PSYCHOLOGICAL READINESS FOR SCHOOL OF CHILDREN WITH ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY

В статье рассматривается проблема психологической готовности к школьному обучению детей с синдромом дефицита внимания с гиперактивностью, являющаяся актуальной для исследования в связи со значительной представленностью данного синдрома в детской популяции. В работе использованы методики эмпирического исследования, статистические методы. Изложены результаты эмпирического исследования психологической готовности к обучению в школе младших школьников с обсуждаемым синдромом. В результате проведенного анализа было выявлено, что у младших школьников с данным синдромом не сформирована психологическая готовность к школе, им присущ низкий уровень сформированности произвольно – контекстного типа общения с взрослым, низкий уровень «кооперативно – соревновательного» типа общения, отвечающего за успешность овладения общими способами решения задач, достоверно отличающиеся от показателей сверстников. Полученные данные могут представлять интерес для специалистов дошкольного и школьного образования, научных сотрудников, в контексте готовности детей к школьному обучению и профилактики школьной дезадаптации.The problem of psychological readiness for school training of children with attention deficit disorder with hyperactivity which is important for the research in connection with considerable representation of this syndrome in children’s population is considered in the article. Techniques of empirical study, statistical methods are used in the work. Results of empirical study of psychological readiness for school training of the primary school age students with the mentioned syndrome are presented. As a result of the carried-out analysis, it has been revealed that primary school age students with this syndrome are not ready for school, they are characteristic of low degree of well-formedness of the voluntary-contextual type of communication with the adults, low level of the “cooperative-competitive” type of communication which is responsible for successful acquisition of the general ways of the problem solution, truly different from the agemates’ characteristics. The obtained data can be of interest to specialists of preschool and school education, research associates, in the context of readiness of children for school training and prevention of school disadaptation

The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis

Multiple myeloma (MM) evolves from a highly prevalent premalignant condition termed MGUS. The factors underlying the malignant transformation of MGUS are unknown. We report a MGUS/MM phenotype in transgenic mice with Eμ-directed expression of the XBP-1 spliced isoform (XBP-1s), a factor governing unfolded protein/ER stress response and plasma-cell development. Eμ-XBP-1s elicited elevated serum Ig and skin alterations. With age, Eμ-xbp-1s transgenics develop features diagnostic of human MM, including bone lytic lesions and subendothelial Ig deposition. Furthermore, transcriptional profiles of Eμ-xbp-1s lymphoid and MM cells show aberrant expression of known human MM dysregulated genes. The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis

An inhibitor of oxidative phosphorylation exploits cancer vulnerability.

Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to an incomplete understanding of tumor contexts in which OXPHOS is essential. Here, we report the discovery of IACS-010759, a clinical-grade small-molecule inhibitor of complex I of the mitochondrial electron transport chain. Treatment with IACS-010759 robustly inhibited proliferation and induced apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, likely owing to a combination of energy depletion and reduced aspartate production that leads to impaired nucleotide biosynthesis. In models of brain cancer and AML, tumor growth was potently inhibited in vivo following IACS-010759 treatment at well-tolerated doses. IACS-010759 is currently being evaluated in phase 1 clinical trials in relapsed/refractory AML and solid tumors

The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans.

Histiocytic sarcoma (HS) is a rare malignant proliferation of histiocytes of uncertain molecular pathogenesis. Here, genetic analysis of coincident loss of Pten and Ink4a/Arf tumor suppressors in the mouse revealed a neoplastic phenotype dominated by a premalignant expansion of biphenotypic myelolymphoid cells followed by the development of HS. Pten protein loss occurred only in the histiocytic portion of tumors, suggesting a stepwise genetic inactivation in the generation of HS. Similarly, human HS showed genetic or epigenetic inactivation of PTEN, p16(INK4A), and p14(ARF), supporting the relevance of this genetically engineered mouse model of HS. These genetic and translational observations establish a cooperative role of Pten and Ink4a/Arf in the development of HS and provide mechanistic insights into the pathogenesis of human HS

Modulation of activity of the tumour suppressor p53 by small molecules and damaged DNA

The p53 is a potent tumor suppressor, which becomes activated in response to stress. The activated p53 triggers a cell cycle arrest in GI or apoptosis, ensuring a suppression of a tumor development by the elimination of cells carrying potentially tumorigenic lesions. In this study we addressed the question of the molecular mechanisms of p53 activation by DNA damage. We characterized the ability of the p53 C-terminus to bind different types of DNA lesions and the effect of C-terminal interaction with DNA on the core domain DNA binding. We showed that one unpaired nucleotide within a double-stranded (ds) DNA is sufficient for recognition by the p53 Cterminus, either as a protruding end or as an internal gap in dsDNA. The C-terminal interaction with DNA ends facilitated the core domain binding to DNA, whereas interaction with gaps prevented the core domain-DNA complexing, implying that p53 might adopt distinct conformations upon binding to different DNA lesions. These observations suggest that both singlestrand and doublestrand breaks can serve as a target for p53 C-terminal recognition in vivo and indicate that p53 might recruit different repair factors to the sites of damaged DNA depending on the type of the lesion. Next we addressed the question of the molecular mechanisms of p53 activation and stabilization after DNA damage in cells. Our data suggests that tetrameric p53 bound to DNA ends dissociates to monomers in vitro. Notably, we found that monomeric p53 has an alternative folding in its Nterminus, which is specifically recognized by newly characterized LSP16 anti-p53 antibody. We showed that LSP16 recognizes a cryptic N-terminal epitope exposed specifically in p53 monomer. Using LSP16, we showed that in response to ionizing radiation, p53 rapidly re-localizes to DNA damage sites that also contain gammaH2AX and MRE11 complex. Furthermore, we showed that LSP16-positive p53 is localized in a close vicinity to DNA strand breaks independently of phosphorylation by P13 kinases and of MRE11 repair complex. We propose a model implying that localization of p53 to DNA damage sites serves to initiate p53 activation via induction of the alternative folding of the p53 N-terminus, which prevents Mdm2 binding and thus disrupts the p53/Mdm2 negative feedback loop. This may be viewed as a mechanism that regulates the level of active p53 in an orderly fashion dictated by the extent of DNA damage and repair, thereby coordinating the p53 response with ongoing DNA repair. In addition, alternative folding in the Nterminus upon binding to damaged DNA might create a binding site for a novel protein partner. We hypothesized that the direct interaction of p53 with DNA strand breaks can play a role in p53 activation in vivo. Inactivation of p53 has always been considered as an unwanted event. However, under certain conditions, p53 activity might be harmful to normal tissues. Using the p53-null mice, it was shown that p53 expression is required for induction of cell death in the model of seizure activity. Recent studies have demonstrated the direct involvement of p53 in deaths of neurons, which occur during a pathogenic process in Alzheimer's disease, stroke and traumatic brain injury. Side effects of chemo- and radiotherapy have been shown to be p53-dependent. Taken together, these findings raise the possibility that pharmacological down-regulation of p53 functions might decrease the extent of tissue injury. In order to find a small molecule, the p53- inhibitor, we have screened a series of synthetic peptides and identified peptide 14, derived from p53 itself, which can inhibit p53 specific DNA binding and the transactivation function. Our data demonstrates that peptide 14 can bind p53 in vitro and prevent p53-dependent apoptosis in cells. Peptide14 can serve as a prototype for the development of the p53-specific inhibitor molecule

A prospective randomized clinical trial on accuracy of plastic periodontal probes compared to conventional metal probes around dental implants

BACKGROUND: Plastic probes have increased flexibility and a smaller tip diameter compared to traditional metal probes. The increased flexion when inserting into the sulcus may distort the accuracy of the probing depth measurement. In addition, the smaller diameter tip is able to penetrate deeper into the junctional epithelium and connective tissue apparatus resulting in an elevated measurement. The aim of this study is to compare the accuracy of plastic periodontal probe measurements to measurements with a metal probe around healthy dental implants. METHODS: Patients receiving routine maintenance at the University of Colorado graduate periodontal department, with fully restored dental implants were recruited for this study. Patients were selected prior to their appointment according to their electronic health records and current radiographs. Inclusion criteria patients 18 years of age and older, implants that had been placed and loaded with the final restoration for at least six months, and good oral hygiene. Forty-four implants were evaluated. Two calibrated examiners completed all measurements with plastic and metal probes on six sites per implant. The starting probe was alternated between the plastic and metal. The probing depths were recorded by dental hygienist who worked at that time or surgical dental assistant who was available at the time of examination. All of the data was collected and analyzed using linear mixed model with random intercepts for examiner and implant. RESULTS: There was no significant difference between the accuracy of measurements on the interproximal and the flat surfaces of the implant when comparing metal versus plastic probes (p=0.6483). Probing depth measurements from the plastic probes were greater than from metal probes at five of the six locations. While measurements from metal probes were greater than the plastic probes at only two locations. However, this was not statistically significant. Collapsed across location, measurements from metal probes were 0.05 units greater than measurements from plastic probes (95% CI 0.01 units less to 0.11 units greater). However, this difference was not statistically significant (p=0.1190). DISCUSSION: This study failed to prove any statistically significant difference in accuracy between the metal and plastic probes. However, the shape of the final restoration does play a role in the accuracy and placement of a traditional metal probe. The plastic probe may adapt more easily around these restorations due to its smaller diameter tip, it may also penetrate deeper into the connective tissue resulting in a deeper measurement. The UNC15 metal probe has long been the standard of care for research applications due to the high degree of accuracy with its markings. The plastic probe, similar to the Marque metal probe, has markings every 3 mm allowing for more discrepancy between clinicians. CONCLUSION: Within the limitations of this study, the plastic probe appeared to be as accurate as the traditional metal probe when probing around the dental implants

Effect of COVID-19 on Pet Food Bank Servicing : Quantifying Numbers of Clients Serviced in the Vancouver Downtown Eastside, British Columbia, Canada

Previous research has focused on the benefits and difficulties of pet ownership in people, who are experiencing homelessness. However, many pet services, such as pet food banks, serve a more varied population of people. Furthermore, the effect of the COVID-19 pandemic has not been documented within the context of pet food banks. Vancouver’s Downtown Eastside (DTES) population comprises a notable proportion of the city’s overall population and has a high density of people who are experiencing financial hardships, but some of whom do not always experience homelessness. The purpose of this study was to gain an understanding of the number of clients and pets that are being serviced by a pet food bank, whether that has changed over time, and if it was impacted by the COVID-19 pandemic. We analyzed available attendance and service records from The British Columbia Society for the Prevention of Cruelty to Animals pet food bank between 2013 and 2020. We found that a median of 100 clients attended the food bank each week and that most of the companion animals serviced were cats (72.5%), then followed by dogs (25.2%), and rats (1.2%). Servicing was not consistent over time, with a weekly pattern of decreased attendance every fourth week of the month, which coincided with income assistance payments. This suggests that either servicing needs are decreased with income assistance or that the week of the month may present an access to care challenge. We also observed a decrease in the clientele attending in 2020 compared to previous years, suggesting an effect of COVID-19. Specifically, this trend was present for cats, rats, rabbits, and “other” companion animals, but not for dogs; the number of dog owners receiving services did not change in 2020, suggesting a difference between needed services in dog vs. other pet owners. The yearly trends shed light on the impact of COVID-19 on vulnerable populations, highlighting the need for additional support through times of crisis. Overall, the data show a complex relationship between pet service provision and other community issues and highlight the need to consider pet food banks within the greater social services networks.Land and Food Systems, Faculty ofReviewedFacultyUndergraduat

Simplified Method for <i>Agrobacterium</i>-Mediated Genetic Transformation of <i>Populus</i> x <i>berolinensis</i> K. Koch

The rapid advancement of genetic technologies has made it possible to modify various plants through both genetic transformation and gene editing techniques. Poplar, with its rapid in vitro growth and regeneration enabling high rates of micropropagation, has emerged as a model system for the genetic transformation of woody plants. In this study, Populus × berolinensis K. Koch. (Berlin poplar) was chosen as the model organism due to its narrow leaves and spindle-shaped crown, which make it highly suitable for in vitro manipulations. Various protocols for the Agrobacterium-mediated transformation of poplar species have been developed to date. However, the genetic transformation procedures are often constrained by the complexity of the nutrient media used for plant regeneration and growth, which could potentially be simplified. Our study presents a cheaper, simplified, and relatively fast protocol for the Agrobacterium-mediated transformation of Berlin poplar. The protocol involved using internode sections without axillary buds as explants, which were co-cultivated in 10 µL droplets of bacterial suspension directly on the surface of a solid agar-based medium without rinsing and sterile paper drying after inoculation. We used only one regeneration Murashige and Skoogbased medium supplemented with BA (0.2 mg·L−1), TDZ (0.02 mg·L−1), and NAA (0.01 mg·L−1). Acetosyringone was not used as an induction agent for vir genes during the genetic transformation. Applying our protocol and using the binary plasmid pBI121 carrying the nptII selective and uidA reporter genes, we obtained the six transgenic lines of poplar. Transgenesis was confirmed through a PCR-based screening of kanamycin-selected regenerants for the presence of both mentioned genes, Sanger sequencing, and tests for detecting the maintained activity of both genes. The transformation efficiency, considering the 100 explants taken originally, was 6%

Eranthis Salisb. (Ranunculaceae) in South Siberia: Insights into Phylogeography and Taxonomy

Eranthis Salisb. (Ranunculaceae) is a herbaceous plant genus, including few species disjunctively distributed throughout the temperate zone from Southeastern Europe to Eastern Asia. Until recently, only Eranthis sibirica DC. was known in South Siberia, being considered endemic and tertiary relict. Not long ago, Eranthis tanhoensis Erst was also described in Siberia. We report here a reconstruction of the phylogenetic relationships between the Siberian Eranthis species based on nuclear (ITS) and plastid (trnL + trnL-trnF + trnH-psbA) DNA. The phylogeographic structure of Siberian Eranthis is distinguished by the presence of the two &ldquo;eastern&rdquo; and &ldquo;western&rdquo; supergroups, which most likely formed as a result of disjunction caused by active mountain uplifts during the late Neogene&ndash;early Quaternary and subsequent progressive Pleistocene cooling. The eastern supergroup combines lineage I, containing populations from the eastern Khamar-Daban Ridge, the Eastern Sayan Mountains, and the Tannu-Ola Ridge, and lineage II containing western Khamar-Daban populations. The western supergroup includes only lineage III, containing Western Sayan populations. Our data clearly show that E. tanhoensis is nested in the E. sibirica clade, thereby indicating that its description as a separate species is unjustified, as it compromises the monophyletic status of E. sibirica. Therefore, we suggest here to consider E. tanhoensis as a synonym of E. sibirica