A weakened interface in the P182L variant of HSP27 associated with severe Charcot‐Marie‐Tooth neuropathy causes aberrant binding to interacting proteins

HSP27 is a human molecular chaperone that forms large, dynamic oligomers and functions in many aspects of cellular homeostasis. Mutations in HSP27 cause Charcot‐Marie‐Tooth (CMT) disease, the most common inherited disorder of the peripheral nervous system. A particularly severe form of CMT disease is triggered by the P182L mutation in the highly conserved IxI/V motif of the disordered C‐terminal region, which interacts weakly with the structured core domain of HSP27. Here, we observed that the P182L mutation disrupts the chaperone activity and significantly increases the size of HSP27 oligomers formed in vivo, including in motor neurons differentiated from CMT patient‐derived stem cells. Using NMR spectroscopy, we determined that the P182L mutation decreases the affinity of the HSP27 IxI/V motif for its own core domain, leaving this binding site more accessible for other IxI/V‐containing proteins. We identified multiple IxI/V‐bearing proteins that bind with higher affinity to the P182L variant due to the increased availability of the IxI/V‐binding site. Our results provide a mechanistic basis for the impact of the P182L mutation on HSP27 and suggest that the IxI/V motif plays an important, regulatory role in modulating protein–protein interactions.     

The phenotypic characteristics of T-lymphocytes that interact with hematopoietic stem cells: the expression of the antigens Lyt-1, Lyt-2 and L3T4]

The role of T-lymphocytes, bearing antigens Lyt-1, Lyt-2 and L3T4, in regulation of the functional activity of blood-forming precursor cells of syngen and non-syngen origin was investigated. The treatment of cells of murine lymphatic nidi with monoclonal antibodies to the above antigens and with the complement did not abolish the capacity of T-lymphocytes of controlling proliferation and differentiation of syngen and allogen blood-forming precursor cells. The subpopulation characteristics of lymphocytes interacting with the stem cells is discussed.     

Acoustic signal characters in interspecific hybrids of bank and red-backed voles

It has been found that distress signals of bank and northern red-backed voles and their hybrids do not differ in qualitative characters, but the modes of the acoustic signal parameters in many cases differ in the hybrids depending on their origin and can be correlated with the inheritance of some morphological characters that are typical for the species. It is noted that the distress-signal frequencies (quartiles) differ significantly in the first-generation hybrids of various origin and their characteristics are closer to those of the paternal parent species. It has been found that the inheritance of the frequency characteristics by the second-generation hybrids does not have a well-pronounced regularity.     

Synchronization of proliferating cells in the liver, gastric glands and duodenum

Multiple injections (5-6 times) of hydroxyurea to hepatectomized rats lead to synchronization of 78% of proliferating cells in the regenerating liver. The amount of DNA-synthesizing cells of the foveolar epithelium of the pyloric glands of the gastric mucosa increases 2.7-fold, the proliferation in slowly renewing Brunner glands of the duodenum is dramatically activated.     

Individual differences in the levels of pain sensitivity and analgesic effect of morphine in noninbred mice

The initial threshold of pain sensitivity and the degree of morphine analgesia (12, 12, 70 mg/kg, i. p.) were assessed during mechanical, thermal and electrical stimulation, respectively, in noninbred white male mice. Two tests were performed, the second a week after the first one. A slight positive correlation (r = +0.39) between the initial threshold of pain reaction and the analgetic effect of morphine was found only during electrical stimulation in the first test, and positive correlation between the first and the second test during electrical and mechanical stimulation (0.34 and 0.27, respectively) was determined. The degree of morphine analgesia in different animals during second testing could either increase or decrease. It is suggested that previous testing of morphine analgetic effect cannot predict the efficacy of analgesia during the second testing and that the initial threshold of pain sensitivity cannot serve as a reliable predictor of morphine analgesia level.     

Dynamics of the duration of tracheal forced expiratory noises during long-term isolation in the Mars-500 experiment

The dynamics of the duration of tracheal forced expiratory noises in a group of volunteers were studied before, during, and after a 520-day confinement. The duration did not change in most volunteers. Two volunteers exhibited significant changes in the duration of tracheal sounds and some spirometric parameters. The increase in the duration of tracheal forced expiratory noises and the decrease in spirometric parameters reveal ventilation impairment of the obstructive type. Analysis of the duration of tracheal forced expiratory noise dynamics during prolonged confinement has proven to be a sensitive technique to test ventilation function changes.     

The effect of a temporal shift in diurnal geomagnetic variation on roach Rutilus rutilus L. embryos: A comparison with effects of simulated geomagnetic storms

A study was made of the effects that 6- and 12-h shifts in diurnal geomagnetic variation relative to the night–day light cycles exert on roach Ritulus ritulus L. embryos. Either temporal shift in diurnal geomagnetic variation stimulated blastomere proliferation and early prelarval hatching in exposed embryos compared to controls. Underyearlings developing from exposed embryos displayed higher locomotor activity in a plusshaped maze, a lower number of rays in the anal fin, a redistribution of vertebrae through sections of the vertebral column, and a higher number of seismosensory system openings in the mandibular and preopercular bones. The effects were similar to those described previously for roaches exposed to a simulated geomagnetic storm during embryonic development. The results support the hypothesis that animals perceive geomagnetic storms as a dramatic disturbance that occurs in the habitual diurnal geomagnetic variation at an unusual time relative to the night–day light cycle, which acts as a primary zeitgeber of circadian biological rhythms.

     

Application of the Principal Components Method and the Proportional Hazards Regression Model to Analysis of Survival Data

One of factor analysis techniques, viz. the principal components method, and the proportional hazards regression model (Cox, 1972) are applied in this work to study the significance of various factors characterizing the patient, the disease, and the method of treatment in the survival. The application of these methods to analysis of survival data for cervical cancer patients has shown, in particular, the tumor growth rate to be the crucial factor in distribution of the patients survival time and to be even more important than the therapy characteristics.     

Circadian rhythms in zebrafish (Danio rerio) behaviour and the sources of their variability

Over recent decades, changes in zebrafish (Danio rerio) behaviour have become popular quantitative indicators in biomedical studies. The circadian rhythms of behavioural processes in zebrafish are known to enable effective utilization of energy and resources, therefore attracting interest in zebrafish as a research model. This review covers a variety of circadian behaviours in this species, including diurnal rhythms of spawning, feeding, locomotor activity, shoaling, light/dark preference, and vertical position preference. Changes in circadian activity during zebrafish ontogeny are reviewed, including ageing-related alterations and chemically induced variations in rhythmicity patterns. Both exogenous and endogenous sources of inter-individual variability in zebrafish circadian behaviour are detailed. Additionally, we focus on different environmental factors with the potential to entrain circadian processes in zebrafish. This review describes two principal ways whereby diurnal behavioural rhythms can be entrained: (i) modulation of organismal physiological state, which can have masking or enhancing effects on behavioural endpoints related to endogenous circadian rhythms, and (ii) modulation of period and amplitude of the endogenous circadian rhythm due to competitive relationships between the primary and secondary zeitgebers. In addition, different peripheral oscillators in zebrafish can be entrained by diverse zeitgebers. This complicated orchestra of divergent influences may cause variability in zebrafish circadian behaviours, which should be given attention when planning behavioural studies.