Kaposi sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV-8), is the primary etiologic cause of Kaposi sarcoma (KS) and KSHV Inflammatory Cytokine Syndrome (KICS). Patients with KICS demonstrate symptoms of systemic inflammation, high KSHV viral load, elevation of inflammatory markers, and increased mortality. Management requires rapid diagnosis, treatment of underlying HIV, direct treatment of KS, and addressing the hyperimmune response.
View Article and Find Full Text PDFBackground: Histoplasma is a fungal pathogen found in many parts of the world. In North America, its distribution is traditionally thought to be endemic to the Ohio and Mississippi River valleys. Development of histoplasmosis after Histoplasma exposure is related to degree of inoculum exposure and susceptibility, for example, immunocompromised status.
View Article and Find Full Text PDFThe germinal center (GC) is the stage of B cell differentiation that gives rise to a majority of B cell lymphomas. Here, we present an experimental coculture system for the ex vivo expansion and genetic manipulation of human GC B cells purified from discarded tonsil tissue. This system can be used to investigate the impact of defined genetic alterations, either individually or in combination, upon the growth and survival of human GC B cells in vitro.
View Article and Find Full Text PDFTargeting current therapies to treat or prevent the loss of pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off-target effects. Current efforts to target the β-cell are limited by a lack of β-cell-specific targets and the inability to test multiple targeting moieties with the same delivery vehicle. Here, we fabricate a tailorable polycaprolactone nanocapsule (NC) in which multiple different targeting peptides can be interchangeably attached for β-cell-specific delivery.
View Article and Find Full Text PDFThe use of plant genetic resources (PGR)-wild relatives, landraces, and isolated breeding gene pools-has had substantial impacts on wheat breeding for resistance to biotic and abiotic stresses, while increasing nutritional value, end-use quality, and grain yield. In the Global South, post-Green Revolution genetic yield gains are generally achieved with minimal additional inputs. As a result, production has increased, and millions of hectares of natural ecosystems have been spared.
View Article and Find Full Text PDFGlucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB).
View Article and Find Full Text PDFTargeting of current therapies to treat or prevent loss of pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off target effects. Current efforts to target the β-cell are limited by a lack of β-cell specific targets and the inability to test multiple targeting moieties with the same delivery vehicle. Here we fabricate a novel tailorable polycaprolactone nanocapsule (NC) where multiple different targeting peptides can be interchangeably attached for β-cell specific delivery.
View Article and Find Full Text PDFMiliary tuberculosis is a form of disseminated tuberculosis that can be difficult to detect when the classic pattern is absent on chest radiograph and advanced cross-sectional imaging is not readily available. While the focused assessment with sonography for HIV-associated tuberculosis (FASH) protocol for extrapulmonary tuberculosis emphasizes easy-to-teach findings, experienced sonographers may detect additional, subtler signs that can aid in diagnosis. We report a case of a 20-year-old man with miliary tuberculosis diagnosed on computed tomography of the chest.
View Article and Find Full Text PDFThe glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor involved in the regulation of blood glucose levels and food intake. Stabilized agonists targeting GLP-1R are used in the treatment of type 2 diabetes and have recently become a breakthrough obesity therapy. Here, we revisit a classic article in Diabetes by Thorens et al.
View Article and Find Full Text PDFSince the emergence of Ug99 wheat stem rust in Uganda in 1998 (Pretorius et al. 2000), the threat of movement into South Asia has been a concern due to long-distance dispersal capacity of airborne spores (Brown and Hovmøller 2002; Singh et al. 2008; Meyer et al.
View Article and Find Full Text PDFCrop type observation is crucial for various environmental and agricultural remote sensing applications including land use and land cover mapping, crop growth monitoring, crop modelling, yield forecasting, disease surveillance, and climate modelling. Quality-controlled georeferenced crop type information is essential for calibrating and validating machine learning algorithms. However, publicly available field data is scarce, particularly in the highly dynamic smallholder farming systems of sub-Saharan Africa.
View Article and Find Full Text PDFPolatuzumab vedotin (Pola-V) is an antibody-drug conjugate directed to the CD79B subunit of the B-cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in diffuse large B-cell lymphoma (DLBCL). To identify determinants of Pola-V sensitivity, we used CRISPR-Cas9 screening for genes that modulated Pola-V toxicity for lymphomas or the surface expression of its target, CD79B.
View Article and Find Full Text PDFBackground: Preclinical models of cancer can be of translational benefit when assessing how different biomarkers are regulated in response to particular treatments. Detection of molecular biomarkers in preclinical models of cancer is difficult due inter-animal variability in responses, combined with limited accessibility of longitudinal data.
Methods: Nonlinear mixed-effects modelling (NLME) was used to analyse tumour growth data based on expected tumour growth rates observed 7 days after initial doses (DD7) of Radiotherapy (RT) and Combination of RT with DNA Damage Response Inhibitors (DDRi).
Epstein-Barr virus (EBV) is an important cause of human lymphomas, including Burkitt lymphoma (BL). EBV+ BLs are driven by Myc translocation and have stringent forms of viral latency that do not express either of the two major EBV oncoproteins, EBNA2 (which mimics Notch signaling) and LMP1 (which activates NF-κB signaling). Suppression of Myc-induced apoptosis, often through mutation of the TP53 (p53) gene or inhibition of pro-apoptotic BCL2L11 (BIM) gene expression, is required for development of Myc-driven BLs.
View Article and Find Full Text PDFGlucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are transmembrane receptors involved in insulin, glucagon and somatostatin secretion from the pancreatic islet. Therapeutic targeting of GLP1R and GIPR restores blood glucose levels in part by influencing beta cell, alpha cell and delta cell function. Despite the importance of the incretin-mimetics for diabetes therapy, our understanding of GLP1R and GIPR expression patterns and signaling within the islet remain incomplete.
View Article and Find Full Text PDFThe secretion of insulin from the pancreas relies on both gap junctions and subpopulations of beta cells with specific intrinsic properties.
View Article and Find Full Text PDFDiffuse large B cell lymphoma (DLBCL) is an aggressive, profoundly heterogeneous cancer, presenting a challenge for precision medicine. Bruton's tyrosine kinase (BTK) inhibitors block B cell receptor (BCR) signaling and are particularly effective in certain molecular subtypes of DLBCL that rely on chronic active BCR signaling to promote oncogenic NF-κB. The MCD genetic subtype, which often acquires mutations in the BCR subunit, CD79B, and in the innate immune adapter, MYD88, typically resists chemotherapy but responds exceptionally to BTK inhibitors.
View Article and Find Full Text PDFVery high (spatial and temporal) resolution satellite (VHRS) and high-resolution unmanned aerial vehicle (UAV) imagery provides the opportunity to develop new crop disease detection methods at early growth stages with utility for early warning systems. The capability of multispectral UAV, SkySat and Pleiades imagery as a high throughput phenotyping (HTP) and rapid disease detection tool for wheat rusts is assessed. In a randomized trial with and without fungicide control, six bread wheat varieties with differing rust resistance were monitored using UAV and VHRS.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
November 2023
We previously developed, synthesized and tested light-activated sulfonylureas for optical control of K channels and pancreatic beta cell activity in vitro and in vivo. Such technology relies on installation of azobenzene photoswitches onto the sulfonylurea backbone, affording light-dependent isomerization, alteration in ligand affinity for SUR1 and hence K channel conductance. Inspired by molecular dynamics simulations and to further improve photoswitching characteristics, we set out to develop a novel push-pull closed ring azobenzene unit, before installing this on the sulfonylurea glimepiride as a small molecule recipient.
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