Teachers in cross-border regions are constantly exposed to situations which are characterised by a rich linguistic and cultural diversity. The article presents the model of cross-border classrooms ...which was developed in the project EDUKA2. A special emphasis is paid to the role of teacher as reflective practitioner which presupposes knowledge, skills and personality traits necessary for meeting the challenges of the contemporary classroom. The empirical part presents the results of a study aimed at encouraging teachers to reflect upon their teaching and critically examine which changes they could implement in their work on the basis of the knowledge and experiences gained during the project training activities. The results indicate that the teachers are well aware of the benefits provided by the cross-border territory and are willing to implement changes in their teaching practice.
Qualitative research involving 36 students of the Faculty of Philosophy of the University of Banja Luka and the Faculty of Education of the University of Primorska was conducted in 2020 with the aim ...of examining the elements of university teaching methodology in the context of students’ situational learning during the COVID-19 pandemic. An introspective written interview was applied in the study, based on the assumptions of developmental research and an interpretive approach. By applying a thematic content analysis, three interrelated categories were identified (an emotional component of the teaching methodology approach; students’ engagement and the teaching methodology elements in the context of the wider community; the teaching methodology elements in the students’ literary activities), with the emotional component as the most dominant. Research results point to the need of focusing more attention to the emotional dimension of the students’ learning process, as well as their willingness to act in the community by taking on a more active role within the contextualized and constructivist-based university teaching methodology model.Key words: contextualized teaching; COVID-19; preschool teachers’ competencies; situational learning; therapeutic fairy tales for children. --- Kvalitativno istraživanje u kojem je sudjelovalo 36 studenata Filozofskog fakulteta Sveučilišta u Banjoj Luci i Pedagoškog fakulteta Sveučilišta Primorska provedeno je 2020. godine, a cilj mu je bio ispitati metodičke elemente nastave u kontekstu situacijskoga učenja studenata tijekom pandemije COVID 19. U studiji, zasnovanoj na idejama o razvojnim istraživanjima i na interpretativnom pristupu, primijenjen je introspektivni pisani intervju i putem tematske analize sadržaja izdvojene su tri ključne, međusobno povezane kategorije (emocionalna komponenta metodičkoga pristupa, angažman studenata i metodički elementi u kontekstu šire zajednice; metodički elementi u književnim aktivnostima studenata), od kojih se emocionalna komponenta prikazala najdominantnijom. Implikacije istraživanja ukazuju na potrebu da se više pozornosti posveti emocionalnoj dimenziji procesa učenja studenata, kao i njihovoj potrebi za djelovanjem u zajednici preuzimajući aktivniju ulogu uz pomoć kontekstualiziranoga, konstruktivističkoga metodičkoga modela sveučilišne nastave.Ključne riječi: COVID 19; kompetencije odgajatelja; kontekstualizirana nastava; situacijsko učenje; terapijske bajke za djecu.
Učitelji v obmejnem prostoru so v razredu nenehno izpostavljeni situacijam, za katere je značilna izrazita jezikovna in kulturna raznolikost. V príspevku je predstavljen model tako imenovanih ...čezmejnih razredov, ki je bil razvit v okviru projekta EDUKA2. Pri tem je izpostavljena zlasti vloga učitelja kot reflektivnega praktika, ki predpostavlja znanje, spretnosti in osebnostne lastnosti, s katerimi se bo ta sposoben soočiti z izzivi sodobnega razreda. V empiričnem delu je predstavljena raziskava, katere namen je bil učitelje spodbuditi k refleksiji in kritičnemu razmisleku o tem, kakšne spremembe bi lahko uvedli pri svojem pedagoškem delu na osnovi znanja in izkušenj, pridobljenih na usposabljanju v okviru projekta. Rezultati kažejo, da se učitelji zavedajo prednosti, ki jih nudi čezmejni prostor, in da so pripravljeni uvesti spremembe v svojo pedagoško prakso.
Kvalitativno istraživanje u kojem je sudjelovalo 36 studenata Filozofskog fakulteta
Sveučilišta u Banjoj Luci i Pedagoškog fakulteta Sveučilišta Primorska provedeno
je 2020. godine, a cilj mu je bio ...ispitati metodičke elemente nastave u kontekstu
situacijskoga učenja studenata tijekom pandemije COVID 19. U studiji, zasnovanoj
na idejama o razvojnim istraživanjima i na interpretativnom pristupu, primijenjen
je introspektivni pisani intervju i putem tematske analize sadržaja izdvojene su tri
ključne, međusobno povezane kategorije (emocionalna komponenta metodičkoga
pristupa, angažman studenata i metodički elementi u kontekstu šire zajednice;
metodički elementi u književnim aktivnostima studenata), od kojih se emocionalna
komponenta prikazala najdominantnijom. Implikacije istraživanja ukazuju
na potrebu da se više pozornosti posveti emocionalnoj dimenziji procesa učenja
studenata, kao i njihovoj potrebi za djelovanjem u zajednici preuzimajući aktivniju
ulogu uz pomoć kontekstualiziranoga, konstruktivističkoga metodičkoga modela
sveučilišne nastave.
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Aspirin-exacerbated respiratory disease (AERD) is a severe disease involving dysregulated type 2 inflammation. However, the role other inflammatory pathways play in AERD is poorly ...understood.
We sought to broadly define the inflammatory milieu of the upper respiratory tract in AERD and to determine the effects of IL-4Rα inhibition on mediators of nasal inflammation.
Twenty-two AERD patients treated with dupilumab for 3 months were followed over 3 visits and compared to 10 healthy controls. Nasal fluid was assessed for 45 cytokines and chemokines using Olink Target 48. Blood neutrophils and cultured human mast cells, monocytes/macrophages, and nasal fibroblasts were assessed for response to IL-4/13 stimulation in vitro.
Of the nasal fluid cytokines measured, nearly one third were higher in AERD patients compared to healthy controls, including IL-6 and the IL-6 family–related cytokine oncostatin M (OSM), both of which correlated with nasal albumin levels, a marker of epithelial barrier dysregulation. Dupilumab significantly decreased many nasal mediators, including OSM and IL-6. IL-4 stimulation induced OSM production from mast cells and macrophages but not from neutrophils, and OSM and IL-13 stimulation induced IL-6 production from nasal fibroblasts.
In addition to type 2 inflammation, innate and IL-6–related cytokines are also elevated in the respiratory tract in AERD. Both OSM and IL-6 are locally produced in nasal polyps and likely promote pathology by negatively affecting epithelial barrier function. IL-4Rα blockade, although seemingly directed at type 2 inflammation, also decreases mediators of innate inflammation and epithelial dysregulation, which may contribute to dupilumab’s therapeutic efficacy in AERD.
Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological ...activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark mitochondrial stasis and fragmentation independent of causal
mutation. In mice expressing human
T105M, intermittent mitofusin activation with a small molecule, MiM111, normalized CMT2A neuromuscular dysfunction, reversed pre-treatment axon and skeletal myocyte atrophy, and enhanced axon regrowth by increasing mitochondrial transport within peripheral axons and promoting in vivo mitochondrial localization to neuromuscular junctional synapses. MiM111-treated
T105M mouse neurons exhibited accelerated primary outgrowth and greater post-axotomy regrowth, linked to enhanced mitochondrial motility. MiM111 is the first pre-clinical candidate for CMT2A.
To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we ...performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
•Loss-of-function mutations in KIF5A are a cause of amyotrophic lateral sclerosis•ALS-associated KIF5A mutations are distinct from HSP and CMT mutations in KIF5A•Identification of KIF5A highlights the role of cytoskeleton in ALS pathogenesis
Using a large-scale genome-wide association study and exome sequencing, we identified KIF5A as a novel gene associated with ALS. Our data broaden the phenotype resulting from mutations in KIF5A and highlight the importance of cytoskeletal defects in the pathogenesis of ALS.
Mitochondrial fusion is essential to mitochondrial fitness and cellular health. Neurons of patients with genetic neurodegenerative diseases often exhibit mitochondrial fragmentation, reflecting an ...imbalance in mitochondrial fusion and fission (mitochondrial dysdynamism). Charcot-Marie-Tooth (CMT) disease type 2A is the prototypical disorder of impaired mitochondrial fusion caused by mutations in the fusion protein mitofusin (MFN)2. Yet, cultured CMT2A patient fibroblast mitochondria are often reported as morphologically normal. Metabolic stress might evoke pathological mitochondrial phenotypes in cultured patient fibroblasts, providing a platform for the pre-clinical individualized evaluation of investigational therapeutics. Here, substitution of galactose for glucose in culture media was used to redirect CMT2A patient fibroblasts (MFN2 T105M, R274W, H361Y, R364W) from glycolytic metabolism to mitochondrial oxidative phosphorylation, which provoked characteristic mitochondrial fragmentation and depolarization and induced a distinct transcriptional signature. Pharmacological MFN activation of metabolically reprogrammed fibroblasts partially reversed the mitochondrial abnormalities in CMT2A and CMT1 and a subset of Parkinson's and Alzheimer's disease patients, implicating addressable mitochondrial dysdynamism in these illnesses.
Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.
To identify the genetic variants associated ...with juvenile ALS.
In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.
De novo variants present only in the index case and not in unaffected family members.
Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.
These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.
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