Replication in Cells of Hematopoietic Origin Is Necessary for Dengue Virus Dissemination

Dengue virus (DENV) is a mosquito-borne pathogen for which no vaccine or specific therapeutic is available. Although it is well established that dendritic cells and macrophages are primary sites of DENV replication, it remains unclear whether non-hematopoietic cellular compartments serve as virus reservoirs. Here, we exploited hematopoietic-specific microRNA-142 (miR-142) to control virus tropism by inserting tandem target sites into the virus to restrict replication exclusively in this cell population. In vivo use of this virus restricted infection of CD11b+, CD11c+, and CD45+ cells, resulting in a loss of virus spread, regardless of the route of administration. Furthermore, sequencing of the targeted virus population that persisted at low levels, demonstrated total excision of the inserted miR-142 target sites. The complete conversion of the virus population under these selective conditions suggests that these immune cells are the predominant sources of virus amplification. Taken together, this work highlights the importance of hematopoietic cells for DENV replication and showcases an invaluable tool for the study of virus pathogenesis

The role of multi-slice computed tomography in stable angina management: a current perspective

Contrast-enhanced CT coronary angiography (CTCA) has evolved as a reliable alternative imaging modality technique and may be the preferred initial diagnostic test in patients with stable angina with intermediate pre-test probability of CAD. However, because CTCA is moderately predictive for indicating the functional significance of a lesion, the combination of anatomic and functional imaging will become increasingly important. The technology will continue to improve with better spatial and temporal resolution at low radiation exposure, and CTCA may eventually replace invasive coronary angiography. The establishment of the precise role of CTCA in the diagnosis and management of patients with stable angina requires high-quality randomised study designs with clinical outcomes as a primary outcome

The growth inhibitory potential and antimetastatic effect of camel urine on breast cancer cells in vitro and in vivo

Although it may sound unpleasant, camel urine has been consumed extensively for years in the Middle East as it is believed to be able to treat a wide range of diseases such as fever, cold, or even cancer. People usually take it by mixing small drops with camel milk or take it directly. The project aims to study the effects of camel urine in inhibiting the growth potential and metastatic ability of 4T1 cancer cell line in vitro and in vivo. Based on the MTT result, the cytotoxicity of camel urine against 4T1 cell was established, and it was dose-dependent. Additionally, the antimetastatic potential of camel urine was tested by running several assays such as scratch assay, migration and invasion assay, and mouse aortic ring assay with promising results in the ability of camel urine to inhibit metastatic process of the 4T1 cells. In order to fully establish camel urine’s potential, an in vivo study was carried out by treating mice inoculated with 4T1 cells with 2 different doses of camel urine. By the end of the treatment period, the tumor in both treated groups had reduced in size as compared to the control group. Additional assays such as the TUNEL assay, immunophenotyping, cytokine level detection assay, clonogenic assay, and proteome profiler demonstrated the capability of camel urine to reduce and inhibit the metastatic potential of 4T1 cells in vivo. To sum up, further study of anticancer properties of camel urine is justified, as evidenced through the in vitro and in vivo studies carried out. Better results were obtained at higher concentration of camel urine used in vivo. Apart from that, this project has laid out the mechanisms employed by the substance to inhibit the growth and the metastatic process of the 4T1 cell

NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis

While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors, the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane. An important outcome of cytosolic recognition is the induction of IFNα and IFNβ, which are critical mediators of immunity against both bacteria and viruses. Like many intracellular pathogens, a significant fraction of the transcriptional response to Mycobacterium tuberculosis infection depends on these type I interferons, but the recognition pathways responsible remain elusive. In this work, we demonstrate that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that responds to bacterial peptidoglycan, and this event requires membrane damage that is actively inflicted by the bacterium. Unexpectedly, this recognition triggers the expression of type I interferons in a Tbk1- and Irf5-dependent manner. This response is only partially impaired by the loss of Irf3 and therefore, differs fundamentally from those stimulated by bacterial DNA, which depend entirely on this transcription factor. This difference appears to result from the unusual peptidoglycan produced by mycobacteria, which we show is a uniquely potent agonist of the Nod2/Rip2/Irf5 pathway. Thus, the Nod2 system is specialized to recognize bacteria that actively perturb host membranes and is remarkably sensitive to mycobacteria, perhaps reflecting the strong evolutionary pressure exerted by these pathogens on the mammalian immune system

ICAR: endoscopic skull‐base surgery

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Royal Society Scientific Meeting: Extracellular vesicles in the tumour microenvironment

Cancer cells do not grow as an isolated homogeneous mass; tumours are, in fact, complex and heterogeneous collections of cancer and surrounding stromal cells, collectively termed the tumour microenvironment. The interaction between cancer cells and stromal cells in the tumour microenvironment has emerged as a key concept in the regulation of cancer progression. Understanding the intercellular dialogue in the tumour microenvironment is therefore an important goal. One aspect of this dialogue that has not been appreciated until recently is the role of extracellular vesicles (EVs). EVs are small vesicles released by cells under both normal and pathological conditions; they can transfer biological molecules between cells leading to changes in phenotype. EVs have emerged as important regulators of biological processes and can be dysregulated in diseases such as cancer; rapidly growing interest in their biology and therapeutic potential led to the Royal Society hosting a Scientific Meeting to explore the roles of EVs in the tumour microenvironment. This cross-disciplinary meeting explored examples of how aberrant crosstalk between tumour and stromal cells can promote cancer progression, and how such signalling can be targeted for diagnostic, prognostic and therapeutic benefit. In this review, and the special edition of Philosophical Transactions of the Royal Society B that follows, we will provide an overview of the content and outcomes of this exciting meeting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'