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Exploring the Effects of RNase H2 Regulation and Protein Lysine Acetylation on Genomic Stability
No full textIUIMaintenance of genomic integrity during DNA replication requires precise coordination of multiple enzymatic processes. The antiparallel nature of the duplex DNA necessitates asymmetric replication, where the leading strand is synthesized continuously while the lagging strand is synthesized discontinuously as Okazaki fragments. In human cells, approximately 50 million Okazaki fragments are generated per replication cycle and must be matured and seamlessly joined to produce an intact lagging strand. Defects in this process contribute to genomic instability and have been implicated in cancer development. The Okazaki fragment maturation (OFM) process involves a coordinated action of several key enzymes: DNA Polymerase δ (Pol δ) synthesizes and displaces the preceding fragment creating a flap, which is then processed by flap endonuclease 1 (FEN1) and the remaining nick is sealed by DNA LigI. Additionally, despite their high fidelity, replicative polymerases can occasionally incorporate ribonucleotides during synthesis, which is processed by Ribonuclease H2 (RNase H2) in the ribonucleotide excision repair (RER) pathway. Central to both pathways is proliferating cell nuclear antigen (PCNA), a sliding clamp that mediates these activities through protein-protein interactions via PCNA-interaction peptide (PIP) domains. The fidelity and efficiency of lagging strand synthesis therefore depend critically on the sequential handoff of DNA substrate between these coordinated enzymes. This study investigates two regulatory mechanisms that modulate protein function and influence pathway efficiency and overall genome stability. First, we examined RNase H2’s role as a potential coordinator linking OFM and RER pathways. Our results reveal bidirectional stimulatory interactions between RNase H2 and key downstream enzymes - Pol δ, FEN1, and DNA LigI, suggesting a coordinated regulatory network. Second, we investigated how lysine acetylation, a dynamic post-translational modification, affects the enzymatic activity of RNase H2, Pol δ, and RPA. In vitro acetylation studies demonstrate enhanced enzymatic activity for all three proteins, indicating that this modification may serve as a governing mechanism controlling OFM efficiency. Collectively, our findings suggest that these protein interaction networks, and regulatory mechanisms offer potential therapeutic targets for cancer and other diseases associated with genomic instability
Sinus Tarsi Versus Extensile Lateral Approach For Calcaneal Fractures - A Multicenter Study
No full textIntroduction: The optimal surgical approach for intraarticular calcaneal fractures remains debated. This study compares deep infection rates between the extended lateral (EL) and sinus tarsi (ST) approaches.
Methods: A retrospective review was conducted of 782 patients treated surgically for OTA 82B/C calcaneal fractures across 15 institutions. Deep infection was defined as requiring surgical débridement or treatment for osteomyelitis. Risk factors were identified using univariate and multivariate analyses.
Results: Of 782 fractures, 444 were treated with EL and 338 with ST. Deep infections occurred in 6.8% of EL and 3.0% of ST cases (P = 0.017). Multivariate analysis found that surgical approach (P = 0.03) and age (P < 0.001) were independent risk factors. EL had more wound complications; ST had more symptomatic implants.
Conclusion: The ST approach was associated with lower rates of deep infection and wound complications, even in higher-risk patients
The Editorial Decision-Making Process: Evaluating Aims & Scope Alignment
No full textThis editorial describes the decision-making process involved in the peer-reviewed interdisciplinary social science journal Review of Religious Research . Inspired by visuals of how a bill becomes a law, this decision-tree visualization walks readers through the process for how a manuscript becomes a published article. Article publication is a social process that involves many experts: the editor plus multiple reviewers and sometimes editorial board members. This step-by-step description leads toward three important takeaways. First is myth busting editorial gatekeeping by recognizing the importance of peer reviewers and editorial board members. Second is a rationale for reviewer recommendations to editors and explanation of what is acceptable to state directly to authors versus the role of confidential comments to the editor. Third is the crucial importance of the journal Aims & Scope in assessing fit with this journal. Clarifying how manuscript decisions get made can build author understanding, further socialize reviewers, and accentuate the weight of editorial board member input for quality reviewing
Indocyanine Green as a Marker for Tissue Ischemia in Spinal Tumor Resections and Extended Revisions: A Technical Note
No full textBackground/Objectives: The increasing complexity of spinal oncology procedures, particularly in en-bloc tumor resections, creates challenges in tissue perfusion assessment due to extended operative times and extensive surgical dissection. Real-time visualization of tissue perfusion can be achieved with ICG using commercially available handheld imaging systems, offering potential advantages in spinal oncology cases. This study assessed the utility of ICG in analyzing soft-tissue viability during complex spine procedures extending beyond 7.5 h, with a particular focus on oncologic resections. Methods: Three cases that required over 7.5 h of operative time were chosen for ICG utilization. These cases included an en-bloc malignant peripheral nerve sheath tumor resection, an en-bloc resection of a malignant epithelioid neoplasm, and a long-segment fusion revision for pseudoarthrosis. At the conclusion of the critical portion of the procedure, a handheld intraoperative fluorescence camera was utilized to visualize the tissue penetration of intravenous ICG. Results: Prior to injecting ICG, devascularized tissue was not clearly visible. Injecting ICG allowed clear separation of vascularized (fluorescing) and devascularized (non-fluorescing) tissues. One region of non-florescent tissue was later confirmed to be devascularized with MRI and experienced postoperative infection. Conclusions: As the complexity of spinal oncology procedures increases, ICG fluorescence imaging offers a novel method for real-time assessment of tissue perfusion. This technique may be particularly valuable in extensive tumor resections, post-radiation cases, and revision surgeries where tissue viability is at risk. Further investigation in the spinal oncology population could help establish whether early identification of poorly perfused tissues impacts wound healing outcomes
Sense of Belonging: Chancellor's Student Advisory Board Research Project 2025
No full textThe Chancellor's Student Advisory Board's final presentation for Spring 2025 investigates the impact of the IU/Purdue split on student morale and sense of belonging at Indiana University Indianapolis. The team conducted research through surveys and personal outreach, gathering insights from 120 respondents. Findings reveal mixed feelings about campus connection and the perceived value of degrees post-split. Recommendations include hosting open forums, increasing faculty involvement, and emphasizing the university's strengths to foster a supportive community. The presentation calls for proactive measures to ensure every student feels seen, heard, and valued during this transitional period
Neutrophil NADPH oxidase promotes bacterial eradication and regulates NF-κB-Mediated inflammation via NRF2 signaling during urinary tract infections
No full textThe precise role of neutrophil-derived reactive oxygen species (ROS) in combating bacterial uropathogens during urinary tract infections (UTI) remains largely unexplored. In this study, we elucidate the antimicrobial significance of NADPH oxidase 2 (NOX2)-derived ROS, as opposed to mitochondrial ROS, in facilitating neutrophil-mediated eradication of uropathogenic Escherichia coli (UPEC), the primary causative agent of UTI. Furthermore, NOX2-derived ROS regulate NF-κB-mediated inflammatory responses in neutrophils against UPEC by inducing the release of nuclear factor erythroid 2-related factor 2 (Nrf2) from its inhibitor, Kelch-like ECH-associated protein 1 (Keap1). Consistently, the absence of NOX2 (Cybb-/-) in mice led to uncontrolled bacterial infection associated with increased NF-κB signaling, heightened neutrophilic inflammation, and increased bladder pathology during cystitis. These findings underscore a dual role for neutrophil NOX2 in both eradicating UPEC and mitigating neutrophil-mediated inflammation in the urinary tract, revealing a previously unrecognized effector and regulatory mechanism in the control of UTI
The effect of Alzheimer's disease genetic factors on limbic white matter microstructure
No full textIntroduction: White matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences.
Methods: To evaluate how AD genetic risk factors affect limbic WM microstructure - crucial for memory and early impacted in disease - we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores (PGSs) and WM metrics, and interactions with cognitive status.
Results: AD PGSs, variants in TMEM106B, PTK2B, WNT3, and apolipoprotein E (APOE), and interactions involving MS4A6A were significantly linked to WM microstructure.
Discussion: These findings implicate AD-related genetic factors related to neurodevelopment (WNT3), lipid metabolism (APOE), and inflammation (TMEM106B, PTK2B, MS4A6A) that contribute to alternations in WM microstructure in older adults.
Highlights: AD risk variants in TMEM106B, PTK2B, WNT3, and APOE genes showed distinct associations with limbic FW-corrected WM microstructure metrics. Interaction effects were observed between MS4A6A variants and cognitive status. PGS for AD was associated with higher FW content in the limbic system
Parental liver disease mortality is associated with unfavorable outcomes in patients with alcohol-associated hepatitis
No full textBackground: How parental alcohol use disorder and liver disease-related mortality influence the risk and the outcomes of alcohol-associated hepatitis (AH) in the offspring is unknown.
Methods: We analyzed data from 2 prospective observational studies of AH cases and heavy drinking controls (HDCs). Family history of parental alcohol use disorder and liver disease mortality was assessed at the study entry. Logistic regression and Cox proportional hazard models were used to assess the influences of family history on AH development and outcome.
Results: Data from 1356 participants in two prospective cohorts (926 AH cases and 430 HDC) were combined and analyzed. Parental alcohol use disorder was found in 56.9% of AH cases and 61.1% of HDC; parental death due to liver disease was reported in 7.5% of AH cases and 5.7% of HDC. Multivariable logistic regression showed that parental liver disease-related mortality was associated with more than a doubled risk of AH development in the offspring after controlling for their demographic characteristics and drinking behavior (OR=2.26, 95% CI: [1.22, 4.20]). Moreover, among the AH cases, having a parent die of liver disease significantly increased the 90-day mortality of study participants after adjusting for the effects of other risk factors (HR=2.26, 95% CI: [1.05, 4.86]).
Conclusions: The study highlights the influences of parental death due to liver disease on AH development and mortality. Identifying patients at risk of AH through family history might help facilitate discussions on reducing alcohol consumption
Bridging the Gap: Student Access to IU Mental Health Resources: Chancellor's Student Mental Health Council Research Project 2025
No full textThe Chancellor's Student Mental Health Council at Indiana University Indianapolis conducted a study to understand student access to campus mental health resources. This presentation, led by Yamana Uno, Sofia Breuer, and Casandra Carrillo, explores the barriers students face in accessing mental health support, such as time constraints, overwhelming processes, long wait times, and limited service hours. Through focus groups, the research identifies key issues. The findings highlight the need for improved communication strategies, targeted outreach, and enhanced resource accessibility. Recommendations for immediate, short-term, and long-term actions are proposed to address these challenges, including the development of webinars, active involvement of mental health professionals, and the implementation of a Canvas course to centralize resources. The study aims to foster a more supportive and accessible mental health environment for all students at IU Indianapolis
