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The present study examined elicited written English as a foreign language (EFL) narratives produced by 6th grade Hebrew and Arabic speakers in their 4th year of learning EFL. We examined the use of correct verb morphology and morphosyntactic structures, in relation to supporting L1/EFL skills. Fifty-eight pupils (29 Arabic speakers) participated in this study. Assessment tasks included Hebrew and Arabic (L1) morphological awareness (MA), EFL vocabulary, MA and reading comprehension (RC). Arabic speakers were also tested in second language (L2) Hebrew MA. English written narratives were coded for total words, verbs, nouns, correct and complex sentences, and use of verb morphology ("past tense", "present progressive", "3rd person singular", "copula") in obligatory context. Both groups found "3rd person singular" the most challenging, despite between group differences in EFL proficiency. Neither group showed crosslinguistic transfer of MA from L1 to EFL, however, Arabic speakers showed strong associations between HMA and EMA, suggesting possible indirect crosslinguistic influence. Hebrew speakers had strongest associations between EFL RC and MA with all aspects of EFL morphosyntactic use, while Arabic speakers relied on English MA for all aspects of correct morphosyntactic production. Regression analyses showed Hebrew speakers relied solely on English RC for verb and sentence production, whereas Arabic speakers drew on English MA. Results have theoretical and practical implications regarding typological considerations in cross-linguistic transfer, as well as point to specific difficulties and patterns in acquisition of EFL morphosyntax among speakers of Semitic languages, highlighting the role of L1 and EFL contributors to EFL written output.

Abstract RE-1 silencing transcription factor (REST) is a key repressor of neural genes. REST is upregulated under stress signals, aging and neurodegenerative diseases, but although it is upregulated, its function is lost in Alzheimer’s Disease. However, why it becomes inactive remains unclear. Here, we show that the NAD-dependent deacetylase SIRT6 regulates REST expression, location and activity. In the absence of SIRT6, REST is overexpressed but mislocalized, leading to a partial loss of its activity and causing it to become toxic. SIRT6 deficiency abrogates REST and EZH2 interaction, perturbs the location of REST to the heterochromatin Lamin B ring, and leads to REST target gene overexpression. SIRT6 reintroduction or REST methyl-mimic K494M expression rescues this phenotype, while an acetyl-mimic mutant loses its function even in WT cells. Our studies define a novel regulatory switch where, depending on SIRT6 presence, the function of REST is regulated by post-translational modifications on K494 (Ac/me), affecting neuronal gene expression. In WT cells (left), REST functions as a repressor due to its methylation, which allows proper localization and interaction with EZH2. In SIRT6 KO cells (right), REST is overexpressed, but it is mislocalized and acetylated instead of methylated, impairing its interaction with EZH2. REST localizes in the cytoplasm in autophagosomes. The overall increase in REST without SIRT6 results in non-functional and toxic REST proteins. During aging, SIRT6 declines in the brain, while REST is upregulated to protect it. In pathological aging, where SIRT6 levels are very low, the increase in REST without SIRT6 results in non-functional and toxic REST.

The article gives a brief overview of the emergence and development of the cultural-historical theory of higher psychological functions over the century after it was created. Lev Vygotsky began the development of his theory with the study of the instrumental function of “cultural signs” (primarily words) and therefore he gave it the name “instrumental psychology”. The formation of human personality was understood by Vygotsky as the “ingrowing” of social relations into the individual mind and the conscious “mastery of the self”, its psychological functions and affects, by means of signs and basing on concepts. The authors of the article point out the main milestones in the development of cultural-historical psychology, briefly characterise its key concepts, methods and the most important tendencies of its development, up to its most recent trends in Russia, which have already emerged in the 20th century.

The main idea of ​​the article is to trace the development and use of the concept of zone of proximal development (ZPD) in the works of Russian psychologists since its introduction into the conceptual apparatus of cultural-historical psychology by L.S. Vygotsky. The article consists of three parts. The first is devoted to the definition of the concept of ZPD, in which the contradictions between the ideas of the author of the concept and the interpretations of it by other authors are analyzed. The “classical definition” of ZPD is supplemented by the ideas of L.S. Vygotsky, expressed by him in other works. The other two parts of the article are devoted to changes in the methodological functions of the concept at different stages of its development: from an explanatory principle to the subject of research, and from the subject of research to a methodological means for the construction of new subjects of practice-oriented technologies. The general trend is to expand the areas of application of the ZPD concept, to go beyond the initial tasks of explaining and theoretically justifying the special connection between learning and development, and beyond the problems of interaction between a child and an adult. Particular attention is paid to the helping activity of an adult (teacher, psychologist, parent, etc.): the main question is how to help in order to contribute to the development. It is shown that the concept of ZPD is now used in psychotherapy and practice of working with adults with developmental disorders, i.e. it becomes the link between education (learning), development and mental health.

Background: In response to the Truth and Reconciliation Commission of Canada Calls to Action 22 to 24 around health, the Department of Family Medicine at the University of Calgary piloted a novel Indigenous Health Longitudinal Elective (IHLE) to give first year residents longitudinal experiences in Indigenous healthcare environments. The purpose of this evaluation was to capture the successful qualities and identify areas for improvements to ensure feasibility of the IHLE pilot program. Methods: Between November 2022 and April 2023, semi-structured interviews were completed with seven participants of the IHLE and included a mix of residents, preceptors, and clinic staff members. Qualitative thematic analysis was used to gain an in-depth understanding of the IHLE program experiences of all participants. Results: Benefits of the IHLE program include a deeper understanding of the values and priorities critical to working in healthcare with Indigenous peoples in Southern Alberta. Areas for improvement include clarity around IHLE program structure; clearly defining roles and responsibilities for preceptors; increased opportunities for reciprocity and relationality; and a deeper self-reflection process. Conclusion: Recommendations for future iterations of the IHLE include ensuring preceptors are trained and engaged, while providing residents more opportunities for relationality and peer debriefing. Results from this study may also help inform future Indigenous health programming in family medicine.

Bilingual children with a limited command of the second language (L2) often yield unsatisfactory results in L2-based non-word repetition tasks (NWRT) for the assessment of working memory. In this study, monolinguals (MO) and bilinguals (BI) of preschool age acquiring German were compared in regard to their performance on German-based NWRT to choose test items that do not put BI at a disadvantage. Four-year-old children (N = 876) were tested with the German language screenings "Sprachscreening für das Vorschulalter" (SSV) and "Kindersprachscreening" (KiSS), including 38 non-words. BI scored significantly lower in NWRT than MO due to a limited command of German as well as a limited language input (e.g., length of kindergarten attendance). After the statistical deletion of children who did not speak German age-appropriately, BI outperformed MO on the SSV, without significant differences on the KiSS. Performance on NWRT depended on the children's command of the German vocabulary and phonotactics. Several relatively "culture-fair" NWRT items were identified.

This study examined work contexts of lecturers in Israeli academic teacher training colleges in which they perform emotional labor. This study, employing qualitative method and open-ended questionnaires, and participants included 29 lecturers. Thematic content analyses suggest a three concentric circles model of emotional labor in lecturer-student interactions (ELLSI) representing three contexts in which participants performed emotional labor in their interactions with students: Individual, pedagogical and administrative. These findings are in line with previous works on emotional labors among lecturers, which pose lecturers as service providers of their client-students, according to institutional demands. Research limitations, recommendations for future work and applicable aspects will be discussed.

The article provides a transcript of the speeches of the speakers of the Round Table "Functional psychological literacy of parents and teachers as a condition for building effective communication with a child", held at the Moscow State University of Psychological and Education on April 25, 2023. The Round Table addressed the problems of modern "psychology for life": the formation of functional psychological literacy of school teachers and parents in the sphere of communication and interaction with children. The speeches of the speakers of the Round Table were devoted to modern ideas about psychological literacy in psychology; approaches and researches in the field of formation of psychological literacy within the systems "teacher-pupil", "parent-child"; formation of functional psychological literacy of school teachers in communication with pupils; knowledge, skills, abilities of parents in interaction with a child; risk factors in the development of functional psychological literacy in communication and interaction with a child of parents and teachers in the sphere of communication and interaction with a child. Video recording of the speeches is given on the official video channel of PsyJournals.ru.

The microbiota performs multiple functions vital to host fitness, including defense against pathogens and adaptation to dietary changes. Yet, how environmental challenges shape microbiota resilience to nutrient fluctuation remains largely unexplored. Here, we show that transient gut infection can optimize host metabolism toward the usage of carbohydrates. Following acute infection and clearance of the pathogen, mice gained more weight as a result of white adipose tissue expansion. Concomitantly, previously infected mice exhibited enhanced carbohydrate (glucose) disposal and insulin sensitivity. This metabolic remodeling depended on alterations to the gut microbiota, with infection-elicited Betaproteobacteria being sufficient to enhance host carbohydrate metabolism. Further, infection-induced metabolic alteration protected mice against stunting in the context of limited nutrient availability. Together, these results propose that alterations to the microbiota imposed by acute infection may enhance host fitness and survival in the face of nutrient restriction, a phenomenon that may be adaptive in settings where both infection burden and food precarity are prevalent.

Currently, hybrid table beet seeds make up a significant part of the seeds sold in the world due to their high synchrony, root uniformity, and the effect of heterosis. Heterosis breeding of table beet in Russia is developed insufficiently. One of the reasons is the lack of a well-studied homogeneous linear material. Another reason is a long and labor-consuming process of obtaining parent components for classical crossing due to a 2-year cycle of crop development, a pronounced self-incompatibility system, and inbreeding depression. In vitro production of doubled table beet haploids makes it possible to obtain homozygous material in a short time. It can be used in breeding programs as an alternative to traditional inbred lines. Therefore, introduction of the haploidization technology into the table beet breeding programs is of great importance. This article discusses various approaches to the production of doubled beet haploids and describes crucial achievements, major problems, and the ways to solve them. Methods for producing doubled haploids of table beet has not been studied profoundly enough, so they require additional in-depth research aimed at improving their efficiency and reproducibility.

The article analyzes the processes of project management in the implementation of social and environmental programs in the Arctic zone of the Russian Federation. Current regulatory and legal acts aimed at ensuring the development of the Arctic zone are considered. The problems of rational environmental management, development of territories with minimal negative impact on the state of the environment and taking into account the environmental situation in the region is identified. State programs for support and assistance to people living and working in the regions of the Arctic zone of the Russian Federation, aimed at economic support, development of a personnel reserve and health preservation, and environmental projects, are analyzed and presented. The priority importance of social and environmental projects to develop infrastructure, improve the quality of life of the population and preserve the primary ecosystem is noted. The use of methods for calculating environmental safety indices and urban environment quality indices of the Ministry of Construction of the Russian Federation when ranking the subjects of the Arctic zone made it possible to identify the most problematic areas in ensuring the quality of life, and, accordingly, priority areas for the development and implementation of strategic projects. The importance of strategic programs and projects to reduce the level of pollutants, to increase the population’s supply of high-quality drinking water in cities and to improve the quality of the urban environment is emphasized to improve the quality of life of residents of the cities of the Arctic region.

As part of the project “The Tree of Cultural-Historical Psychology” an interview with Boris Danilovich Elkonin is presented — Doctor of Psychology, Professor, Head of the Laboratory “Psychology of the Junior Schoolchild” of the Psychological Institute of the Russian Academy of Education, editor-in-chief of the journal “Cultural-Historical Psychology”.

Background. In recent years, limited phonological short-term memory has become a widely recognized clinical marker for language(-related) impairments both for monolingual and bilingual children. Usually, it is assessed by the repetition of nonwords, sentences, and digit spans. However, in the case of bilingual children, its assessment has been shown to be inaccurate due to the influence of bilinguals’ first language phonotactics and their limited command of the second language. Methods. Monolingual (n = 712) and bilingual (n = 1,004) German preschoolers (age 4;0–4;11 years) were compared with each other with respect to their German language skills and performance in German-based and “quasi-universal” nonword repetition tasks (that is, items following the phonotactic rules of German vs. many world languages). Associations of both kinds of nonword repetition tasks with children’s language impairments were quantified. Results. German language skills of the bilinguals were weaker than those of the monolinguals. Whereas the bilinguals scored significantly lower than the monolinguals in German-based nonwords, there were no considerable differences between these subgroups in quasi-universal items. Poor performance in tasks employing both German-based and quasi-universal nonwords was significantly associated with language impairments. In contrast to quasi-universal nonwords, weak performance in German-based items was more strongly associated with limited German language skills than with language impairments. Conclusions. Because nonword repetition tasks were designed to identify children with language impairments, and not those with a weak command of German, quasi-universal nonwords appear to be more appropriate for language tests than language-specific items.

Non-word repetition tasks are widely used to assess phonological short-term memory (PSTM). Results of previous research on the performance of monolingual and bilingual children in PSTM tasks are inconclusive. Although in some studies bilinguals did outperform monolinguals in the repetition of non-words, most studies reported comparatively weak results of bilingual children, especially when they were tested in their L2. In this study, four-year-old monolingual and bilingual children acquiring German (N = 1,441) were tested with both German-based (GBNW) and quasi-universal non-words (QUNW). It was hypothesized that bilinguals would outperform monolinguals both in (a) GBNW under the condition of comparable German language skills and (b) QUNW without any preconditions because QUNW do not presuppose a good command of German. Bilinguals yielded significantly lower results in GBNW, but not in QUNW. After the exclusion of children with limited German language skills from both groups, bilinguals outperformed monolinguals in both tasks, especially in QUNW. It can be assumed that bilingualism puts higher demands on PSTM than monolingualism and thus contributes to its faster development. Unnecessary medical examinations and therapies that are sometimes prescribed to bilinguals due to a poor performance in German-based PSTM tasks can be avoided if QUNW are used instead of language-specific items.

Introduction. Molecular genetic testing is actively used for prognostication in patients with uveal melanoma (UM). Tissue for genetic analysis may be obtained either by surgical excision or through fine-needle aspiration biopsy (FNAB). Performing genetic testing and FNAB in each institution can differ in surgical techniques and laboratory methodologies.Aim. To present our own experience of performing FNAB-based molecular genetic testing for prognostication in patients with uveal melanoma.Materials and methods. Prognostic FNAB (n = 151) were combined with brachytherapy or stereotactic surgery. Genetic testing was performed by methods based on polymerase chain reaction (GNAQ, GNA11, EIF1AX and SF3B1 mutations) and fluorescence in situ hybridization (copy numbers of PPARG and MYC genes); cytology of FNAB material was also assessed.Results. Fine-needle aspiration biopsy material was informative in 91 % of cases. At the median follow-up of 36 months, 12 cases of distant metastases were detected. Occurrence of the assessed mutations and copy numbers were related to other representative studies. PPARG deletion was shown to be a significant prognostic factor for metastasis-free survival (p

The purpose of this research was to examine the relationship between teachers' perceptions of emotional labor, teacher burnout and teachers' educational levels. The research sample consisted of 170 female Haredi (religiously ultra-orthodox and observant) teachers working in schools throughout Israel. The data were collected using the Emotional Labor of Teaching Scale (TELTS) and Teacher Burnout Questionnaire, and a demographic questionnaire formulated for the present study. The data collected in the study were processed using SPSS software. The two research hypotheses, namely a) teachers characterized by lower levels of burnout will use the natural acting technique associated with emotional labor whereas teachers typified by higher level of burnout will utilize the surface acting or deep acting emotional labor techniques; and b) teachers with higher levels of education will tend to use the natural acting technique associated with emotional labor in contrast to teachers with lower levels of education who will tend to utilize the surface acting or deep acting emotional labor techniques, were analyzed by ANOVA and MANOVA procedures. The main findings indicated that both teachers' burnout levels and teachers' levels of education differentially affected the use of the specific emotional labor techniques (surface, deep or natural acting). The conclusion of this study is that various variables can influence teachers' use of techniques associated with emotional labor. Changes in such variables, such as teachers' level of burnout and level of education, may improve management of emotions in teaching and improve their well-being.

Despite relatively higher rates of dementia among Indigenous populations internationally, research into drivers of disparities in brain health and cognitive function has tended to focus on modifiable risk factors over cultural understandings and contextual determinants. By seeking to characterize social and cultural factors that shape brain health and cognition in Indigenous populations, this mini scoping review expands prevailing schools of thought to include Indigenous knowledge systems. This reveals important gaps in culturally aligned care. It also reclaims horizons for research important to Indigenous Peoples that have garnered diminished attention in biomedical approaches. Twenty-three sources were included for data extraction. This synthesis of 23 sources includes health communication about dementia, health provider knowledge about Indigenous health, culturally relevant screening and assessment tools, and culturally grounded care models. Much of the focus is currently still on modifiable risk factors that reside at individual factors, whereas attention to wider social factors that impact populations is needed, as stressors through isolation, discrimination, and unequal care are widely reported. Going forward, identifying structural barriers to living well and recognizing the importance of connection to culture will benefit both Indigenous and non-Indigenous understandings of brain health.

While performed by all three domains of life, N-glycosylation in Archaea is less well described than are the parallel eukaryal and bacterial processes. Still, what is known of the archaeal version of this universal post-translational modification reveals numerous seemingly domain-specific traits. Specifically, the biosynthesis of archaeal N-linked glycans relies on distinct pathway steps and components, rare sugars and sugar modifications, as well as unique lipid carriers upon which N-linked glycans are assembled. At the same time, Archaea possess the apparently unique ability to simultaneously modify their glycoproteins with very different N-linked glycans. In addition to these biochemical aspects of archaeal N-glycosylation, such post-translational modification has been found to serve a wide range of roles possibly unique to Archaea, including allowing these microorganisms to not only cope with the harsh physical conditions of the niches they can inhabit but also providing the ability to adapt to transient changes in such environments.

Background: Direct support professionals (DSP) are instrumental in supporting the health care of individuals with intellectual disabilities, yet receive little training and support for this role. We implemented a capacity building intervention for DSPs in a community agency in Ontario, Canada. This study evaluated the perceived value and feasibility of the intervention and the value of a structured implementation approach. Method: The intervention included communication tools, a health resource toolkit, and training. A mixed methods evaluation was used to collect feedback from DSPs and people with intellectual disabilities. Results: Participants generally found the intervention valuable and feasible. Although practice change is difficult, extensive engagement and being responsive to feedback were helpful strategies. The primary concern reported by DSPs was resistance from health care providers. Conclusion: An important next step is to engage health care providers to ensure the tools are valuable and feasible for everyone involved in the health encounter.

Defects in tumor-intrinsic interferon (IFN) signaling result in failure of immune checkpoint blockade (ICB) against cancer, but these tumors may still maintain sensitivity to T cell-based adoptive cell therapy (ACT). We generated models of IFN signaling defects in B16 murine melanoma observed in patients with acquired resistance to ICB. Tumors lacking Jak1 or Jak2 did not respond to ICB, whereas ACT was effective against Jak2 KO tumors, but not Jak1 KO tumors, where both type I and II tumor IFN signaling were defective. This was a direct result of low baseline class I major histocompatibility complex (MHC I) expression in B16 and the dependency of MHC I expression on either type I or type II IFN signaling. We used genetic and pharmacologic approaches to uncouple this dependency and restore MHC I expression. Through independent mechanisms, overexpression of NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5) and intratumoral delivery of BO-112, a potent nanoplexed version of polyinosinic:polycytidylic acid (poly I:C), each restored the efficacy of ACT against B16-Jak1 KO tumors. BO-112 activated double-stranded RNA (dsRNA) sensing (via protein kinase R and Toll-like receptor 3) and induced MHC I expression via nuclear factor κB, independent of both IFN signaling and NLRC5. In summary, we demonstrated that in the absence of tumor IFN signaling, MHC I expression is essential and sufficient for the efficacy of ACT. For tumors lacking MHC I expression due to deficient IFN signaling, activation of dsRNA sensors by BO-112 affords an alternative approach to restore the efficacy of ACT.

Many approaches to identify therapeutically relevant neoantigens couple tumor sequencing with bioinformatic algorithms and inferred rules of tumor epitope immunogenicity. However, there are no reference data to compare these approaches, and the parameters governing tumor epitope immunogenicity remain unclear. Here, we assembled a global consortium wherein each participant predicted immunogenic epitopes from shared tumor sequencing data. 608 epitopes were subsequently assessed for T cell binding in patient-matched samples. By integrating peptide features associated with presentation and recognition, we developed a model of tumor epitope immunogenicity that filtered out 98% of non-immunogenic peptides with a precision above 0.70. Pipelines prioritizing model features had superior performance, and pipeline alterations leveraging them improved prediction performance. These findings were validated in an independent cohort of 310 epitopes prioritized from tumor sequencing data and assessed for T cell binding. This data resource enables identification of parameters underlying effective anti-tumor immunity and is available to the research community.

Mechanism-based strategies to overcome resistance to PD-1 blockade therapy are urgently needed. We developed genetic acquired resistant models of JAK1, JAK2, and B2M loss-of-function mutations by gene knockout in human and murine cell lines. Human melanoma cell lines with JAK1/2 knockout became insensitive to IFN-induced antitumor effects, while B2M knockout was no longer recognized by antigen-specific T cells and hence was resistant to cytotoxicity. All of these mutations led to resistance to anti-PD-1 therapy in vivo. JAK1/2-knockout resistance could be overcome with the activation of innate and adaptive immunity by intratumoral Toll-like receptor 9 agonist administration together with anti-PD-1, mediated by natural killer (NK) and CD8 T cells. B2M-knockout resistance could be overcome by NK-cell and CD4 T-cell activation using the CD122 preferential IL2 agonist bempegaldesleukin. Therefore, mechanistically designed combination therapies can overcome genetic resistance to PD-1 blockade therapy. SIGNIFICANCE: The activation of IFN signaling through pattern recognition receptors and the stimulation of NK cells overcome genetic mechanisms of resistance to PD-1 blockade therapy mediated through deficient IFN receptor and antigen presentation pathways. These approaches are being tested in the clinic to improve the antitumor activity of PD-1 blockade therapy.This article is highlighted in the In This Issue feature, p. 1079.

Lack of tumor infiltration by immune cells is the main mechanism of primary resistance to programmed cell death protein 1 (PD-1) blockade therapies for cancer. It has been postulated that cancer cell-intrinsic mechanisms may actively exclude T cells from tumors, suggesting that the finding of actionable molecules that could be inhibited to increase T cell infiltration may synergize with checkpoint inhibitor immunotherapy. Here, we show that p21-activated kinase 4 (PAK4) is enriched in non-responding tumor biopsies with low T cell and dendritic cell infiltration. In mouse models, genetic deletion of PAK4 increased T cell infiltration and reversed resistance to PD-1 blockade in a CD8 T cell-dependent manner. Furthermore, combination of anti-PD-1 with the PAK4 inhibitor KPT-9274 improved anti-tumor response compared with anti-PD-1 alone. Therefore, high PAK4 expression is correlated with low T cell and dendritic cell infiltration and a lack of response to PD-1 blockade, which could be reversed with PAK4 inhibition.