Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Type of study
Language
Publication year range
1.
Cureus ; 15(8): e43826, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37608904

ABSTRACT

Femoral shaft fracture, one of the most common orthopaedic injuries, is usually treated with intramedullary nailing. During the operative procedure patients are placed on a traction table. Traction tables facilitate the procedure but are associated with some risk. Here we are sharing a case of a 35-year-old male healthy young patient who sustained a foot drop post nailing of femoral shaft fracture on a traction table. This patient has had some recovery in six weeks but is still not fully recovered. We think traction tables are a very helpful tool but carry some risks that should be kept on mind for every surgeon, and for the patients too.

2.
mSphere ; 8(1): e0056822, 2023 02 21.
Article in English | MEDLINE | ID: mdl-36719225

ABSTRACT

Having varied approaches to the design and manufacture of vaccines is critical in being able to respond to worldwide needs and newly emerging pathogens. Virus-like particles (VLPs) form the basis of two of the most successful licensed vaccines (against hepatitis B virus [HBV] and human papillomavirus). They are produced by recombinant expression of viral structural proteins, which assemble into immunogenic nanoparticles. VLPs can be modified to present unrelated antigens, and here we describe a universal "bolt-on" platform (termed VelcroVax) where the capturing VLP and the target antigen are produced separately. We utilize a modified HBV core (HBcAg) VLP with surface expression of a high-affinity binding sequence (Affimer) directed against a SUMO tag and use this to capture SUMO-tagged gp1 glycoprotein from the arenavirus Junín virus (JUNV). Using this model system, we have solved the first high-resolution structures of VelcroVax VLPs and shown that the VelcroVax-JUNV gp1 complex induces superior humoral immune responses compared to the noncomplexed viral protein. We propose that this system could be modified to present a range of antigens and therefore form the foundation of future rapid-response vaccination strategies. IMPORTANCE The hepatitis B core protein (HBc) forms noninfectious virus-like particles, which can be modified to present a capturing molecule, allowing suitably tagged antigens to be bound on their surface. This system can be adapted and provides the foundation for a universal "bolt-on" vaccine platform (termed VelcroVax) that can be easily and rapidly modified to generate nanoparticle vaccine candidates.


Subject(s)
Vaccines , Humans , Hepatitis B Core Antigens/genetics , Hepatitis B virus , Glycoproteins , Vaccination
3.
Sci Rep ; 11(1): 9773, 2021 05 07.
Article in English | MEDLINE | ID: mdl-33963233

ABSTRACT

Type I fatty acid synthases (FASs) are critical metabolic enzymes which are common targets for bioengineering in the production of biofuels and other products. Serendipitously, we identified FAS as a contaminant in a cryoEM dataset of virus-like particles (VLPs) purified from P. pastoris, an important model organism and common expression system used in protein production. From these data, we determined the structure of P. pastoris FAS to 3.1 Å resolution. While the overall organisation of the complex was typical of type I FASs, we identified several differences in both structural and enzymatic domains through comparison with the prototypical yeast FAS from S. cerevisiae. Using focussed classification, we were also able to resolve and model the mobile acyl-carrier protein (ACP) domain, which is key for function. Ultimately, the structure reported here will be a useful resource for further efforts to engineer yeast FAS for synthesis of alternate products.


Subject(s)
Fatty Acid Synthases/chemistry , Saccharomycetales/enzymology , Cryoelectron Microscopy , Fatty Acid Synthases/ultrastructure , Models, Molecular , Protein Domains
4.
EBioMedicine ; 46: 522-531, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31327693

ABSTRACT

The gastrointestinal mucosa is critical for maintaining the integrity and functions of the gut. Disruption of this barrier is a hallmark and a risk factor for many intestinal and chronic inflammatory diseases. Inflammatory bowel disease (IBD) and HIV infection are characterized by microbial translocation and systemic inflammation. Despite the clinical overlaps between HIV and IBD, significant differences exist such as the severity of gut damage and mechanisms of immune cell homeostasis. Studies have supported the role of metabolic activation of immune cells in promoting chronic inflammation in HIV and IBD. This inflammatory response persists in HIV+ persons even after long-term virologic suppression by antiretroviral therapy (ART). Here, we review gut dysfunction and microbiota changes during HIV infection and IBD, and discuss how this may induce metabolic reprogramming of monocytes, macrophages and T cells to impact disease outcomes. Drawing from parallels with IBD, we highlight how factors such as lipopolysaccharides, residual viral replication, and extracellular vesicles activate biochemical pathways that regulate immunometabolic processes essential for HIV persistence and non-AIDS metabolic comorbidities. This review highlights new mechanisms and support for the use of immunometabolic-based therapeutics towards HIV remission/cure, and treatment of metabolic diseases.


Subject(s)
Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/physiopathology , HIV Infections/immunology , HIV Infections/metabolism , HIV/immunology , Animals , Cell Membrane Permeability , Comorbidity , Dysbiosis , Energy Metabolism , Fatty Acids/metabolism , Gastrointestinal Microbiome/immunology , HIV Infections/complications , HIV Infections/virology , Humans , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Macrophages/immunology , Macrophages/metabolism , Monocytes/immunology , Monocytes/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...