Cell biological mechanisms of activity-dependent synapse to nucleus translocation of CRTC1 in neurons.

Previous studies have revealed a critical role for CREB-regulated transcriptional coactivator (CRTC1) in regulating neuronal gene expression during learning and memory. CRTC1 localizes to synapses but undergoes activity-dependent nuclear translocation to regulate the transcription of CREB target genes. Here we investigate the long-distance retrograde transport of CRTC1 in hippocampal neurons. We show that local elevations in calcium, triggered by activation of glutamate receptors and L-type voltage-gated calcium channels, initiate active, dynein-mediated retrograde transport of CRTC1 along microtubules. We identify a nuclear localization signal within CRTC1, and characterize three conserved serine residues whose dephosphorylation is required for nuclear import. Domain analysis reveals that the amino-terminal third of CRTC1 contains all of the signals required for regulated nucleocytoplasmic trafficking. We fuse this region to Dendra2 to generate a reporter construct and perform live-cell imaging coupled with local uncaging of glutamate and photoconversion to characterize the dynamics of stimulus-induced retrograde transport and nuclear accumulation

Prevalence of Dermatological Conditions Among Patients with Diabetic Neuropathy in the Rio Grande Valley: A Retrospective Analysis

Background: Diabetic neuropathy, a common complication of diabetes, predisposes patients to various secondary health issues, including dermatological conditions. This study investigates the prevalence and types of skin conditions (ICD-10 codes L00-L99) among patients with diabetic neuropathy within a South Texas population, aiming to uncover potential correlations and their implications in patient management. Method: This research involved a detailed retrospective review of the UT Health RGV medical database over the past five years, focusing on patients diagnosed with diabetic neuropathy (Type 1: E10.40 to E10.49, E10.610, E10.618; Type 2: E11.40 to E11.49, E11.610, E11.618) and any associated L-series skin conditions. Efforts were made to ensure data accuracy by removing duplicates and repeating ICD-10 codes across various visits. Results: Preliminary analysis reveals a significant prevalence of specific skin conditions among diabetic neuropathy patients. Notably, conditions such as cellulitis (L03.115), other local infections of the skin and subcutaneous tissue (L02.91), and unspecified dermatitis (L30.9) are among the most frequently observed. These findings suggest that diabetic neuropathy may be associated with an increased susceptibility to certain infections and inflammatory skin conditions. Detailed prevalence rates and associations will be elaborated in the full presentation. Conclusion: The identification of common dermatological conditions in diabetic neuropathy patients underscores the need for integrated care approaches. This study not only enhances understanding of the interplay between chronic systemic diseases and skin health but also aids in developing tailored treatment and prevention strategies for this vulnerable population

The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning.

Neuronal ApoE receptors are linked to learning and memory, but the pathways governing their abundance, and the mechanisms by which they affect the function of neural circuits are incompletely understood. Here we demonstrate that the E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity. IDOL-dependent changes in ApoER2 abundance modulate dendritic filopodia initiation and synapse maturation. Loss of IDOL in neurons results in constitutive overexpression of ApoER2 and is associated with impaired activity-dependent structural remodeling of spines and defective LTP in primary neuron cultures and hippocampal slices. IDOL-deficient mice show profound impairment in experience-dependent reorganization of synaptic circuits in the barrel cortex, as well as diminished spatial and associative learning. These results identify control of lipoprotein receptor abundance by IDOL as a post-transcriptional mechanism underlying the structural and functional plasticity of synapses and neural circuits

Aging differentially alters the transcriptome and landscape of chromatin accessibility in the male and female mouse hippocampus

Aging-related memory impairment and pathological memory disorders such as Alzheimer’s disease differ between males and females, and yet little is known about how aging-related changes in the transcriptome and chromatin environment differ between sexes in the hippocampus. To investigate this question, we compared the chromatin accessibility landscape and gene expression/alternative splicing pattern of young adult and aged mouse hippocampus in both males and females using ATAC-seq and RNA-seq. We detected significant aging-dependent changes in the expression of genes involved in immune response and synaptic function and aging-dependent changes in the alternative splicing of myelin sheath genes. We found significant sex-bias in the expression and alternative splicing of hundreds of genes, including aging-dependent female-biased expression of myelin sheath genes and aging-dependent male-biased expression of genes involved in synaptic function. Aging was associated with increased chromatin accessibility in both male and female hippocampus, especially in repetitive elements, and with an increase in LINE-1 transcription. We detected significant sex-bias in chromatin accessibility in both autosomes and the X chromosome, with male-biased accessibility enriched at promoters and CpG-rich regions. Sex differences in gene expression and chromatin accessibility were amplified with aging, findings that may shed light on sex differences in aging-related and pathological memory loss

Deer management generally reduces densities of nymphal Ixodes scapularis, but not prevalence of infection with Borrelia burgdorferi sensu stricto

Human Lyme disease–primarily caused by the bacterium Borrelia burgdorferi sensu stricto (s.s.) in North America–is the most common vector-borne disease in the United States. Research on risk mitigation strategies during the last three decades has emphasized methods to reduce densities of the primary vector in eastern North America, the blacklegged tick (Ixodes scapularis). Controlling white-tailed deer populations has been considered a potential method for reducing tick densities, as white-tailed deer are important hosts for blacklegged tick reproduction. However, the feasibility and efficacy of white-tailed deer management to impact acarological risk of encountering infected ticks (namely, density of host-seeking infected nymphs; DIN) is unclear. We investigated the effect of white-tailed deer density and management on the density of host-seeking nymphs and B. burgdorferi s.s. infection prevalence using surveillance data from eight national parks and park regions in the eastern United States from 2014–2022. We found that deer density was significantly positively correlated with the density of nymphs (nymph density increased by 49% with a 1 standard deviation increase in deer density) but was not strongly correlated with the prevalence of B. burgdorferi s.s. infection in nymphal ticks. Further, while white-tailed deer reduction efforts were followed by a decrease in the density of I. scapularis nymphs in parks, deer removal had variable effects on B. burgdorferi s.s. infection prevalence, with some parks experiencing slight declines and others slight increases in prevalence. Our findings suggest that managing white-tailed deer densities alone may not be effective in reducing DIN in all situations but may be a useful tool when implemented in integrated management regimes

Prognostic Value of D-Dimer and Markers of Coagulation for Stratification of Abdominal Aortic Aneurysm growth

Abdominal aortic aneurysm (AAA) is associated with high morbidity and mortality and is an established cause of unbalanced hemostasis. A number of hemostatic biomarkers have been associated with AAA; however, the utility of hemostatic biomarkers in AAA diagnosis and prognosis is unclear. The aim of the present study was to characterize the potential prognostic value of D-dimer and markers of altered hemostasis in a large cohort of patients with AAAs characterized by either fast or slow aneurysm growth (frequency matched for baseline diameter) and subaneurysmal dilations. We measured plasma concentrations of thrombin-antithrombin (TAT) complex, platelet factor 4 (PF4), and D-dimer in 352 patients with either fast-growing AAAs (.2 mm/y), slow-growing AAAs (,2 mm/y), subaneurysmal aortic dilations, or nonaneurysmal aortas. Plasma D-dimer and TAT were significantly elevated in both AAA and subaneurysmal dilation patients compared with controls. Individuals with D-dimer levels $500 ng/mL had 3.09 times the odds of subaneurysms, 6.23 times the odds of slow-growing AAAs, and 7.19 times the odds of fast-growing AAAs than individuals with D-dimer level,500 ng/mL. However, no differences in D-dimer concentration were noted between fast- and slow-growing aneurysms. Plasma D-dimer and TAT were strong independent predictors of AAA growth rate with multivariate analysis revealing a 500-ng/mL increase in D-dimer or 1-mg/mL increase in TAT led to additional 0.21-mm and 0.24-mm changes in aortic diameter per year, respectively. Rising levels of plasma TAT, in addition to D-dimer, may predict disease progression and aneurysm growth in patients with AAA or subaneurysmal dilation