Direct Visualization of Single Nuclear Pore Complex Proteins Using Genetically-Encoded Probes for DNA-PAINT

The nuclear pore complex (NPC) is one of the largest and most complex protein assemblies in the cell and, among other functions, serves as the gatekeeper of nucleocytoplasmic transport. Unraveling its molecular architecture and functioning has been an active research topic for decades with recent cryogenic electron microscopy and super-resolution studies advancing our understanding of the architecture of the NPC complex. However, the specific and direct visualization of single copies of NPC proteins is thus far elusive. Herein, we combine genetically-encoded self-labeling enzymes such as SNAP-tag and HaloTag with DNA-PAINT microscopy. We resolve single copies of nucleoporins in the human Y-complex in three dimensions with a precision of circa 3 nm, enabling studies of multicomponent complexes on the level of single proteins in cells using optical fluorescence microscopy

ПЕРЕБІГ ВІЛ/ГС-КОІНФЕКЦІЇ В ПОЛТАВСЬКІЙ ОБЛАСТІ ЗАЛЕЖНО ВІД ШЛЯХІВ ПЕРЕДАЧІ

Analysis of HIV/HCV-coinfection in Poltava region, depending on the transmission of HIV. It was found that clinical stages III (p=0,038) and IV (p=0,044) were recorded significantly more often at the time of diagnosis of HIV infection among patients with parenteral route of transmission, whereas among patients with sexually transmission, by contrast, clinical stage I (p=0,001) was found more often.In patients with HIV/HCV-coinfection with parenteral route of HIV opportunistic infections (FDPT, oropharyngeal candidiasis, bacterial pneumonia) were often diagnosed at higher levels of CD4-lymphocyte (≥100 cells/ml). There is no difference between group of patients with significant immunodeficiency (level of CD4-lymphocytes <100 cells/microliter) and group of patients with HIV/HCV coinfection in identifying of important opportunistic infections.Проведено аналіз перебігу ВІЛ/ГС інфекції в пацієнтів Полтавської області залежно від шляхів передачі ВІЛ. Виявлено, що на момент встановлення діагнозу ВІЛ-інфекції серед пацієнтів з парентеральним шляхом передачі частіше реєстрували ІІІ (р=0,038) і ІV (р=0,044) клінічні стадії, в той час як серед пацієнтів із статевим шляхом передачі, навпаки, частіше виявляли І клінічну стадію (р=0,001).У ВІЛ/ГС коінфікованих осіб з парентеральним шляхом передачі ВІЛ опортуністичні інфекції вперше діагностований туберкульоз (ВДТБ), кандидоз орофарингеальний, бактерійну пневмонію) частіше діагностували при вищих рівнях СD4-лімфоцитів (≥100 кл./мкл). За наявності вираженого імунодефіциту (рівень СD4-лімфоцитів <100 кл./мкл) відмінностей між групами ВІЛ/ГС коінфікованих пацієнтів щодо виявлення значимих опортуністичних інфекцій не виявлено

Antipyretic drugs: benefits and undesirable consequences

Fever is a defensive and adaptive reaction of the body that develops in response to the action of pathogenic stimuli. It often accompanies various infectious, autoimmune, oncohematological and other diseases. Due to the frequent significant deterioration of children's general health, the occurrence of fever in children gives rise to concern not only in parents, but also in pediatricians. According to temperature level, fever can be classified into different categories: subfebrile - 37.1 to 37.9 °C, moderate -38 to 39 °C, febrile - 39.1 to 41 °C and hyperthermic - above 41 °C. By clinical manifestation distinguish benign, or rose, and malignant, or white, fever. The need to use antipyretic drugs depends not only on the hight of the body temperature elevation, but also on the patient's general health. The clinical guidelines state that the use of acetylsalicylic acid, nimesulide and met-amizole to lower the body temperature in children is not recommended, due to high risk of adverse reactions. Ibuprofen and paracetamol are the drugs of choice to lower body temperature in children both in Russia and abroad. Over 120 comparative studies of these two drug formulations have shown their close efficacy, but ibuprofen is most preferred for the treatment of fever and pain. In order to lower body temperature, parents can uncontrollably use antipyretic drugs in various combinations and incorrect dosages, which leads to severe toxic effects. The article presents a clinical case of Reye's syndrome in a 10-year-old girl, which is most likely associated with the use of aspirin as an antipyretic

Fast Control Systems: Nonlinear Approach

International audienceThis chapter treats the problem of fast control design for nonlinear systems. First, we discusses the question: which nonlinear system can be called fast? Next, we develop some tools for analysis and design of such control systems. The method generalized homogeneity is mainly utilized for these purposes. Finally, we survey possible research directions of the fast control systems

On the notion of gyrogroup

together with CnoFile{1619832}{} Einstein's relativistic velocity addition oplus in the c-ball bold R^3_c of the Euclidean 3-space bold R^3 is nonassociative. Hence, the Einstein groupoid (bold R^3_c,oplus) is not a group. Abstracting the key features of Einstein's groupoid (bold R^3_c,oplus) [see W. Krammer and H. K. Urbantke, Results Math. {bf 33} (1998), no.~3-4, 310--327; [msn] MR1619832 (99i:83003) [/msn]; see the preceding review], the notion of gyrogroup [A. A. Ungar, Found. Phys. {bf 27} (1997), no.~6, 881--951; [msn] MR1477047 (98k:83002) [/msn]] was introduced by the reviewer [Amer. J. Phys. {bf 59} (1991), no.~9, 824--834; [msn] MR1126776 (92g:83003) [/msn]] to describe a grouplike object that shares analogies with groups. The analogies stem from the relativistic effect called Thomas gyration (or, precession), and are emphasized by the prefix "gyro" that is extensively used in terms like gyrogroups, gyroassociative and gyrocommutative laws, gyroautomorphisms, gyrotranslations, etc. Furthermore, the reviewer introduced the gyrosemidirect product group as the product of a gyrogroup and a group that results in a group, in full analogy with the semidirect product group between two groups. The reviewer gave a brief history of the idea of a product of a nongroup groupoid and a group which results in a group, tracing it to Tits, Karzel and Kikkawa [A. A. Ungar, Aequationes Math. {bf 47} (1994), no.~2-3, 240--254; [msn] MR1268034 (95b:30076) [/msn]]. par However, the authors of the paper under review show that the idea should be traced to Sabinin's work, which has been rediscovered by Kikkawa. The authors justifiably claim that the reviewer did not give appropriate credit to Sabinin's pioneering work in this area. They describe the connections between gyrogroup theory and loop theory demonstrating that a gyrogroup is a Bol loop with Bruck identity, and that the reviewer's gyrosemidirect product is a construction that Sabinin has considered in a more general case since 1972 [P. O. Mikheev and L. V. Sabinin, in {it Quasigroups and loops: theory and applications}, 357--430, Heldermann, Berlin, 1990; [msn] MR1125818 [/msn]]. Finally, the authors remark that the discovery of gyrogroups in mathematical physics shows the vitality of quasigroup and loop theory

Modified aptamers enable quantitative sub-10-nm cellular DNA-PAINT imaging

Although current implementations of super-resolution microscopy are technically approaching true molecular-scale resolution, this has not translated to imaging of biological specimens, because of the large size of conventional affinity reagents. Here we introduce slow off-rate modified aptamers (SOMAmers) as small and specific labeling reagents for use with DNA points accumulation in nanoscale topography (DNA-PAINT). To demonstrate the achievable resolution, specificity, and multiplexing capability of SOMAmers, we labeled and imaged both transmembrane and intracellular targets in fixed and live cells