Search

Chromosomal mosaicism is at high occurrence in early developmental-stage embryos, but much lower in those at prenatal stage. Recent studies provided evidence on the viability of mosaic embryos by reporting pregnancy outcomes. Expanded research is warranted to evaluate its clinical significance. This is a multi-center prospective cohort study on 137 mosaic, 476 euploid and 835 non-preimplantation genetic testing (non-PGT) embryos from three in vitro fertilization (IVF) providers of three countries in Asia, applying the same preimplantation genetic testing for aneuploidies (PGT-A) reporting criteria. Mosaic embryo transfers (METs) resulted in a significantly lower clinical pregnancy rate (40.1% versus 59.0% versus 48.4%), lower ongoing/live birth rate (27.1% versus 47.0% versus 35.1%) and higher miscarriage rate (33.3% versus 20.5% versus 27.4%) than euploid and non-PGT transfers, respectively. Pregnancy losses after METs were different between embryos carrying numerical and segmental chromosomal abnormalities (p = 0.04). Our meta-analysis concluded that METs gave rise to pregnancies but were associated with a reduced ongoing/live birth rate and a higher miscarriage rate. All 37 MET live births were confirmed viable, among which 8 completed prenatal genetic testing with normal results. Longitudinal investigation on one MET pregnancy evidenced the aneuploidy depletion hypothesis. This is the first multi-center prospective study reporting a full MET pregnancy outcome with complementary information from prenatal genetic testing as compared to euploid and non-PGT cohorts.

Contamination of ground water by industrial chemicals presents a major environmental and health problem. Soil sorption plays an important role in the transport and movement of such pollutant chemic ...

The multidrug resistance of

Introduction Reciprocal translocations are one of the most common abnormalities in chromosomal structure. Couples with a balanced translocation have an increased risk for infertility and recurrent pregnancy loss. The present study aims to evaluate the ability of next-generation sequencing (NGS) to detect unbalanced chromosomal rearrangements in blastocysts derived from couples with balanced reciprocal translocations. Material & Methods First, the performance of NGS (VeriSeq, Illumina, USA) for unbalanced rearrangement detection was determined. Whole-genome amplification (WGA) products from trophectoderm biopsy samplesof 12 couples with a balanced reciprocal translocation previously analyzed by aCGH (24Sure+array, Illumina, USA) were reanalyzed by NGS. Second, a retrospective study was performed in a private ART clinic in Thailand between January to December 2017. A total of 70 embryos of 10 different couples with a balanced reciprocal translocation were analyzed by NGS and the pregnancy outcomes for couples with normal/balanced embryos available for transfer were followed up. Results NGS was 95.8% concordancefor detecting unbalanced chromosomal rearrangement with aCGH, and 99.7% for overall analyzed chromosomes. We found that NGS can detect segmental aneuploidies as small as 5 Mb in size. Results of 70 embryos revealed 30% normal/balanced embryos. 17.1% of embryos were found to be aneuploid balanced embryos and 2.9% of embryos were mosaic balanced embryos. Imbalanced segmental aneuploidies were detected in 50% of embryos, 47.1% of the imbalances were related to parental translocation while 2.9% of them were not related to parental translocation. Seven couples had normal/balanced embryos available for transfer, 57.1% (4/7) of them had clinical pregnancies as indicated by an intrauterine gestational sac with fetal heartbeat visualized by ultrasound examination at 3 months after embryo transfer. Conclusions Our results demonstrated that NGS hasa high resolution to detect imbalanced segmental rearrangements. The accurate detection of NGS for imbalanced segmental and whole chromosome aneuploidies might improve the IVF success rate and increase thechances of having a healthy child for translocation carriers.

Multiplex PCR was applied to explore the antimicrobial-resistance profiles of 145 gonococci isolated from Bangrak Hospital, Thailand in 2007. All isolates were clearly identified for the plasmid-mediated resistant types of penicillin (Asia, Africa and Toronto) and tetracycline (American and Dutch). This method can also predict the decreased susceptibility to ciprofloxacin by detection of Ser-91 mutation. Prevalence rates of penicillinase-producing Neisseria gonorrhoeae (PPNG) and high-level tetracycline-resistance N. gonorrhoeae (TRNG) were shown to be high as 82.1% and 84.1%, respectively. Most PPNG carried the Africa-type (78.2%) while the American-type (61.8%) was harboured in most TRNG. Mono- and triple-resistance patterns were presented in 2.6% and 79.5% of male, 20.7% and 62.1% of men who have sex with men (MSM), 0% and 75.0% of female, and 10% and 70% of female sex workers (FSW). Additionally, the rate of the Dutch type was high in patients among the age of 35–44 years (57.1%) and female patients (43.8%). The changing types of plasmids have been noticed during the time period of study. The multi-resistance patterns of the gonococcal isolates can be used as an epidemiological index of gonorrhoea and human sexual behaviours. This information will support the management of individual patients as well as the public health surveillance.

Aromatase, which is a rate-limiting enzyme that catalyzes the conversion of androgen to estrogen, plays an essential role in the development of estrogen-dependent breast cancer. Side effects due to aromatase inhibitors (AIs) necessitate the pursuit of novel inhibitor candidates with high selectivity, lower toxicity and increased potency. Designing a novel therapeutic agent against aromatase could be achieved computationally by means of ligand-based and structure-based methods. For over a decade, we have utilized both approaches to design potential AIs for which quantitative structure-activity relationship and molecular docking were used to explore inhibitory mechanisms of AIs towards aromatase. However, such approaches do not consider the effects that aromatase variants have on different AIs. In this study, proteochemometrics modeling was applied to analyze the interaction space between AIs and aromatase variants as a function of their substructural and amino acid features. Good predictive performance was achieved, as rigorously verified by 10-fold cross-validation, external validation, leave-one-compound-out cross-validation, leave-one-protein-out cross-validation and Y-scrambling tests. The investigations presented herein provide important insights into the mechanisms of aromatase inhibitory activity that could aid in the design of novel potent AIs as breast cancer therapeutic agents.

Neisseria gonorrhoeae infection threatens to become an untreatable sexually transmitted disease in the near future owing to the increasing emergence of N. gonorrhoeae strains with reduced susceptibility and resistance to the extended-spectrum cephalosporins (ESCs), i.e. ceftriaxone and cefixime, which are the last remaining option for first-line treatment of gonorrhea. Alteration of the penA gene, encoding penicillin-binding protein 2 (PBP2), is the main mechanism conferring penicillin resistance including reduced susceptibility and resistance to ESCs. To predict and investigate putative amino acid mutations causing β-lactam resistance particularly for ESCs, we applied proteochemometric modeling to generalize N. gonorrhoeae susceptibility data for predicting the interaction of PBP2 with therapeutic β-lactam antibiotics. This was afforded by correlating publicly available data on antimicrobial susceptibility of wild-type and mutant N. gonorrhoeae strains for penicillin-G, cefixime and ceftriaxone with 50 PBP2 protein sequence data using partial least-squares projections to latent structures. The generated model revealed excellent predictability (R 2 = 0.91, Q 2 = 0.77, Q Ext 2 = 0.78). Moreover, our model identified amino acid mutations in PBP2 with the highest impact on antimicrobial susceptibility and provided information on physicochemical properties of amino acid mutations affecting antimicrobial susceptibility. Our model thus provided insight into the physicochemical basis for resistance development in PBP2 suggesting its use for predicting and monitoring novel PBP2 mutations that may emerge in the future.

A proteome reference map ofNeisseria gonorrhoeaewas successfully established using two-dimensional gel electrophoresis in conjunction with matrix-assisted laser desorption ionization–time of flight mass spectrometry. This map was further applied to compare protein expression profiles of high-level spectinomycin-resistant (clinical isolate) and -susceptible (reference strain)N. gonorrhoeaefollowing treatment with subminimal inhibitory concentrations (subMICs) of spectinomycin. Approximately 200 protein spots were visualized by Coomassie brilliant blue G-250 staining and 66 spots representing 58 unique proteins were subsequently identified. Most of the identified proteins were analysed as cytoplasmic proteins and belonged to the class of energy metabolism. Comparative proteomic analysis of whole protein expression of susceptible and resistant gonococci showed up to 96 % similarity while eight proteins were found to be differentially expressed in the resistant strain. In the presence of subMICs of spectinomycin, it was found that 50S ribosomal protein L7/L12, an essential component for ribosomal translocation, was upregulated in both strains, ranging from 1.5- to 3.5-fold, suggesting compensatory mechanisms ofN. gonorrhoeaein response to antibiotic that inhibits protein synthesis. Moreover, the differential expression of proteins involved in energy metabolism, amino acid biosynthesis, and the cell envelope was noticeably detected, indicating significant cellular responses and adaptation against antibiotic stress. Such knowledge provides valuable data, not only fundamental proteomic data, but also knowledge of the mode of action of antibiotic and secondary target proteins implicated in adaptation and compensatory mechanisms.

Introduction Neisseria gonorrhoeae resistance to extended-spectrum cephalosporins as well as treatment failures with ESCs has been increasingly reported in many countries globally. These increasing trends together with the limitation of drugs of choice lead gonorrhoea to become a global health concern. Herein, we aimed to reveal more understanding on the physiological response of gonococci to ESCs using proteomic approach. Methods N. gonorrhoeae reference strain was grown with or without a subinhibitory dose of ESCs. Protein expression was determined by 2-dimensional gel electrophoresis in conjunction with MALDI-TOF/TOF MS analysis. Results In total, 14 and 13 proteins were significantly altered expression following exposure to ceftriaxone and cefixime, respectively. Most of expressed proteins shared a similar expression pattern in response to ceftriaxone and cefixime reflecting similarities in antibiotic mechanisms. ESC antibiotics triggered proteins in a variety of functions, such as membrane protein, transport system, energy metabolism, and stress response, which would help gonococci to survive under drug stress. Interestingly, the subinhibitory dose of ESCs also triggered the expression of gonococcal virulence factors (e.g. azurin and peptidyl-prolyl isomerase), which might be an adaptation mechanism of gonococci in ESC stress and also affect the outcome of gonococcal infection. Conclusion The present work might provide new insights into physiological adaptive networks of gonococci to antimicrobial agents and more understanding toward the mechanism of action, which subsequently may benefit for the further drug discovery of new antimicrobials to combat with resistant gonococci.