Soilborne wheat mosaic virus (SBWMV) 19K protein belongs to a class of cysteine rich proteins that suppress RNA silencing

Amino acid sequence analyses indicate that the Soilborne wheat mosaic virus (SBWMV) 19K protein is a cysteine-rich protein (CRP) and shares sequence homology with CRPs derived from furo-, hordei-, peclu- and tobraviruses. Since the hordei- and pecluvirus CRPs were shown to be pathogenesis factors and/or suppressors of RNA silencing, experiments were conducted to determine if the SBWMV 19K CRP has similar activities. The SBWMV 19K CRP was introduced into the Potato virus X (PVX) viral vector and inoculated to tobacco plants. The SBWMV 19K CRP aggravated PVX-induced symptoms and restored green fluorescent protein (GFP) expression to GFP silenced tissues. These observations indicate that the SBWMV 19K CRP is a pathogenicity determinant and a suppressor of RNA silencing

The role of inflammatory reactions in xenotransplantation

Since the original description of hyperacute rejection of the kidney, numerous experimental and clinical studies have attempted to define the precise mechanism(s) of this process. While our interpretation of HAR has advanced, one must recognize this phenomenon as multifactorial and the product of a complex immune/inflammatory reaction. The non-specific effector inflammatory cascade that ensues once an antigen-antibody reaction has initiated hyperacute rejection serves as the target for therapeutic intervention by various modalities. Classically, the platelet-coagulation system has been considered to be the most important and has received the greatest attention. These therapeutic modalities have included heparin, aspirin, dextran, citrate, defibrinating agents, cobra and venom factor, induction of thrombocytopenia by antibodies, and various prostaglandins. All these approaches have been either too toxic or the results too inconclusive to be accepted for generalized use. The difficulty in overcoming the inflammatory process in hyperacute rejection and in explaining the discrepancies in the therapeutic results rest not only in the complexity of the biological reactions, but also in their resiliency and redundancy. That is, there are numerous alternative mediator pathways that can back up the same set of functions. Thus, the inhibition of one arm of an inflammatory reaction can easily be replaced by the release of other inflammatory autocoids with complete mediation of the disease process

Urothelial Inverted Papilloma of the Lower Urinary Tract—A Benign Lesion or a Precursor of Malignancy?

ObjectiveWe investigated the clinical characteristics and follow-up results of patients with a lower urinary tract inverted papilloma (IP) in our hospital, with the intention of clarifying whether certain groups require more aggressive surveillance.Materials and MethodsWe conducted a retrospective study of lower urinary tract IP, using the pathology database of Taipei Veterans General Hospital, from September 1992 to February 2008. In total, 67 patients were enrolled. Patients' clinical characteristics, symptoms, tumor locations, and follow-up data were analyzed.ResultsAmong the 67 patients diagnosed with IP, 59 were male and eight were female, with a mean age of 67.9 ± 12.4 years. Gross hematuria and lower-urinary-tract symptoms were the most common symptoms. All of the patients received transurethral resection as initial treatment. Thirty-eight of these patients were monitored for a median of 21 months (range: 3–168 months). Seven patients had synchronous urothelial malignancies, and one had recurrent IP during follow-up. No patient had subsequent urothelial carcinoma or IP recurrence without a synchronous or previous urothelial malignancy during follow-up.ConclusionThere is a low incidence of developing a subsequent malignancy with a simple IP lesion during follow-up. Rigorous surveillance may be unnecessary in IP patients without a synchronous or previous urothelial malignancy

Randomised pragmatic waitlist trial with process evaluation investigating the effectiveness of peer support after brain injury: protocol.

Traumatic brain injury (TBI) is an important global health problem. Formal service provision fails to address the ongoing needs of people with TBI and their family in the context of a social and relational process of learning to live with and adapt to life after TBI. Our feasibility study reported peer support after TBI is acceptable to both mentors and mentees with reported benefits indicating a high potential for effectiveness and likelihood of improving outcomes for both mentees and their mentors. To (a) test the effectiveness of a peer support intervention for improving participation, health and well-being outcomes after TBI and (b) determine key process variables relating to intervention, context and implementation to underpin an evidence-based framework for ongoing service provision. A randomised pragmatic waitlist trial with process evaluation. Mentee participants (n=46) will be included if they have moderate or severe TBI and are no more than 18 months post-injury. Mentor participants (n=18) will be people with TBI up to 6 years after injury, who were discharged from inpatient rehabilitation at least 1 year prior. The primary outcome will be mentee participation, measured using the Impact on Participation and Autonomy questionnaire after 22 weeks. Primary analysis of the continuous variables will be analysis of covariance with baseline measurement as a covariate and randomised treatment as the main explanatory predictor variable at 22 weeks. Process evaluation will include analysis of intervention-related data and qualitative data collected from mentors and service coordinators. Data synthesis will inform the development of a service framework for future implementation. Ethics approval has been obtained from the New Zealand Health and Disability Ethics Committee (19/NTB/82) and Auckland University of Technology Ethics Committee (19/345). Dissemination of findings will be via traditional academic routes including publication in internationally recognised peer-reviewed journals. ACTRN12619001002178. [Abstract copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

Geo-environmental mapping using physiographic analysis: constraints on the evaluation of land instability and groundwater pollution hazards in the Metropolitan District of Campinas, Brazil

Geo-environmental terrain assessments and territorial zoning are useful tools for the formulation and implementation of environmental management instruments (including policy-making, planning, and enforcement of statutory regulations). They usually involve a set of procedures and techniques for delimitation, characterisation and classification of terrain units. However, terrain assessments and zoning exercises are often costly and time-consuming, particularly when encompassing large areas, which in many cases prevent local agencies in developing countries from properly benefiting from such assessments. In the present paper, a low-cost technique based on the analysis of texture of satellite imagery was used for delimitation of terrain units. The delimited units were further analysed in two test areas situated in Southeast Brazil to provide estimates of land instability and the vulnerability of groundwater to pollution hazards. The implementation incorporated procedures for inferring the influences and potential implications of tectonic fractures and other discontinuities on ground behaviour and local groundwater flow. Terrain attributes such as degree of fracturing, bedrock lithology and weathered materials were explored as indicators of ground properties. The paper also discusses constraints on- and limitations of- the approaches taken

Biophysically Realistic Filament Bending Dynamics in Agent-Based Biological Simulation

An appealing tool for study of the complex biological behaviors that can emerge from networks of simple molecular interactions is an agent-based, computational simulation that explicitly tracks small-scale local interactions – following thousands to millions of states through time. For many critical cell processes (e.g. cytokinetic furrow specification, nuclear centration, cytokinesis), the flexible nature of cytoskeletal filaments is likely to be critical. Any computer model that hopes to explain the complex emergent behaviors in these processes therefore needs to encode filament flexibility in a realistic manner. Here I present a numerically convenient and biophysically realistic method for modeling cytoskeletal filament flexibility in silico. Each cytoskeletal filament is represented by a series of rigid segments linked end-to-end in series with a variable attachment point for the translational elastic element. This connection scheme allows an empirically tuning, for a wide range of segment sizes, viscosities, and time-steps, that endows any filament species with the experimentally observed (or theoretically expected) static force deflection, relaxation time-constant, and thermal writhing motions. I additionally employ a unique pair of elastic elements – one representing the axial and the other the bending rigidity– that formulate the restoring force in terms of single time-step constraint resolution. This method is highly local –adjacent rigid segments of a filament only interact with one another through constraint forces—and is thus well-suited to simulations in which arbitrary additional forces (e.g. those representing interactions of a filament with other bodies or cross-links / entanglements between filaments) may be present. Implementation in code is straightforward; Java source code is available at www.celldynamics.org

Au-ZSM-5 catalyses the selective oxidation of CH4 to CH3OH and CH3COOH using O2

The oxidation of methane, the main component of natural gas, to selectively form oxygenated chemical feedstocks using molecular oxygen has been a long-standing grand challenge in catalysis. Here, using gold nanoparticles supported on the zeolite ZSM-5, we introduce a method to oxidize methane to methanol and acetic acid in water at temperatures between 120 and 240 °C using molecular oxygen in the absence of any added coreductant. Electron microscopy reveals that the catalyst does not contain gold atoms or clusters, but rather gold nanoparticles are the active component, while a mechanism involving surface adsorbed species is proposed in which methanol and acetic acid are formed via parallel pathways. [Figure not available: see fulltext.]

Histoplasma capsulatum proteome response to decreased iron availability

<p>Abstract</p> <p>Background</p> <p>A fundamental pathogenic feature of the fungus <it>Histoplasma capsulatum </it>is its ability to evade innate and adaptive immune defenses. Once ingested by macrophages the organism is faced with several hostile environmental conditions including iron limitation. <it>H. capsulatum </it>can establish a persistent state within the macrophage. A gap in knowledge exists because the identities and number of proteins regulated by the organism under host conditions has yet to be defined. Lack of such knowledge is an important problem because until these proteins are identified it is unlikely that they can be targeted as new and innovative treatment for histoplasmosis.</p> <p>Results</p> <p>To investigate the proteomic response by <it>H. capsulatum </it>to decreasing iron availability we have created <it>H. capsulatum </it>protein/genomic databases compatible with current mass spectrometric (MS) search engines. Databases were assembled from the <it>H. capsulatum </it>G217B strain genome using gene prediction programs and expressed sequence tag (EST) libraries. Searching these databases with MS data generated from two dimensional (2D) in-gel digestions of proteins resulted in over 50% more proteins identified compared to searching the publicly available fungal databases alone. Using 2D gel electrophoresis combined with statistical analysis we discovered 42 <it>H. capsulatum </it>proteins whose abundance was significantly modulated when iron concentrations were lowered. Altered proteins were identified by mass spectrometry and database searching to be involved in glycolysis, the tricarboxylic acid cycle, lysine metabolism, protein synthesis, and one protein sequence whose function was unknown.</p> <p>Conclusion</p> <p>We have created a bioinformatics platform for <it>H. capsulatum </it>and demonstrated the utility of a proteomic approach by identifying a shift in metabolism the organism utilizes to cope with the hostile conditions provided by the host. We have shown that enzyme transcripts regulated by other fungal pathogens in response to lowering iron availability are also regulated in <it>H. capsulatum </it>at the protein level. We also identified <it>H. capsulatum </it>proteins sensitive to iron level reductions which have yet to be connected to iron availability in other pathogens. These data also indicate the complexity of the response by <it>H. capsulatum </it>to nutritional deprivation. Finally, we demonstrate the importance of a strain specific gene/protein database for <it>H. capsulatum </it>proteomic analysis.</p