Methodology of Assessing Risks to Sustainable supply Chain of an Insurance Company

Tough competition for one of the unique resources the companies strive for is a set of stable communications with their suppliers who act as stakeholders for the business in the supply chain management strategy. Thus, there is a link between the resource concept of competitiveness and the concept of stakeholder management. Such an approach makes it necessary to develop a distribution model between stakeholders of limited funds to pay for them, ensuring their satisfaction and stable participation in the exchange process. This requires clear definitions of financial flows in logistics and supply chain management. The paper presents a model for determining the significance of relations with the insurance company’s shareholders. The first hypothesis concerns the possibility to describe the relative importance of the resource supplied by each stakeholder, and its place in the ranked series. At the same time, the authors propose such a series both for a developing regional company and for a developed federal insurer. Such a series should correspond to the ranked series of growth rates of payment for each resource acquired from the corresponding stakeholder. The second hypothesis is that these series of relative position of indicators growth rates corresponding the significance series of a particular resource can serve as a standard for monitoring the insurer's stable relations with stakeholders. The degree of discrepancy between the actual indicators included in the series and the standard ones can be used as a measurement of the risk to insurance reserves sufficiency of an insurance company due to unreliable communications with stakeholders and problems in accessing required resources. Regular monitoring the accordance with the standard balance of the main indicators of insurance activities ensures guaranteed compliance with regulatory requirements, the fulfillment of insurance commitments to policyholders, profitability of investors' capital, and meeting their commitments to intermediaries, staff and management

SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles

RanGAP1 was the first documented substrate for conjugation with the ubiquitin-like protein SUMO-1. However, the functional significance of this conjugation has not been fully clarified. We sought to examine RanGAP1 behavior during mitosis. We found that RanGAP1 associates with mitotic spindles and that it is particularly concentrated at foci near kinetochores. Association with kinetochores appeared soon after nuclear envelope breakdown and persisted until late anaphase, but it was lost coincident with nuclear envelope assembly in telophase. A mutant RanGAP1 protein lacking the capacity to be conjugated to SUMO-1 no longer associated with spindles, indicating that conjugation was essential for RanGAP1's mitotic localization. RanBP2, a nuclear pore protein that binds SUMO-1–conjugated RanGAP1 during interphase, colocalized with RanGAP1 on spindles, suggesting that a complex between these two proteins may be involved in mitotic targeting of RanGAP1. This report shows for the first time that SUMO-1 conjugation is required for mitotic localization of RanGAP1, and suggests that a major role of SUMO-1 conjugation to RanGAP1 may be the spatial regulation of the Ran pathway during mitosis

The Central Bank of the Russian Federation as a mega-regulator of financial markets

The article discloses the concept and types of financial markets. The article analyzes the reasons for creating a mega-regulator of the financial market of Russia and the prospects of its development. The investigation focuses on the functions and powers of the Central Bank of Russia as a mega-regulator of the financial market. As a result of the research, the prospects for the development of the Central Bank of the Russian Federation as a mega-regulator of the financial market are revealed

Organization of chromatin and histone modifications at a transcription site

According to the transcription factory model, localized transcription sites composed of immobilized polymerase molecules transcribe chromatin by reeling it through the transcription site and extruding it to form a surrounding domain of recently transcribed decondensed chromatin. Although transcription sites have been identified in various cells, surrounding domains of recently transcribed decondensed chromatin have not. We report evidence that transcription sites associated with a tandem gene array in mouse cells are indeed surrounded by or adjacent to a domain of decondensed chromatin composed of sequences from the gene array. Formation of this decondensed domain requires transcription and topoisomerase IIα activity. The decondensed domain is enriched for the trimethyl H3K36 mark that is associated with recently transcribed chromatin in yeast and several mammalian systems. Consistent with this, chromatin immunoprecipitation demonstrates a comparable enrichment of this mark in transcribed sequences at the tandem gene array. These results provide new support for the pol II factory model, in which an immobilized polymerase molecule extrudes decondensed, transcribed sequences into its surroundings

CKAP2 ensures chromosomal stability by maintaining the integrity of microtubule nucleation sites

Integrity of the microtubule spindle apparatus and intact cell division checkpoints are essential to ensure the fidelity of distributing chromosomes into daughter cells. Cytoskeleton-associated protein 2, CKAP2, is a microtubule-associated protein that localizes to spindle poles and aids in microtubule stabilization, but the exact function and mechanism of action are poorly understood. In the present study, we utilized RNA interference to determine the extent to which the expression of CKAP2 plays a role in chromosome segregation. CKAP2-depleted cells showed a significant increase of multipolar mitoses and other spindle pole defects. Notably, when interrogated for microtubule nucleation capacity, CKAP2-depleted cells showed a very unusual phenotype as early as two minutes after release from mitotic block, consisting of dispersal of newly polymerized microtubule filaments through the entire chromatin region, creating a cage-like structure. Nevertheless, spindle poles were formed after one hour of mitotic release suggesting that centrosome-mediated nucleation remained dominant. Finally, we showed that suppression of CKAP2 resulted in a higher incidence of merotelic attachments, anaphase lagging, and polyploidy. Based on these results, we conclude that CKAP2 is involved in the maintenance of microtubule nucleation sites, focusing microtubule minus ends to the spindle poles in early mitosis, and is implicated in maintaining genome stability

Human condensin function is essential for centromeric chromatin assembly and proper sister kinetochore orientation.

Condensins I and II in vertebrates are essential ATP-dependent complexes necessary for chromosome condensation in mitosis. Condensins depletion is known to perturb structure and function of centromeres, however the mechanism of this functional link remains elusive. Depletion of condensin activity is now shown to result in a significant loss of loading of CENP-A, the histone H3 variant found at active centromeres and the proposed epigenetic mark of centromere identity. Absence of condensins and/or CENP-A insufficiency produced a specific kinetochore defect, such that a functional mitotic checkpoint cannot prevent chromosome missegregation resulting from improper attachment of sister kinetochores to spindle microtubules. Spindle microtubule-dependent deformation of both inner kinetochores and the HEC1/Ndc80 microtubule-capturing module, then results in kinetochore separation from the Aurora B pool and ensuing reduced kinase activity at centromeres. Moreover, recovery from mitosis-inhibition by monastrol revealed a high incidence of merotelic attachment that was nearly identical with condensin depletion, Aurora B inactivation, or both, indicating that the Aurora B dysfunction is the key defect leading to chromosome missegregation in condensin-depleted cells. Thus, beyond a requirement for global chromosome condensation, condensins play a pivotal role in centromere assembly, proper spatial positioning of microtubule-capturing modules and positioning complexes of the inner centromere versus kinetochore plates

Changes in loading distribution in patients with Charcot foot during long-term follow-up

Background. The inactive stage of the diabetic Charcot arthropathy foot (CA) is characterised by fixed foot deformities and an absence of inflammation. However, it remains unclear if the shape of the foot and its biomechanics change during long-term follow-up. Aim. To evaluate changes in loading distribution of the affected foot, in patients with inactive CA, during long-term follow-up. Materials and methods. Twenty seven patients with unilateral inactive CA (19 females, 8 males) were studied. Computer pedography (emed AT, novel gmbh) was performed and baseline and the last studies were analysed. Maximal peak pressures (PP) were obtained for the first and the last studies and the percentage of the PP change was calculated for the total follow-up period and for periods: 24 months, 2448 months, 48 months. Results. PP increased: under the hallux 50%; 1st metatarsal30.7%; 2nd toe20%; 2nd toe6%; midfoot9%. PP decreased under 35 toes up to 67%. Significant changes at the first period were found under 35 toes only (62%). The increase in loading under the other parts of the foot appeared at 24 months; however, these changes became significant between 24 and 48 months and peaked after 48 months of follow-up. The maximal increase of PP was noticed under the hallux, the 2nd toe, metatarsals 13 and the midfoot. Conclusions. We revealed the gradual redistribution of PP, under the different parts of the foot, in patients with inactive CA. This redistribution reflects changes in the shape of the affected foot. The loading increased under the hallux, the 2nd toe and the corresponding metatarsals, 3rd metatarsal and midfoot, and decreased under the 35 toes. These changes increased during the follow-up, becoming more pronounced after 4 or more years. Our data may be useful for constructing custom-made footwear for patients with CA

In vivo kinetics of Cajal body components

Cajal bodies (CBs) are subnuclear domains implicated in small nuclear ribonucleoprotein (snRNP) biogenesis. In most cell types, CBs coincide with nuclear gems, which contain the survival of motor neurons (SMN) complex, an essential snRNP assembly factor. Here, we analyze the exchange kinetics of multiple components of CBs and gems in living cells using photobleaching microscopy. We demonstrate differences in dissociation kinetics of CB constituents and relate them to their functions. Coilin and SMN complex members exhibit relatively long CB residence times, whereas components of snRNPs, small nucleolar RNPs, and factors shared with the nucleolus have significantly shorter residence times. Comparison of the dissociation kinetics of these shared proteins from either the nucleolus or the CB suggests the existence of compartment-specific retention mechanisms. The dynamic properties of several CB components do not depend on their interaction with coilin because their dissociation kinetics are unaltered in residual nuclear bodies of coilin knockout cells. Photobleaching and fluorescence resonance energy transfer experiments demonstrate that coilin and SMN can interact within CBs, but their interaction is not the major determinant of their residence times. These results suggest that CBs and gems are kinetically independent structures