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Aims To investigate low molecular weight compounds produced in vitro by Lysobacter capsici AZ78 and their toxic activity against sporangia of plant pathogenic oomycetes. Methods and Results Assays carried out in vitro showed that L. capsici AZ78 drastically inhibits the growth of plant pathogenic oomycetes. Accordingly, the preventive application of culture filtrates of L. capsici AZ78 on grapevine and tomato plants reduced the infections, respectively, caused by Plasmopara (Pl.) viticola and Phytophthora infestans. The subsequent chemical analysis of the culture filtrates of L. capsici AZ78 by spectroscopic (essentially 1D and 2D 1H NMR and 13C NMR and ESI MS spectra) and optical methods led to the identification of the 2,5-diketopiperazine cyclo( l-Pro- l-Tyr) that inhibited the development of P. infestans sporangia in vitro and on tomato leaves. Furthermore, a genomic region with high sequence identity with genes coding for a hybrid polyketide synthase and nonribosomal peptide synthetase was detected in L. capsici AZ78. Conclusions Lysobacter capsici AZ78 produces cyclo( l-Pro- l-Tyr) in vitro that was effective in killing the sporangia of P. infestans and Pl. viticola in vitro. Moreover, this low molecular weight compound prevents the occurrence of late blight lesions when applied on tomato leaves. Significance and Impact of the Study The application of L. capsici AZ78 cells or its own culture filtrates effectively controls both P. infestans and Pl. viticola. Cyclo( l-Pro- l-Tyr) produced by L. capsici AZ78 is toxic against sporangia of both these oomycetes. These data enforce the potential in the use of Lysobacter members for the control of plant pathogenic oomycetes and provide the basis for the development of new low-impact fungicides based on cyclo( l-Pro- l-Tyr). [ABSTRACT FROM AUTHOR]

An abstract on the study relating to the strategy for biological control of plasmopara viticola using a combination of copper with lysobacter capsici AZ78 is presented.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading cause of cancer death worldwide. PDACs are characterized by centrosome aberrations, but whether centrosome-related genes influence patient outcomes has not been tested., Methods: Publicly available RNA-sequencing data of patients diagnosed with PDAC were interrogated with unsupervised approaches to identify centrosome protein-encoding genes with prognostic relevance. Candidate genes were validated by immunohistochemistry and multiplex immunofluorescence in a set of clinical PDAC and normal pancreatic tissues., Results: Results showed that two genes CEP250 and CEP170, involved in centrosome linker and centriolar subdistal appendages, were expressed at high levels in PDAC tissues and were correlated with prognosis of PDAC patients in independent databases. Large clustered γ-tubulin-labelled centrosomes were linked together by aberrant circular and planar-shaped CEP250 arrangements in CEP250-high expressing PDACs. Furthermore, PDACs displayed prominent centrosome separation and reduced CEP164-centrosomal labelling associated with acetylated-tubulin staining compared to normal pancreatic tissues. Interestingly, in a small validation cohort, CEP250-high expressing patients had shorter disease free- and overall-survival and almost none of those who received gemcitabine plus nab-paclitaxel first-line therapy achieved a clinical response. In contrast, weak CEP250 expression was associated with long-term survivors or responses to medical treatments., Conclusions: Alteration of the centriolar cohesion and appendages has effect on the survival of patients with PDAC., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

In recent years, research into the complex interactions and crosstalk between plants and their associated microbiota, collectively known as the plant microbiome has revealed the pivotal role of microbial communities for promoting plant growth and health. Plants have evolved intricate relationships with a diverse array of microorganisms inhabiting their roots, leaves, and other plant tissues. This microbiota mainly includes bacteria, archaea, fungi, protozoans, and viruses, forming a dynamic and interconnected network within and around the plant. Through mutualistic or cooperative interactions, these microbes contribute to various aspects of plant health and development. The direct mechanisms of the plant microbiome include the enhancement of plant growth and development through nutrient acquisition. Microbes have the ability to solubilize essential minerals, fix atmospheric nitrogen, and convert organic matter into accessible forms, thereby augmenting the nutrient pool available to the plant. Additionally, the microbiome helps plants to withstand biotic and abiotic stresses, such as pathogen attacks and adverse environmental conditions, by priming the plant's immune responses, antagonizing phytopathogens, and improving stress tolerance. Furthermore, the plant microbiome plays a vital role in phytohormone regulation, facilitating hormonal balance within the plant. This regulation influences various growth processes, including root development, flowering, and fruiting. Microbial communities can also produce secondary metabolites, which directly or indirectly promote plant growth, development, and health. Understanding the functional potential of the plant microbiome has led to innovative agricultural practices, such as microbiome-based biofertilizers and biopesticides, which harness the power of beneficial microorganisms to enhance crop yields while reducing the dependency on chemical inputs. In the present review, we discuss and highlight research gaps regarding the plant microbiome and how the plant microbiome can be used as a source of single and synthetic bioinoculants for plant growth and health., Competing Interests: Declaration of Competing Interest There is no conflict of interest for this review proposal among all authors., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction: Basic helix-loop-helix (bHLH) transcription factors are expressed in various organs and are involved in diverse developmental processes. The mouse atonal homolog 8 (Atoh8), a bHLH transcription factor, plays a crucial role in various developmental processes, especially as a regulator of neurogenesis in the retina. Besides, Atoh8 expression has been observed in the central nervous system. The function of Atoh8 during the postnatal neurogenesis is still unclear., Methods: This study focuses on elucidating the impact of Atoh8 on postnatal neurogenesis in the brain, particularly in selected regions: the subventricular zone (SVZ), rostral migratory stream (RMS), and olfactory bulb (OB), across different life stages, using male homozygous Atoh8-knockout (M6KO) mice. Our morphometric analysis is based on immunohistochemically labeled markers for neuroblasts (doublecortin) and proliferation (phospho-histone H3, PHH3) as well as pan neuronal markers., Results: In Atoh8-/- mice, alteration in the postnatal neurogenesis can be observed. Immunohistochemical analysis revealed a significant reduction in doublecortin-positive neuroblasts within the SVZ of neonatal M6KO mice compared to wild-type mice. Interestingly, no differences in cell number and distribution were observed in the subsequent migration of neuroblasts through the RMS to the OB. Proliferating PHH3-positive neuronal progenitor cells were significantly diminished in the proliferation rate in both the SVZ and RMS of neonatal and young M6KO mice. Furthermore, in the glomerular layer of the OB, significantly fewer neurons were detected in the neonatal stage., Conclusion: In conclusion, Atoh8 emerges as a positive regulator of postnatal neurogenesis in the brain. Its role encompasses the promotion of neuroblast formation, modulation of proliferation rates, differentiation, and maintenance of mature neurons. Understanding the intricacies of Atoh8 function provides valuable insights into the complex regulatory mechanisms governing neurogenesis., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

This research work focuses on evaluating the development of our three-step digitization approach, designed to transform traditional lectures into engaging digital learning experiences. Aimed at offering an easy-to-use solution for educators, this approach addresses the pressing challenges of modern educational environments by enhancing accessibility, engagement, and effectiveness of learning through digital means.Quantitative analysis demonstrated a notable increase in knowledge gain for students engaged with the digital format (t(230) = -2.795, p = 0.006) over traditional methods. Additionally, it was observed that the online setting significantly improved concentration levels (t(230) = -5.801, p < .001) and reduced distractions (t(230) = 2.848, p = 0.005). Emotional assessments, based on the Achievement Emotions Questionnaire (AEQ), indicated an elevation in enjoyment (t(230) = -4.717, p < .001) and a reduction in anxiety (t(230) = 9.446, p < .001) within the digital learning environment. A substantial preference for the digital course format was expressed by 61.0% of participants, with 71.4% acknowledging its superior efficiency compared to 14.3% for traditional lectures.Qualitative feedback underscored the digital format's flexibility, comprehensive learning experience, and immediate feedback as key benefits. Nevertheless, nuances such as a preferred understanding in face-to-face interactions and the absence of a social component in digital settings were noted.To conclude, the findings from this study illuminate the significant advantages of the three-step digitization approach in meeting contemporary educational challenges. By facilitating an enhanced knowledge acquisition and fostering a supportive emotional climate, this approach signifies a promising direction for the future of medical education and beyond, fusing the convenience of digital solutions with the depth and engagement of traditional learning methodologies., (© 2024. The Author(s).)

In vertebrates, the lateral body wall muscle formation is thought to be initiated by direct outgrowth of the dermomyotomes resulting in the elongation of the hypaxial myotomes. This contrasts with the formation of the muscles of the girdle, limbs and intrinsic tongue muscles, which originate from long-range migrating progenitors. Previous work shows that the migration of these progenitors requires CXCR4 which is specifically expressed in the migrating cells, but not in the dermomyotome. Here, we show that cells in the ventrolateral-lip (VLL) of the dermomyotome at the flank level express CXCR4 in a pattern consistent with that of Pax3 and MyoR. In ovo gain-of-function experiments using electroporation of SDF-1 constructs into the VLL resulted in increased expression of c-Met, Pax3 and MyoD. In contrast, a loss-of-function approach by implantation of CXCR4-inhibitor beads into the VLL of the flank region caused a reduction in the expression of these markers. These data show that CXCR4 is expressed in the VLL, and by experimentally manipulating the CXCR4/SDF-1 signaling, we demonstrate the importance of this axis in body wall muscle development., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In vitro culture systems that structurally model human myogenesis and promote PAX7 + myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis toward limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single-cell comparison to human fetal and adult myogenic progenitor /satellite cells reveals distinct molecular signatures for non-dividing myogenic progenitors in activated ( CD44 High / CD98 + / MYOD1 + ) and dormant ( PAX7 High / FBN1 High / SPRY1 High ) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis., Competing Interests: LM, HJ, UK, GG, MK, MS, OP, DZ, MB, DH, GM, DG, JK, MA, JS, SH, RA, HS, MV, BB, HZ No competing interests declared, JY is partially employed by Next & Bio Inc, (© 2023, Mavrommatis et al.)

Previous research work has already demonstrated that both the form of teaching as well as different teaching methods directly influence students' learning experience along with their psychobiological responses at the endocrine and autonomic level. Aiming to gain deeper insights into the constitution of the learning experience, this study examined the influence of external factors such as generally perceived life stress and self-efficacy on the immediate learning experience in different learning environments. Therefore, a randomized experimental field study was conducted in which both psychological constructs and physiological data (heart rate variability) were collected from healthy first-year medical students ( n = 101) during the COVID-19 pandemic. In an effort to determine the consistency of the effects across various teaching formats, the same content of a practical histology course was carried out in a face-to-face setting as well as in passive and active online teaching. While self-efficacy was a strong predictor for positive course perceptions in all learning conditions (Pearson's r = 0.41-0.58), generally perceived worries correlated with higher anxiety during passive online learning and face-to-face learning (Pearson's r = 0.21-0.44), a finding supported by the negative correlation between the level of perceived life demands and enjoyment during the learning unit (Pearson's r = -0.40--0.43). Here, we additionally report initial evidence pointing towards the role of reduced general life stress as a resilience factor for the expression of physiological stress parameters in an academic context (small-sized effect; Pearson's r = 0.18). The data gathered in this study illustrate the relevance of emerging emotional manifestations-either aversive; negative effect or positive; protective effect-for the immediate learning process and thus establish a connection between medical education and the importance of mental health and wellbeing-especially discussed against the background of current social and political challenges in increasingly complex societal structures.

Numerous research results have already pointed towards the negative influence of increased mental stress on educational processes and motivational criteria. It has also been shown that the global public health crisis induced by COVID-19 was related to anxiety symptoms and elevated levels of distress. To holistically elucidate the dynamics of the pandemic-related mental stress of first-year medical students, the associated parameters of three different cohorts were measured at the beginning of the pandemic-related restrictions on university life in Germany (20/21), at the peak of the COVID-19-related restrictions (21/22) and during the easing of the restrictions in the winter term 22/23. In a repeated cross-sectional study design, the constructs of worries, tension, demands and joy were collected from first-year medical students ( n = 578) using the Perceived Stress Questionnaire. The results demonstrate significantly increased values of the constructs worries ( p < 0.001), tension ( p < 0.001) and demands ( p < 0.001) at the peak of the pandemic related restrictions compared to the previous and following year as well as significantly decreasing values of general joy of life during the observed period of 3 years (all p -values < 0.001). A confirmatory factor analysis was performed to verify the questionnaire's factor structure regarding the addressed target group during the pandemic (CFI: 0.908, RMSEA: 0.071, SRMR: 0.052). These data, collected over a period of three years, provide information regarding dynamically manifesting mental stress during the COVID-19 pandemic, and refer to new areas of responsibility for the faculties to adequately counteract future crisis situations.