White-nose syndrome, winter duration, and pre-hibernation climate impact abundance of reproductive female bats.

White-nose syndrome (WNS) is an infectious disease that disrupts hibernation in bats, leading to premature exhaustion of fat stores. Though we know WNS does impact reproduction in hibernating female bats, we are unsure how these impacts are exacerbated by local climate factors. We compiled data from four southeastern U.S. states and used generalized linear mixed effects models to compare effects of WNS, pre-hibernation climate variables, and winter duration on the number of reproductive females in species across the range of WNS susceptibility. We predicted we would see a decline in the number of reproductive females in WNS-susceptible species, with the effect exaggerated by longer winter durations and pre-hibernation climate variables that lead to reductions in foraging. We found that the number of reproductive females in WNS-susceptible species was positively correlated with pre-hibernation local climate conditions conducive to foraging; however, WNS-susceptible species experienced an overall decline with the presence of WNS and as winter duration increased. Our long-term dataset provides evidence that pre-hibernation climate, specifically favorable summer weather conditions for foraging, greatly influences the reproduction, regardless of WNS status.

Incidence and Risk Factors for ICU-Associated Delirium in the Alert Geriatric Trauma Population.

BACKGROUND: This study analyzed the overall incidence of delirium, comorbid conditions, injury patterns, and pharmacological risk factors for the development of delirium in an alert, geriatric trauma population. METHODS: IRB-approved, prospective, consecutive cohort series at two Southeastern Level 1 trauma centers from June 11 to August 15, 2023. Delirium was assessed using the Confusion Assessment Method (CAM) score. Comorbidities and medications were detailed from electronic medical records. Inclusion criteria: age ≥55, GCS ≥14, and ICU admission for trauma. Patients on a ventilator were excluded. Data was analyzed using SPSS version 28 (Armonk, NY: IBM Corp). RESULTS: In total, 196 patients met inclusion criteria. Incidences of delirium for Hospital 1 (n = 103) and Hospital 2 (n = 93) were 15.5% and 12.9%, respectively, with an overall incidence of 14.3% and with no statistical differences between hospitals (P = .599). CAD, CKD, dementia, stroke history, and depression were statistically significant risk factors for developing delirium during ICU admission. Inpatient SSRI/SNRIs, epinephrine/norepinephrine, and lorazepam were significant risk factors. Injury patterns, operative intervention, and use of lidocaine infusions and gabapentin were not statistically significant in delirium development. Using binary linear regression (BLR) analysis, independent risk factors for delirium were dementia, any stage CKD, home SSRI/SRNI prescription, any spine injury and cerebrovascular disease, or injury. DISCUSSION: Comorbidities of CAD, CHF, CKD, and depression, and these medications: home lorazepam and ICU epinephrine/norepinephrine statistically are more common in patients developing delirium. Dementia, CKD, home SSRI/SRNI and stroke/cerebrovascular disease/injury, and spine injuries are independent predictors by BLR.

NTH1 Is a New Target for Ubiquitylation-Dependent Regulation by TRIM26 Required for the Cellular Response to Oxidative Stress.

Endonuclease III-like protein 1 (NTH1) is a DNA glycosylase required for the repair of oxidized bases, such as thymine glycol, within the base excision repair pathway. We examined regulation of NTH1 protein by the ubiquitin proteasome pathway and identified the E3 ubiquitin ligase tripartite motif 26 (TRIM26) as the major enzyme targeting NTH1 for polyubiquitylation. We demonstrate that TRIM26 catalyzes ubiquitylation of NTH1 predominantly on lysine 67 present within the N terminus of the protein in vitro In addition, the stability of a ubiquitylation-deficient protein mutant of NTH1 (lysine to arginine) at this specific residue was significantly increased in comparison to the wild-type protein when transiently expressed in cultured cells. We also demonstrate that cellular NTH1 protein is induced in response to oxidative stress following hydrogen peroxide treatment of cells and that accumulation of NTH1 on chromatin is exacerbated in the absence of TRIM26 through small interfering RNA (siRNA) depletion. Stabilization of NTH1 following TRIM26 siRNA also causes significant acceleration in the kinetics of DNA damage repair and cellular resistance to oxidative stress, which can be recapitulated by moderate overexpression of NTH1. This demonstrates the importance of TRIM26 in regulating the cellular levels of NTH1, particularly under conditions of oxidative stress.

Ubiquitylation-dependent regulation of NEIL1 by Mule and TRIM26 is required for the cellular DNA damage response.

Endonuclease VIII-like protein 1 (NEIL1) is a DNA glycosylase involved in initiating the base excision repair pathway, the major cellular mechanism for repairing DNA base damage. Here, we have purified the major E3 ubiquitin ligases from human cells responsible for regulation of NEIL1 by ubiquitylation. Interestingly, we have identified two enzymes that catalyse NEIL1 polyubiquitylation, Mcl-1 ubiquitin ligase E3 (Mule) and tripartite motif 26 (TRIM26). We demonstrate that these enzymes are capable of polyubiquitylating NEIL1 in vitro, and that both catalyse ubiquitylation of NEIL1 within the same C-terminal lysine residues. An siRNA-mediated knockdown of Mule or TRIM26 leads to stabilisation of NEIL1, demonstrating that these enzymes are important in regulating cellular NEIL1 steady state protein levels. Similarly, a mutant NEIL1 protein lacking residues for ubiquitylation is more stable than the wild type protein in vivo We also demonstrate that cellular NEIL1 protein is induced in response to ionising radiation (IR), although this occurs specifically in a Mule-dependent manner. Finally we show that stabilisation of NEIL1, particularly following TRIM26 siRNA, contributes to cellular resistance to IR. This highlights the importance of Mule and TRIM26 in maintaining steady state levels of NEIL1, but also those required for the cellular DNA damage response.