The essential kinase TgGSK regulates centrosome division and endodyogeny in .

Intracellular replication is crucial for the success of apicomplexan parasites, including . Therefore, essential players in parasite replication present potential targets for drug development. In this study, we have characterized TgGSK, a glycogen synthase kinase homolog that plays an important role in endodyogeny.

HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14.

High-risk human papillomavirus (HPV) oncoproteins inactivate cellular tumor suppressors to reprogram host cell signaling pathways. HPV E7 proteins bind and degrade the tumor suppressor PTPN14, thereby promoting the nuclear localization of the YAP1 oncoprotein and inhibiting keratinocyte differentiation. YAP1 is a transcriptional coactivator that drives epithelial cell stemness and self-renewal.

Radiation Research Society Journal-based Historical Review of the Use of Biomarkers for Radiation Dose and Injury Assessment: Acute Health Effects Predictions.

A multiple-parameter based approach using radiation-induced clinical signs and symptoms, hematology changes, cytogenetic chromosomal aberrations, and molecular biomarkers changes after radiation exposure is used for biodosimetry-based dose assessment. In the current article, relevant milestones from Radiation Research are documented that forms the basis of the current consensus approach for diagnostics after radiation exposure. For example, in 1962 the use of cytogenetic chromosomal aberration using the lymphocyte metaphase spread dicentric assay for biodosimetry applications was first published in Radiation Research.

HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14.

High-risk human papillomavirus (HPV) oncoproteins inactivate cellular tumor suppressors to reprogram host cell signaling pathways. HPV E7 proteins bind and degrade the tumor suppressor PTPN14, thereby promoting the nuclear localization of the YAP1 oncoprotein and inhibiting keratinocyte differentiation. YAP1 is a transcriptional coactivator that drives epithelial cell stemness and self-renewal.

Natural-history Characterization of a Murine Partial-body Irradiation Model System: Establishment of a Multiple-Parameter Based GI-ARS Severity-Scoring System.

The purpose of this investigation was to characterize the natural history of a murine total-abdominal-irradiation exposure model to measure gastrointestinal acute radiation injury. Male CD2F1 mice at 12 to 15 weeks old received total-abdominal irradiation using 4-MV linear accelerator X-rays doses of 0, 11, 13.5, 15, 15.

Optimizing chemical-induced premature chromosome condensation assay for rapid estimation of high-radiation doses.

In the event of exposure to high doses of radiation, prompt dose estimation is crucial for selecting appropriate treatment modalities, such as cytokine therapy or stem cell transplantation. The chemical-induced premature chromosome condensation (PCC) method offers a simple approach for such dose estimation with significant radiation exposure, but its 48-h incubation time poses challenges for early dose assessment. In this study, we optimized the chemical-induced PCC assay for more rapid dose assessment.

Severity scoring systems for radiation-induced GI injury - prioritization for use of GI-ARS medical countermeasures.

Purpose: Severity scoring systems for ionizing radiation-induced gastrointestinal injury have been used in animal radiation models, human studies involving the use of radiation therapy, and human radiation accidents. Various radiation exposure scenarios (i.e.

Combined radiation injury and its impacts on radiation countermeasures and biodosimetry.

Purpose: Preparedness for medical responses to major radiation accidents and the increasing threat of nuclear warfare worldwide necessitates an understanding of the complexity of combined radiation injury (CI) and identifying drugs to treat CI is inevitably critical. The vital sign and survival after CI were presented. The molecular mechanisms, such as microRNA pathways, NF-κB-iNOS-IL-18 pathway, C3 production, the AKT-MAPK cross-talk, and TLR/MMP increases, underlying CI in relation to organ injury and mortality were analyzed.

Mitotic index maximization with no effect on radiation-induced dicentric chromosome frequency.

Purpose: The dicentric chromosome (Dic) assay, which is the gold standard for biological dose assessment in radiation emergency medicine, requires an analysis of at least 500 lymphocyte metaphases or 100 Dic aberrations. Therefore, peripheral blood culture conditions able to obtain a high frequency of metaphases for efficient dose evaluation should be optimized. However, the type of blood cultures [i.

The Tyrosine Phosphatase PRL Regulates Attachment of Toxoplasma gondii to Host Cells and Is Essential for Virulence.

The pathogenesis of Toxoplasma gondii is mainly due to tissue damage caused by the repeating lytic cycles of the parasite. Many proteins localized to the pellicle of the parasite, particularly kinases, have been identified as critical regulators of the lytic cycle. However, little is known about the associated protein phosphatases.

Early molecular markers for retrospective biodosimetry and prediction of acute health effects.

Radiation-induced biological changes occurring within hours and days after irradiation can be potentially used for either exposure reconstruction (retrospective dosimetry) or the prediction of consecutively occurring acute or chronic health effects. The advantage of molecular protein or gene expression (GE) (mRNA) marker lies in their capability for early (1-3 days after irradiation), high-throughput and point-of-care diagnosis, required for the prediction of the acute radiation syndrome (ARS) in radiological or nuclear scenarios. These molecular marker in most cases respond differently regarding exposure characteristics such as e.

Early-response multiple-parameter biodosimetry and dosimetry: risk predictions.

The accepted generic multiple-parameter and early-response biodosimetry and dosimetry assessment approach for suspected high-dose radiation (i.e. life-threatening) exposure includes measuring radioactivity associated with the exposed individual (if appropriate); observing and recording prodromal signs/symptoms; obtaining serial complete blood counts with white-blood-cell differential; sampling blood for the chromosome-aberration cytogenetic bioassay using the 'gold standard' dicentric assay (premature chromosome condensation assay for exposures >5 Gy photon acute doses equivalent), measurement of proteomic biomarkers and gene expression assays for dose assessment; bioassay sampling, if appropriate, to determine radioactive internal contamination; physical dose reconstruction, and using other available opportunistic dosimetry approaches.

Celebrating 60 Years of Accomplishments of the Armed Forces Radiobiology Research Institute1.

Chartered by the U.S. Congress in 1961, the Armed Forces Radiobiology Research Institute (AFRRI) is a Joint Department of Defense (DoD) entity with the mission of carrying out the Medical Radiological Defense Research Program in support of our military forces around the globe.

RENEB Inter-Laboratory comparison 2017: limits and pitfalls of ILCs.

Purpose: In case of a mass-casualty radiological event, there would be a need for networking to overcome surge limitations and to quickly obtain homogeneous results (reported aberration frequencies or estimated doses) among biodosimetry laboratories. These results must be consistent within such network. Inter-laboratory comparisons (ILCs) are widely accepted to achieve this homogeneity.

Improved harvest and fixation methodology for isolated human peripheral blood mononuclear cells in cytokinesis-block micronucleus assay.

Purpose: In suspected radiation exposures, cytokinesis-block micronucleus (CBMN) assay is used for biodosimetry by detecting micronuclei (MN) in binucleated (BN) cells in whole blood and isolated peripheral blood mononuclear cell (PBMC) cultures. Standardized harvest protocols for whole blood were published by the International Atomic Energy Agency (IAEA) in 2001 (Technical report no. 405) and 2011 (EPR-Biodosimetry).

Automated Dicentric Aberration Scoring for Triage Dose Assessment: 60Co Gamma Ray Dose-response at Different Dose Rates.

The objective of this study was to establish radiation dose-response calibration curves using automated dicentric scoring to support rapid and accurate cytogenetic triage dose-assessment. Blood was drawn from healthy human volunteers and exposed to Co gamma rays at several dose rates (i.e.

The Secreted Acid Phosphatase Domain-Containing GRA44 from Toxoplasma gondii Is Required for c-Myc Induction in Infected Cells.

During host cell invasion, the eukaryotic pathogen forms a parasitophorous vacuole to safely reside within the cell, while it is partitioned from host cell defense mechanisms. From within this safe niche, parasites sabotage multiple host cell systems, including gene expression, apoptosis, and intracellular immune recognition, by secreting a large arsenal of effector proteins. Many parasite proteins studied for active host cell manipulative interactions have been kinases.

Construction of fluorescence in situ hybridization (FISH) translocation dose-response calibration curve with multiple donor data sets using R, based on ISO 20046:2019 recommendations.

Dose-response curve (DRC) generation is an important aspect in cytogenetic biodosimetry for accurate dose estimation for individuals suspected of prior irradiation. DRC construction with dicentric chromosomes after acute radiation is well-established following the publication of the IAEA EPR-Biodosimetry 2011 and ISO 19238:2014. However, the short half-life of dicentrics might not be suitable for retrospective dose estimation in radiation medical workers, radiation accident clean-up workers and the general public living in areas with higher than average amount of radiation.

BABOON RADIATION QUALITY (MIXED-FIELD NEUTRON AND GAMMA, GAMMA ALONE) DOSE-RESPONSE MODEL SYSTEMS: ASSESSMENT OF H-ARS SEVERITY USING HAEMATOLOGIC BIOMARKERS.

Results from archived (1986 and 1996) experiments were used to establish a baboon radiation-quality dose-response database with haematology biomarker time-course data following exposure to mixed-fields (i.e. neutron to gamma ratio: 5.

A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells.

The propagation of Toxoplasma gondii is accomplished by repeated lytic cycles of parasite attachment to a host cell, invasion, replication within a parasitophorous vacuole, and egress from the cell. This lytic cycle is delicately regulated by calcium-dependent reversible phosphorylation of the molecular machinery that drives invasion and egress. While much progress has been made elucidating the protein kinases and substrates central to parasite propagation, little is known about the relevant protein phosphatases.

CONCEPTS OF OPERATIONS FOR A US DOSIMETRY AND BIODOSIMETRY NETWORK.

The USA must be prepared to provide a prompt, coordinated and integrated response for radiation dose and injury assessment for suspected radiation exposure, whether it involves isolated cases or mass casualties. Dose estimation for radiation accidents typically necessitates a multiple parameter diagnostics approach that includes clinical, biological and physical dosimetry to provide an early-phase radiation dose. A US Individual Dosimetry and Biodosimetry Network (US-IDBN) will increase surge capacity for civilian and military populations in a large-scale incident.

System for Scoring Severity of Acute Radiation Syndrome Response in Rhesus Macaques ().

We developed a clinical assessment tool for use in an NHP radiation model to 1) quantify severity responses for subsyndromes of the acute radiation syndrome (ARS; that is, hematopoietic and others) and 2) identify animals that required enhanced monitoring. Our assessment tool was based primarily on the MEdical TREatment ProtocOLs for Radiation Accident Victims (METREPOL) scoring system but was adapted for NHP to include additional indices (for example, behaviors) for use in NHP studies involving limited medical intervention. Male ( = 16) and female ( = 12) rhesus macaques (; 5 groups: sham and 1.

Use of Proteomic and Hematology Biomarkers for Prediction of Hematopoietic Acute Radiation Syndrome Severity in Baboon Radiation Models.

Use of plasma proteomic and hematological biomarkers represents a promising approach to provide useful diagnostic information for assessment of the severity of hematopoietic acute radiation syndrome. Eighteen baboons were evaluated in a radiation model that underwent total-body and partial-body irradiations at doses of Co gamma rays from 2.5 to 15 Gy at dose rates of 6.

Using Clinical Signs and Symptoms for Medical Management of Radiation Casualties - 2015 NATO Exercise.

The utility of early-phase (≤5 days) radiation-induced clinical signs and symptoms (e.g., vomiting, diarrhea, erythema and changes in blood cell counts) was examined for the prediction of later occurring acute radiation syndrome (ARS) severity and the development of medical management strategies.

U.S. Department of Defense Multiple-Parameter Biodosimetry Network.

The U.S. Department of Defense (USDOD) service members are at risk of exposure to ionizing radiation due to radiation accidents, terrorist attacks and national defense activities.