High resolution maps of chromatin reorganization through mouse meiosis reveal novel features of the 3D meiotic structure.

When germ cells transition from the mitotic cycle into meiotic prophase I (MPI), chromosomes condense into an array of chromatin loops that are required to promote homolog pairing and genetic recombination. To identify the changes in chromosomal conformation, we isolated nuclei on a trajectory from spermatogonia to the end of MPI. At each stage along this trajectory, we built genomic interaction maps with the highest temporal and spatial resolution to date.

Detection of Mpox Virus Using Microbial Cell-Free DNA: The Potential of Pathogen-Agnostic Sequencing for Rapid Identification of Emerging Pathogens.

Background: The 2022 global outbreak of Monkeypox virus (MPXV) highlighted challenges with polymerase chain reaction detection as divergent strains emerged and atypical presentations limited the applicability of swab sampling. Recommended testing in the United States requires a swab of lesions, which arise late in infection and may be unrecognized. We present MPXV detections using plasma microbial cell-free DNA (mcfDNA) sequencing.

Cataloging Human Allelic Variation Using Long-Read Sequencing Reveals Population Specificity and Two Distinct Groupings of Related Alleles.

The PRDM9 protein determines sites of meiotic recombination in humans by directing meiotic DNA double-strand breaks to specific loci. Targeting specificity is encoded by a long array of CH zinc fingers that bind to DNA. This zinc finger array is hypervariable, and the resulting alleles each have a potentially different DNA binding preference.

Meiotic recombination mirrors patterns of germline replication in mice and humans.

Genetic recombination generates novel trait combinations, and understanding how recombination is distributed across the genome is key to modern genetics. The PRDM9 protein defines recombination hotspots; however, megabase-scale recombination patterning is independent of PRDM9. The single round of DNA replication, which precedes recombination in meiosis, may establish these patterns; therefore, we devised an approach to study meiotic replication that includes robust and sensitive mapping of replication origins.

Training-of-Trainers Neuroscience and Mental Health Teacher Education in Liberia Improves Self-Reported Support for Students.

Education programs have been central to reestablishing social norms, rebuilding public educational institutions, and addressing public attitudes toward mental illness in Liberia following a protracted civil war and the Ebola epidemic. The aim of this study was to determine if a program combining an understanding of neuroscience with mental health literacy content could increase teachers' awareness of students' mental health issues and produce changes in teacher attitudes and classroom practices. A tiered Training-of-Trainers approach was employed.

Tiered Neuroscience and Mental Health Professional Development in Liberia Improves Teacher Self-Efficacy, Self-Responsibility, and Motivation.

After acquiring knowledge of the neuroscience of learning, memory, stress and emotions, teachers incorporate more cognitive engagement and student-centered practices into their lessons. However, the role understanding neuroscience plays in teachers own affective and motivational competencies has not yet been investigated. The goal of this study was to investigate how learning neuroscience effected teachers' self-efficacy, beliefs in their ability to teach effectively, self-responsibility and other components of teacher motivation.

Rat PRDM9 shapes recombination landscapes, duration of meiosis, gametogenesis, and age of fertility.

Background: Vertebrate meiotic recombination events are concentrated in regions (hotspots) that display open chromatin marks, such as trimethylation of lysines 4 and 36 of histone 3 (H3K4me3 and H3K36me3). Mouse and human PRDM9 proteins catalyze H3K4me3 and H3K36me3 and determine hotspot positions, whereas other vertebrates lacking PRDM9 recombine in regions with chromatin already opened for another function, such as gene promoters. While these other vertebrate species lacking PRDM9 remain fertile, inactivation of the mouse Prdm9 gene, which shifts the hotspots to the functional regions (including promoters), typically causes gross fertility reduction; and the reasons for these species differences are not clear.

After the break: DSB end processing in mouse meiosis.

The exchange of genetic information between parental chromosomes in meiosis is an integral process for the creation of gametes. To generate a crossover, hundreds of DNA double-strand breaks (DSBs) are introduced in the genome of each meiotic cell by the SPO11 protein. The nucleolytic resection of DSB-adjacent DNA is a key step in meiotic DSB repair, but this process has remained understudied.

Ensuring meiotic DNA break formation in the mouse pseudoautosomal region.

Sex chromosomes in males of most eutherian mammals share only a small homologous segment, the pseudoautosomal region (PAR), in which the formation of double-strand breaks (DSBs), pairing and crossing over must occur for correct meiotic segregation. How cells ensure that recombination occurs in the PAR is unknown. Here we present a dynamic ultrastructure of the PAR and identify controlling cis- and trans-acting factors that make the PAR the hottest segment for DSB formation in the male mouse genome.

A cross-category puffing topography, mouth level exposure and consumption study among Italian users of tobacco and nicotine products.

Actual use studies play a key part in evaluating the reduced risk potential of tobacco and nicotine products. This study was undertaken to determine the puffing topography, mouth level exposure (MLE) and average daily consumption (ADC) relating to two commercially available tobacco heating products (THPs) and a prototype electronic cigarette (or e-cigarette) among Italian non-mentholated 7 mg ISO tar cigarette smokers. The study was conducted in Milan, Italy, with three groups of approximately 50 participants.

Cell-type-specific genomics reveals histone modification dynamics in mammalian meiosis.

Meiosis is the specialized cell division during which parental genomes recombine to create genotypically unique gametes. Despite its importance, mammalian meiosis cannot be studied in vitro, greatly limiting mechanistic studies. In vivo, meiocytes progress asynchronously through meiosis and therefore the study of specific stages of meiosis is a challenge.

Histone methyltransferase PRDM9 is not essential for meiosis in male mice.

A hallmark of meiosis is the rearrangement of parental alleles to ensure genetic diversity in the gametes. These chromosome rearrangements are mediated by the repair of programmed DNA double-strand breaks (DSBs) as genetic crossovers between parental homologs. In mice, humans, and many other mammals, meiotic DSBs occur primarily at hotspots, determined by sequence-specific binding of the PRDM9 protein.

Adductor canal versus femoral triangle anatomical locations for continuous catheter analgesia after total knee arthroplasty: a multicentre randomised controlled study.

Background: Adductor canal (AC) catheters are being used to provide continuous postoperative analgesia after total knee arthroplasty (TKA) surgery. There are anatomical arguments that most AC catheters are being inserted into the femoral triangle (FT) compartment of the thigh rather than the AC compartment. The clinical relevance of this is unknown with respect to motor weakness, quality of analgesia, and opioid consumption.

REC114 Partner ANKRD31 Controls Number, Timing, and Location of Meiotic DNA Breaks.

Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here, we unveil mouse ANKRD31 as a lynchpin governing multiple aspects of DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to the pseudoautosomal regions (PARs) of sex chromosomes.

Extensive sex differences at the initiation of genetic recombination.

Meiotic recombination differs between males and females; however, when and how these differences are established is unknown. Here we identify extensive sex differences at the initiation of recombination by mapping hotspots of meiotic DNA double-strand breaks in male and female mice. Contrary to past findings in humans, few hotspots are used uniquely in either sex.

Interrogating the Functions of PRDM9 Domains in Meiosis.

Homologous recombination is required for proper segregation of homologous chromosomes during meiosis. It occurs predominantly at recombination hotspots that are defined by the DNA binding specificity of the PRDM9 protein. PRDM9 contains three conserved domains typically involved in regulation of transcription; yet, the role of PRDM9 in gene expression control is not clear.

Analysis of Meiotic Double-Strand Break Initiation in Mammals.

The repair of programmed DNA double-strand breaks (DSBs) physically tethers homologous chromosomes in meiosis to allow for accurate segregation through meiotic cell divisions. This process, known as recombination, also results in the exchange of alleles between parental chromosomes and contributes to genetic diversity. In mammals, meiotic DSBs occur predominantly in a small fraction of the genome, at sites known as hotspots.

Erratum: The evolutionary turnover of recombination hot spots contributes to speciation in mice.

Due to a technical error in processing the figures in the above-mentioned article, Figures 3, A and B; 4B; 5B; and 6, A and C contained errors or missing elements. The errors have been corrected in both the PDF and full-text HTML files online.

Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice.

The DNA-binding protein PRDM9 directs positioning of the double-strand breaks (DSBs) that initiate meiotic recombination in mice and humans. Prdm9 is the only mammalian speciation gene yet identified and is responsible for sterility phenotypes in male hybrids of certain mouse subspecies. To investigate PRDM9 binding and its role in fertility and meiotic recombination, we humanized the DNA-binding domain of PRDM9 in C57BL/6 mice.

The evolutionary turnover of recombination hot spots contributes to speciation in mice.

Meiotic recombination is required for the segregation of homologous chromosomes and is essential for fertility. In most mammals, the DNA double-strand breaks (DSBs) that initiate meiotic recombination are directed to a subset of genomic loci (hot spots) by sequence-specific binding of the PRDM9 protein. Rapid evolution of the DNA-binding specificity of PRDM9 and gradual erosion of PRDM9-binding sites by gene conversion will alter the recombination landscape over time.

DNA recombination. Recombination initiation maps of individual human genomes.

DNA double-strand breaks (DSBs) are introduced in meiosis to initiate recombination and generate crossovers, the reciprocal exchanges of genetic material between parental chromosomes. Here, we present high-resolution maps of meiotic DSBs in individual human genomes. Comparing DSB maps between individuals shows that along with DNA binding by PRDM9, additional factors may dictate the efficiency of DSB formation.

A population-based study of the association between bullous pemphigoid and neurologic disorders.

Background: Bullous pemphigoid (BP) has been associated with neurologic disorders.

Objective: We sought to analyze the association between BP and neurologic disorders.

Methods: We retrospectively identified residents of Olmsted County, Minnesota, with a first lifetime diagnosis of BP between January 1, 1960, and December 31, 2009.

Incidence of bullous pemphigoid and mortality of patients with bullous pemphigoid in Olmsted County, Minnesota, 1960 through 2009.

Background: Bullous pemphigoid (BP) is an autoimmune blistering disease that is associated with increased mortality.

Objective: We sought to determine the incidence and mortality of patients with BP.

Methods: A total of 87 residents of Olmsted County, Minnesota, were identified who had their first lifetime diagnosis of BP from January 1960 through December 2009.

The application of virtual microscopy in a dermatopathology educational setting: assessment of attitudes among dermatopathologists.

Objectives: Whole-slide imaging with virtual microscopy is increasingly used as a tool in resident education and training, board certification and maintenance of certification examinations, and diagnostic evaluation. The objective of this study was to determine attitudes toward virtual microscopy compared with traditional glass slide microscopy during a continuing medical education dermatopathology workshop.

Methods: Twenty-three board-certified, practicing or retired dermatopathologists were given 26 "advanced" cases to review using both virtual microscopy and traditional glass slides.