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Meiotic recombination is essential for the accurate chromosome segregation and the generation of genetic diversity through crossover and gene conversion events. Although this process has been studied extensively in a few selected model species, understanding how its properties vary across species remains limited. For instance, the ancestral ZMM pathway that generates interference-dependent crossovers has undergone multiple losses throughout evolution, suggesting variations in the regulation of crossover formation. In this context, we first characterized the meiotic recombination landscape and properties of the Kluyveromyces lactis budding yeast. We then conducted a comprehensive analysis of 29,151 recombination events (19, 212 COs and 9, 939 NCOs) spanning 577 meioses in the five budding yeast species Saccharomyces cerevisiae, Saccharomyces paradoxus, Lachancea kluyveri, Lachancea waltii and K. lactis. Eventually, we found that the Saccharomyces yeasts displayed higher recombination rates compared to the non-Saccharomyces yeasts. In addition, bona fide crossover interference and associated crossover homeostasis were detected in the Saccharomyces species only, adding L. kluyveri and K. lactis to the list of budding yeast species that lost crossover interference. Finally, recombination hotspots, although highly conserved within the Saccharomyces yeasts are not conserved beyond the Saccharomyces genus. Overall, these results highlight great variability in the recombination landscape and properties through budding yeasts evolution. Author summary: Meiotic recombination ensures proper chromosome segregation and promoting genetic diversity. Studies in Saccharomyces cerevisiae have provided mechanistic insights into the process of meiotic recombination, but the evolutionary diversity of the meiotic recombination pathway itself is not well understood. Here, we examined recombination in the non-model yeast Kluyveromyces lactis and compared it with four closely related budding yeast species—S. paradoxus, L. waltii, L. kluyveri, S. cerevisiae—to explore the evolution of the crossover pathway. We observed significant variation in recombination rates among these species alongside the loss of the crossover interference pathway. While crossover assurance is essential in S. cerevisiae and S. paradoxus, it seems defective in non-Saccharomyces yeasts, suggesting alternative mechanisms ensuring faithful meiosis. Additionally, recombination hotspots are conserved only within Saccharomyces yeasts but not beyond, highlighting considerable variability in the recombination landscape across budding yeast evolution. [ABSTRACT FROM AUTHOR]

Simple Summary: The benefit of spatially fractionated radiotherapy for brain tumors is maximized through Synchrotron Microbeam Radiation Therapy (MRT). In 2021, the clinical transfer phase of MRT began: the first brain-tumor-bearing dog patients were treated under clinical conditions in view of the forthcoming clinical transfer. As a primary endpoint, the tolerance of normal brain tissues to MRT was evaluated, while the efficacy in reducing tumor volume was considered as a secondary endpoint. We here present acute to subacute neurologic radiotolerance and tumor volume reduction after MRT for brain tumor treatment in canine patients included in our ongoing veterinary trial, proving that MRT is a safe tool for spontaneous brain tumor treatment in dogs. Synchrotron Microbeam Radiation Therapy (MRT) has repeatedly proven its superiority compared with conventional radiotherapy for glioma control in preclinical research. The clinical transfer phase of MRT has recently gained momentum; seven dogs with suspected glioma were treated under clinical conditions to determine the feasibility and safety of MRT. We administered a single fraction of 3D-conformal, image-guided MRT. Ultra-high-dose rate synchrotron X-ray microbeams (50 µm-wide, 400 µm-spaced) were delivered through five conformal irradiation ports. The PTV received ~25 Gy peak dose (within microbeams) per port, corresponding to a minimal cumulated valley dose (diffusing between microbeams) of 2.8 Gy. The dogs underwent clinical and MRI follow-up, and owner evaluations. One dog was lost to follow-up. Clinical exams of the remaining six dogs during the first 3 months did not indicate radiotoxicity induced by MRT. Quality of life improved from 7.3/10 [±0.7] to 8.9/10 [±0.3]. Tumor-induced seizure activity decreased significantly. A significant tumor volume reduction of 69% [±6%] was reached 3 months after MRT. Our study is the first neuro-oncologic veterinary trial of 3D-conformal Synchrotron MRT and reveals that MRT does not induce acute to subacute radiotoxicity in normal brain tissues. MRT improves quality of life and leads to remarkable tumor volume reduction despite low valley dose delivery. This trial is an essential step towards the forthcoming clinical application of MRT against deep-seated human brain tumors. [ABSTRACT FROM AUTHOR]

Background Etiological diagnosis is a key to therapeutic adaptation and improved prognosis, particularly for infections such as endocarditis. In blood culture–negative endocarditis (BCNE), 22% of cases remain undiagnosed despite an updated comprehensive syndromic approach. This prompted us to develop a new diagnostic approach. Methods Eleven valves from 10 BCNE patients were analyzed using a method that combines human RNA bait-depletion with phi29 DNA polymerase-based multiple displacement amplification and shotgun DNA sequencing. An additional case in which a microbe was serendipitously visualized by immunofluorescence was analyzed using the same method, but after laser capture microdissection. Results Background DNA prevented any diagnosis in cases analyzed without microdissection because the majority of sequences were contaminants. Moraxella sequences were dramatically enriched in the stained microdissected region of the additional case. A consensus genome sequence of 2.4 Mbp covering more than 94% of the Moraxella osloensis KSH reference genome was reconstructed with 234X average coverage. Several antibiotic-resistance genes were observed. Etiological diagnosis was confirmed using Western blot and specific polymerase chain reaction with sequencing on a different valve sample. Conclusions Microdissection could be a key to the metagenomic diagnosis of infectious diseases when a microbe is visualized but remains unidentified despite an updated optimal approach. Moraxella osloensis should be tested in blood culture–negative endocarditis. [ABSTRACT FROM AUTHOR]