemented synoptic reporting within their departments/programs. Case study methodology will be used to study these initiatives (the cases) in-depth, explore which factors were barriers or facilitators of implementation and use, examine relationships amongst factors, and uncover which factors appear to be similar and distinct across cases. The cases were selected as they converge and differ with respect to factors that are likely to influence the implementation and use of an innovation in practice. Data will be collected through in-depth interviews, document analysis, observation of training sessions, and examination/use of the synoptic reporting tools. An audit will be performed to determine/quantify use. Analysis will involve production of a case record/history for each case, in-depth analysis of each case, and cross-case analysis, where findings will be compared and contrasted across cases to develop theoretically informed, generalisable knowledge that can be applied to other settings/contexts. Ethical approval was granted for this study.</p> <p>Discussion</p> <p>This study will contribute to our knowledge base on the multi-level factors, and the relationships amongst factors in specific contexts, that influence implementation and use of innovations such as synoptic reporting in healthcare. Such knowledge is critical to improving our understanding of implementation processes in clinical settings, and to helping researchers, clinicians, and managers/administrators develop and implement ways to more effectively integrate innovations into routine clinical care.</p
Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites
Resistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecular tests with particular parasite markers is not perfect, due in part to individuals who are able to clear genotypically drug-resistant parasites. This study aimed to identify molecular markers in the human genome that correlate with the clearance of malaria parasites after drug treatment, despite the drug resistance profile of the protozoan as predicted by molecular approaches
The Role of Transporters in the Pharmacokinetics of Orally Administered Drugs
Drug transporters are recognized as key players in the processes of drug absorption, distribution, metabolism, and elimination. The localization of uptake and efflux transporters in organs responsible for drug biotransformation and excretion gives transporter proteins a unique gatekeeper function in controlling drug access to metabolizing enzymes and excretory pathways. This review seeks to discuss the influence intestinal and hepatic drug transporters have on pharmacokinetic parameters, including bioavailability, exposure, clearance, volume of distribution, and half-life, for orally dosed drugs. This review also describes in detail the Biopharmaceutics Drug Disposition Classification System (BDDCS) and explains how many of the effects drug transporters exert on oral drug pharmacokinetic parameters can be predicted by this classification scheme
Differentiation of extranodal non-Hodgkins lymphoma from squamous cell carcinoma of the maxillary sinus: a multimodality imaging approach
A simple polyol-free synthesis route to Gd2O3 nanoparticles for MRI applications: an experimental and theoretical study
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