Predator-Induced Vertical Behavior of a Ctenophore

Although many studies have focused on Mnemiopsis leidyi predation, little is known about the role of this ctenophore as prey when abundant in native and invaded pelagic systems. We examined the response of the ctenophore M. leidyi to the predatory ctenophore Beroe ovata in an experiment in which the two species could potentially sense each other while being physically separated. On average, M. leidyi responded to the predator’s presence by increasing variability in swimming speeds and by lowering their vertical distribution. Such behavior may help explain field records of vertical migration, as well as stratified and near-bottom distributions of M. leidyi

Эффективность и безопасность вакцины Гам-КОВИД-Вак у пациентов с иммуновоспалительными ревматическими заболеваниями: предварительные данные проспективного наблюдения

Objective: to study the efficacy and safety of the Gam-COVID-Vac vaccine in patients with immunoinflammatory rheumatic diseases (IRD) in a prospective study.Material and methods. The study included 42 patients with IRD and 57 individuals without IRD (control group) who received at least one component of Gam-COVID-Vac. Immunization with the first component of the vaccine was carried out from March 25th to August 1st, 2022, the second – 3 weeks after the first dose. On days 1, 3 and 7 after administration of the first and second components, the study participants provided information on adverse events (AEs) by telephone. All subjects were examined by a rheumatologist 1, 3 and 6 months after complete immunization. The observation period after immunization with the second dose was 6 months.Results and discussion. 42 patients received the first component of the vaccine, and 39 patients received two components. In the control group, 57 subjects were immunized with two components of the vaccine. 30–180 days after vaccination with two components of Gam-COVID-Vac, 3 (7.7%) patients were diagnosed with SARS-CoV-2 infection, which was confirmed by polymerase chain reaction. In all cases, a mild course of COVID-19 without signs of pneumonia was observed. There were no cases of COVID-19 in the control group. After immunization with the first component, a combination of at least one local and one systemic AE (SAE) was documented in 28.6% of patients with IRD and 33.3% of individuals in the control group (p>0.05). No AEs were recorded in 42.9% and 36.8% of cases respectively (p>0.05). After vaccination with the second component, a combination of ≥1 local AE and SAE was recorded in 15.4 % of patients with IRD and 22.8% of individuals in the control group (p>0.05). No AEs occurred in 71.8% and 56.1% of cases respectively (p>0.05). In 10.3% of patients with IRD and 12.3 % of those without IRD (p>0.05), a combination of local and systemic AEs was recorded after the introduction of both first and second components. No AEs were observed in 35.9% and 28.1% of cases, respectively (p>0.05). The overall rate of IRD exacerbations was 4.8%.Conclusion. Based on the available data, vaccination against COVID-19 appears to be effective and quite safe in patients with IRD.Цель исследования – изучить эффективность и безопасность вакцины Гам-КОВИД-Вак у больных с иммуновоспалительными ревматическими заболеваниями (ИВРЗ) в проспективном исследовании.Материал и методы. В исследование включено 42 пациента с ИВРЗ и 57 лиц без ИВРЗ (контрольная группа), получивших как минимум один компонент Гам-КОВИД-Вак. Иммунизация первым компонентом вакцины проводилась с 25 марта по 1 августа 2022 г., вторым – через 3 нед после введения первой дозы. В 1-й, на 3-й и 7-й день после введения первого и второго компонентов информацию о нежелательных явлениях (НЯ) участники исследования сообщали по телефону. Через 1, 3 и 6 мес после полной вакцинации все они были осмотрены ревматологом. Период наблюдения после иммунизации второй дозой составил 6 мес.Результаты и обсуждение. Первый компонент вакцины получили 42 пациента, два компонента – 39. В контрольной группе 57 испытуемых иммунизированы двумя компонентами вакцины. Через 30–180 дней после вакцинации двумя компонентами Гам-КОВИД-Вак инфекция SARS-CoV-2, подтвержденная методом полимеразной цепной реакции, диагностирована у 3 (7,7%) больных. При этом во всех случаях отмечено легкое течение COVID-19 без признаков пневмонии. В контрольной группе случаев COVID-19 не было. После иммунизации первым компонентом сочетание как минимум 1 местного и 1 системного НЯ (СНЯ) документировано у 28,6% пациентов с ИВРЗ и 33,3% лиц контрольной группы (p>0,05). НЯ не зарегистрированы соответственно в 42,9% и 36,8% случаев (p>0,05). После вакцинации вторым компонентом сочетание 1 местного НЯ и СНЯ зафиксировано у 15,4% больных с ИВРЗ и 22,8% лиц контрольной группы (p>0,05). НЯ отсутствовали в 71,8% и 56,1% случаев соответственно (p>0,05). У 10,3% пациентов с ИВРЗ и 12,3% лиц без ИВРЗ (p>0,05) сочетание местных и системных НЯ зарегистрировано после введения как первого, так и второго компонента. Не отмечено НЯ в 35,9% и 28,1% случаев соответственно (p>0,05). Общая частота обострений ИВРЗ составила 4,8%.Заключение. Согласно полученным данным, вакцинация против COVID-19 у больных с ИВРЗ представляется эффективной и достаточно безопасной

Терапевтический лекарственный мониторинг метотрексата и его метаболитов в эритроцитах и мононуклеарах больных ревматоидным артритом

Objective: to assess the time course of changes in the concentration of methotrexate (MTX) and its main metabolites in the red blood cells (RBC) and mononuclear cells (MNC) of patients with rheumatoid arthritis (RA), by taking into account individual characteristics (age, statin therapy, and smoking).Patients and methods. The investigation enrolled 33 MTX-treated patients (mean age 53.2±11.7 years) with RA, who underwent therapeutic drug monitoring to measure the RBC and MNC concentrations of free MTX and MTX polyglutamates (MTXPGs) with 2, 3, and 4 glutamate residues (MTXPG 2–4) in using tandem chromatomass spectrometry after 4, 12, and 24 weeks of therapy.Results and discussion. Following 12 weeks, the concentration of MTXPG4 in the MNC was higher in patients taking statins, while that of MTX and MTXPG2 in the RBC were significantly lower than in smokers. At 24 weeks, older patients were observed to have a higher MTX level and a lower MTXPG4 concentration in the RBC.Conclusion. After 24 weeks of therapy, the RBC concentration of MTPG4 was lower and that of MTX was higher in older patients than in others, which confirms data on a slower MTX metabolism in the elderly. The use of statins is likely to have a positive impact on the accumulation of MTXPG. There is a statistically significantly lower RBC concentration of MTXPG in at 12 weeks of therapy.Цель исследования – оценка динамики концентрации метотрексата (МТ) и его основных метаболитов в эритроцитах (ЭР) и мононуклеарах (МО) у больных ревматоидным артритом (РА) с учетом индивидуальных особенностей (возраст, терапия статинами и курение).Пациенты и методы. В исследование включено 33 больных РА, получающих МТ (средний возраст 53,2±11,7 года), у которых проводили терапевтический лекарственный мониторинг с определением концентрации свободного МТ, а также МТ полиглутаматов (МТПГ) с 2, 3 и 4 глутаматными остатками (МТПГ 2–4) в ЭР и МО с помощью тандемной хроматомасс-спектрометрии после 4, 12 и 24 нед терапии.Результаты и обсуждение. Через 12 нед концентрация МТПГ4 в МО была выше у больных, получавших статины, а концентрация МТ и МТПГ2 в ЭР оказалась значимо ниже у курильщиков. На 24-й неделе в ЭР у больных старшего возраста отмечены более высокий уровень МТ и более низкая концентрация МТПГ4.Заключение. После 24 нед терапии в ЭР у больных старшего возраста концентрация МТПГ4 была ниже, а уровень МТ – выше, чем у остальных пациентов, что подтверждает данные о более медленном метаболизме МТ в пожилом возрасте. Прием статинов, вероятно, оказывает положительное влияние на накопление МТПГ. У курильщиков выявлена статистически значимо более низкая концентрация МТПГ в ЭР на 12-й неделе терапии

Анализ зависимости между ответом на терапию метотрексатом и его фармакокинетическими показателями при ревматоидном артрите

The development of therapeutic drug monitoring of methotrexate (MT) remains an important and unresolved problem.Objective: to study the dynamics of the concentration of MT metabolites in groups of patients with different responses to MT therapy, to identify the clinical features of these groups.Patients and methods. The study included 79 patients with rheumatoid arthritis (RA), including 65 (82%) women and 14 (18%) men (mean age 53±11 years). MT monoglutamate was measured in erythrocytes (ER) and mononuclear cells (MO), as well as the main MT metabolites: polyglutamates with 2, 3 and 4 glutamate residues (MTPG2-4), as well as 7-hydroxymethotrexate (7-OH-MT) after 4, 12, 24 and 36 weeks after the start of MT treatment.Results and discussion. Among the patients who completed the 24-week follow-up, 34 responded to MT therapy (Group 1) and 36 did not respond to it (Group 2). Patients of the two groups did not differ in the concentration of various metabolites of MT after 4 weeks, age, body mass index, duration of RA, DAS28 value, radiological stage, functional class, presence of extra-articular manifestations, single and cumulative doses of MT. In the 1st group after 12 weeks of therapy, a higher concentration of 7-OH-MT (ER) was detected, after 24 weeks – a higher concentration of 7-OH-MT (MO) and a lower level of MTPH3 (ER).Conclusion. The concentration of 7-OH-MT after 12 and 24 weeks of therapy was higher in the group of patients who responded to therapy. 7-OH-MT appears to be a more persistent metabolite of MT and therefore more applicable for therapeutic drug monitoring of MT. The level of MT and its metabolites (MT monoglutamate, MTPG2 and 7-OH-MT) gradually decreases over time in responders to therapy. A 7-OH-MT concentration of 14.5 nmol/l may be a predictor of a good response to MT therapy.Разработка терапевтического лекарственного мониторинга метотрексата (МТ) остается важной и до конца не решенной задачей.Цель исследования – изучить динамику концентрации метаболитов МТ в группах пациентов с разным ответом на терапию МТ, выявить клинические особенности этих групп.Пациенты и методы. В исследование включено 79 больных ревматоидным артритом (РА), среди которых было 65 (82%) женщин и 14 (18%) мужчин (средний возраст – 53±11 лет). Проводилось определение в эритроцитах (ЭР) и мононуклерах (МО) моноглутамата МТ, а также основных метаболитов МТ: полиглутаматов с 2, 3 и 4 глутаматными остатками (МТПГ2–4) и 7-гидроксиметотрексата (7-ОН-МТ) через 4, 12, 24 и 36 нед после начала лечения МТ.Результаты и обсуждение. Среди завершивших 24-недельное наблюдение пациентов 34 ответили на терапию МТ (1-я группа) и 36 на нее не ответили (2-я группа). Пациенты двух групп не различались по концентрации различных метаболитов МТ через 4 нед, возрасту, индексу массы тела, длительности РА, величине DAS28, рентгенологической стадии, функциональному классу, наличию внесуставных проявлений, разовой и кумулятивной дозам МТ. В 1-й группе через 12 нед терапии выявлена более высокая концентрация 7-ОН-МТ (ЭР), через 24 нед – более высокая концентрация 7-ОН-МТ (МО) и более низкий уровень МТПГ3 (ЭР).Заключение. Концентрация 7-ОН-МТ после 12 и 24 нед терапии оказалась выше в группе больных, ответивших на терапию. 7-ОНМТ представляется более стойким метаболитом МТ и, следовательно, более применим для терапевтического лекарственного мониторинга МТ. Уровень МТ и его метаболитов (моноглутамата МТ, МТПГ2 и 7-ОН-МТ) у ответивших на терапию со временем постепенно снижается. Концентрация 7-OH-MT 14,5 нмоль/л может являться предиктором хорошего ответа на терапию МТ

Bigger, Faster, Better? Rhetorics and Practices of Large-Scale Research in Contemporary Bioscience

publication-status: Publishedtypes: ArticleEditorial for Special Issu

State-of-the-art microscopy to understand islets of Langerhans:what to expect next?

The discovery of Langerhans and microscopic description of islets in the pancreas were crucial steps in the discovery of insulin. Over the past 150 years, many discoveries in islet biology and type 1 diabetes have been made using powerful microscopic techniques. In the past decade, combination of new probes, animal and tissue models, application of new biosensors and automation of light and electron microscopic methods and other (sub)cellular imaging modalities have proven their potential in understanding the beta cell under (patho)physiological conditions. The imaging evolution, from fluorescent jellyfish to real-time intravital functional imaging, the revolution in automation and data handling and the increased resolving power of analytical imaging techniques are now converging. Here, we review innovative approaches that address islet biology from new angles by studying cells and molecules at high spatiotemporal resolution and in live models. Broad implementation of these cellular imaging techniques will shed new light on cause/consequence of (mal)function in islets of Langerhans in the years to come

Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

<p>Abstract</p> <p>Background</p> <p>Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells.</p> <p>Methods</p> <p>Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured <it>in vivo </it>with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed <it>ex vivo </it>with fluorescence imaging.</p> <p>Results</p> <p>We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells.</p> <p>Conclusion</p> <p>The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.</p

Learning from Data Journeys

This is the final version. Available on open access from Springer via the DOI in this recordThis chapter discusses the idea of data journeys as an investigative tool and a theoretical framework for this volume and broader scholarship on data. Building on a relational and historicized understanding of data as lineages, I reflect on the methodological, conceptual and social challenges involved in mapping, analysing and comparing the production, movement and use of data within and across research fields - and some of the strategies developed to cope with such difficulties. I then provide an overview of the significant variation among the data practices garnered in this volume. Specific nodes of difference and similarity across data journeys are identified, while also emphasising the extent to which such commonalities are dependent on specific situations of inquiry. In closing, I highlight the significance of this approach towards addressing concerns raised by data-centric science and the emergence of big and open data.European CommissionAlan Turing Institut