Apoptosis in mouse fetal and neonatal oocytes during meiotic prophase one

Background The vast majority of oocytes formed in the fetal ovary do not survive beyond birth. Possible reasons for their loss include the elimination of non-viable genetic constitutions arising through meiosis, however, the precise relationship between meiotic stages and prenatal apoptosis of oocytes remains elusive. We studied oocytes in mouse fetal and neonatal ovaries, 14.5–21 days post coitum, to examine the relationship between oocyte development and programmed cell death during meiotic prophase I. Results Microspreads of fetal and neonatal ovarian cells underwent immunocytochemistry for meiosis- and apoptosis-related markers. COR-1 (meiosis-specific) highlighted axial elements of the synaptonemal complex and allowed definitive identification of the stages of meiotic prophase I. Labelling for cleaved poly-(ADP-ribose) polymerase (PARP-1), an inactivated DNA repair protein, indicated apoptosis. The same oocytes were then labelled for DNA double strand breaks (DSBs) using TUNEL. 1960 oocytes produced analysable results. . Oocytes at all stages of meiotic prophase I stained for cleaved PARP-1 and/or TUNEL, or neither. Oocytes with fragmented (19.8%) or compressed (21.2%) axial elements showed slight but significant differences in staining for cleaved PARP-1 and TUNEL to those with intact elements. However, fragmentation of axial elements alone was not a good indicator of cell demise. Cleaved PARP-1 and TUNEL staining were not necessarily coincident, showing that TUNEL is not a reliable marker of apoptosis in oocytes. Conclusions Our data indicate that apoptosis can occur throughout meiotic prophase I in mouse fetal and early postnatal oocytes, with greatest incidence at the diplotene stage. Careful selection of appropriate markers for oocyte apoptosis is essential

The hidden costs of dietary restriction: Implications for its evolutionary and mechanistic origins

Dietary restriction (DR) extends life span across taxa. Despite considerable research, universal mechanisms of DR have not been identified, limiting its translational potential. Guided by the conviction that DR evolved as an adaptive, pro-longevity physiological response to food scarcity, biomedical science has interpreted DR as an activator of pro-longevity molecular pathways. Current evolutionary theory predicts that organisms invest in their soma during DR, and thus when resource availability improves, should outcompete rich-fed controls in survival and/or reproduction. Testing this prediction in Drosophila melanogaster (N > 66,000 across 11 genotypes), our experiments revealed substantial, unexpected mortality costs when flies returned to a rich diet following DR. The physiological effects of DR should therefore not be interpreted as intrinsically pro-longevity, acting via somatic maintenance. We suggest DR could alternatively be considered an escape from costs incurred under nutrient-rich conditions, in addition to costs associated with DR

A Product Formula for the Normalized Volume of Free Sums of Lattice Polytopes

The free sum is a basic geometric operation among convex polytopes. This note focuses on the relationship between the normalized volume of the free sum and that of the summands. In particular, we show that the normalized volume of the free sum of full dimensional polytopes is precisely the product of the normalized volumes of the summands.Comment: Published in the proceedings of 2017 Southern Regional Algebra Conferenc

Small bound for birational automorphism groups of algebraic varieties (with an Appendix by Yujiro Kawamata)

We give an effective upper bound of |Bir(X)| for the birational automorphism group of an irregular n-fold (with n = 3) of general type in terms of the volume V = V(X) under an ''albanese smoothness and simplicity'' condition. To be precise, |Bir(X)| < d_3 V^{10}. An optimum linear bound |Bir(X)|-1 < (1/3)(42)^3 V is obtained for those 3-folds with non-maximal albanese dimension. For all n > 2, a bound |Bir(X)| < d_n V^{10} is obtained when alb_X is generically finite, alb(X) is smooth and Alb(X) is simple.Comment: Mathematische Annalen, to appea

Affine T-varieties of complexity one and locally nilpotent derivations

Let X=spec A be a normal affine variety over an algebraically closed field k of characteristic 0 endowed with an effective action of a torus T of dimension n. Let also D be a homogeneous locally nilpotent derivation on the normal affine Z^n-graded domain A, so that D generates a k_+-action on X that is normalized by the T-action. We provide a complete classification of pairs (X,D) in two cases: for toric varieties (n=\dim X) and in the case where n=\dim X-1. This generalizes previously known results for surfaces due to Flenner and Zaidenberg. As an application we compute the homogeneous Makar-Limanov invariant of such varieties. In particular we exhibit a family of non-rational varieties with trivial Makar-Limanov invariant.Comment: 31 pages. Minor changes in the structure. Fixed some typo

Spectral properties of entanglement witnesses

Entanglement witnesses are observables which when measured, detect entanglement in a measured composed system. It is shown what kind of relations between eigenvectors of an observable should be fulfilled, to allow an observable to be an entanglement witness. Some restrictions on the signature of entaglement witnesses, based on an algebraic-geometrical theorem will be given. The set of entanglement witnesses is linearly isomorphic to the set of maps between matrix algebras which are positive, but not completely positive. A translation of the results to the language of positive maps is also given. The properties of entanglement witnesses and positive maps express as special cases of general theorems for $k$-Schmidt witnesses and $k$-positive maps. The results are therefore presented in a general framework.Comment: published version, some proofs are more detailed, mistakes remove

Class and rank of differential modules

A differential module is a module equipped with a square-zero endomorphism. This structure underpins complexes of modules over rings, as well as differential graded modules over graded rings. We establish lower bounds on the class--a substitute for the length of a free complex--and on the rank of a differential module in terms of invariants of its homology. These results specialize to basic theorems in commutative algebra and algebraic topology. One instance is a common generalization of the equicharacteristic case of the New Intersection Theorem of Hochster, Peskine, P. Roberts, and Szpiro, concerning complexes over noetherian commutative rings, and of a theorem of G. Carlsson on differential graded modules over graded polynomial rings.Comment: 27 pages. Minor changes; mainly stylistic. To appear in Inventiones Mathematica

Five-year study assessing the clinical utility of anti-Müllerian hormone measurements in reproductive-age women with cancer

An important discussion point before chemotherapy is ovarian toxicity, a side-effect that profoundly affects young women with cancer. Their quality of life after successful treatment, including the ability to conceive, is a major concern. We asked whether serum anti-Müllerian hormone (AMH) measurements before chemotherapy for two most common malignancies are predictive of long-term changes in ovarian reserve? A prospective cohort study measured serum AMH in 66 young women with lymphoma and breast cancer, before and at 1 year and 5 years after chemotherapy, compared with 124 healthy volunteers of the same age range (18-43 years). Contemporaneously, patients reported their menses and live births during 5-year follow-up. After adjustment for age, serum AMH was 1.4 times higher (95% CI 1.1 to 1.9; P < 0.02) in healthy volunteers than in cancer patients before chemotherapy. A strong correlation was observed between baseline and 5-year AMH in the breast cancer group (P < 0.001, regression coefficient = 0.58, 95% CI 0.29 to 0.89). No significant association was found between presence of menses at 5 years and serum AMH at baseline (likelihood ratio test from logistics regression analysis). Reproductive-age women with malignancy have lower serum AMH than healthy controls even before starting chemotherapy. Pre-chemotherapy AMH was significantly associated with long-term ovarian function in women with breast cancer. At key time points, AMH measurements could be used as a reproductive health advisory tool for young women with cancer. Our results highlight the unsuitability of return of menstruation as a clinical indicator of ovarian reserve after chemotherapy. [Abstract copyright: Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.

On a new compactification of moduli of vector bundles on a surface, IV: Nonreduced moduli

The construction for nonreduced projective moduli scheme of semistable admissible pairs is performed. We establish the relation of this moduli scheme with reduced moduli scheme built up in the previous article and prove that nonreduced moduli scheme contains an open subscheme which is isomorphic to moduli scheme of semistable vector bundles.Comment: 20 pages, additions and removal

Shapes of free resolutions over a local ring

We classify the possible shapes of minimal free resolutions over a regular local ring. This illustrates the existence of free resolutions whose Betti numbers behave in surprisingly pathological ways. We also give an asymptotic characterization of the possible shapes of minimal free resolutions over hypersurface rings. Our key new technique uses asymptotic arguments to study formal Q-Betti sequences.Comment: 14 pages, 1 figure; v2: sections have been reorganized substantially and exposition has been streamline