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"Gray, Mark"
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Why do poxviruses still matter?
Poxviruses comprise many members that infect both vertebrate and invertebrate animals, including humans. Despite the eradication of the historically notorious smallpox, poxviruses remain significant public health concerns and serious endemic diseases. This short review briefly summarizes the present, historical, and future threats posed by poxviruses to public health, wildlife and domestic animals, the role poxviruses have played in shaping modern medicine and biomedical sciences, the insight poxviruses have provided into complex life processes, and the utility of poxviruses in biotechniques and in fighting other infectious diseases and cancers. It is anticipated that readers will appreciate the great merit and need for continued strong support of poxvirus research; research which benefits not only the expansion of fundamental biological knowledge but also the battle against diverse diseases.
Journal Article
Post-Operative Monitoring of Intestinal Tissue Oxygenation Using an Implantable Microfabricated Oxygen Sensor
Anastomotic leakage (AL) is a common and dangerous post-operative complication following intestinal resection, causing substantial morbidity and mortality. Ischaemia in the tissue surrounding the anastomosis is a major risk-factor for AL development. Continuous tissue oxygenation monitoring during the post-operative recovery period would provide early and accurate early identification of AL risk. We describe the construction and testing of a miniature implantable electrochemical oxygen sensor that addresses this need. It consisted of an array of platinum microelectrodes, microfabricated on a silicon substrate, with a poly(2-hydroxyethyl methacrylate) hydrogel membrane to protect the sensor surface. The sensor was encapsulated in a biocompatible package with a wired connection to external instrumentation. It gave a sensitive and highly linear response to variations in oxygen partial pressure in vitro, although over time its sensitivity was partially decreased by protein biofouling. Using a pre-clinical in vivo pig model, acute intestinal ischaemia was robustly and accurately detected by the sensor. Graded changes in tissue oxygenation were also measurable, with relative differences detected more accurately than absolute differences. Finally, we demonstrated its suitability for continuous monitoring of tissue oxygenation at a colorectal anastomosis over a period of at least 45 h. This study provides evidence to support the development and use of implantable electrochemical oxygen sensors for post-operative monitoring of anastomosis oxygenation.
Journal Article
Gunmetal gray
\"After five years on the run, Court Gentry is back on the inside at the CIA. But his first mission makes him wish he had stayed on the outs when a pair of Chinese agents try to take him down in Hong Kong. Normally the Chinese prefer to stay eyes-only on foreign agents. So why are they on such high alert? Court's high stakes hunt for answers takes him across Southeast Asia and leads to his old friend Donald Fitzroy, who is being held hostage by the Chinese\"--Amazon.com.
Book
Development and characterisation of acquired radioresistant breast cancer cell lines
Background
Radiotherapy plays an important role in the multimodal treatment of breast cancer. The response of a breast tumour to radiation depends not only on its innate radiosensitivity but also on tumour repopulation by cells that have developed radioresistance. Development of effective cancer treatments will require further molecular dissection of the processes that contribute to resistance.
Methods
Radioresistant cell lines were established by exposing MDA-MB-231, MCF-7 and ZR-751 parental cells to increasing weekly doses of radiation. The development of radioresistance was evaluated through proliferation and colony formation assays. Phenotypic characterisation included migration and invasion assays and immunohistochemistry. Transcriptomic data were also generated for preliminary hypothesis generation involving pathway-focused analyses.
Results
Proliferation and colony formation assays confirmed radioresistance. Radioresistant cells exhibited enhanced migration and invasion, with evidence of epithelial-to-mesenchymal-transition. Significantly, acquisition of radioresistance in MCF-7 and ZR-751 cell lines resulted in a loss of expression of both ERα and PgR and an increase in EGFR expression; based on transcriptomic data they changed subtype classification from their parental luminal A to HER2-overexpressing (MCF-7 RR) and normal-like (ZR-751 RR) subtypes, indicating the extent of phenotypic changes and cellular plasticity involved in this process. Radioresistant cell lines derived from ER+ cells also showed a shift from ER to EGFR signalling pathways with increased MAPK and PI3K activity.
Conclusions
This is the first study to date that extensively describes the development and characterisation of three novel radioresistant breast cancer cell lines through both genetic and phenotypic analysis. More changes were identified between parental cells and their radioresistant derivatives in the ER+ (MCF-7 and ZR-751) compared with the ER- cell line (MDA-MB-231) model; however, multiple and likely interrelated mechanisms were identified that may contribute to the development of acquired resistance to radiotherapy.
Journal Article
Mission critical
\"The Gray Man deals in death with mathematical precision, but this time he may finally find himself on the wrong side of the equation ... Court Gentry's flight on a CIA transport plane is interrupted when a security team brings a hooded man aboard. The mysterious passenger is being transported to England where a joint CIA/MI6 team will interrogate him about a mole in Langley. When they land at an isolated airbase in the UK, they are attacked by a hostile force that kidnaps the prisoner. Gentry, the lone survivor, is ordered to track down the assassins and rescue the asset. In Virginia, an assault on a CIA safe house leaves dead and wounded agents littering a suburban neighborhood. The object of the attack is Court's former lover, Zoya Zakharova. She escapes, but with a team of killers on her trail. Now, two different agents on two different continents are battling blind against the impossible--but each may be holding the piece the other needs to fight their way out\"-- Provided by publisher.
Book
Wonder Woman. Vol. 6, Children of the Gods
\"Until recently, Wonder Woman had no clue she had a twin brother, taken away from Themyscira in the dead of night. The mysterious Jason (the only male ever born on the island) has been hidden somewhere far from the sight of gods and men...but his life and Wonder Woman's are about to intersect in a terrifying way. Before she can unravel that secret, Diana has to contend with the return of Grail, who is tracking down her half-siblings, the offspring of Zeus. As each demigod dies, the energy is channeled to Grail's father and master, the reborn Darkseid. And now Wonder Woman will be drawn into the battle against the deadly Lord of Apokolips. Will Jason fight at her side, or do his loyalties lie elsewhere?\"
Book
Single cell transcriptomics reveals dendritic cell subsets in bovine afferent lymph and immune cell-resolved responses to BCG vaccination
Bovine tuberculosis (bTB), caused by Mycobacterium bovis ( M. bovis ), remains an ongoing global issue for human and animal health. The Bacille Calmette Guerin (BCG) vaccine offers immunity against bTB, however, the mechanisms underlying the heterogenous protective response, including variations across species and age groups requires further investigation. In this study, we focused on dendritic cells (DCs), which are crucial for adaptive immune stimulation following BCG vaccination. By capturing afferent lymph DCs (ALDCs) migrating from the skin, we investigated shifts in DC profiles and potential subset-specific functions in response to BCG vaccination. Single-cell RNA sequencing (scRNA-seq) was performed on samples from Bos taurus calves (n=3) before and after BCG vaccination, capturing the transcriptome of 20,761 individual cells expressing on average 3,036 genes, which were clustered into ALDCs, monocytes, T-cells, B-cells and NK cells. The ALDC subsets were further identified as cDC1 and cDC2. In homeostasis, ALDCs expressing potential subset-specific genes for cDC1, including ENSBTAG00000056208, STX4 , NEBL , ADAM23 , ART3 , and cDC2; FN1 , PSPH , FGL2 , SHOX2 , and WWTR1 were identified. Following BCG vaccination, while both DC subsets exhibited gene expression signatures indicative of antigen-presenting function, migration, and DC maturation, cDC1 showed upregulation of genes consistent with metabolic alterations and lymphocyte recruitment, whereas cDC2 upregulated genes consistent with inflammatory responses. Overall, this study comprehensively describes the transcriptomic landscape of bovine ALDC subsets, providing evidence for the importance of subset-specific genes to BCG vaccination responses, while advancing knowledge on how ALDCs contribute to protective immunity against bTB.
Journal Article