Meiotic DSB patterning: A multifaceted process

Meiosis is a specialized two-step cell division responsible for genome haploidization and the generation of genetic diversity during gametogenesis. An integral and distinctive feature of the meiotic program is the evolutionarily conserved initiation of homologous recombination (HR) by the developmentally programmed induction of DNA double-strand breaks (DSBs). The inherently dangerous but essential act of DSB formation is subject to multiple forms of stringent and self-corrective regulation that collectively ensure fruitful and appropriate levels of genetic exchange without risk to cellular survival. Within this article we focus upon an emerging element of this control—spatial regulation—detailing recent advances made in understanding how DSBs are evenly distributed across the genome, and present a unified view of the underlying patterning mechanisms employed

Treatment of insomnia in myasthenia gravis-A prospective study on non-benzodiazepine hypnotics in the treatment of myasthenia gravis patients with insomnia

Objectives: This study aimed to evaluate the efficacy and safety of non-benzodiazepine hypnotics in the treatment of myasthenia gravis (MG) patients with insomnia. Methods: This is a prospective longitudinal study. Outpatients who met the criteria for stable MG and insomnia diagnosis according to the International Classification of Sleep Disorders (third edition) were included in the study. They took a regular dose of non-benzodiazepine hypnotics (zolpidem 10 mg per night or zopiclone 7.5 mg per night) based on their own preferences. Patients received psychotherapy (including sleep health education) and were followed up for 4–5 weeks. Cases with lung diseases, respiratory disorders, or inappropriate use of hypnotic medications were excluded. The primary outcome is the difference in total Pittsburgh Sleep Quality Index (PSQI) score between baseline and the end of follow-up period. Secondary outcomes include the difference in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) between baseline and the end of follow-up period and the safety of medication. Results: A total of 75 MG patients with insomnia were included in this study. After 4–5 weeks of treatment, the total PSQI score and MG-ADL score were lower than baseline (p < 0.01). No patients had an increased MG-ADL score. The incidence rate of adverse events was 16.0% (12 cases), including dizziness (6 cases, 8.0%), drowsiness (3 cases, 4.0%), fatigue (2 cases, 2.7%), and nausea (1 case, 1.3%), all of which were mild. No patients had new onset breathing disorders. Conclusion: Non-benzodiazepine hypnotics are safe and effective for stable MG patients who need insomnia treatment

Multiple sex partner behavior in female undergraduate students in China: A multi-campus survey

<p>Abstract</p> <p>Background</p> <p>China is realizing increases in women engaged in premarital sex and multiple sex partner behavior. Our aim was to examine prevalence and determinants of multiple sex partner behavior among female undergraduates in China.</p> <p>Methods</p> <p>Anonymously completed questionnaires were received from 4,769 unmarried female undergraduates, recruited using randomized cluster sampling by type of university and students' major and grade. Items captured demographic, family, peer and work influence, and student factors (major, academic performance, and sex-related knowledge and attitudes). To examine risk factors for sexual behaviors, we used multi-level logistic regression, yielding odds ratios (OR) and 95% confidence intervals (95% CI).</p> <p>Results</p> <p>Of 4,769 female students, 863 (18.10%) reported ever having sexual intercourse, and 5.31% reported having multiple sex partners (29.32% of all women having sexual intercourse). Several demographic, family, peer and work influences, and student factors (including major, performance, knowledge, and attitude toward sex) were risk factors for ever having sex. However, risk factors for multiple sex partners only included working in a place of entertainment, having current close friends that were living with boyfriends, poor academic performance, and positive attitudes toward multiple partners. These women also were more likely to practice masturbation, start having sex at a younger age, have sex with married men and/or men not their "boyfriends" at first coitus, and not use condoms consistently.</p> <p>Conclusion</p> <p>A small but important subset of Chinese female undergraduates is engaged in unprotected sex with multiple sex partners. Interventions need to target at risk women, stressing the importance of consistent condom use.</p

Synthesis of Monodisperse Nanocrystals via Microreaction: Open-to-Air Synthesis with Oleylamine as a Coligand

Microreaction provides a controllable tool to synthesize CdSe nanocrystals (NCs) in an accelerated fashion. However, the surface traps created during the fast growth usually result in low photoluminescence (PL) efficiency for the formed products. Herein, the reproducible synthesis of highly luminescent CdSe NCs directly in open air was reported, with a microreactor as the controllable reaction tool. Spectra investigation elucidated that applying OLA both in Se and Cd stock solutions could advantageously promote the diffusion between the two precursors, resulting in narrow full-width-at-half maximum (FWHM) of PL (26 nm). Meanwhile, the addition of OLA in the source solution was demonstrated helpful to improve the reactivity of Cd monomer. In this case, the focus of size distribution was accomplished during the early reaction stage. Furthermore, if the volume percentage (vol.%) of OLA in the precursors exceeded a threshold of 37.5%, the resulted CdSe NCs demonstrated long-term fixing of size distribution up to 300 s. The observed phenomena facilitated the preparation of a size series of monodisperse CdSe NCs merely by the variation of residence time. With the volume percentage of OLA as 37.5% in the source solution, a 78 nm tuning of PL spectra (from 507 to 585) was obtained through the variation of residence time from 2 s to 160 s, while maintaining narrow FMWH of PL (26–31 nm) and high QY of PL (35–55%)

The Mixed-Lineage Kinase DLK Is a Key Regulator of 3T3-L1 Adipocyte Differentiation

The mixed-lineage kinase (MLK) family member DLK has been proposed to serve as a regulator of differentiation in various cell types; however, its role in adipogenesis has not been investigated. In this study, we used the 3T3-L1 preadipocyte cell line as a model to examine the function of DLK in adipocyte differentiation.Immunoblot analyses and kinase assays performed on 3T3-L1 cells showed that the expression and activity of DLK substantially increase as differentiation occurs. Interestingly, DLK appears crucial for differentiation since its depletion by RNA interference impairs lipid accumulation as well as expression of the master regulators of adipogenesis C/EBPalpha and PPARgamma2 at both the mRNA and protein levels. In contrast, neither the expression nor the DNA binding activity of C/EBPbeta, an activator for C/EBPalpha and PPARgamma, is affected by DLK loss.Taken together, these results suggest that DLK is important for expression of mature adipocyte markers and that its action most likely takes place via regulation of C/EBPbeta transcriptional activity and/or initiation of C/EBPalpha and PPARgamma2 gene transcription

Meiotic Recombination Hotspots of Fission Yeast Are Directed to Loci that Express Non-Coding RNA

Polyadenylated, mRNA-like transcripts with no coding potential are abundant in eukaryotes, but the functions of these long non-coding RNAs (ncRNAs) are enigmatic. In meiosis, Rec12 (Spo11) catalyzes the formation of dsDNA breaks (DSBs) that initiate homologous recombination. Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous. In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.). Furthermore, we tested and rejected the hypothesis that the ncRNA loci and DSB peaks localize preferentially, but independently, to a third entity on the chromosomes.Meiotic DSB hotspots are directed to loci that express polyadenylated ncRNAs. This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots. It also reveals a likely biological function for enigmatic ncRNAs. We propose specific mechanisms by which ncRNA molecules, or some aspect of RNA metabolism associated with ncRNA loci, help to position recombination protein complexes at DSB hotspots within chromosomes

Genomic Structure of and Genome-Wide Recombination in the Saccharomyces cerevisiae S288C Progenitor Isolate EM93

The diploid isolate EM93 is the main ancestor to the widely used Saccharomyces cerevisiae haploid laboratory strain, S288C. In this study, we generate a high-resolution overview of the genetic differences between EM93 and S288C. We show that EM93 is heterozygous for >45,000 polymorphisms, including large sequence polymorphisms, such as deletions and a Saccharomyces paradoxus introgression. We also find that many large sequence polymorphisms (LSPs) are associated with Ty-elements and sub-telomeric regions. We identified 2,965 genetic markers, which we then used to genotype 120 EM93 tetrads. In addition to deducing the structures of all EM93 chromosomes, we estimate that the average EM93 meiosis produces 144 detectable recombination events, consisting of 87 crossover and 31 non-crossover gene conversion events. Of the 50 polymorphisms showing the highest levels of non-crossover gene conversions, only three deviated from parity, all of which were near heterozygous LSPs. We find that non-telomeric heterozygous LSPs significantly reduce meiotic recombination in adjacent intervals, while sub-telomeric LSPs have no discernable effect on recombination. We identified 203 recombination hotspots, relatively few of which are hot for both non-crossover gene conversions and crossovers. Strikingly, we find that recombination hotspots show limited conservation. Some novel hotspots are found adjacent to heterozygous LSPs that eliminate other hotspots, suggesting that hotspots may appear and disappear relatively rapidly

Long-term outcomes of early childhood science education: insight from a cross-national comparative case study on conceptual understanding of science

The purpose of this research was to explore the long term outcomes of either participating or not participating in early childhood science education on Grade 6 students’ conceptual understanding of science. The research is situated in a conceptual framework that evokes Piagetian developmental levels as both potential curriculum constraints and potential models of efficacy. The research design was a multiple case study of Grade 6 children from three schools in China (n=140) who started formal science education in the third grade, and Grade 6 children from three matched schools in Australia (n=105) who started learning science in kindergarten. The students’ understanding was assessed by a science quiz and in-depth interview. The data showed that participating children from the high socio-economic schools in China and Australia had similar understandings of science. Divergence between the medium and low socio-economic schools, however, indicated that the grounding in early childhood science education in Australia may have placed these children at an advantage. Alternative explanations for the divergence including the nature of classroom instruction in the two countries are discussed