The nucleus acts as a ruler tailoring cell responses to spatial constraints

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMThe microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. Here, we found that cells measure the degree of spatial confinement using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, upregulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force enabling their passage through restrictive pores in complex three-dimensional (3D) environments, a process relevant to cancer cell invasion, immune responses and embryonic developmentThe research leading to these results has received funding from the People Programme (Marie Skłodowska-Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement PCOFUND-GA-2013-609102, through the PRESTIGE programme coordinated by Campus France. A.J.L. was supported by the Marie Curie & PRESTIGE Fellowship (grant 609102), London Law Trust Medal Fellowship (grant MGS9403), and a Career Grant for Incoming International Talent (grant 875764) from the Austrian Research Promotion Agency (FFG). D.J.M. was supported by the National Center of Competence in Research (NCCR) Molecular Systems Engineering. This work was also supported by the Institut Pierre-Gilles de Gennes-IPGG (Equipement d’Excellence, “Investissements d’avenir,” program ANR-10-EQPX-34 and Laboratoire d’Excellence, “Investissements d’avenir” program ANR-10-IDEX-0001-02 PSL and ANR-10-LABX-31. This work was additionally supported by the Institut National du Cancer (INCa grant 2018-PL Bio-02) to M.P. and INCa (grant 2019-PL BIO-07) and INSERM Plan Cancer Single Cell (grant 19CS007-00) to N.M. and M.P. R.J.P. was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM126054. R.F. received funding from the National Institutes of Health (grants R35GM133522-01 and R33CA235254-02). J.M.G.G. was financed by Instituto de Salud Carlos III (ISCIII) (PI17/01395; PI20/00306) and I3 SNS program. M.D. was supported by the National Institute of General Medical Sciences (grant K99GM123221). N.S.D.S. received a Marie Skłodowska-Curie Individual Fellowship (DCBIO 751735) and an EMBO Long-Term Fellowship (ALTF 1298-2016). I.Z. was supported by a Metchnikov Fellowship from the Franco-Russian Scientific Cooperation Program and the Russian Science Foundation (grant 16-15-10288

The Crystal Structure of Yeast Fatty Acid Synthase, a Cellular Machine with Eight Active Sites Working Together

SummaryIn yeast, the whole metabolic pathway for making 16- and 18-carbon fatty acids is carried out by fatty acid synthase, a 2.6 megadalton molecular-weight macromolecular assembly containing six copies of all eight catalytic centers. We have determined its crystal structure, which illuminates how this enzyme is initially activated and then carries out multiple steps of synthesis in each of six sterically isolated reaction chambers. Six of the catalytic sites are in the wall of the assembly facing an acyl carrier protein (ACP) bound to the ketoacyl synthase domain. Two-dimensional diffusion of substrates to the catalytic sites may be achieved by the electrostatically negative ACP swinging to each of the six electrostatically positive catalytic sites. The phosphopantetheinyl transferase domain lies outside the shell of the assembly, inaccessible to ACP that lies inside, suggesting that the attachment of the pantetheine arm to ACP must occur before complete assembly of the complex

Mathematical description of stress-strain state of trunnion of ball mill taking into account temperature field

The article considers the trunnion of a ball mill in the framework of theory of elasticity, which is subjected to an uneven thermal impact due to the heating of the load. Equations describing the radial displacement of the point inside the trunnion of a ball mill are obtained. The equations describing the movement of trunnion points of the ball mill are derive

“Overcoming Inhuman Difficulties”: I.V. Stalin Crimean State Medical Institute in the Period of the Great Patriotic War (According to Documents from the State Archive of the Russian Federation)

Introduction. The article focuses mainly on the activities of I.V. Stalin Crimean State Medical Institute during the Great Patriotic War, its main areas of work. Comprehensive scientific developments on this issue are not available in Russian historiography. Methods and materials. The research is carried out based on a variety of archival sources from the funds of the State Archive of the Russian Federation (SARF, Moscow), which are introduced into scientific discourse for the first time. Various groups of documents are widely involved: correspondence of S.R. Tatevosov, director of the institute, with the authorities on the functioning of the university; directives, decrees of state institutions reflected in the activities of the medical institute; university reporting and planning documentation. Analysis. Employees and students of Crimean Medical Institute were forced to leave the peninsula after the outbreak of the Great Patriotic War, from the moment of the threat of occupation of the Crimea. The university team had to be evacuated along the route: Armavir – Tbilisi – Krasnovodsk – Dzhambul – again Armavir – Ordzhonikidze – Baku – Krasnovodsk – Kzyl-Orda. Their wanderings lasted almost a year, however, the university did not stop its activities for a single day as the front was in dire need of medical specialists. Two turnouts graduated in Kzyl-Orda in incredibly difficult conditions. In total, from June 1941 to July 1944, the institute trained 850 doctors, wherefore the university staff was awarded with personal thanks of I.V. Stalin. Results. The heroic history of I.V. Stalin Crimean State Medical Institute during the Great Patriotic War has been restored. The activity of lecturers of the institute during the period of forced evacuation to the territory of the Kazakh Soviet Socialist Republic (the city of Kzyl-Orda) has been analyzed. The stage of resuming the work of the university after its re-evacuation to Simferopol has been recreated in detail, the measures taken to prepare for the beginning of the first academic year in the Crimea in the autumn of 1944 have been restored. In order to prepare the study, the authors have carried out a detailed historiographic analysis, and have selected the source base carefully

Selyamet Gerai Gazebo in Bakhchisarai Palace Complex

The plans of the Bakhchisarai Khan Palace of the 18th–20th centuries (G. Trombaro, W. Hastie, N. P. Krasnov, A. L. Rotach) feature an ‘Old Palace’ of the Crimean khans, probably built in the 16th century under Khan Sahib I Gerai (reigned in 1532–1551), and later sources only refer to a surviving gallery. Throughout its existence, the palace was guarded by the khans and was invariably restored after the destruction, being one of the first structures in the territory of the palace complex, serving as a symbol of Khan's power associated with the birth of the new capital – Bakhchisaray. In the 1820s the ‘Old Palace’ was dismantled as a completely dilapidated structure, but the restorers preserved its gallery, which was later named the Selyamet Gerai Gazebo. The gazebo with a fountain in the center of the room, which stood on a high basement, with a marble colonnade and arched openings of a lancet shape, was decorated with stucco decor and painting in naturalistic and baroque style, which was included in the art and craft of Turkey and the Crimean Khanate in the second half of the 16th–18th centuries. The gazebo was destroyed in the middle of the 20th century

Peptides against autoimmune neurodegeneration

© 2017 Bentham Science Publishers. The mammalian immune system is a nearly perfect defensive system polished by a hundred million years of evolution. Unique flexibility and adaptivity have created a virtually impenetrable barrier to numerous exogenous pathogens that are assaulting us every moment. Unfortunately, triggers that remain mostly enigmatic will sometimes persuade the immune system to retarget against self-antigens. This civil war remains underway, showing no mercy and taking no captives, eventually leading to irreversible pathological changes in the human body. Research that has emerged during the last two decades has given us hope that we may have a chance to overcome autoimmune diseases using a variety of techniques to "reset" the immune system. In this report, we summarize recent advances in utilizing short polypeptides - mostly fragments of autoantigens - in the treatment of autoimmune neurodegeneration

Plasticity of an extra-strong nanocrystalline stainless steel controlled by the "dislocation-segregation'' interaction

We study three structurally different states of nanocrystalline 316 steel and show that the state, where boundaries containing excess concentration of alloying elements are combined with mobile dislocations in grain interiors, allows maintaining extraordinarily high strength and remarkably enhanced plasticity. Underlying mechanisms featuring interaction between the segregations and mobile dislocations are discussed

Memorizing and reproducing the sequence of movements by younger schoolchildren and adolescents: age-specific mistakes

Background. The paper describes the results of the experimental study of working memory in early schoolchildren and adolescents. The capacity of working memory develops through preadolescence to adolescence, while the developmental changes of representations of serial order are not clear enough so far. Objective. The accuracy of delayed reproduction of movements (the open polygonal chains, trajectories) reveals. The sample included 32 early schoolchildren (mean age 10.4±0.75 years old) and 25 adolescents (mean age 14.6±0.3 years old). The subjects reproduced trajectories of different length (from 4 to 6 elements) using the graphical tablet. Another factor in the experiment carried out was a mode of stimulus presentation: the trajectories in were presented either as a static line-drawing (static mode) or a small moving pointer (dynamic mode). Design. The errors of reproduction in two age groups and in different conditions were analyzed. We distinguished three types of errors: (1) severe distortions which are caused by inability to keep the sequence in working memory; (2) insertions or omissions of elements of the trajectory which are related to the problems of encoding the visual spatial information in the motor representation; (3) distortions of proportions of the trajectories, which are related with visual-motor coordination during motor reproduction of the sequences. Research results showed that in adolescence the accuracy of delayed reproduction is better than in early ages. The most obvious difference in accuracy between the groups of early schoolchildren and adolescents were observed in dynamic mode. The analysis of different types of errors revealed that adolescents less often make insertions and omissions of elements. It may be caused by development of executive functions in adolescents. Conclusion. The study showed that the capacity of working memory increases in adolescents. In addition, the precision of the representation of serial information are higher in adolescents in the more complicated dynamic mode