Solid-State Microwave Electronics

Contains reports on three research projects.National Aeronautics and Space Administration (Grant NGR-22-009-163

Solid-State Microwave Electronics

Contains reports on three research projects.National Aeronautics and Space Administration (Grant NGL 22-009-163)Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E

Solid-State Microwave Electronics

Contains reports on three research projects.National Aeronautics and Space Administration (Grant NGL-22-009-163)Joint Services Electronics Programs (U.S. Army, U.S. Navy, and U.S. Air Force)under Contract DA28-043-AMC-02536(E

Subclinical hyperthyroidism in the course of autonomous nodules — clinical evaluation

Introduction: Subclinical hyperthyroidism (SCH), also known as mildly symptomatic hyperthyroidism, has recently been diagnosed more frequently. One of the main endogenous causes of this disorder is autonomously functioning thyroid nodule (AFTN). Despite the fact that it is usually asymptomatic, SCH entails repercussions on the cardiovascular system and bone, and it carries a risk of progression to overt hyperthyroidism with a typical clinical picture. Treatment is still controversial, and its benefits are widely debated in literature. Material and methods: From 459 patients authors selected a group of 49 patients (10.6% of all subjects with hyperthyroidism), 41 women (83.7%) with AFTN at the stage SCH treated in the Outpatient Endocrinological Clinic and the Department of Endocrinology of the Medical University of Lublin over a three-year period. The method applied in the study was a retrospective analysis of medical records with a particular account of medical history, physical examination, and additional tests obtained during the process of diagnostic and therapeutic procedures. Results: Forty-one patients (83.7%) suffered from typical symptoms of hyperthyroidism; only eight patients (16.3%) were asymptomatic. The most frequently reported symptoms were tachycardia in women (51.2%) and anxiety in men (50%). The type of thyrostatic drugs and the length of therapy did not affect the outcome of iodine-131 therapy. In the vast majority of the patients (87.8%) radioidodine therapy was effective; 30 patients (61.2%) reached euthyreosis and 13 patients (22.5%) developed hypothyroidism. Conclusions: Most patients with SCH in the course of AFTN suffered from typical symptoms of overt hyperthyroidism; only every sixth patient was asymptomatic. The volume of autonomous adenomas did not affect the result of 131I therapy; however, the impact of AFTN volume as well as the thyroid volume on RIT efficacy requires futher investigation. In the vast majority of patients 131I therapy was an effective method of treatment, and an earlier therapeutic effect was observed more often in the patients with focal lesions located in theright lobe.

Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines

Toxoplasma gondii is a major source of congenital disease worldwide, but the cellular and molecular factors associated with its vertical transmission are largely unknown. In humans, the placenta forms the key interface between the maternal and fetal compartments and forms the primary barrier that restricts the hematogenous spread of microorganisms. Here, we utilized primary human trophoblast (PHT) cells isolated from full-term placentas and human midgestation chorionic villous explants to determine the mechanisms by which human trophoblasts restrict and respond to T. gondii infection. We show that placental syncytiotrophoblasts, multinucleated cells that are in direct contact with maternal blood, restrict T. gondii infection at two distinct stages of the parasite lytic cycle—at the time of attachment and also during intracellular replication. Utilizing comparative transcriptome sequencing (RNA-seq) transcriptional profiling, we also show that human placental trophoblasts from both the second and third trimesters respond uniquely to T. gondii infection compared to trophoblast cell lines, typified by the upregulation of several immunity-related genes. One of the most differentially induced genes was the chemokine CCL22, which relies on the secretion of a parasite effector(s) either during or after invasion for its induction. Collectively, our findings provide new insights into the mechanisms by which the human placenta restricts the vertical transmission of T. gondii at early and late stages of human pregnancy and demonstrate the existence of at least two interferon-independent pathways that restrict T. gondii access to the fetal compartment. IMPORTANCE Toxoplasma gondii is a major source of congenital disease worldwide and must breach the placental barrier to be transmitted from maternal blood to the developing fetus. The events associated with the vertical transmission of T. gondii are largely unknown. Here, we show that primary human syncytiotrophoblasts, the fetus-derived cells that comprise the primary placental barrier, restrict T. gondii infection at two distinct stages of the parasite life cycle and respond to infection by inducing a unique immunomodulatory transcriptional profile. Collectively, our findings provide important insights into the mechanisms by which human syncytiotrophoblasts restrict T. gondii infection at early and late stages of human pregnancy, identify both permissive and resistant human placental cell types, and identify the placenta-enriched signaling pathways induced in response to infection

Solid-State Microwave Electronics

Contains reports on status of research and nine research projects.National Aeronautics and Space Administration (Grant NGR-22-009-163

ORBIS (Open Research Biopharmaceutical Internships Support) – Building Bridges Between Academia and Pharmaceutical Industry to Improve Drug Development

Peer reviewe

Highlights of the mini-symposium on extracellular vesicles in inter-organismal communication, held in Munich, Germany, August 2018

All living organisms secrete molecules for intercellular communication. Recent research has revealed that extracellular vesicles (EVs) play an important role in inter-organismal cell-to-cell communication by transporting diverse messenger molecules, including RNA, DNA, lipids and proteins. These discoveries have raised fundamental questions regarding EV biology. How are EVs biosynthesized and loaded with messenger/cargo molecules? How are EVs secreted into the extracellular matrix? What are the EV uptake mechanisms of recipient cells? As EVs are produced by all kind of organisms, from unicellular bacteria and protists, filamentous fungi and oomycetes, to complex multicellular life forms such as plants and animals, basic research in diverse model systems is urgently needed to shed light on the multifaceted biology of EVs and their role in inter-organismal communications. To help catalyse progress in this emerging field, a mini-symposium was held in Munich, Germany in August 2018. This report highlights recent progress and major questions being pursued across a very diverse group of model systems, all united by the question of how EVs contribute to inter-organismal communication

T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice.

Chronic lymphocytic leukaemia (CLL) cells require microenvironmental support for their proliferation. This can be recapitulated in highly immunocompromised hosts in the presence of T cells and other supporting cells. Current primary CLL xenograft models suffer from limited duration of tumour cell engraftment coupled with gradual T-cell outgrowth. Thus, a greater understanding of the interaction between CLL and T cells could improve their utility. In this study, using two distinct mouse xenograft models, we investigated whether xenografts recapitulate CLL biology, including natural environmental interactions with B-cell receptors and T cells, and whether manipulation of autologous T cells can expand the duration of CLL engraftment. We observed that primary CLL xenografts recapitulated both the tumour phenotype and T-cell repertoire observed in patients and that engraftment was significantly shorter for progressive tumours. A reduction in the number of patient T cells that were injected into the mice to 2-5% of the initial number or specific depletion of CD8+ cells extended the limited xenograft duration of progressive cases to that characteristic of indolent disease. We conclude that manipulation of T cells can enhance current CLL xenograft models and thus expand their utility for investigation of tumour biology and pre-clinical drug assessment

Solid-State Microwave Electronics

Contains research objectives and reports on status of research projects.National Aeronautics and Space Administration (Grant NGR-22-009-163