EPR and optical spectroscopy of neodymium ions in KMgF3 and KZnF3 crystals

KMgF3 and KZnF3 crystals doped with Nd3+ ions were studied using EPR and optical spectroscopy methods. Several types of paramagnetic centers of Nd3+: KMgF3 - two of tetragonal and one of rhombic symmetry; KZnF3 - one of tetragonal and one of trigonal symmetry were found. Parameters of the corresponding spin Hamiltonians were determined. Using optical spectroscopy paramagnetic centers Nd2+ and Nd4+ in KMgF3 were found. © 1993 Springer

ВАКЦИНОТЕРАПИЯ НА ОСНОВЕ ДЕНДРИТНЫХ КЛЕТОК У БОЛЬНЫХ ПОЧЕЧНО-КЛЕТОЧНЫМ РАКОМ

Objective: to study the efficiency and tolerance of autologous vaccine therapy based on dendritic cells (DC) in patients with renal cell carcinoma (RCC) and to examine changes in immunological parameters and their association with the efficiency of the therapy. Subjects and methods. Twenty-nine patients with RCC received autologous vaccine therapy based on DC in 2002 to 2008. Therapy was performed in the induction mode in 16 patients before disease progression and in the adjuvant mode (8 vaccinations) in 13 patients after radical nephrectomy (grade III) or radical metastasectomy. Peripheral blood monocyte-derived DCs treated with autologous tumor lysate were used to prepare the vaccine. Results. In a group of 16 patients with distant metastases, partial regressions were recorded in 2 (12.5%) patients and long (> 6-month) stabilizations of a tumor process were observed in other 2 (12.5%) patients. The median time prior to progression was 3 (range 1.5-12) months. Thirteen patients on adjuvant treatment did not achieve the median time to progression: 4 patients showed no signs of disease progression ?12 to ?25 months after metastasectomy. Patients with a clinical effect (disease regression or long stabilization) showed a significant increase in the populations of CD3+CD8+ and CD3-CD16+ T lymphocytes (natural killers (NK) cells) after 3 vaccinations from 23.3 to 27.2% (p = 0.018) and from 15.17 to 20.3%, respectively (p = 0.03). Prior to vaccine therapy, the count of CD3+CD16+-NK cells was thrice greater in patients with the progressive disease than that in the donor group - 11.2 and 3.5%, respectively. The baseline count of CD4+CD25+ Т lymphocytes in patients with progressive disease was also significantly higher than that in patients with the clinical effect - 12.01 and 5.6%, respectively. Conclusion. In patients with RCC, DC-based vaccine therapy is able to induce a specific anti-tumor immune response that is transformed into the clinical effect in some cases. The baseline count of suppressor T lymphocyte (NKT and T-reg) populations may be a factor that predicts the efficiency of autologous DC-based vaccine therapy in patients with RCC. This immunotherapeutic approach merits further study, by defining the indications for its application in patients with RCC.Цель исследования - определить эффективность и переносимость аутологичной вакцинотерапии на основе дендритных клеток (ДК) у больных почечно-клеточным раком (ПКР). Изучить динамику иммунологических показателей и их связь с эффективностью лечения. Материалы и методы. В период с 2002 по 2008 г. 29 больных ПКР получили аутологичную вакцинотерапию на основе ДК. У 16 пациентов с наличием отдаленных метастазов терапия проведена в индукционном режиме до прогрессирования болезни и у 13 - в адъювантном режиме (8 вакцинаций) после выполнения радикальной нефрэктомии (III степени) или радикальной метастазэктомии. Для приготовления вакцины использовали культивированные из моноцитов периферической крови ДК, обработанные аутологичным опухолевым лизатом. Результаты. В группе из 16 больных с наличием отдаленных метастазов у 2 (12,5%) зафиксированы частичные регрессии, еще у 2 (12,5%) пациентов наблюдались длительные стабилизации опухолевого процесса (>6 мес). Медиана времени до прогрессирования составила 3 (1,5-12+) мес. У 13 больных, получавших адъювантное лечение, медиана времени до прогрессирования не достигнута: 4 пациента после метастазэктомии наблюдаются без признаков прогрессирования болезни от ?d12 до ?d25 мес У больных с клиническим эффектом (регрессия или длительная стабилизация болезни) наблюдалось достоверное увеличение популяции CD3+CD8+ и CD3-CD16+ (натуральные киллеры - НК) Т-лимфоцитов после 3 вакцинаций с 23,3 до 27,2% (р=0,018) и с 15,17 до 20,3% (р=0,03) соответственно. У больных с прогрессирующим течением заболевания число CD3+CD16+-НКT-лимфоцитов до начала вакцинотерапии в 3 раза превышало значение этого показателя в донорской группе - 11,2 и 3,5% соответственно. Исходное содержание CD4+CD25+-популяции Т-лимфоцитов у пациентов с прогрессированием болезни также было достоверно выше, чем у больных с клиническим эффектом - 12,01 и 5,6% соответственно. Выводы. Вакцинотерапия, проведенная на основе ДК, способна индуцировать специфический противоопухолевый иммунный ответ у больных ПКР, который в отдельных случаях трансформируется в клинический эффект. Исходное содержание супрессорных популяций Т-лимфоцитов (НКT и T-reg) может являться фактором, прогнозирующим эффективность проведения вакцинотерапии на основе аутологичных ДК у больных ПКР. Целесообразно дальнейшее изучение данного иммунотерапевтического подхода с определением показаний к его использованию у больных ПКР

The Transcription Factor YY1 Is a Substrate for Polo-Like Kinase 1 at the G2/M Transition of the Cell Cycle

Yin-Yang 1 (YY1) is an essential multifunctional zinc-finger protein. It has been shown over the past two decades to be a critical regulator of a vast array of biological processes, including development, cell proliferation and differentiation, DNA repair, and apoptosis. YY1 exerts its functions primarily as a transcription factor that can activate or repress gene expression, dependent on its spatial and temporal context. YY1 regulates a large number of genes involved in cell cycle transitions, many of which are oncogenes and tumor-suppressor genes. YY1 itself has been classified as an oncogene and was found to be upregulated in many cancer types. Unfortunately, our knowledge of what regulates YY1 is very minimal. Although YY1 has been shown to be a phosphoprotein, no kinase has ever been identified for the phosphorylation of YY1. Polo-like kinase 1 (Plk1) has emerged in the past few years as a major cell cycle regulator, particularly for cell division. Plk1 has been shown to play important roles in the G/M transition into mitosis and for the proper execution of cytokinesis, processes that YY1 has been shown to regulate also. Here, we present evidence that Plk1 directly phosphorylates YY1 in vitro and in vivo at threonine 39 in the activation domain. We show that this phosphorylation is cell cycle regulated and peaks at G2/M. This is the first report identifying a kinase for which YY1 is a substrate

Combined Point-of-Care Nucleic Acid and Antibody Testing for SARS-CoV-2 following Emergence of D614G Spike Variant

Rapid COVID-19 diagnosis in the hospital is essential, although this is complicated by 30%–50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant dominates the pandemic and it is unclear how serological tests designed to detect anti-spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild-type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95% CI 57.8–92.9) by rapid NAAT alone. The combined point of care antibody test and rapid NAAT is not affected by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity

Effective control of sars-cov-2 transmission between healthcare workers during a period of diminished community prevalence of covid-19

Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to nearzero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK ‘lockdown’. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent ‘hubs’ of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely

Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591