GSK-3β is essential for physiological electric field-directed Golgi polarization and optimal electrotaxis

Endogenous electrical fields (EFs) at corneal and skin wounds send a powerful signal that directs cell migration during wound healing. This signal therefore may serve as a fundamental regulator directing cell polarization and migration. Very little is known of the intracellular and molecular mechanisms that mediate EF-induced cell polarization and migration. Here, we report that Chinese hamster ovary (CHO) cells show robust directional polarization and migration in a physiological EF (0.3–1 V/cm) in both dissociated cell culture and monolayer culture. An EF of 0.6 V/cm completely abolished cell migration into wounds in monolayer culture. An EF of higher strength (≥1 V/cm) is an overriding guidance cue for cell migration. Application of EF induced quick phosphorylation of glycogen synthase kinase 3β (GSK-3β) which reached a peak as early as 3 min in an EF. Inhibition of protein kinase C (PKC) significantly reduced EF-induced directedness of cell migration initially (in 1–2 h). Inhibition of GSK-3β completely abolished EF-induced GA polarization and significantly inhibited the directional cell migration, but at a later time (2–3 h in an EF). Those results suggest that GSK-3β is essential for physiological EF-induced Golgi apparatus (GA) polarization and optimal electrotactic cell migration

УСТОЙЧИВОСТЬ ГЕНОТИПОВ ТВЕРДОЙ ПШЕНИЦЫ К ЧЕРНОМУ ЗАРОДЫШУ

Поиск эффективных источников иммунитета пшеницы к распространенным в регионе заболеваниям и включение наиболее ценных доноров в селекционные программы – важнейшие составляющие стратегии создания устойчивых к фитопатогенам сортов. Заболевание черный зародыш, проявляющееся потемнением зерна в области зародыша, встречается во всех регионах возделывания Triticum durum Desf. В условиях Приобской лесостепи Алтайского края в 2014-2015 гг. проведено изучение 58 сортов и линий яровой твердой пшеницы различного географического происхождения по устойчивости к возбудителям черноты зародыша. Установлено широкое разнообразие генотипов по степени устойчивости к данному заболеванию. Условия вегетации вносят сопоставимый с генотипом вклад в проявление признака: доли влияния факторов «генотип» и «условия вегетации» составили 45,8 и 41,1% соответственно. Взаимодействие факторов статистически значимо и равнялось 13,1%. Выделены сортообразцы с наименьшей степенью поражения: Салют Алтая, Памяти Янченко, Алтайский янтарь, Солнечная 573, Ангел, Омский изумруд, 1480d-2, Луч 25, Харьковская 46, Донская элегия, Оренбургская 10, Divide. Сорта Алтайского НИИСХ, Оренбургского НИИСХ, Донского ЗНИИСХ и Сибирского НИИСХ характеризуются невысоким уровнем поражения (5,84 – 7,36%). Выявленные источники устойчивости, согласно хозяйственно-биологической оценке, не имеют негативных признаков и свойств, препятствующих их использованию в программах на устойчивость к черному зародышу

Immunogenicity of immunomodulatory, antibody-based, oncology therapeutics

The increasing use of multiple immunomodulatory (IMD) agents for cancer therapies (e.g. antibodies targeting immune checkpoints, bispecific antibodies, and chimeric antigen receptor [CAR]-T cells), is raising questions on their potential immunogenicity and effects on treatment. In this review, we outline the mechanisms of action (MOA) of approved, antibody-based IMD agents, potentially related to their immunogenicity, and discuss the reported incidence of anti-drug antibodies (ADA) as well as their clinical relevance in patients with cancer. In addition, we discuss the impact of the administration route and potential strategies to reduce the incidence of ADA and manage treated patients. Analysis of published reports indicated that the risk of immunogenicity did not appear to correlate with the MOA of anti-programmed death 1 (PD-1)/PD-ligand 1 monoclonal antibodies nor to substantially affect treatment with most of these agents in the majority of patients evaluated to date. Treatment with B-cell depleting agents appears associated with a low risk of immunogenicity. No significant difference in ADA incidence was found between the intravenous and subcutaneous administration routes for a panel of non-oncology IMD antibodies. Additionally, while the data suggest a higher likelihood of immunogenicity for antibodies with T-cell or antigen-presenting cell (APC) targets versus B-cell targets, it is possible to have targets expressed on APCs or T cells and still have a low incidence of immunogenicity.status: publishe

Immunogenicity of immunomodulatory, antibody-based, oncology therapeutics

Abstract The increasing use of multiple immunomodulatory (IMD) agents for cancer therapies (e.g. antibodies targeting immune checkpoints, bispecific antibodies, and chimeric antigen receptor [CAR]-T cells), is raising questions on their potential immunogenicity and effects on treatment. In this review, we outline the mechanisms of action (MOA) of approved, antibody-based IMD agents, potentially related to their immunogenicity, and discuss the reported incidence of anti-drug antibodies (ADA) as well as their clinical relevance in patients with cancer. In addition, we discuss the impact of the administration route and potential strategies to reduce the incidence of ADA and manage treated patients. Analysis of published reports indicated that the risk of immunogenicity did not appear to correlate with the MOA of anti-programmed death 1 (PD-1)/PD-ligand 1 monoclonal antibodies nor to substantially affect treatment with most of these agents in the majority of patients evaluated to date. Treatment with B-cell depleting agents appears associated with a low risk of immunogenicity. No significant difference in ADA incidence was found between the intravenous and subcutaneous administration routes for a panel of non-oncology IMD antibodies. Additionally, while the data suggest a higher likelihood of immunogenicity for antibodies with T-cell or antigen-presenting cell (APC) targets versus B-cell targets, it is possible to have targets expressed on APCs or T cells and still have a low incidence of immunogenicity