Rejuvenation of Meiotic Cohesion in Oocytes during Prophase I Is Required for Chiasma Maintenance and Accurate Chromosome Segregation

Chromosome segregation errors in human oocytes are the leading cause of birth defects, and the risk of aneuploid pregnancy increases dramatically as women age. Accurate segregation demands that sister chromatid cohesion remain intact for decades in human oocytes, and gradual loss of the original cohesive linkages established in fetal oocytes is proposed to be a major cause of age-dependent segregation errors. Here we demonstrate that maintenance of meiotic cohesion in Drosophila oocytes during prophase I requires an active rejuvenation program, and provide mechanistic insight into the molecular events that underlie rejuvenation. Gal4/UAS inducible knockdown of the cohesion establishment factor Eco after meiotic S phase, but before oocyte maturation, causes premature loss of meiotic cohesion, resulting in destabilization of chiasmata and subsequent missegregation of recombinant homologs. Reduction of individual cohesin subunits or the cohesin loader Nipped B during prophase I leads to similar defects. These data indicate that loading of newly synthesized replacement cohesin rings by Nipped B and establishment of new cohesive linkages by the acetyltransferase Eco must occur during prophase I to maintain cohesion in oocytes. Moreover, we show that rejuvenation of meiotic cohesion does not depend on the programmed induction of meiotic double strand breaks that occurs during early prophase I, and is therefore mechanistically distinct from the DNA damage cohesion re-establishment pathway identified in G2 vegetative yeast cells. Our work provides the first evidence that new cohesive linkages are established in Drosophila oocytes after meiotic S phase, and that these are required for accurate chromosome segregation. If such a pathway also operates in human oocytes, meiotic cohesion defects may become pronounced in a woman\u27s thirties, not because the original cohesive linkages finally give out, but because the rejuvenation program can no longer supply new cohesive linkages at the same rate at which they are lost

Rejuvenation of Meiotic Cohesion in Oocytes during Prophase I Is Required for Chiasma Maintenance and Accurate Chromosome Segregation

Chromosome segregation errors in human oocytes are the leading cause of birth defects, and the risk of aneuploid pregnancy increases dramatically as women age. Accurate segregation demands that sister chromatid cohesion remain intact for decades in human oocytes, and gradual loss of the original cohesive linkages established in fetal oocytes is proposed to be a major cause of age-dependent segregation errors. Here we demonstrate that maintenance of meiotic cohesion in Drosophila oocytes during prophase I requires an active rejuvenation program, and provide mechanistic insight into the molecular events that underlie rejuvenation. Gal4/UAS inducible knockdown of the cohesion establishment factor Eco after meiotic S phase, but before oocyte maturation, causes premature loss of meiotic cohesion, resulting in destabilization of chiasmata and subsequent missegregation of recombinant homologs. Reduction of individual cohesin subunits or the cohesin loader Nipped B during prophase I leads to similar defects. These data indicate that loading of newly synthesized replacement cohesin rings by Nipped B and establishment of new cohesive linkages by the acetyltransferase Eco must occur during prophase I to maintain cohesion in oocytes. Moreover, we show that rejuvenation of meiotic cohesion does not depend on the programmed induction of meiotic double strand breaks that occurs during early prophase I, and is therefore mechanistically distinct from the DNA damage cohesion re-establishment pathway identified in G2 vegetative yeast cells. Our work provides the first evidence that new cohesive linkages are established in Drosophila oocytes after meiotic S phase, and that these are required for accurate chromosome segregation. If such a pathway also operates in human oocytes, meiotic cohesion defects may become pronounced in a woman\u27s thirties, not because the original cohesive linkages finally give out, but because the rejuvenation program can no longer supply new cohesive linkages at the same rate at which they are lost

Complete genome sequence of Streptococcus agalactiae strain 01173, isolated from Kuwaiti wild fish

© 2020 Santi et al. Here, we report the complete genome of piscine Streptococcus agalactiae 01173 serotype Ia, which was generated using long-read sequencing technology. The bacteria were isolated from wild fish displaying signs of streptococcosis, from a fish kill incident in Kuwait

Mental health problems in people with learning disabilities: prevention, assessment and management

This guideline covers preventing, assessing and managing mental health problems in people with learning disabilities in all settings (including health, social care, education, and forensic and criminal justice). It aims to improve assessment and support for mental health conditions, and help people with learning disabilities and their families and carers to be involved in their care

Aging Predisposes Oocytes to Meiotic Nondisjunction When the Cohesin Subunit SMC1 Is Reduced

In humans, meiotic chromosome segregation errors increase dramatically as women age, but the molecular defects responsible are largely unknown. Cohesion along the arms of meiotic sister chromatids provides an evolutionarily conserved mechanism to keep recombinant chromosomes associated until anaphase I. One attractive hypothesis to explain age-dependent nondisjunction (NDJ) is that loss of cohesion over time causes recombinant homologues to dissociate prematurely and segregate randomly during the first meiotic division. Using Drosophila as a model system, we have tested this hypothesis and observe a significant increase in meiosis I NDJ in experimentally aged Drosophila oocytes when the cohesin protein SMC1 is reduced. Our finding that missegregation of recombinant homologues increases with age supports the model that chiasmata are destabilized by gradual loss of cohesion over time. Moreover, the stage at which Drosophila oocytes are most vulnerable to age-related defects is analogous to that at which human oocytes remain arrested for decades. Our data provide the first demonstration in any organism that, when meiotic cohesion begins intact, the aging process can weaken it sufficiently and cause missegregation of recombinant chromosomes. One major advantage of these studies is that we have reduced but not eliminated the SMC1 subunit. Therefore, we have been able to investigate how aging affects normal meiotic cohesion. Our findings that recombinant chromosomes are at highest risk for loss of chiasmata during diplotene argue that human oocytes are most vulnerable to age-induced loss of meiotic cohesion at the stage at which they remain arrested for several years

Shape description and matching using integral invariants on eccentricity transformed images

Matching occluded and noisy shapes is a problem frequently encountered in medical image analysis and more generally in computer vision. To keep track of changes inside the breast, for example, it is important for a computer aided detection system to establish correspondences between regions of interest. Shape transformations, computed both with integral invariants (II) and with geodesic distance, yield signatures that are invariant to isometric deformations, such as bending and articulations. Integral invariants describe the boundaries of planar shapes. However, they provide no information about where a particular feature lies on the boundary with regard to the overall shape structure. Conversely, eccentricity transforms (Ecc) can match shapes by signatures of geodesic distance histograms based on information from inside the shape; but they ignore the boundary information. We describe a method that combines the boundary signature of a shape obtained from II and structural information from the Ecc to yield results that improve on them separately

Amplifying deceivers’ flawed metacognition: Encouraging disclosures after delays with a model statement

Truth tellers provide less detail in delayed than in immediate interviews (likely due to forgetting), whereas liars provide similar amounts of detail in immediate and delayed interviews (displaying a metacognitive stability bias effect). We examined whether liar’s flawed metacognition after delays could be exploited by encouraging interviewees to provide more detail via a Model Statement. Truthful and deceptive participants were interviewed immediately (n = 78) or after a three-week delay (n = 78). Half the participants in each condition listened to a Model Statement before questioning. In the Immediate condition, truth tellers provided more details than liars. This pattern was unaffected by the Model Statement. In the Delayed condition, truth tellers and liars provided a similar amount of detail in the Model Statement-absent condition, whereas in the Model Statement-present condition, liars provided more details than truth tellers

Eco knockdown in mid-prophase causes premature disassembly of the SC.

<p>(Top) C(3)G immunostaining is shown for oocytes from females containing the UAS-Eco RNAi^GD transgene in the absence of driver (Control), the presence of the matα driver (Eco KD) and the presence of the matα driver and a UAS-Dicer-2 transgene to increase Eco RNAi efficiency (Eco KD + Dcr-2). Long continuous threads of SC are apparent in Control oocytes until stage 6. In contrast, premature disassembly of the SC is visible in Eco KD and Eco KD + Dcr-2 oocytes starting as early as stage 2. Images for each stage were captured and processed identically and projections of deconvolved Z-series are shown. Scale bar, 2 µm. (Bottom) Quantification of SC defects is presented. Oocytes with SC disassembly were assigned to one of three categories with increasing severity: broken threads, short threads and spots. In Control oocytes, SC disassembly is not detected until stage 6. In contrast, premature disassembly of the SC is detectable beginning at stage 2 in the Eco KD oocytes. As prophase I progresses, both the severity of the defects and the percentage of oocytes affected increase. When Dicer-2 is overexpressed, the phenotype is enhanced at all stages, in both the percentage of oocytes with defects and the severity of defects. At least 20 oocytes were scored for each genotype at each stage.</p