Search Results (9)

This article examines the representation of mental illness, emergency treatment, and recovery, in Ned Vizzini’s 2006 Young Adult novel, It’s kind of a funny story. Existing criticism has predominantly pursued what we term “diagnostic realist” approaches, which evaluate fictional representations against clinical criteria. We both affirm what this work achieves and make the case for extending it. Drawing on work on disability representation in Young Adult Literature and perspectives from Mad Studies, we propose that a social model lens, which locates mental difference within social and structural contexts rather than within individual pathology, opens out further possibilities for understanding what this and related novels do. We then demonstrate how close attention to Vizzini’s artistry—including to his use of romance conventions, figurative language, intertextuality, and first-person focalisation—reveals a text that does not simply mirror mental illness realistically, but which actively dramatises how social environments, institutional structures, and modes of creative expression shape the experience of and recovery from mental ill health. Rather than displacing diagnostic approaches, we argue that these wider critical paradigms, inclusive of the social model and attendant attention to craft, can enhance understanding of the help such novels can provide for different kinds of readers. Full article

Oudemansiella raphanipes is a prized edible mushroom renowned for its “three-high, one-low” nutritional profile (high protein, fiber, vitamins; low fat). However, the stage-specific molecular dynamics governing its development and their potential link to its superior nutrition remain unknown, hindering targeted genetic improvement. This study aimed to decipher the first comprehensive transcriptomic atlas across its five key developmental stages and to explore potential molecular signatures linked to its distinctive nutrition. We first confirmed the superior nutritional profile of O. raphanipes via comparative analysis with nine commercial mushrooms. RNA sequencing (RNA-seq) was performed on samples from five defined developmental stages (spores, mycelia, primordia, closed-cap and open-cap fruiting bodies), followed by de novo transcriptome assembly, functional annotation, and differential expression analysis. Results revealed extensive transcriptional reprogramming, with the most dramatic changes occurring at the spore-to-mycelium transition (19,827 differentially expressed genes). Stage-specific pathway enrichment highlighted regulators of germination (e.g., ribosome, transmembrane transport), primordium formation (e.g., glycerophospholipid metabolism, GTPase signaling), fruiting body development (e.g., starch/sucrose metabolism, terpenoid synthesis), and maturation (e.g., glycolysis, fatty acid biosynthesis, transcription factors MADS-box/bZIP). We identified 588 stage-exclusive genes in spores and 515 constitutively upregulated genes linked to energy metabolism and proteostasis. Crucially, integrating nutritional phenotypes with stage-resolved transcriptomics revealed that sustained transcriptional programs in mature fruiting bodies are associated with its nutritional excellence; e.g., upregulation of ribosomal/amino acid metabolic pathways aligns with high protein content, while active fatty acid degradation correlates with low fat levels. Our study provides the first multi-stage transcriptomic blueprint for O. raphanipes development, revealing stage-specific regulators and proposing molecular associations for its nutritional traits. This resource offers a foundational basis and candidate genetic targets for future breeding strategies aimed at enhancing agronomic and nutritional traits in this prized fungus. Full article

Current descriptions of the history of subtotal cholecystectomy require more details and accuracy. This study presented a narrative review of the articles on partial resections of the gallbladder published between 1898 and 2022. The Scale for the Assessment of Narrative Review Articles items guided the style and content of this paper. The systematic literature search yielded 165 publications. Of them, 27 were published between 1898 and 1984. The evolution of the partial resections of the gallbladder began in the last decade of the 19th century when Kehr and Mayo performed them. The technique of partial resection of the gallbladder leaving the hepatic wall in situ was well known in the 3rd and 4th decades of the 20th century. In 1931, Estes emphasised the term ‘partial cholecystectomy’. In 1947, Morse and Barb introduced the term ‘subtotal cholecystectomy’. Madding and Farrow popularised it in 1955–1959. Bornman and Terblanche revitalised it in 1985. This term became dominant in 2014. From a subtotal cholecystectomy technical execution perspective, it is either a single-stage (when it includes only the resectional component) or two-stage (when it also entails closure of the remnant of the gallbladder or cystic duct) operation. Recent papers on classifications of partial resections of the gallbladder indicate the extent of gallbladder resection. Subtotal cholecystectomy is an umbrella term for incomplete cholecystectomies. ‘Subtotal open-tract cholecystectomy’ and ‘subtotal closed-tract cholecystectomy’ are terms that characterise the type of completion of subtotal cholecystectomy. Full article

Ethephon (ET) is an ethylene-releasing plant growth regulator (PGR) that can delay the bloom time in Prunus, thus reducing the risk of spring frost, which is exacerbated by global climate change. However, the adoption of ET is hindered by its detrimental effects on tree health. Little knowledge is available regarding the mechanism of how ET shifts dormancy and flowering phenology in peach. This study aimed to further characterize the dormancy regulation network at the transcriptional level by profiling the gene expression of dormant peach buds from ET-treated and untreated trees using RNA-Seq data. The results revealed that ET triggered stress responses during endodormancy, delaying biological processes related to cell division and intercellular transportation, which are essential for the floral organ development. During ecodormancy, ET mainly impeded pathways related to antioxidants and cell wall formation, both of which are closely associated with dormancy release and budburst. In contrast, the expression of dormancy-associated MADS (DAM) genes remained relatively unaffected by ET, suggesting their conserved nature. The findings of this study signify the importance of floral organogenesis during dormancy and shed light on several key processes that are subject to the influence of ET, therefore opening up new avenues for the development of effective strategies to mitigate frost risks. Full article

During meiosis, homologous chromosomes must recognize, pair, and recombine with one another to ensure the formation of inter-homologue crossover events, which, together with sister chromatid cohesion, promote correct chromosome orientation on the first meiotic spindle. Crossover formation requires the assembly of axial elements, proteinaceous structures that assemble along the length of each chromosome during early meiosis, as well as checkpoint mechanisms that control meiotic progression by monitoring pairing and recombination intermediates. A conserved family of proteins defined by the presence of a HORMA (HOp1, Rev7, MAd2) domain, referred to as HORMADs, associate with axial elements to control key events of meiotic prophase. The highly conserved HORMA domain comprises a flexible safety belt sequence, enabling it to adopt at least two of the following protein conformations: one closed, where the safety belt encircles a small peptide motif present within an interacting protein, causing its topological entrapment, and the other open, where the safety belt is reorganized and no interactor is trapped. Although functional studies in multiple organisms have revealed that HORMADs are crucial regulators of meiosis, the mechanisms by which HORMADs implement key meiotic events remain poorly understood. In this review, we summarize protein complexes formed by HORMADs, discuss their roles during meiosis in different organisms, draw comparisons to better characterize non-meiotic HORMADs (MAD2 and REV7), and highlight possible areas for future research. Full article

Background: Sleep-Related Breathing Disorders are characterized by repeated episodes of complete or partial obstruction of the upper airway during sleep. Mandibular advancement devices represent a non-invasive treatment in reducing the number of respiratory events and in decreasing symptoms. The advancement extent of these devices is responsible for the mandibular roto-translation and its effects on the temporomandibular joint. Methods: This study defined a systematic method to assess the mandible roto translation that is caused by MADs according to a scan-to-CAD approach. Starting from a closed mouth position and simulating the oral appliance at different settings it was possible to define a local reference system that is useful for the evaluation of the mandibular roto-translation. This latter was then applied to evaluate the movements of the condyle and the mandibular dental arch. Results: MAD1 resulted in a reduced mouth opening and protrusion, while MAD2 enabled a higher degree of motion of the mandible useful for patients who need an important protrusion. Conclusions: The two devices present different dynamics. Results that are achievable employing this method can be directly used by practitioners in comparing MADs, as well as by researchers in evaluating MADs effects. Full article

This work focuses on the accuracy estimation of canopy height models (CHMs) derived from image matching of Pléiades stereo imagery over forested mountain areas. To determine the height above ground and hence canopy height in forest areas, we use normalised digital surface models (nDSMs), computed as the differences between external high-resolution digital terrain models (DTMs) and digital surface models (DSMs) from Pléiades image matching. With the overall goal of testing the operational feasibility of Pléiades images for forest monitoring over mountain areas, two questions guide this work whose answers can help in identifying the optimal acquisition planning to derive CHMs. Specifically, we want to assess (1) the benefit of using tri-stereo images instead of stereo pairs, and (2) the impact of different viewing angles and topography. To answer the first question, we acquired new Pléiades data over a study site in Canton Ticino (Switzerland), and we compare the accuracies of CHMs from Pléiades tri-stereo and from each stereo pair combination. We perform the investigation on different viewing angles over a study area near Ljubljana (Slovenia), where three stereo pairs were acquired at one-day offsets. We focus the analyses on open stable and on tree covered areas. To evaluate the accuracy of Pléiades CHMs, we use CHMs from aerial image matching and airborne laser scanning as reference for the Ticino and Ljubljana study areas, respectively. For the two study areas, the statistics of the nDSMs in stable areas show median values close to the expected value of zero. The smallest standard deviation based on the median of absolute differences (σ_MAD) was 0.80 m for the forward-backward image pair in Ticino and 0.29 m in Ljubljana for the stereo images with the smallest absolute across-track angle (−5.3°). The differences between the highest accuracy Pléiades CHMs and their reference CHMs show a median of 0.02 m in Ticino with a σ_MAD of 1.90 m and in Ljubljana a median of 0.32 m with a σ_MAD of 3.79 m. The discrepancies between these results are most likely attributed to differences in forest structure, particularly tree height, density, and forest gaps. Furthermore, it should be taken into account that temporal vegetational changes between the Pléiades and reference data acquisitions introduce additional, spurious CHM differences. Overall, for narrow forward–backward angle of convergence (12°) and based on the used software and workflow to generate the nDSMs from Pléiades images, the results show that the differences between tri-stereo and stereo matching are rather small in terms of accuracy and completeness of the CHM/nDSMs. Therefore, a small angle of convergence does not constitute a major limiting factor. More relevant is the impact of a large across-track angle (19°), which considerably reduces the quality of Pléiades CHMs/nDSMs. Full article

Overexpression of mitotic arrest-deficient proteins Mad1 and Mad2, two components of spindle assembly checkpoint, is a risk factor for chromosomal instability (CIN) and a trigger of many genetic disorders. Mad2 transition from inactive open (O-Mad2) to active closed (C-Mad2) conformations or Mad2 binding to specific partners (cell-division cycle protein 20 (Cdc20) or Mad1) were targets of previous pharmacogenomics studies. Here, Mad2 binding to Cdc20 and the interconversion rate from open to closed Mad2 were predicted and the molecular features with a critical contribution to these processes were determined by extending the quantitative structure-activity relationship (QSAR) method to large-size proteins such as Mad2. QSAR models were built based on available published data on 23 Mad2 mutants inducing CIN-related functional changes. The most relevant descriptors identified for predicting Mad2 native and mutants action mechanism and their involvement in genetic disorders are the steric (van der Waals area and solvent accessible area and their subdivided) and energetic van der Waals energy descriptors. The reliability of our QSAR models is indicated by significant values of statistical coefficients: Cross-validated correlation q² (0.53–0.65) and fitted correlation r² (0.82–0.90). Moreover, based on established QSAR equations, we rationally design and analyze nine de novo Mad2 mutants as possible promoters of CIN. Full article

The Mad2 protein, with two distinct conformations of open- and closed-states, is a key player in the spindle checkpoint. The closed Mad2 state is more active than the open one. We carried out conventional and targeted molecular dynamics simulations for the two stable Mad2 states and their conformational transition to address the dynamical transition mechanism from the open to the closed state. The intermediate structure in the transition process shows exposure of the β6 strand and an increase of space around the binding sites of β6 strand due to the unfolding of the β7/8 sheet and movement of the β6/4/5 sheet close to the αC helix. Therefore, Mad2 binding to the Cdc20 protein in the spindle checkpoint is made possible. The interconversion between these two states might facilitate the functional activity of the Mad2 protein. Motion correlation analysis revealed the allosteric network between the β1 strand and β7/8 sheet via communication of the β5-αC loop and the β6/4/5 sheet in this transition process. Full article