Specific Sequences in the N-terminal Domain of Human Small Heat Shock Protein HSPB6 Dictate Preferential Heterooligomerization with the Orthologue HSPB1

Small heat-shock proteins (sHSPs) are a conserved group of molecular chaperones with important roles in cellular proteostasis. Although sHSPs are characterized by their small monomeric weight, they typically assemble into large polydisperse oligomers that vary in both size and shape but are principally composed of dimeric building blocks. These assemblies can include different sHSP orthologues, creating additional complexity that may affect chaperone activity. However, the structural and functional properties of such hetero-oligomers are poorly understood. We became interested in hetero-oligomer formation between human heat-shock protein family B (small) member 1 (HSPB1) and HSPB6, which are both highly expressed in skeletal muscle. When mixed in vitro, these two sHSPs form a polydisperse oligomer array composed solely of heterodimers, suggesting preferential association that is determined at the monomer level. Previously, we have shown that the sHSP N-terminal domains (NTDs), which have a high degree of intrinsic disorder, are essential for the biased formation. Here we employed iterative deletion mapping to elucidate how the NTD of HSPB6 influences its preferential association with HSPB1 and show that this region has multiple roles in this process. First, the highly conserved motif RLFDQXFG is necessary for subunit exchange among oligomers. Second, a site ∼20 residues downstream of this motif determines the size of the resultant hetero-oligomers. Third, a region unique to HSPB6 dictates the preferential formation of heterodimers. In conclusion, the disordered NTD of HSPB6 helps regulate the size and stability of hetero-oligomeric complexes, indicating that terminal sHSP regions define the assembly properties of these proteins

Experts see it all: configural effects in action observation

Biological motion perception is influenced by observers’ familiarity with the observed action. Here we used classical dance as a means to investigate how visual and motor experience modulates perceptual mechanism for configural processing of actions. While some ballet moves are performed by only one gender, male and female dancers train together and acquire visual knowledge of all ballet moves. 24 expert ballet dancers (12 female) and matched non-expert participants viewed pairs of upright and inverted point light female and common dance movements. Visual discrimination between different exemplars of the same movement presented upright was significantly better in experts than controls, while no differences were found when the same stimuli were presented upside down. These results suggest expertise influences configural action processing. Within the expert group, effects were stronger for female participants than for males, while no differences were found between movement types. This observer gender effect could suggest an additional role for motor familiarity in action perception, over and above visual experience. Our results are consistent with a specific motor contribution to configural processing of action

New trends in the treatment of patients with rheumatoid arthritis (literature review)

Abstract. Rheumatoid arthritis is an autoimmune disease characterized by chronic inflammation that causes the destruction of cartilage and bone, ultimately leading to disability, disability, loss of function, reduced quality of life, and reduced life expectancy. Statistical data show that every fifth patient who seeks medical help from a doctor has a joint syndrome of various degrees of damage. Modern treatment options for patients with rheumatoid arthritis are mostly based on a compromise between the severity of the disease, prognostic factors, the proven effectiveness of the drug and the risk of developing side effects. At the moment, disease-modifying antirheumatic drugs (DMARDs), which can be combined with nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticosteroids, are quite often used. DMARDs are divided into synthetic (methotrexate), targeted synthetic DMARDs (Janus kinase inhibitor) and biological DMARDs. Although a wide range of biologic DMARDs are available today, their comparative effectiveness remains uncertain

Prevention of emotional burnout of teachers of higher educational medical institutions

Abstract. Emotional burnout syndrome is a condition manifested by psycho-emotional, mental and physical exhaustion, which leads to the paralysis of our forces and feelings and is accompanied by a loss of joy and satisfaction in life in response to long-term exposure to stressful and psycho-traumatic factors. Analysis of the problem of "emotional burnout", which is a response to chronic emotional stress, confirms its destructive effect on the professional activity and personality of a medical university teacher. Burnout intensifies in conditions of distance learning and quarantine restrictions. The teaching activity of scientific and pedagogical workers of universities requires constant self-development, improvement of professional knowledge, abilities and skills, somatic and mental health, which are limited in quarantine conditions. Timely prevention of a teacher's professional deformation and stabilization of his psycho-emotional state will prevent the occurrence of emotional burnout and contribute to the quality performance of his professional duties. The reason for the development of emotional burnout at work is "chronic fatigue", caused by a discrepancy between the personality and the demands placed on it. Constant stresses associated, first of all, with the peculiarities of professional activity, namely: information overload, extreme situations, intensive level of communication, high degree of responsibility – contribute to the development of the syndrome of "emotional burnout" in teachers of higher education and are accompanied by disorders of psychosomatic and of a somatopsychic nature. The lack of conditions for relieving psychological fatigue and insufficient competence in matters of preserving and strengthening professional health deepen the problems arising in this situation among teachers. Recommendations for the prevention of emotional burnout of medical university teachers should include: optimization of the work and rest regime; reasonable load distribution; reduction of conflict at work; psychological relief; manifestation of self-care; a careful attitude to work planning in the conditions of "quarantine" education, a balanced approach to the amount of independent tasks for students and the most important thing in this situation – work should be a joy. That is why the study of the peculiarities of development and ways of prevention requires a systematic approach, the use of various methods, as well as the development of modern technologies to preserve psychological health among teachers of higher educational institutions and is an urgent issue today

Introduction of T-786C endothelial NO-synthase for interruptions and development of rheumatoid arthritis

Abstract. Rheumatoid arthritis is a systemic autoimmune disease characterized by a chronic course, causing erosive and destructive changes in the joints and involving the internal organs and systems of the body in the pathogenesis. The etiology of rheumatoid arthritis is still not fully understood, but both genetic and environmental factors contribute to the development of the disease. Several genetic features have been linked to rheumatoid arthritis, as have several environmental factors, such as cigarette smoke, dust exposure, and the microbiome. Other environmental factors, as well as hormonal influences, may explain the higher risk of developing this disease in women

Emergence and Evolution of Cooperation Under Resource Pressure

We study the influence that resource availability has on cooperation in the context of hunter-gatherer societies. This paper proposes a model based on archaeological and ethnographic research on resource stress episodes, which exposes three different cooperative regimes according to the relationship between resource availability in the environment and population size. The most interesting regime represents moderate survival stress in which individuals coordinate in an evolutionary way to increase the probabilities of survival and reduce the risk of failing to meet the minimum needs for survival. Populations self-organise in an indirect reciprocity system in which the norm that emerges is to share the part of the resource that is not strictly necessary for survival, thereby collectively lowering the chances of starving. Our findings shed further light on the emergence and evolution of cooperation in hunter-gatherer societies.Spanish Ministry of Science and Innovation Project CSD2010-00034 (SimulPast CONSOLIDER-INGENIO 2010) and HAR2009-06996; from the Argentine National Scientific and Technical Research Council (CONICET): Project PIP-0706; from the Wenner-Gren Foundation for Anthropological Research: Project GR7846; and from the project H2020 FET OPEN RIA IBSEN/66272

Modern approaches to the treatment of arterial hypertension, abdominal obesity and type 2 diabetes in patients with rheumatoid arthritis (literature review)

Abstract. The development of modern approaches to the pharmacotherapy of rheumatoid arthritis (RA) in combination with arterial hypertension (AH), abdominal obesity (AB), and type 2 diabetes mellitus (T2DM) remains relevant today. In particular, due to inadequate control of systemic inflammation, simultaneous administration of a large number of potentially dangerous drugs: nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and glucocorticosteroids (GCs), a comorbid pathology occurs that complicates the course and treatment of RA. In order to solve this problem, it is necessary to correct the risk factors of RA, choose an adequate disease-modifying antirheumatic therapy (DMRT) and treat concomitant pathology. This will improve the prognosis and improve the quality of life of RA patients

Personalized treatment of patients with rheumatoid arthritis depending on the T-786С eNOS gene promoter polymorphism and concomitant pathology

Purpose: optimization of rheumatoid arthritis treatment depending on the T-786C polymorphism of the eNOS gene promoter and comorbid pathology. Conclusions. Therefore, after the treatment, a decrease in the level of acute-phase indicators of inflammation was observed in all polymorphic variants of the T-786C eNOS gene, but it was the most significant in carriers of the TT genotype

A clinical case in the practice of a rheumatologist: systemic lupus erythomus with inflammation of organs and systems

Abstract. Systemic lupus erythematosus (SLE) is one of the most serious systemic connective tissue diseases that develops more often in young women and girls, although it can occur at any age. Patients with SLE still have a high risk of death (3 times higher than in the general population). Early diagnosis, intensification of basic therapy and minimization of the dose of glucocorticoids (GC), assessment of cardiovascular risk and treatment of cardiovascular diseases are considered to be the basis for improving the prognosis in SLE

Holistic Processing of Words Modulated by Reading Experience

Perceptual expertise has been studied intensively with faces and object categories involving detailed individuation. A common finding is that experience in fulfilling the task demand of fine, subordinate-level discrimination between highly similar instances is associated with the development of holistic processing. This study examines whether holistic processing is also engaged by expert word recognition, which is thought to involve coarser, basic-level processing that is more part-based. We adopted a paradigm widely used for faces – the composite task, and found clear evidence of holistic processing for English words. A second experiment further showed that holistic processing for words was sensitive to the amount of experience with the language concerned (native vs. second-language readers) and with the specific stimuli (words vs. pseudowords). The adoption of a paradigm from the face perception literature to the study of expert word perception is important for further comparison between perceptual expertise with words and face-like expertise