Delayed effects of radiation exposure in a C57L/J mouse model of partial body irradiation with ~2.5% bone marrow shielding.

Introduction: Mouse models of radiation injury are critical to the development of medical countermeasures (MCMs) against radiation. Now that MCMs against hematopoietic acute radiation syndrome (H-ARS) have achieved regulatory approval, attention is shifting to develop MCMs against the adverse effects of gastrointestinal acute radiation syndrome (GI-ARS) and delayed effects of acute radiation exposure (DEARE). The C57L/J mouse model of partial body irradiation (PBI) with 2.

Intermittent fasting: consider the risks of disordered eating for your patient.

This is a commentary on "Intermittent fasting: is there a role in the treatment of diabetes? A review of the literature and guide for primary care physicians" by Albosta et al. While this article adequately summarized the biochemical clinical advantages and limitations, we feel it failed to mention a few drawbacks, primarily the risk for disordered eating and eating disorders. Here we delve into the emerging data on intermittent fasting or time-restricted feeding in patient populations and urge clinicians to consider these risks prior to encouragement of intermittent fasting.

Does regular antenatal exercise promote exclusive breastfeeding during the first 3 months of life? Secondary analyses of a randomized controlled trial.

Introduction: Exclusive breastfeeding (EBF) and antenatal exercise are independently associated with positive short- and long-term health effects for women and their children. The aims of the study were to investigate whether antenatal exercise promotes EBF three months postpartum and further to explore factors associated with EBF at three months postpartum.

Methods: This study was a follow-up of a Norwegian two-center randomized controlled trial to assess the effect of an antenatal exercise protocol.

Inducible Knockout of 14-3-3β Attenuates Proliferation and Spheroid Formation in a Human Glioblastoma Cell Line U87MG.

Glioblastomas (GBs) are the most common and malignant brain tumors in adults. A protein encoded by the gene YWHAB, 14-3-3β, is commonly found to be upregulated throughout the initiation and progression of GB. The 14-3-3β has oncogenic roles in several different types of cancer cells through interactions with proteins such as Bad, FBI1, Raf-1, Cdc25b, and others.

Survival and Hematologic Benefits of Romiplostim After Acute Radiation Exposure Supported FDA Approval Under the Animal Rule.

Purpose: Patients exposed to acute high doses of ionizing radiation are susceptible to dose-dependent bone marrow depression with resultant pancytopenia. Romiplostim (RP; Nplate) is a recombinant thrombopoietin receptor agonist protein that promotes progenitor megakaryocyte proliferation and platelet production and is an approved treatment for patients with chronic immune thrombocytopenia. The goal of our study was to evaluate the postirradiation survival and hematologic benefits of a single dose of RP with or without pegfilgrastim (PF; Neulasta, granulocyte colony stimulating factor) by conducting a well-controlled, treatment-concealed, good laboratory practice-compliant study in rhesus macaques that was compliant with the United States Food and Drug Administration Animal Rule regulatory approval pathway.

Longitudinal multi-omic changes in the transcriptome and proteome of peripheral blood cells after a 4 Gy total body radiation dose to Rhesus macaques.

Background: Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days and at the cytogenetic level out to 56 days after exposure. We combine the global transcriptomic and proteomic responses in peripheral whole blood to assess the impact of acute TBI exposure at extended times post irradiation.

The progression of radiation injury in a Wistar rat model of partial body irradiation with ∼5% bone marrow shielding.

Purpose: To describe the dose response relationship and natural history of radiation injury in the Wistar rat and its suitability for use in medical countermeasures (MCM) testing.

Materials & Methods: In two separate studies, male and female rats were exposed to partial body irradiation (PBI) with 5% bone marrow sparing. Animals were X-ray irradiated from 7 to 12 Gy at 7-10 weeks of age.

Chronic depletion of vertebrate lipids in Aedes aegypti cells dysregulates lipid metabolism and inhibits innate immunity without altering dengue infectivity.

Aedes aegypti is the primary vector of dengue virus (DENV) and other arboviruses. Previous literature suggests that vertebrate and invertebrate lipids and the nutritional status of mosquitoes modify virus infection. Here, we developed a vertebrate lipid-depleted Ae.

Postglacial species arrival and diversity buildup of northern ecosystems took millennia.

What drives ecosystem buildup, diversity, and stability? We assess species arrival and ecosystem changes across 16 millennia by combining regional-scale plant sedimentary ancient DNA from Fennoscandia with near-complete DNA and trait databases. We show that postglacial arrival time varies within and between plant growth forms. Further, arrival times were mainly predicted by adaptation to temperature, disturbance, and light.

Heavy-Ion-Induced Lung Tumors: Dose- & LET-Dependence.

There is a limited published literature reporting dose-dependent data for in vivo tumorigenesis prevalence in different organs of various rodent models after exposure to low, single doses of charged particle beams. The goal of this study is to reduce uncertainties in estimating particle-radiation-induced risk of lung tumorigenesis for manned travel into deep space by improving our understanding of the high-LET-dependent dose-response from exposure to individual ion beams after low particle doses (0.03-0.

Functional Magnetic Resonance Imaging and Applications in Dermatology.

As a noninvasive imaging modality able to show the dynamic changes in neurologic activity, functional magnetic resonance imaging has revolutionized the ability to both map and further understand the functional regions of the brain. Current applications range from neurosurgical planning to an enormous variety of investigational applications across many diverse specialties. The main purpose of this article is to provide a foundational understanding of how functional magnetic resonance imaging is being used in research by outlining the underlying basic science, specific methods, and direct investigational and clinical applications.

Identification of Essential Genes Using Sequential CRISPR and siRNA Screens.

Genome-wide CRISPR and siRNA screening methodologies are powerful tools that are aptly suited to the discovery of essential genes. In this chapter, we outline our methods to conduct sequential CRISPR and siRNA screens to quickly and efficiently identify essential genes within a collection of cell lines. The utilization of both screening methodologies provides a pipeline that minimizes costs and time while enabling the robust detection of candidate genes.

Sedimentary ancient DNA shows terrestrial plant richness continuously increased over the Holocene in northern Fennoscandia.

The effects of climate change on species richness are debated but can be informed by the past. Here, we generated a sedimentary ancient DNA dataset covering 10 lakes and applied novel methods for data harmonization. We assessed the impact of Holocene climate changes and nutrients on terrestrial plant richness in northern Fennoscandia.

Long-term demise of sub-Antarctic glaciers modulated by the Southern Hemisphere Westerlies.

The accelerated melting of ice on the Antarctic Peninsula and islands in the sub-Antarctic suggests that the cryosphere is edging towards an irreversible tipping point. How unusual is this trend of ice loss within the frame of natural variability, and to what extent can it be explained by underlying climate dynamics? Here, we present new high-resolution reconstructions of long-term changes in the extents of three glaciers on the island of South Georgia (54°S, 36°W), combining detailed analyses of glacial-derived sediments deposited in distal glacier-fed lakes and cosmogenic exposure dating of moraines. We document that the glaciers of South Georgia have gradually retracted since the Antarctic cold reversal (ACR, 14.

Intermittent fasting: is there a role in the treatment of diabetes? A review of the literature and guide for primary care physicians.

Background: Type 2 Diabetes is a metabolic disorder characterized by hyperglycemia that causes numerous complications with significant long-term morbidity and mortality. The disorder is primarily due to insulin resistance particularly in liver, skeletal muscle, and adipose tissue. In this review, we detail the hormonal mechanisms leading to the development of diabetes and discuss whether intermittent fasting should be considered as an alternative, non-medicinal treatment option for patients with this disorder.

Atmospheric circulation over Europe during the Younger Dryas.

The Younger Dryas (YD) was a period of rapid climate cooling that occurred at the end of the last glaciation. Here, we present the first palaeoglacier-derived reconstruction of YD precipitation across Europe, determined from 122 reconstructed glaciers and proxy atmospheric temperatures. Positive precipitation anomalies (YD versus modern) are found along much of the western seaboard of Europe and across the Mediterranean.

Total body irradiation models in NHPs - consideration of animal sex and provision of supportive care to advance model development.

Purpose: Harmonized animal models are an indispensable tool for the development of safe and effective medical countermeasures (MCMs) against radiation injury, and rhesus macaques (referred herein as NHPs) play a critical role in FDA approval of radiation medical countermeasures for acute and delayed radiation syndromes. Reliance on such models requires that they be well characterized, which consists, in part, of a reproducible dose to mortality response relationship (DRR). However, data describing the DRR for both male and female NHPs from the same study are scarce.

Disentangling source of moisture driving glacier dynamics and identification of 8.2 ka event: evidence from pore water isotopes, Western Himalaya.

Two atmospheric circulation patterns, the Indian Summer Monsoon (ISM) and mid-latitude Westerlies control precipitation and thus glacier variability in the Himalaya. However, the role of the ISM and westerlies in controlling climate and thus past glacier variability in the Himalaya is poorly understood because of the paucity of the ice core records. In this article, we present a new Holocene paleorecord disentangling the presence of the ISM and mid-latitude westerlies and their effect on glacier fluctuations during the Holocene.

Particle radiation-induced dysregulation of protein homeostasis in primary human and mouse neuronal cells.

Space particle radiations may cause significant damage to proteins and oxidative stress in the cells within the central nervous system and pose a potential health hazard to humans in long-term manned space explorations. Dysregulation of the ubiquitin-proteasome system as evidenced by abnormal accumulation of polyubiquitin (pUb) chain linkages has been implicated in several age-related neurodegenerative disorders by mechanisms that may involve the inter-neuronal spread of toxic misfolded proteins, the induction of chronic neuroinflammation, or the inappropriate inhibition or activation of key enzymes, which could lead to dysfunction in, for example, proteolysis, or the accumulation of post-translationally-modified substrates.In this study, we employed a quantitative proteomics method to evaluate the impact of particle-radiation induced alterations in three major pUb-linked chains at lysine residues Lys-48 (K-48), Lys-63 (K-63), and Lys-11 (K-11), and probed for global proteomic changes in mouse and human neural cells that were irradiated with low doses of 250 MeV proton, 260 MeV/u silicon or 1 GeV/u iron ions.

KANSL2 and MBNL3 are regulators of pancreatic ductal adenocarcinoma invasion.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. One major reason for this is that PDAC quickly metastasizes to other organs, thereby making its treatment difficult. The molecular machinery driving PDAC metastasis is still poorly understood.

Salivary Metabolomics of Total Body Irradiated Nonhuman Primates Reveals Long-Term Normal Tissue Responses to Radiation.

Purpose: To identify metabolomic biomarkers of acute radiation exposure in saliva that show time-dependent changes.

Methods And Materials: Nonhuman primates were exposed to 4 Gy of total body irradiation with γ-rays. Saliva was collected from 7 animals twice before and at days 1, 3, 5, 7, 15, 21, 28, and 60 after irradiation.

Pediatric patients with acute lymphoblastic leukemia generate abundant and functional neoantigen-specific CD8 T cell responses.

Cancer arises from the accumulation of genetic alterations, which can lead to the production of mutant proteins not expressed by normal cells. These mutant proteins can be processed and presented on the cell surface by major histocompatibility complex molecules as neoepitopes, allowing CD8 T cells to mount responses against them. For solid tumors, only an average 2% of neoepitopes predicted by algorithms have detectable endogenous antitumor T cell responses.

Pharmacodynamics of romiplostim alone and in combination with pegfilgrastim on acute radiation-induced thrombocytopenia and neutropenia in non-human primates.

Evaluation of the pharmacodynamics (PD) and pharmacokinetics (PK) of romiplostim alone and in combination with pegfilgrastim in a non-human primate (NHP) model of acute radiation syndrome (ARS). Male and female rhesus macaques were subjected to Cobalt-60 γ irradiation, at a dose of 550 cGy 24 h prior to subcutaneous administration of either romiplostim alone as a single (2.5 or 5.