Phosphatidylserine Targets Single-Walled Carbon Nanotubes to Professional Phagocytes In Vitro and In Vivo

Broad applications of single-walled carbon nanotubes (SWCNT) dictate the necessity to better understand their health effects. Poor recognition of non-functionalized SWCNT by phagocytes is prohibitive towards controlling their biological action. We report that SWCNT coating with a phospholipid “eat-me” signal, phosphatidylserine (PS), makes them recognizable in vitro by different phagocytic cells - murine RAW264.7 macrophages, primary monocyte-derived human macrophages, dendritic cells, and rat brain microglia. Macrophage uptake of PS-coated nanotubes was suppressed by the PS-binding protein, Annexin V, and endocytosis inhibitors, and changed the pattern of pro- and anti-inflammatory cytokine secretion. Loading of PS-coated SWCNT with pro-apoptotic cargo (cytochrome c) allowed for the targeted killing of RAW264.7 macrophages. In vivo aspiration of PS-coated SWCNT stimulated their uptake by lung alveolar macrophages in mice. Thus, PS-coating can be utilized for targeted delivery of SWCNT with specified cargoes into professional phagocytes, hence for therapeutic regulation of specific populations of immune-competent cells

Role of patriotic education of adolescents in present-day green society

The paper discusses the purpose of formation of spiritual and moral values in young generation when taking martial arts classes, including karate. It is noted that patriotic upbringing should play an integral role in physical development and fitness of the athletes. The paper explains the meaning of socially important cultural values in martial arts practice and looks into spiritual and moral development to prevent breaking social norms of conduct among adolescents. Person-centred approach is of vital importance for spiritual and moral education, since it draws on the athletes’ motivation. The person-centred approach emphasises the autonomy, emotional component, moral and ethical development of the trainees. A particular focus is given to the problem of moral guidance and the lack of patriotism among the students of educational institutions. Mass media fail to pay due attention to the patriotic upbringing what results in the absence of generation-bridging and weaker patriotic feelings among children. There are not many schools that run military-patriotic classes. Hence, spiritual and moral education works for effective development of patriotism among martial arts athletes

Features of socialization and school adaptation of children with autism spectrum disorders

The paper analyzes the theoretical foundations of social adaptation of children with autism spectrum disorders. Attention is focused on the widespread prevalence of autism not only in the Russian Federation, but also abroad, which makes the problem of social adaptation of children with autism spectrum disorders relevant today. The paper presents the data of a sociological survey on the problems of social adaptation and the organization of the educational process for children with autism. The paper reveals statistical indicators on the problems of autism in world practice and in the Russian Federation, focuses on disorders of the mental and psychological state, shows a deficit of emotional reactions, disturbances in the communicative sphere, and the lack of independence of children with autism. It is also noted that these children are immersed only in their own problems, not noticing the world around them

Establishment of a Pilot Newborn Screening Program for Spinal Muscular Atrophy in Saint Petersburg

Spinal muscular atrophy 5q (SMA) is one of the most common neuromuscular inherited diseases and is the most common genetic cause of infant mortality. SMA is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently developed drugs can improve the motor functions of infants with SMA when they are treated in the pre-symptomatic stage. With aim of providing an early diagnosis, newborn screening (NBS) for SMA using a real-time PCR assay with dried blood spots (DBS) was performed from January 2022 through November 2022 in Saint Petersburg, which is a representative Russian megapolis. Here, 36,140 newborns were screened by the GenomeX real-time PCR-based screening test, and three genotypes were identified: homozygous deletion carriers (4 newborns), heterozygous carriers (772 newborns), and wild-type individuals (35,364 newborns). The disease status of all four newborns that screened positive for the homozygous SMN1 deletion was confirmed by alternate methods. Two of the newborns had two copies of SMN2, and two of the newborns had three copies. We determined the incidence of spinal muscular atrophy in Saint Petersburg to be 1 in 9035 and the SMA carrier frequency to be 1 in 47. In conclusion, providing timely information regarding SMN1, confirmation of disease status, and SMN2 copy number as part of the SMA newborn-screening algorithm can significantly improve clinical follow-up, testing of family members, and treatment of patients with SMA

Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling

The purpose of this study was to investigate whether caveolin-3 (Cav3) regulates localization of β(2)-adrenergic receptor (β(2)AR) and its cAMP signaling in healthy or failing cardiomyocytes. We co-expressed wildtype Cav3 or its dominant-negative mutant (Cav3DN) together with the Förster resonance energy transfer (FRET)-based cAMP sensor Epac2-camps in adult rat ventricular myocytes (ARVMs). FRET and scanning ion conductance microscopy were used to locally stimulate β(2)AR and to measure cytosolic cAMP. Cav3 overexpression increased the number of caveolae and decreased the magnitude of β(2)AR-cAMP signal. Conversely, Cav3DN expression resulted in an increased β(2)AR-cAMP response without altering the whole-cell L-type calcium current. Following local stimulation of Cav3DN-expressing ARVMs, β(2)AR response could only be generated in T-tubules. However, the normally compartmentalized β(2)AR-cAMP signal became diffuse, similar to the situation observed in heart failure. Finally, overexpression of Cav3 in failing myocytes led to partial β(2)AR redistribution back into the T-tubules. In conclusion, Cav3 plays a crucial role for the localization of β(2)AR and compartmentation of β(2)AR-cAMP signaling to the T-tubules of healthy ARVMs, and overexpression of Cav3 in failing myocytes can partially restore the disrupted localization of these receptors

Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection: a potential mechanism of tumor-immune privilege

Despite the existence of tumor-specific immune cells, most tumors have devised strategies to avoid immune attack. We demonstrate here that galectin-1 (Gal-1), a negative regulator of T cell activation and survival, plays a pivotal role in promoting escape from T cell-dependent immunity, thus conferring immune privilege to tumor cells. Blockade of immunosuppressive Gal-1 in vivo promotes tumor rejection and stimulates the generation of a tumor-specific T cell-mediated response in syngeneic mice, which are then able to resist subsequent challenge with wild-type Gal-1-sufficient tumors. Our data indicate that Gal-1 signaling in activated T cells constitutes an important mechanism of tumor-immune escape and that blockade of this inhibitory signal can allow for and potentiate effective immune responses against tumor cells, with profound implications for cancer immunotherapyFil: Rubinstein, Natalia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alvarez, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Zwirner, Norberto Walter. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Ilarregui, Juan Martin. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bravo, Alicia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Jose Mordoh. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Leonardo Fainboim. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin