Endometrial receptivity in women of reproductive age with "thin" and "absolutely thin" endometrium

Aim. To evaluate the expression of steroid receptors (estrogen [ER] and progesterone [PR]) in the endometrium during the implantation window in females with a history of fertility disorders in "thin" and "absolutely thin" endometrium versus healthy females. Materials and methods. A prospective comparative study was conducted. The study group (n=42) included patients with "thin" endometrium (7 mm M-echo 5 mm at cycle days 1113 according to ultrasound); the comparison group (n=10) included females with "absolutely thin" (5 mm according to ultrasound in the pre-ovulatory days) endometrium (females in both groups had a history of infertility and miscarriage of unclear reasons in the anamnesis); the control group included 16 healthy fertile females. A Pipelle biopsy of the uterine mucosa was performed on day 68 after ovulation, and a peripheral blood sample was obtained to measure the concentration of sex steroids (estradiol [E2] and progesterone [P]). Endometrial samples were examined by histological and immunohistochemical methods (ER, PR expression). Results. All study participants had an ovulatory cycle of P16.1 nmol/L (day 68 after ovulation) and normal estrogen levels (E2, pmol/L). E2/P was similar in all cohorts (p0.05 for all measures). ER and PR expression in the endometrium similar to those in healthy females was detected in 20% of patients in the study and comparison groups (M-echo = 4.83.1 mm): 21% (9/42) and 20% (2/10), respectively. ER and PR expression in the endometrial glands and ER expression in the endometrial stroma were significantly different (p0.05) from healthy females in 79% (41/52) of patients with "thin" endometrium and 80% (8/10) of patients with "absolutely thin" endometrium. No differences in the ER or PR expression in the endometrium in females with hypoplastic endometrium were found (p0.05). Conclusion. The M-echo value does not accurately determine endometrial hormonal-receptor abnormalities: 20% of the study participants with hypoplastic endometrium had ER and PR expression comparable to those in healthy females. No differences were found in the expression of endometrial estrogen and progesterone receptors in females with "thin" and "absolutely thin" endometrium

Endometrial expression of FOX proteins (FOXA1 and FOXA2) in women of reproductive age with different endometrial thickness: prospective cohort comparative study

Aim. To evaluate the expression of FOX proteins (FOXA1 and FOXA2) in the endometrium during the implantation window in women with a history of reproductive dysfunctions with different thickness of the endometrium. Materials and methods. The prospective cohort comparative study was conducted. The main group included patients with "thin" endometrium (7 mm according to ultrasound on preovulatory days; n=52), the comparison group consisted of women with normal endometrial thickness (7 mm according to ultrasound; n=62; women of both groups with reproductive dysfunctions of unknown reason), the control group included 16 healthy fertile women. Aspiration biopsy of the endometrium was performed on the 68 days after ovulation, as well as venipuncture to obtain a sample of peripheral blood to determine the levels of sex steroids (estradiol E2 and progesterone P). A combined histological and immunohistochemical study of endometrial biopsies was performed. Results. All women had ovulatory values of progesterone P16.1 nmol/l (68 days after ovulation) and normoestrogenemia (E2, pmol/l) in the blood. E2/P was similar in all groups (p0, 05). A pronounced expression of FOXA1 was noted in women with thin endometrium significantly more often (p0.05) with various hormone-receptor characteristics of the endometrium (42% n=22 out of 52) compared with healthy participants (0%; n=0). Reduced FOXA2 expression in the uterine mucosa was significantly more often detected on 68 days after ovulation in women with "thin" endometrium (56% n=29 of 52) than in women with normal endometrial thickness, both in women from the comparison group and in healthy women from the control group (p0.05). In a generalized analysis of the expression of FOX proteins in the endometrium on days 68 after ovulation, it was generally found that every second (50%; n=57 out of 114) women with a history of reproductive disorders (with a reduced and normal M-echo value) expression of proteomic markers differed from healthy women. In the case of "thin" endometrium, more than two thirds of patients (71%; n=37 out of 52) showed differences in endometrial expression of FOX proteins compared with women without a burdened reproductive history. Conclusion. In the majority of women (71%) with a thin endometrium and a history of reproductive dysfunctions, the expression of FOX proteins in the endometrium differed from the control group. Overall, endometrial expression of FOX proteins, which is likely to be different from healthy women, in patients with reproductive dysfunctions of unknown origin is a significant predictor of reproductive failure. At the same time, such an isolated indicator as M-echo value 7 mm according to ultrasound data is not an absolute prognostic marker of endometrial receptivity disorders

On pairwise distances and median score of three genomes under DCJ

In comparative genomics, the rearrangement distance between two genomes (equal the minimal number of genome rearrangements required to transform them into a single genome) is often used for measuring their evolutionary remoteness. Generalization of this measure to three genomes is known as the median score (while a resulting genome is called median genome). In contrast to the rearrangement distance between two genomes which can be computed in linear time, computing the median score for three genomes is NP-hard. This inspires a quest for simpler and faster approximations for the median score, the most natural of which appears to be the halved sum of pairwise distances which in fact represents a lower bound for the median score. In this work, we study relationship and interplay of pairwise distances between three genomes and their median score under the model of Double-Cut-and-Join (DCJ) rearrangements. Most remarkably we show that while a rearrangement may change the sum of pairwise distances by at most 2 (and thus change the lower bound by at most 1), even the most "powerful" rearrangements in this respect that increase the lower bound by 1 (by moving one genome farther away from each of the other two genomes), which we call strong, do not necessarily affect the median score. This observation implies that the two measures are not as well-correlated as one's intuition may suggest. We further prove that the median score attains the lower bound exactly on the triples of genomes that can be obtained from a single genome with strong rearrangements. While the sum of pairwise distances with the factor 2/3 represents an upper bound for the median score, its tightness remains unclear. Nonetheless, we show that the difference of the median score and its lower bound is not bounded by a constant.Comment: Proceedings of the 10-th Annual RECOMB Satellite Workshop on Comparative Genomics (RECOMB-CG), 2012. (to appear

CAMSA: a tool for comparative analysis and merging of scaffold assemblies

Abstract Background Despite the recent progress in genome sequencing and assembly, many of the currently available assembled genomes come in a draft form. Such draft genomes consist of a large number of genomic fragments (scaffolds), whose positions and orientations along the genome are unknown. While there exists a number of methods for reconstruction of the genome from its scaffolds, utilizing various computational and wet-lab techniques, they often can produce only partial error-prone scaffold assemblies. It therefore becomes important to compare and merge scaffold assemblies produced by different methods, thus combining their advantages and highlighting present conflicts for further investigation. These tasks may be labor intensive if performed manually. Results We present CAMSA—a tool for comparative analysis and merging of two or more given scaffold assemblies. The tool (i) creates an extensive report with several comparative quality metrics; (ii) constructs the most confident merged scaffold assembly; and (iii) provides an interactive framework for a visual comparative analysis of the given assemblies. Among the CAMSA features, only scaffold merging can be evaluated in comparison to existing methods. Namely, it resembles the functionality of assembly reconciliation tools, although their primary targets are somewhat different. Our evaluations show that CAMSA produces merged assemblies of comparable or better quality than existing assembly reconciliation tools while being the fastest in terms of the total running time. Conclusions CAMSA addresses the current deficiency of tools for automated comparison and analysis of multiple assemblies of the same set scaffolds. Since there exist numerous methods and techniques for scaffold assembly, identifying similarities and dissimilarities across assemblies produced by different methods is beneficial both for the developers of scaffold assembly algorithms and for the researchers focused on improving draft assemblies of specific organisms

Overexpression of estrogen and progesterone receptors as indicator of endometrial receptivity disorder in women with early miscarriage

Background ― The endometrial factor is important in miscarriage (MC) pathogenesis. Objective. To perform a morphofunctional evaluation of endometrium in the patients with uncertain MC cause in anamnesis. Material and methods ― We examined 48 women 23-40 yo [30 (27, 35)]: the main group consisted of 33 patients with early MC in their medical history, while the control group included 15 healthy fertile women. All women had an ovulatory menstrual cycle, normal levels of gonadotropic and thyroid hormones, prolactin, and androgens. Ultrasound and hormonal examinations, along with morphological investigation of endometrial biopsies were performed. Data presented as median with lower and upper quartiles – Me (LQ, UQ). Results ― In 64% (n=21) of women in the main group, we detected inferior secretory phase of their endometrial cycle, focal fibrosis of endometrial stroma; synchronous overexpression of estrogen (ER) and progesterone (PR) receptors in endometrial glands and stroma. ER in the glands was 240 (160, 280) vs. 130 (80, 210) in the stroma, while PR values were 270 (210, 290) in the glands vs. 270 (240, 280) in the stroma: differences from the control group were significant (p<0.01). Remaining women in the main group (36%, n=12) and all women in the control group had full secretory transformation of the endometrium and normal expression of ER and PR. The levels of estradiol and PR in the blood of women with early MC in anamnesis, with different variants of ER and PR expression in the endometrium, did not differ significantly from the control group and corresponded to the reference values. Conclusion ― Nearly two-thirds of women with early miscarriage in anamnesis exhibited overexpression of ER and PR in the endometrium, which may be one of the indicators of its decreased receptivity status

The complete sequence of a human genome.

Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion-base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies

The complete sequence of a human genome.

Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion-base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies

Mosquito genomics. Highly evolvable malaria vectors: the genomes of 16 Anopheles mosquitoes.

Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts