A meiotic driver hijacks an epigenetic reader to disrupt mitosis in noncarrier offspring.

Killer meiotic drivers (KMDs) are selfish genetic elements that distort Mendelian inheritance by selectively killing meiotic products lacking the KMD element, thereby promoting their own propagation. Although KMDs have been found in diverse eukaryotes, only a limited number of them have been characterized at the molecular level, and their killing mechanisms remain largely unknown. In this study, we identify that a gene previously deemed essential for cell survival in the fission yeast Schizosaccharomyces pombe is a single-gene KMD. This gene, tdk1, kills nearly all tdk1Δ progeny in a tdk1+ × tdk1Δ cross. By analyzing polymorphisms of tdk1 among natural strains, we identify a resistant haplotype, HT3. This haplotype lacks killing ability yet confers resistance to killing by the wild-type tdk1. Proximity labeling experiments reveal an interaction between Tdk1, the protein product of tdk1, and the epigenetic reader Bdf1. Interestingly, the nonkilling Tdk1-HT3 variant does not interact with Bdf1. Cryoelectron microscopy further elucidated the binding interface between Tdk1 and Bdf1, pinpointing mutations within Tdk1-HT3 that disrupt this interface. During sexual reproduction, Tdk1 forms stable Bdf1-binding nuclear foci in all spores after meiosis. These foci persist in germinated tdk1Δ progeny and impede chromosome segregation during mitosis by generating aberrant chromosomal adhesions. This study identifies a KMD that masquerades as an essential gene and reveals the molecular mechanism by which this KMD hijacks cellular machinery to execute killing. Additionally, we unveil that losing the hijacking ability is an evolutionary path for this single-gene KMD to evolve into a nonkilling resistant haplotype.

Neonatal respiratory distress syndrome and underlying mechanisms in cloned cattle.

Neonatal respiratory distress is a major mortality factor in cloned animals, but the pathogenesis of this disease is rarely investigated. In this study, four neonatal cloned cattle, born after full-term gestation, exhibited symptoms of neonatal respiratory distress syndrome (NRDS), which included symptoms of hyaline membrane disease as well as disordered surfactant homeostasis in their collapsed lungs. No differences in DNA methylation or histone modifications correlated with the suppressed SPB and SPC transcription observed in the cloned cattle group (p > 0.05), whereas TTF-1 occupancy at SPB and SPC promoter regions in cloned cattle was significantly reduced to 24% and 20% that of normal lungs, respectively (SPB, p < 0.05; SPC, p < 0.01). Decreased TTF1 expression, dysregulation of SPB and SPC transcription by TTF-1, and disordered proteolytic processing of Surfactant protein B precursor together potentially contribute to the disruption of surfactant homeostasis and NRDS in bovine clones. Elucidation of the associated mechanisms should facilitate the development of novel preventive or therapeutic strategies to reduce the mortality rate of cloned animals and to improve the efficiency of SCNT technology.

Transcriptomic profiling reveals disordered regulation of surfactant homeostasis in neonatal cloned bovines with collapsed lungs and respiratory distress.

Respiratory distress is a major cause of mortality in cloned neonatal animals, but its pathogenesis remains poorly understood. Here, we used necropsy and histology procedures to evaluate the lungs of cloned neonatal bovines dying of respiratory distress, finding incomplete lung dilation, alveolar collapse, and thickened alveolar walls. Comparison of the transcriptomes between collapsed lungs of cloned bovines and their normal counterparts revealed 1373 differentially expressed genes in collapsed lungs (p < 0.05, fold change >1.5 or <1.5-1 ), many of which were associated with surfactant biosynthesis, secretion, transport, recycling, and degradation. ERK/MAPK and Notch signaling pathways were among the canonical pathways relevant to surfactant homeostasis. Expression of the genes encoding Surfactant protein B (SPB) and Surfactant protein C (SPC)-which control surfactant lipid packing, spreading, and stability-were significantly lower in collapsed lungs of cloned neonates at the transcript (p < 0.01) and protein levels (p < 0.05) relative to that in normal lungs. Thus, our results provide an initial view into the changes in gene expression in cloned newborns with lung collapse and respiratory distress, and present a valuable resource for developing novel preventive or therapeutic strategies to reduce the mortality rate of cloned animals and to improve the efficiency of somatic cell nuclear transfer technology.

Long-Term Clinical and Imaging Results of Oblique Lateral Interbody Fusion for Degenerative Lumbar Spondylolisthesis: A Systematic Review and Meta-Analysis.

The efficacies and safety of oblique lateral interbody fusion (OLIF) for degenerative lumbar spondylolisthesis (DLS) remains controversial, and long-term clinical efficacies in particular need to be explored. This study is designed accordingly, therefore, we searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, ProQuest, OVID, and SinoMed for literature, regardless of publication date or language. Taking 12 months after operation as the shortest limit, the outcome measures were extracted, including visual analog scale (VAS), Oswetry dysfunction index (ODI), Japanese Orthopaedic Association (JOA) score, intervertebral disk height (IDH), foraminal height (FH), lumbar lordosis (LL), segment lordosis (SL), slip ratio, and incidence of surgical complications. Meta-analysis was performed by RevMan 5.4 and Stata 16.0, and results were expressed with MD and 95% CI, and two-sided p-values with p < 0.05 being statistically significant. In total, 17 clinical studies (n = 689 patients) were screened, with an average patient age of 63.4 years. Our study revealed that VAS decreased by 4.55 (low back pain) and 5.46 (leg pain) points, respectively. And ODI score decreased by an average of 33.82% while JOA score increased by an average of 11.56 points. In terms of imaging indicators, mean IDH and FH increased by 4.18 and 4.91 mm, mean LL and SL improved by 9.22° and 2.46°, respectively. Besides, mean slip ratio decreased by 10.45%. The incidence of complications was statistically analyzed in 18 studies, with a rate of 4%-54% and an overall incidence of 19%. To sum up, our study was the first to focus on the long-term efficacies of OLIF treatment for DLS, and to provide further clinical evidence. However, long-term follow-up multicenter randomized controlled trials are still needed for further evaluation.

A holistic approach to campus well-being: Steps to Leaps at Purdue University.

In response to the increasing demand of mental health solutions, Purdue University launched the Steps to Leaps initiative in 2019 to promote student well-being. It provided the tools and resources to build students' resilience skills and establish lifelong habits to help them realize their personal definitions of success. Working collaboratively with students, faculty, and front- line staff, the initiative identified five pillars, to address these concerns: well-being, leadership/professional development, impact, networks and grit. This article briefly outlined the program implementation and provides relevant theoretical frameworks in a case study format. It then summarized twelve key lessons learned from the two years of practice and concluded with a community perspective.