Emerging evidence indicates the involvement of O-GlcNAc modification in placental development and pregnant health through mechanisms that are not well understood. Herein, by applying the quantitative O-GlcNAc proteomics, we established a database of O-GlcNAcylated proteins in human placental trophoblasts. Hundreds of proteins that were dynamically O-GlcNAcylated during trophoblast differentiation were identified, among which cystathionine γ-lyase (CSE) exhibited the most significant change. Site-specific analysis by mass spectrometry revealed Ser138 as the core O-GlcNAc site in CSE, and its O-GlcNAcylation promoted the enzymatic activity to produce H2S, which in turn repressed trophoblast differentiation via inhibiting androgen receptor dimerization. Consistently, in preeclamptic placentas, remarkably enhanced CSE O-GlcNAcylation and H2S production were associated with restricted trophoblast differentiation. The findings establish a resource of O-GlcNAc dynamics in human placenta, and provide a deeper insight into the biological significance of O-GlcNAcylation in placental development as well as potential therapeutic targets for the relevant pregnant complications.A prerequisite for intelligent behavior is to understand how stimuli are related and to generalize this knowledge across contexts. Generalization can be challenging when relational patterns are shared across contexts but exist on different physical scales. Here, we studied neural representations in humans and recurrent neural networks performing a magnitude comparison task, for which it was advantageous to generalize concepts of "more" or "less" between contexts. Using multivariate analysis of human brain signals and of neural network hidden unit activity, we observed that both systems developed parallel neural "number lines" for each context. In both model systems, these number state spaces were aligned in a way that explicitly facilitated generalization of relational concepts (more and less). These findings suggest a previously overlooked role for neural normalization in supporting transfer of a simple form of abstract relational knowledge (magnitude) in humans and machine learning systems.The DREAM complex orchestrates cell quiescence and the cell cycle. However, how the DREAM complex is deregulated in cancer remains elusive. Here, we report that PAF (PCLAF/KIAA0101) drives cell quiescence exit to promote lung tumorigenesis by remodeling the DREAM complex. PAF is highly expressed in lung adenocarcinoma (LUAD) and is associated with poor prognosis. Importantly, Paf knockout markedly suppressed LUAD development in mouse models. PAF depletion induced LUAD cell quiescence and growth arrest. PAF is required for the global expression of cell-cycle genes controlled by the repressive DREAM complex. Mechanistically, PAF inhibits DREAM complex formation by binding to RBBP4, a core DREAM subunit, leading to transactivation of DREAM target genes. Furthermore, pharmacological mimicking of PAF-depleted transcriptomes inhibited LUAD tumor growth. Our results unveil how the PAF-remodeled DREAM complex bypasses cell quiescence to promote lung tumorigenesis and suggest that the PAF-DREAM axis may be a therapeutic vulnerability in lung cancer. We conducted a systematic review to examine the role of a novel sublingual vaccine - Uromune - for prevention of recurrent urinary tract infection (rUTI) to understand its potential role for Canadian women suffering from rUTI. Databases were searched for studies published from 2010-2020 that investigated use of Uromune in the management of rUTI. Only original clinical studies that included use of Uromune as prophylaxis for uncomplicated rUTI in women that included UTI-free rate following initiation of vaccine as an outcome were included. Of 73 publications related to Uromune and UTIs, 19 unique clinical studies were identified evaluating Uromune for prevention of rUTI. Five studies met our inclusion criteria for primary review. These included 1408 women treated with Uromune. In two retrospective comparative studies, subjects treated with Uromune daily for three months (519 women in total) had significantly higher UTI-free rates (35-90%) than subjects treated with six months of antibiotic prophylaxis (0% in 499 women in total) over 15 months (p<0.001 for both studies). In three prospective, uncontrolled studies, UTI-free rates for subjects treated with Uromune ranged from 33-78% over 9-24 months. No major safety issues were identified in these trials. Additional unique studies evaluating Uromune for rUTI that did not meet our criteria added consistent confirmation of the potential effectiveness and safety of Uromune to prevent rUTI. Although these findings require confirmation in currently active, prospective clinical studies, including a randomized placebo-controlled trial, Uromune may be an alternative to antibiotics to prevent rUTI in Canadian women. Although these findings require confirmation in currently active, prospective clinical studies, including a randomized placebo-controlled trial, Uromune may be an alternative to antibiotics to prevent rUTI in Canadian women. Adolescents and young adults are a vulnerable patient population for development of substance use disorder. However, the long-term impact of opioid prescribing in young adult patients with renal colic is not known. Our objective was to describe rates of opioid prescription and identify risk factors for persistent opioid use in patients age 25 years or younger with renal colic from kidney stones. Using previously validated, linked administrative databases, we performed a population-based, retrospective cohort study of opioid-naive patients age 25 years or younger with renal colic between July 1, 2013 and September 30, 2017 in Ontario. All family practitioner, urgent care, and specialist visits in the province were captured. Our primary outcome was persistent opioid use, defined as filling a prescription for an opioid between 91 and 180 days after initial visit. https://www.selleckchem.com/products/ozanimod-rpc1063.html Ontario uses a narcotic monitoring system, which captures all opioids dispensed in the province. Of the 6962 patients identified, 56% were prescribed an opioid at presentation and 34% of those were dispensed more than 200 oral morphine equivalents.