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Divergence of cis-regulatory elements drives species-specific traits1, but how this manifests in the evolution of the neocortex at the molecular and cellular level remains unclear. Here we investigated the gene regulatory programs in the primary motor cortex of human, macaque, marmoset and mouse using single-cell multiomics assays, generating gene expression, chromatin accessibility, DNA methylome and chromosomal conformation profiles from a total of over 200,000 cells. From these data, we show evidence that divergence of transcription factor expression corresponds to species-specific epigenome landscapes. We find that conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome. Transposable elements contribute to nearly 80% of the human-specific candidate cis-regulatory elements in cortical cells. Through machine learning, we develop sequence-based predictors of candidate cis-regulatory elements in different species and demonstrate that the genomic regulatory syntax is highly preserved from rodents to primates. Finally, we show that epigenetic conservation combined with sequence similarity helps to uncover functional cis-regulatory elements and enhances our ability to interpret genetic variants contributing to neurological disease and traits.

Introduction: Microcystis aeruginosa (M. aeruginosa), one of the most prevalent blue-green algae in aquatic environments, produces microcystin by causing harmful algal blooms (HAB). This study investigated the combined effects of nutrients and cyanobacterial subpopulation competition on synthesizing microcystin-LR. Method: In varied nitrogen and phosphorus concentrations, cyanobacterial coculture, and algicidal DCMU presence, the growth was monitored by optical density analysis or microscopic counting, and the microcystin production was analyzed using high-performance liquid chromatography-UV. Furthermore, growth and toxin production were predicted using MATLAB. Results and discussion: First, coculturing with a fast-growing cyanobacterium Synechococcus elongatus UTEX 2973 (S. elongatus) reduced M. aeruginosa biomass and microcystin production at 30oC. Under high nitrogen and low phosphorus conditions, S. elongatus is mostly effective, with up to 94.7% and 92.4% limitation of M. aeruginosa growth and toxin synthesis, respectively. Second, this biological strategy became less effective at 23oC, where S. elongatus grew slower. Third, photosynthesis inhibitor DCMU (3-(3,4-dichlorophenyl)-1,1-dimethylurea) hindered M. aeruginosa growth (at 0.1 mg/L) and microcystin production (at 0.02 mg/L). DCMU was also effective for controlling microcystin production in S. elongatus – M. aeruginosa cocultures. Based on experimental results, a multi-substrate, multi-species kinetic model was built to describe coculture growth and population interactions. Conclusion: Future research should examine more complex models to further develop and refine to facilitate the derivation of more effective recommendations for health prevention programs, particularly for mothers and girls. [ABSTRACT FROM AUTHOR]

The genetic landscape of urologic cancers has evolved with the identification of actionable mutations that impact diagnosis, prognosis, and therapeutic strategies. This narrative review consolidates existing literature on genetic mutations across key urologic cancers, including bladder, renal, prostate, upper tract urothelial, testicular, and penile. The review highlights mutations in DNA damage repair genes, such as BRCA1/2 and PTEN, as well as pathway alterations like FGFR and PD-L1 overexpression. These mutations influence tumor behavior and therapeutic outcomes, emphasizing the need for precision oncology approaches. Molecular profiling, through tools like next-generation sequencing, has revolutionized patient care by enabling targeted treatment strategies, especially in cancers with distinct molecular subtypes such as luminal or basal bladder cancer and clear cell renal carcinoma. Emerging therapies, including FGFR inhibitors and immune checkpoint blockade, offer new treatment avenues, although resistance mechanisms remain a challenge. We also emphasize the importance of biomarker identification for personalized management, especially in metastatic settings where treatment intensification is often required. Future research is needed to further elucidate our understanding of the genetics affecting urologic cancers, which will help develop novel, individualized therapies to enhance oncologic outcomes. [ABSTRACT FROM AUTHOR]

Background: Muscle-invasive bladder cancer (MIBC) is a potentially fatal disease, especially in the setting of locally advanced or node-positive disease. Adverse outcomes have also primarily been associated with low-income status, as has been reported in other cancers. While the adoption of neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC) and pelvic lymph node dissection (PLND) has improved outcomes, these standard-of-care treatments may be underutilized in lower-income patients. We sought to investigate the economic disparities in NAC and PLND receipt and survival outcomes in MIBC. Methods: Utilizing the National Cancer Database, a retrospective cohort analysis of cT2-4N0-3M0 BCa patients with urothelial histology who underwent RC was conducted. The impact of income level on overall survival (OS) and the likelihood of receiving NAC and PLND was evaluated. Results: A total of 25,823 patients were included. This study found that lower-income patients were less likely to receive NAC and adequate PLND (≥15 LNs). Moreover, lower-income patients exhibited worse OS (Median OS 55.9 months vs. 68.2 months, p < 0.001). Our findings also demonstrated that higher income, treatment at academic facilities, and recent years of diagnosis were associated with an increased likelihood of receiving standard-of-care modalities and improved survival. Conclusions: Even after controlling for clinicodemographic variables, income independently influenced the receipt of standard MIBC treatments and survival. Our findings identify an opportunity to improve the quality of care for lower-income MIBC patients through concerted efforts to regionalize multi-modal urologic oncology care. [ABSTRACT FROM AUTHOR]

Background: Partial cystectomy (PC) offers potential benefits for select patients with muscle-invasive bladder cancer (MIBC). However, the oncologic efficacy of PC may be compromised due to the underutilization of standard-of-care modalities, such as neoadjuvant chemotherapy (NAC) and pelvic lymph node dissection (PLND). We aimed to assess factors influencing the incorporation of NAC and PLND with PC and evaluate their impact on overall survival (OS)., Methods: We identified 2,832 patients with cT2-4N0M0 bladder cancer (BCa) who underwent PC between 2004 and 2019 using the National Cancer Database (NCDB). The primary endpoint was OS. Kaplan-Meier analysis compared OS in treatment modalities in PC patients. Multivariate Cox Proportional Hazards (CPH) model assessed the impact of age, sex, race, insurance, income, Charlson-Deyo Index (CDI), clinical T-stage, facility type, histology, surgical margins, NAC, PLND adequacy [≥10 lymph node (LN) yield], and adjuvant radiation treatment on OS. Multivariate logistic regressions were performed to examine predictors of NAC and PLND receipt in PC patients., Results: Two hundred and thirty-one patients received multi-agent NAC with PC. NAC treatment with PLND was associated with significantly improved OS (P<0.001). Median OS was 43.9 months in patients treated with PC alone, while median OS was not reached in PC patients treated with NAC & PLND. Furthermore, patients who received NAC without any PLND had a median OS of 50.6 months, while those treated with PLND without NAC had a median OS of 76.5 months. This persisted in the adjusted CPH model, where private insurance, NAC, and PLND significantly improved OS, especially when PLND yielded ≥10 LN. Conversely, age >80 years old, CDI >2, cT3-4, positive margins, and adjuvant radiation all increased adjusted mortality risk. After controlling for clinicopathologic variables, females were less likely to receive PLND [odds ratio (OR) 0.719, P=0.005], while NAC was more likely administered to PC patients diagnosed from 2016-2019 (OR 5.295, P<0.001). PC patients who received NAC were more likely to have PLND performed as part of their treatment regimen (OR 2.189, P<0.001). Additionally, patients treated at academic centers were more likely to have NAC administered and PLND performed (OR 1.745, P=0.003; OR 2.465, P<0.001, respectively)., Conclusions: Despite guideline recommendations, the utilization of NAC and PLND with PC remains insufficient. Our analysis underscores the significant OS benefit of these recommended treatments as part of MIBC care. Importantly, we highlight a gradual increase in NAC and PLND receipt in recent years, centered largely at academic facilities. Notably, gender disparities exist in PLND receipt, emphasizing the need for further investigation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-165/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)