Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar Depression

BackgroundMood disorders associate with peripheral markers of low-grade inflammation, among which circulating levels of interleukin-1β (IL-1β) consistently predict diagnosis and poor outcomes. Antidepressant chronotherapeutics (total sleep deprivation and light therapy, TSD+LT) prompts response in drug-resistant bipolar depression, but its effect on peripheral inflammation were never assessed. Here we explored the effects of TSD+LT on IL-1β signaling.MethodsWe studied the ratio between IL-1β and its receptor antagonist (IL-1β:IL1ra) in 33 healthy participants, and in 26 inpatients with a major depressive episode in course of Bipolar Disorder, before and after treatment with three cycles of repeated TSD+LT, interspersed with sleep recovery nights, administered during 1 week. Treatment effects of mood and on IL-1β:IL1ra were analyzed in the context of the Generalized Linear Model (GLM).ResultsAt baseline, patients had higher IL-1β, IL1ra, and IL-1β:IL1ra than controls. Treatment significantly decreased IL-1β:IL1ra, by decreasing IL-1β and increasing IL1ra, the effect being proportional to baseline levels and normalizing values. Patients with higher baseline levels showed the highest decrease in IL-1β:IL-1ra, which associated with the immediate antidepressant response at the first cycle; while patients with lower baseline values showed negligible changes in the IL-1β:IL-1ra, unrelated to treatment response.ConclusionWe observed a parallel change of inflammatory biomarkers and severity of depression after chronotherapeutics, suggesting that a reduction in inflammation associated with depression could contribute to the mechanism of action of TSD+LT, and warranting interest for controlled studies addressing the role of inflammation in the recovery from bipolar depression.

Clonal evolution in serially passaged Cryptococcus neoformans x deneoformans hybrids reveals a heterogenous landscape of genomic change

Cryptococcus neoformans x deneoformans hybrids (also known as serotype AD hybrids) are basidiomycete yeasts that are common in a clinical setting. Like many hybrids, the AD hybrids are largely locked at the F1 stage and are mostly unable to undergo normal meiotic reproduction. However, these F1 hybrids, which display a high (∼10%) sequence divergence are known to genetically diversify through mitotic recombination and aneuploidy, and this diversification may be adaptive. In this study, we evolved a single AD hybrid genotype in six diverse environments by serial passaging and then used genome resequencing of evolved clones to determine evolutionary mechanisms of adaptation. The evolved clones generally increased fitness after passaging, accompanied by an average of 3.3 point mutations, 2.9 loss of heterozygosity (LOH) events, and 0.7 trisomic chromosomes per clone. LOH occurred through nondisjunction of chromosomes, crossing over consistent with break-induced replication, and gene conversion, in that order of prevalence. The breakpoints of these recombination events were significantly associated with regions of the genome with lower sequence divergence between the parents and clustered in subtelomeric regions, notably in regions that had undergone introgression between the two parental species. Parallel evolution was observed, particularly through repeated homozygosity via nondisjunction, yet there was little evidence of environment-specific parallel change for either LOH, aneuploidy, or mutations. These data show that AD hybrids have both a remarkable genomic plasticity and yet are challenged in the ability to recombine through sequence divergence and chromosomal rearrangements, a scenario likely limiting the precision of adaptive evolution to novel environments.

An Overview of the Geomorphological Characteristics of the Pergamon Micro-Region (Bakırçay and Madra River Catchments, Aegean Region, West Turkey)

Current landforms are the basis for understanding past geomorphodynamics and human activities. Based on multiple materials and methods, including geomorphometric analyses of a digital elevation model and visual interpretations of satellite images, different landscape units of the Bakırçay and Madra River catchments in the environs of ancient Pergamon are described. The area was mainly shaped by tectonics that formed a horst-and-graben structure; small Miocene horsts and NE-trending subgrabens in the Kozak and Yunt Dağı Mountains were separated by the NEE-trending Plio-Pleistocene Bergama Graben. The asymmetry in relief, drainage network, and sediment accumulation between the Kozak Mountains to the north and the Yunt Dağı Mountains to the south of the lower Bakırçay plain characterize the Pergamon Micro-Region. The regional relief characteristics, with wide flat basin and plateau areas, are suitable for agriculture. Complemented by its richness in natural resources, the Pergamon Micro-Region became a preferred settlement area, with evidence of human impact since the Hellenistic–Roman period at the latest. As a consequence of settlement activities, several landscape engineering measures were implemented simultaneously with a parallel change in morphodynamics.

Topographic Quadrant Analysis of Peripapillary Superficial Microvasculature in Optic Disc Drusen

Background: Limited information is known about the topographic effect of optic disc drusen (ODD) on peripapillary retinal nerve fibers and microvasculature.Objective: This study aims to understand the structural and functional impact of ODD in different quadrants of the optic disc.Methods: We performed a retrospective case-control study of 22 ODD patients (34 eyes) and 26 controls (33 eyes) to compare optical coherence tomography (OCT) retinal nerve fiber layer (RNFL), OCT angiography (OCTA), and corresponding static perimetry mean deviation (MD) calculated using the modified Garway-Heath map in different quadrants of the optic disc. OCTA was analyzed using custom MATLAB script to measure six parameters in a peripapillary annulus with large vessel removal: vessel area density (VAD), vessel skeleton density (VSD), vessel perimeter index (VPI), vessel complexity index (VCI), flux, and vessel diameter index (VDI).Results: Quadrant analysis revealed that OCTA VAD and VCI were significantly decreased in superior, nasal, and inferior but not temporal quadrant. RNFL, VSD, and VPI were significantly impacted only in the superior and nasal quadrants. Corresponding visual field MDs in all ODD eyes were not different in the four quadrants, although eyes with MD equal or worse than −5 dB (32%) had worst visual field corresponding to the superior quadrant of the optic disc (inferior arcuate visual field). Structure-structure comparison of OCT and OCTA showed high correlation of RNFL with multiple OCTA measurements in the superior, nasal, and inferior quadrants but not temporal quadrant. Structure-function analysis revealed significant correlation of VAD and VCI and visual field MD in every quadrant, but RNFL was only significantly correlated in the superior and inferior quadrants.Conclusions: Peripapillary VAD and VCI are decreased in more quadrants than RNFL, supporting the clinical utility of performing OCTA in addition to OCT. Consistent with the most common locations of ODD, five OCT/OCTA measurements (VAD, VCI, RNFL, VSD, VPI) are decreased in the superior and nasal quadrants. OCT/OCTA measurements were significantly impacted in contrast to the relatively mild effect on corresponding visual field MD, consistent with the idea that a decrease in objective structural and vascular measurements occurs without parallel change in subjective visual function in ODD.

Clonal evolution in serially passaged Cryptococcus neoformans x deneoformans hybrids reveals a heterogenous landscape of mitotic recombination

Cryptococcus neoformans x deneoformans hybrids (also known as serotype AD hybrids) are basidiomycete yeasts that are common in a clinical setting. Like many hybrids, the AD hybrids are largely locked at the F1 stage and are mostly unable to undergo normal meiotic reproduction. However, these F1 hybrids, which display a high (∼10%) sequence divergence are known to genetically diversify through mitotic recombination and aneuploidy, and this diversification may be adaptive. In this study, we evolved a single AD hybrid genotype to six diverse environments by serial passaging and then used genome resequencing of evolved clones to determine evolutionary mechanisms of adaptation. The evolved clones generally increased fitness after passaging, accompanied by an average of 3.3 point mutations and 2.9 loss of heterozygosity (LOH) events per clone. LOH occurred through nondisjunction of chromosomes, crossing over consistent with break-induced replication, and gene conversion, in that order of prevalence. The breakpoints of these recombination events were significantly associated with regions of the genome with lower sequence divergence between the parents and clustered in subtelomeric regions, notably in regions that had undergone introgression between the two parental species. Parallel evolution was observed, particularly through repeated homozygosity via nondisjunction, yet there was little evidence of environment-specific parallel change for either LOH, aneuploidy, or mutations. These data show that AD hybrids have both a remarkable genomic plasticity and yet are challenged in the ability to recombine through sequence divergence and chromosomal rearrangements, a scenario likely limiting the precision of adaptive evolution to novel environments.

Digitális pedagógiai tapasztalatok tanítóként: lehetőségek a karanténpedgógiában

Az elmúlt évtizedben már számos kutatás bizonyította, hogy a pedagógusok megváltozott feladatai és szerepei, a módszertani kultúra és a komplex szemlélet a digitális kompetencia fejlesztésével párhuzamosan megjelenik (Fehér, 1999; Kirschner-Woperies, 2003; Law, Chow és Yuen, 2005). A tanítási-tanulási folyamat résztvevőiként a pedagógusok is részesei a rendkívüli iramban változó lehetőségeknek, melyek az iskola különböző „valós és virtuális” terein egyre inkább biztosítottá válnak (UNESCO, 2011). 2020 márciusában 6 a koronavírus-járvány miatt bevezetett digitális munkarend által – korábban még nem tapasztalt módon – aktuálissá vált mindaz, amit a „távoktatás”, „digitális oktatás”, „otthontanulás” és szinonimáik képviseltek. A pedagógusok, diákok és szülők egyik napról a másikra kerültek át az osztálytermi környezetből a digitális platformok világába, megváltoztatva szerepeiket, feladataikat és kompetenciahatáraikat. Felmérésünk azzal a céllal készült, hogy feltárja a tanítók hogyan igyekeztek megtalálni a tantárgyi specialitásnak, informatikai tudásuknak, rendelkezésre álló eszközeiknek, a diákoknak és a szülőknek leginkább adekvát megoldásokat. Kutatásunkban kvantitatív módszert alkalmazva, online kérdőíves vizsgálattal mértük fel az 1-6. osztályban tanító pedagógusok véleményét és gyakorlatát a digitális munkarendben történő oktatással kapcsolatban (N=71). Előadásunk a tanítók által alkalmazott karanténpedagógiára vonatkozó öszszefüggésekre világít rá a következő aspektusokból: eszközök, internet a távoktatásban, a pedagógusok digitális kompetenciája, a tananyagok küldésének felülete, kapcsolattartás a tanulókkal és szülőkkel. Fókuszba kerültek az alkalmazott digitális platformok és eszközök, azzal a céllal, hogy feltárjuk az elmúlt időszakban aktuális alsó tagozatos oktatás és nevelés főbb aspektusait. A digitális munkarend, valamint az online eszközök kiválasztásának és kipróbálásának tanítói tapasztalatait is vizsgáltuk az önértékelésen alapuló tanítói digitális kompetenciák feltárása mellett. A kapott leíró statisztikai elemzések megerősítik, hogy a digitális munkarenddel kialakuló távolléti oktatási struktúra rendszerezettségében, illetve következetes használatában plasztikus eltérések jelentkeztek. Példaként említhető a kapcsolattartási mintázatok egyenetlensége és a formális (Kréta)/informális kapcsolattartási struktúra (Messenger/Facebook csoport) használatának eltérő megoszlása. Konkrét számadatokkal mérve a szülőkkel való kapcsolattartásban kiemelkedett az egyéb lehetőségek mellett a Facebook csoport (59%), és a Messenger (53%) használata a formális platformként említett Krétával (22%) szemben. Összefoglalva, az eredmények hozzájárulhatnak az általános iskolákban működő online oktatás gyakorlatának megismeréséhez, a pedagógiai praxis lehetőségeinek bővítéséhez, ugyanakkor megerősítjük Lévai (2016) felvetését is, miszerint a pedagógusok felelőssége számottevő és árulkodó abból a szempontból is, hogy mit mutatnak róluk digitális lábnyomaik, illetve az online elérhető felületek. ---- Lower-primary-school teachers’ digital educational experience: possibilities in lockdown induced pedagogy ----- The past couple decades have seen a parallel change in teachers’ tasks and roles, methodologies, educational approaches and the development of their digital competences (Fehér, 2009; KirschnerWoperies, 2003; Law, Chow and Yuen, 2005). Also teachers as participants of the teaching-learning process experience the rapid evolution of the possibilities in the real-life and virtual platforms of school (UNESCO, 2011). In March, 2020 unprecedentedly digital education was launched due to the coronavirus pandemic and “distance education”, “digital education”, “home schooling” (at present regarded as synonyms) had become reality. All at once, teachers, students and parents were transmitted from real-life classrooms into the world of virtual platforms, which modified their roles, tasks and competence boundaries. Our survey was conducted to explore how lower-primary-school teachers experimented to find the most adequate solutions related to the issues of their teaching areas and digital knowledge. Also, we aimed to detect the most characteristic challenges that the respondent teachers had to face during the lockdown period online education processes. Our quantitative research was conducted to collect data via an online questionnaire to elicit beliefs and practices of lower-primary-school teachers of 1-6-forms regarding their work during lockdown digital education (N=71). The main focus of our research was the interrelationships of lockdown induced pedagogy from the following aspects: tools in digital education, teachers’ digital competence (based on self-assessment), the platforms of sharing teaching contents and of contacting students and parents. The focal points of our study were the applied digital platforms and tools and to gain insights into the teachers’ digital competences based on their self-evaluation. We also explored the respondent teachers’ choices and experience regarding the online tools of digital education. The results of descriptive statistics showed that there were differences in the structure and consistent use of digital education during the lockdown. As an example, the distribution of the formal Kréta platform and other informal ones (Messenger/Facebook group) is uneven in terms of contact between teachers and parents. Also, the Facebook group (59%) and Messenger (53%) platforms outnumber the use of Kréta (22%) during teacher-parent communication. In sum, our results can contribute to a better understanding of the practice of online education at primary-schools, and also to the extension of the teaching repertoire in 1-6 forms. These findings are also compatible with Lévai’s (2016) results, that is teachers’ digital footsteps and the online platforms that they use can reveal a lot about them, which is a great professional responsibility.

Managing a Curriculum Innovation Process

Curriculum reform is a long-term project that needs to be managed through detailed strategy. To create this strategy, the management team has to analyse the current situation by doing a thorough environmental scan and by identifying the gap between the current state and the desired program. To be implemented, the vision of the new program needs to rely on the generation of several potential avenues to come up with optimal solutions, likely involving some form of innovation. Indeed, to come up with the most promising ideas, there needs to be an environment conducive to reflection and experimentation. Throughout the phases of analysis, decision making and implementation, specific activities need to be organised to engage college members. Furthermore, such a profoundly impacting project needs to include a parallel change management strategy to account for expected human resistance, both individual and collective (internal culture). This article proposes a method and several concrete actions to help leaders and managers support the development and implementation of a new and innovative curriculum to promote and support advancement of local professional practice.

Values, environmental vulnerabilities, and implications on adaptation: Evidence from an indigenous Raika community in Rajasthan, India

Global environmental change has exacerbated the vulnerabilities of pastoral communities in India, who have already been sidelined in the current development and modernization discourse. The Raikas are one of the largest groups of indigenous nomadic pastoralists residing in the semi-arid regions of Northwest India. They are facing the brunt of shrinking grazing areas, social marginalization, and economic pressures. The past two decades have witnessed additional challenges, such as water scarcity and rainfall variability, which have pushed them beyond their adaptive threshold. These churnings have led to a radical shift in their values and climate adaptation strategies. However, the role and importance of social values in shaping their response to environmental change are not well understood. This study conducted life history interviews and focus group discussions with community members to examine social values and their linkages with climate adaptation decision-making in Raikas. The findings demonstrate that the community’s livelihood, health, and social cohesion are severely affected by environmental change, entwined with social, economic, and political stressors. There is a parallel change taking place in their social values. Their values related to esteem, self-actualization, safety, and belongingness have witnessed shifts, leading them away from pastoralism. This has ramifications on their adaptation decision-making. Their time-tested and preferred choice of adaptation in the face of drought and water scarcity – seasonal livestock migration – is no longer desirable. New adaptation options, such as urban migration, have emerged, while traditional measures have declined in popularity. There is an urgent need to understand and engage with a broader set of methodologies and literature to facilitate the integration of social values in vulnerability and adaptation assessments. The inclusion of social values presents an opportunity to understand the subjective limits of adaptation better as well as to expand adaptation pathways.