FIGL1 attenuates meiotic interhomolog repair and is counteracted by the RAD51 paralog XRCC2 and the chromosome axis protein ASY1 during meiosis.

Two recombinases, RAD51 and DMC1, catalyze meiotic break repair to ensure crossovers (COs) between homologous chromosomes (interhomolog) rather than between sisters (intersister). FIDGETIN-LIKE-1 (FIGL1) downregulates both recombinases. However, the understanding of how FIGL1 functions in meiotic repair remains limited.

Interference length reveals regularity of crossover placement across species.

Crossover interference is a phenomenon that affects the number and positioning of crossovers in meiosis and thus affects genetic diversity and chromosome segregation. Yet, the underlying mechanism is not fully understood, partly because quantification is difficult. To overcome this challenge, we introduce the interference length L that quantifies changes in crossover patterning due to interference.

FIGNL1-FIRRM is essential for meiotic recombination and prevents DNA damage-independent RAD51 and DMC1 loading.

During meiosis, nucleoprotein filaments of the strand exchange proteins RAD51 and DMC1 are crucial for repairing SPO11-generated DNA double-strand breaks (DSBs) by homologous recombination (HR). A balanced activity of positive and negative RAD51/DMC1 regulators ensures proper recombination. Fidgetin-like 1 (FIGNL1) was previously shown to negatively regulate RAD51 in human cells.

A fully sequenced collection of homozygous EMS mutants for forward and reverse genetic screens in Arabidopsis thaliana.

Genetic screens are powerful tools for biological research and are one of the reasons for the success of the thale cress Arabidopsis thaliana as a research model. Here, we describe the whole-genome sequencing of 871 Arabidopsis lines from the Homozygous EMS Mutant (HEM) collection as a novel resource for forward and reverse genetics. With an average 576 high-confidence mutations per HEM line, over three independent mutations altering protein sequences are found on average per gene in the collection.

Enhanced recombination empowers the detection and mapping of Quantitative Trait Loci.

Modern plant breeding, such as genomic selection and gene editing, is based on the knowledge of the genetic architecture of desired traits. Quantitative trait loci (QTL) analysis, which combines high throughput phenotyping and genotyping of segregating populations, is a powerful tool to identify these genetic determinants and to decipher the underlying mechanisms. However, meiotic recombination, which shuffles genetic information between generations, is limited: Typically only one to two exchange points, called crossovers, occur between a pair of homologous chromosomes.

Harnessing clonal gametes in hybrid crops to engineer polyploid genomes.

Heterosis boosts crop yield; however, harnessing additional progressive heterosis in polyploids is challenging for breeders. We bioengineered a 'mitosis instead of meiosis' (MiMe) system that generates unreduced, clonal gametes in three hybrid tomato genotypes and used it to establish polyploid genome design. Through the hybridization of MiMe hybrids, we generated '4-haplotype' plants that encompassed the complete genetics of their four inbred grandparents, providing a blueprint for exploiting polyploidy in crops.

Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase III randomized trial.

Background & Aims: Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24.

Factors Associated With Isolated Fallopian Tube Torsion in Pediatric Patients.

Background: Isolated fallopian tube torsion (IFTT) is a rare form of adnexal torsion that is more difficult to diagnose, which may lead to delays in treatment. Our objectives were to identify clinical and radiologic factors associated with surgically-confirmed IFTT and compare them with those of patients without torsion and with adnexal torsion (AT) in a large pediatric population.

Methods: We conducted a retrospective chart review of all patients who underwent surgery for suspected adnexal torsion from 2016 to 2019.

Hsp90 inhibition leads to an increase in surface expression of multiple immunological receptors in cancer cells.

Heat shock protein 90 (Hsp90) is a molecular chaperone important for maintaining protein homeostasis (proteostasis) in the cell. Hsp90 inhibitors are being explored as cancer therapeutics because of their ability to disrupt proteostasis. Inhibiting Hsp90 increases surface density of the immunological receptor Major Histocompatibility Complex 1 (MHC1).

A pan-genome of 69 Arabidopsis thaliana accessions reveals a conserved genome structure throughout the global species range.

Although originally primarily a system for functional biology, Arabidopsis thaliana has, owing to its broad geographical distribution and adaptation to diverse environments, developed into a powerful model in population genomics. Here we present chromosome-level genome assemblies of 69 accessions from a global species range. We found that genomic colinearity is very conserved, even among geographically and genetically distant accessions.

Meiosis: The silk moth and the elephant.

In most eukaryotes, balanced chromosome segregation at meiosis requires crossovers, but female Bombyx mori lack these structures. Instead, the synaptonemal complex is repurposed to compensate for this absence of crossovers, a remarkable example of exaptation.

Amenorrhea in adolescents using the etonogestrel contraceptive implant.

Objective: Clinical factors related to development of amenorrhea in adolescents with the etonogestrel contraceptive implant are not well-understood. The purpose of this study is to describe what baseline clinical characteristics are associated with amenorrhea in adolescents with a contraceptive implant 12 months after placement.

Study Design: This retrospective cohort study included 252 post-menarchal individuals aged 12-22 years with a contraceptive implant placed between 2016-2020.

Control of meiotic crossover interference by a proteolytic chaperone network.

Meiosis is a specialized eukaryotic division that produces genetically diverse gametes for sexual reproduction. During meiosis, homologous chromosomes pair and undergo reciprocal exchanges, called crossovers, which recombine genetic variation. Meiotic crossovers are stringently controlled with at least one obligate exchange forming per chromosome pair, while closely spaced crossovers are inhibited by interference.

Structural variation and DNA methylation shape the centromere-proximal meiotic crossover landscape in Arabidopsis.

Background: Centromeres load kinetochore complexes onto chromosomes, which mediate spindle attachment and allow segregation during cell division. Although centromeres perform a conserved cellular function, their underlying DNA sequences are highly divergent within and between species. Despite variability in DNA sequence, centromeres are also universally suppressed for meiotic crossover recombination, across eukaryotes.

SCEP1 and SCEP2 are two new components of the synaptonemal complex central element.

The synaptonemal complex (SC) is a proteinaceous structure that forms between homologous chromosomes during meiosis prophase. The SC is widely conserved across species, but its structure and roles during meiotic recombination are still debated. While the SC central region is made up of transverse filaments and central element proteins in mammals and fungi, few central element proteins have been identified in other species.

Efficacy and Safety of Sofosbuvir/Velpatasvir Plus Ribavirin in Patients with Hepatitis C Virus-Related Decompensated Cirrhosis.

A fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) plus weight-based ribavirin (RBV) for 12 weeks is recommended for the treatment of patients with hepatitis C virus (HCV)-associated decompensated cirrhosis. However, large global studies, while confirming the effectiveness of SOF/VEL in a broad range of patients, often exclude these patients. This Phase 2, single-arm, open-label study in adult patients with HCV-associated decompensated cirrhosis in France and the USA aimed to provide further data on the safety and efficacy of SOF/VEL plus RBV for 12 weeks in this population.

Psychological Symptoms and Service Utilization in Prepubertal and Pubertal Transgender and Gender-Diverse Patients.

Study Objective: To describe the demographic characteristics and psychological symptoms of gender-diverse patients and to compare symptoms between prepubertal and pubertal subgroups METHODS: This was a retrospective chart review of all gender-diverse patients seen by at least 1 provider at the Nemours Gender Wellness Program from March 2015 to December 2020. The extracted data included demographic and psychosocial characteristics at baseline and 1-year follow-up visits. Pubertal status was determined by Tanner staging by a pediatric endocrinologist or gynecologist.

Meiotic recombination is confirmed to be unusually high in the fission yeast .

In most eukaryotes, meiotic crossovers (COs) are limited to 1-3 per chromosome, and are prevented from occurring close to one another by CO interference. The fission yeast , an exception to these general rules, was reported to have the highest CO number per chromosome and no or weak interference. However, global CO frequency was indirectly estimated, calling for confirmation.

Characterization of cell-fate decision landscapes by estimating transcription factor dynamics.

Time-specific modulation of gene expression during differentiation by transcription factors promotes cell diversity. However, estimating their dynamic regulatory activity at the single-cell level and in a high-throughput manner remains challenging. We present FateCompass, an integrative approach that utilizes single-cell transcriptomics data to identify lineage-specific transcription factors throughout differentiation.

HEIP1 is required for efficient meiotic crossover implementation and is conserved from plants to humans.

Crossovers (CO) shuffle genetic information and physically connect homologous chromosomal pairs, ensuring their balanced segregation during meiosis. COs arising from the major class I pathway require the activity of the well-conserved group of ZMM proteins, which, in conjunction with MLH1, facilitate the maturation of DNA recombination intermediates specifically into COs. The HEI10 Interacting Protein 1 (HEIP1) was identified in rice and proposed to be a new, plant-specific member of the ZMM group.