Anabolic steroids (AS) are synthetic testosterone-derivatives developed by the pharmaceutical industry to mimic testosterone biological effects. So far, AS have been implicated in the treatment of pathological conditions, such as hypogonadism, anemia, and cachexia. Since their discovery, though, AS have been illicitly used by elite and recreational athletes, bodybuilders and weightlifters in order to enhance athletic and aesthetic performance. This practice is characterized by cycles of administration and withdrawal, the combination of different AS compounds, and administration of doses 50 – 1000 times higher than those recommended for therapeutic purposes. AS excess has been correlated to cardiovascular detrimental effects, including cardiac hypertrophy, arrhythmias, and hypertension. Particularly, acute myocardial infarction (AMI) has been extensively reported by clinical and post-mortem studies. Atherosclerosis, hypercoagulability state, increased thrombogenesis and vasospasm have arisen as potential causes of myocardial ischemia in AS users. Additionally, several experimental reports have demonstrated that AS can increase the susceptibility to cardiac ischemia/reperfusion injury, whereas the cardioprotection elicited by physical exercise and ischemic postconditioning is blunted. Altogether, these factors can contribute to increased AMI morbidity and mortality during AS excess, particularly when AS are combined with other compounds, such as thyroid hormones, growth hormones, insulin, and diuretics.NF-κB is a transcription factor that activates super enhancers (SEs) and typical enhancers (TEs) and triggers threshold and graded gene expression, respectively. However, the mechanisms by which NF-κB selectively participates in these enhancers remain unclear. Here we show using mouse primary B lymphocytes that SE activity simultaneously associates with chromatin opening and enriched NF-κB binding, resulting in a higher fold change and threshold expression upon B cell receptor (BCR) activation. The higher fold change results from longer DNA, whereas the threshold response is explained by synergy in DNA-NF-κB binding and is supported by the coexistence of PU.1 and NF-κB in a SE before cell stimulation. This model indicates that the pre-existing NF-κB functions as a seed and triggers its processive binding upon BCR activation. Our mathematical modeling of the single-cell transcriptome reveals an additional role for SEs in divergent clonal responses in B cells.Rumination is a characteristic feature of several clinical disorders (e.g., major depressive disorder, insomnia disorder). Emerging evidence suggests that a reduced flexibility in the balance between proactive and reactive control might be related to trait rumination. This study aimed to investigate the proactive-reactive control balance in the context of trait rumination. In the current study, we investigated behavioral performance and event-related potentials (ERPs) while participants were performing an AX- Continuous Performance Task, to evaluate whether a shift towards more reactive control (i.e., conflict monitoring and resolution) at the expense of proactive control (i.e., maintenance and updating of task-relevant information) is associated with increased trait rumination. Our behavioral results as well as our ERP results did not demonstrate that a shift towards more reactive control at the expense of proactive control was associated with increased trait rumination. Future research is needed to investigate the proactive-reactive control balance in the context of trait rumination. This study is the first to explore the recruitment dynamics of cognitive control using behavioral as well as electrophysiological measures in the context of rumination.Side differences in the limb symmetry index during hop tests have been rarely investigated in uninjured athletes. Unknown differences can result in false interpretation of hop tests and affect return to sport decision. Hypothesis was that un-injured athletes in Judo and Taekwondo have side differences in hop test and that asymmetries can be predicted based on the athletes fighting display. Differences, risk relationships were analyzed using the chi-squared test and the odds ratio. A two-tailed p value of90. Moreover, 57.4% (n=66) reached longer jumping distance with the standing leg. Ignoring such pre-existent side differences in evaluation of hop tests and not knowing which limb was dominant prior the injury, can lead to premature or delayed return to sports in the rehabilitation process. Therefore, it might be helpful to refer to individual jump lengths for each limb in case of injury by using hop tests in pre-season screening in professional athletes in Judo and Taekwondo.Loss of follicles together with decreased oocyte quality and quantity contribute to age-associated ovarian senescence and infertility. Although underlying mechanisms for ovarian senescence are still unknown, mitochondrial dysfunctions have been reported. Here, we showed age-dependent decreases in ovarian Nicotinamide Adenine Dinucleotide (NAD+) levels in mice whereas supplementing aging mice with nicotinamide riboside (NR), an NAD+ precursor, increased ovarian NAD+ content. We found that increases in ovarian NAD+ levels in aging mice led to increased number of ovarian follicles and ovulatory potential as well as increased live birth rate. NR supplementation also reduced levels of reactive oxygen species and decreased spindle anomalies in aging oocytes, together with increased mitochondrial membrane potential (ΔΨm) and decreased mitochondrial clustering. In addition, NR supplementation improved ovarian mitochondrial energy metabolism. Our data suggested that supplementation with NAD+ precursors in vivo and in vitro could be potential therapeutic approaches for treating age-related ovarian infertility.The advent of base editors (BEs) holds great potential for correcting pathogenic-related point mutations to treat relevant diseases. However, Cas9 nickase (nCas9)-derived BEs lead to DNA double-strand breaks, which can trigger unwanted DNA damage response (DDR). Here, we show that the original version of catalytically dead Cas12a (dCas12a)-conjugated BEs induce a basal level of DNA breaks and minimally activate DDR proteins, including H2AX, ATM, ATR, and p53. By fusing dCas12a with engineered human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A), we further develop the BEACON (base editing induced by human APOBEC3A and Cas12a without DNA break) system to achieve enhanced deamination efficiency and editing specificity. Efficient C-to-T editing is achieved by BEACON in mammalian cells at levels comparable to AncBE4max, with only low levels of DDR and minimal RNA off-target mutations. CP456773 Importantly, BEACON induces in vivo base editing in mouse embryos, and targeted C-to-T conversions are detected in F0 mice.