Koç University

Intermittent hypoxia (IH), the defining physiological feature of obstructive sleep apnea, has been strongly linked to cardiovascular morbidity, yet the early myocardial effects of short-term IH remain poorly characterized. In this study, we investigated whether brief IH exposure elicits adaptive anti-apoptotic signaling or early injurious activation of intrinsic apoptotic pathways in the murine heart. Adult male C57BL/6J mice were randomized into four groups (n = 8 per group): room air for 1 day, IH for 1 day, room air for 7 days, and IH for 7 days. IH consisted of alternating 30 s cycles of normoxia (21% O₂) and hypoxia (6% O₂) for 8 h/day for either one day or seven consecutive days. Cardiac tissues from the right ventricle, left ventricle, and interventricular septum were analyzed using histological assessment, apoptotic index quantification, and Western blot analysis of intrinsic apoptotic and hypoxia-related signaling pathways. One day of IH resulted in reduced apoptotic activity and increased expression of the anti-apoptotic protein Bcl-2, consistent with an early adaptive, preconditioning-like response. In contrast, seven days of IH markedly increased apoptosis, and was associated with elevated BAX, cleaved PARP, p53, and HIF-1α expression, indicating activation of intrinsic mitochondrial apoptotic pathways. A more pronounced effect was observed in the right ventricle. Fibrotic remodeling was minimal across all groups, suggesting that apoptosis precedes structural myocardial remodeling. These findings reveal a time-dependent transition from early anti-apoptotic adaptation to intrinsic apoptotic activation during short-term IH exposure and provide insight into the early myocardial consequences of intermittent hypoxia.

The performance of ultrasound technologies, including biomedical imaging, therapeutics, and industrial inspection, is fundamentally dependent on the efficient transmission of acoustic energy between the transducer and the target medium. This is conventionally achieved through the use of acoustic couplants. Traditional gel couplants are limited by dehydration and lack of mechanical support, rendering them incompatible with evolving ultrasound interfaces. Dry and semi-dry couplants have been explored; however, their poor tunability and higher attenuation relative to water-based gels restrict their utilization. In recent years, hydrogels have emerged as a promising class of materials to address such requirements. Due to their high water content, they provide an acoustic impedance closely matching soft tissue to minimize reflection losses; furthermore, their physical and mechanical properties are highly tailorable. This review critically analyzes the evolution of couplants, focusing on advanced material design strategies of hydrogels to overcome the inherent limitations of traditional couplants and meet the emerging demands of next-generation transducers.

Abstract Once nearly eradicated from Europe, grey wolves ( Canis lupus ) have recently undergone a remarkable demographic recovery, but their long-term survival remains precarious. By analyzing 1,001 genomes, we uncover a mosaic of distinct evolutionary lineages, not a single recovering population. Northern populations exhibit Asian wolf ancestry, while southern populations preserve ancient Holocene lineages, with dog introgression varying by region. Isolated wolves from the Scandinavian, Italian, and Iberian peninsulas harbored particularly high levels of inbreeding and fixed deleterious mutations. Signatures of genome erosion were widespread across Europe, with many populations falling well short of the minimum size recommended for long-term survival. Our study reveals the complex tapestry of wolf ancestry and variation across Europe, which calls for nuanced, regional conservation plans founded in genetic monitoring.

Inherited kidney diseases represent a genetically and clinically heterogeneous group of disorders affecting both pediatric and adult populations. Advances in next-generation sequencing (NGS) have improved diagnostic precision; however, genotype-phenotype correlations and diagnostic yield vary substantially across disease entities. We retrospectively evaluated 165 patients referred for genetic testing due to suspected inherited kidney disease. Patients were classified into three clinical groups: polycystic kidney disease, Alport syndrome, and other syndromic patients with inherited kidney diseases. Genetic analysis was performed using NGS with Human Phenotype Ontology-based gene filtering and included evaluation of both single-nucleotide variants and copy number variations. Overall diagnostic yield differed markedly between groups. A molecular diagnosis was achieved in 71.4% of Alport patients, 41.0% of PKD patients, and 70.2% of patients in the Other syndromic group. In the Alport group, variants were identified exclusively in COL4A3, COL4A4, and COL4A5, with pathogenicity and gene involvement correlating with disease severity and the presence of extrarenal manifestations. The PKD group showed predominant involvement of PKD1, followed by PKHD1 and PKD2, while a substantial proportion of patients remained genetically negative, reflecting technical and biological complexity. The Other group exhibited pronounced genetic heterogeneity, with variants distributed across multiple genes involved in tubular, glomerular, metabolic, and ciliopathy-related pathways. Computational assessments demonstrated that several variants of uncertain significance (VUS) were located in functionally critical domains and were predicted to disrupt protein stability, intermolecular interactions, or conserved structural motifs, thereby supporting the biological plausibility of their potential pathogenic impact. Phenotype-driven NGS enables effective molecular diagnosis across diverse inherited kidney diseases while revealing disease-specific differences in diagnostic yield and genotype-phenotype correlations. Systematic inclusion of variants of uncertain significance and careful integration of genetic and clinical data are essential for accurate interpretation and long-term patient management. Collectively, this study enhances understanding of inherited kidney diseases and underscores the value of integrating comprehensive genomic and computational approaches into routine nephrogenetic practice.

ABSTRACT This article offers an analysis of the commemorations of the Madımak Hotel massacre in Sivas in 1993. In the first part, the article reconstructs the commemorations of the period 1994–2008. In this phase, the commemorations organised mainly by secular and left‐wing collective actors had a spatially fragmented character, dispersed between Ankara, Istanbul, and Sivas, but produced a homogeneous narrative that reclassified the event as an attack on the republic and its values by religious‐reactionary forces, effectively marginalising the Alevi references. In the central part, the article analyses the period from 2008 to today in which it is the ‘Turkish’ and European Alevi associations that have assumed the monopoly of commemorations. This part also includes an ethnography of the commemorations, based on participant observation from 2013 to 2024, which allows us to observe first of all the central role of Alevi organisations in transforming those of Sivas into the main commemorations of the massacre, marginalising those of Ankara and Istanbul. Alevi organisations then transformed the genre of commemorations, leading to their ‘Alevisation,’ firstly through the extension of the commemoration time and the inclusion of Alevi spaces. The ‘Alevisation’ includes the transformation of the narrative produced by the commemorative performance through a set of elements—banners, slogans, speeches, music—reclassifying the event as yet another massacre that affected the Alevis. Commemorations, therefore, become one of the main occasions for the Alevi movement to stage and reproduce the constituent elements of its identity, transmit them across generations, as well as give voice to the movement's claims. Subsequently the article shows how the commemorations in Sivas over time have taken on a plural and fragmented character. In particular, the transformation by the state of the Madımak Hotel into a cultural centre in 2011, contested by the Alevis, was a crucial turning point. From then on, an official commemoration was held annually at the cultural centre. This commemoration offered a narrative of the event, similar to the one incorporated into the memorial corner inside the cultural centre, which avoids reclassifying the event as a massacre, excludes Alevi references and aims to absolve the city of Sivas from the stigma of being co‐responsible for the event. However, in the final part the article suggests that this memorialisation of the massacre in Sivas urban space is the result of a process of negotiation, which does not have a fixed character but is in constant transformation.

The population of migrant, refuge, and asylum-seeking children and adolescents across the globe has increased in recent decades. These minors often undergo adverse experiences that negatively impact their mental health and psychosocial well-being (MHPWB). In light of the transient nature and multiple stressors inherent in the transit stage, this scoping review was conducted to characterize the evidence on interventions aimed at promoting the MHPWB of minors during their migration journey. Following the PRISMA-ScR guidelines, we systematically searched the MEDLINE, Embase, Global Health, APA PsycInfo, and Web of Science databases, as well as the Google Scholar search engine, for studies published between January 2010 and September 2025 that included the evaluation of some aspect of interventions aimed at promoting MHPWB in minors during transit, regardless of the language and location where the study was conducted. Systematic reviews of the literature were excluded. The data most relevant to answering the research questions were presented in tables and accompanied by a narrative synthesis. Of the 1,835 unique documents identified, 28 met the inclusion criteria. Most of the interventions had been implemented in refugee camps and were aimed at school-age children and adolescents who had been forcibly displaced, mainly from the Middle East. Most of the interventions combined different approaches, such as psychoeducation and cognitive-behavioral therapy, and had a family or group approach. All interventions reported some degree of positive change on children's MHPWB. However, few studies considered at-risk subgroups, and no interventions targeted two of the main forcibly displaced populations at the time of the study, Venezuelans and South Sudanese. Our study effectively describes existing interventions aimed at promoting MHPWB for minors in transit and their effectiveness and/or implementation process, as well as identifies gaps in the current evidence and lessons learned that can help improve future interventions.