7-ketocholesterol contributes to microglia-driven increases in astrocyte reactive oxygen species in Alzheimer's disease.

Oxidative stress is a prominent feature of Alzheimer's disease. Within this context, cholesterol undergoes oxidation, producing the pro-inflammatory product 7-ketocholesterol (7-KC). In this study, we observe elevated levels of 7-KC in the brains of the 3xTg mouse model of AD.

Opinions and Suggestions on Nematode Faunal Analysis.

We briefly review the history and development of recognizing nematode assemblages as indicators of environmental conditions. We highlight the effects of spatio-temporal successional changes in nematode assemblages on the auto-regeneration of ecosystem functions after disturbance. We expand on the need for herbivory components in the analysis of soil nematode assemblages in recognition of the important impact of plant parasitism on the resources and productivity of the soil system.

Systematic review of multivariable prognostic models for outcomes at least 30 days after hip fracture finds 18 mortality models but no nonmortality models warranting validation.

Objectives: Prognostic models have the potential to aid clinical decision-making after hip fracture. This systematic review aimed to identify, critically appraise, and summarize multivariable prediction models for mortality or other long-term recovery outcomes occurring at least 30 days after hip fracture.

Study Design And Setting: MEDLINE, Embase, Scopus, Web of Science, and CINAHL databases were searched up to May 2023.

LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction.

Lymphoid restricted membrane protein (LRMP) is a specific regulator of the hyperpolarization-activated cyclic nucleotide-sensitive isoform 4 (HCN4) channel. LRMP prevents cAMP-dependent potentiation of HCN4, but the interaction domains, mechanisms of action, and basis for isoform-specificity remain unknown. Here, we identify the domains of LRMP essential for this regulation, show that LRMP acts by disrupting the intramolecular signal transduction between cyclic nucleotide binding and gating, and demonstrate that multiple unique regions in HCN4 are required for LRMP isoform-specificity.

Mechanical activation of TWIK-related potassium channel by nanoscopic movement and rapid second messenger signaling.

Rapid conversion of force into a biological signal enables living cells to respond to mechanical forces in their environment. The force is believed to initially affect the plasma membrane and then alter the behavior of membrane proteins. Phospholipase D2 (PLD2) is a mechanosensitive enzyme that is regulated by a structured membrane-lipid site comprised of cholesterol and saturated ganglioside (GM1).

Incidental Diagnosis of Williams Syndrome in an Adult With Recurrent Hypercalcemia.

Williams syndrome (WS) is a rare genetic disorder with multisystem involvement associated with hypercalcemia. The cause of this hypercalcemia is poorly understood and while primarily associated with WS children, it is also observed in adults. A 51-year-old woman with intellectual disability, renal insufficiency, recurrent pancreatitis, and intermittent hypercalcemia despite partial parathyroidectomy presented with hypercalcemia to 14 mg/dL (3.

Epidermal Growth Factor Receptors in Vascular Endothelial Cells Contribute to Functional Hyperemia in the Brain.

Functional hyperemia-activity-dependent increases in local blood perfusion-underlies the on-demand delivery of blood to regions of enhanced neuronal activity, a process that is crucial for brain health. Importantly, functional hyperemia deficits have been linked to multiple dementia risk factors, including aging, chronic hypertension, and cerebral small vessel disease (cSVD). We previously reported crippled functional hyperemia in a mouse model of genetic cSVD that was likely caused by depletion of phosphatidylinositol 4,5-bisphosphate (PIP) in capillary endothelial cells (EC) downstream of impaired epidermal growth factor receptor (EGFR) signaling.

Epidermal growth factor receptors in vascular endothelial cells contribute to functional hyperemia in the brain.

Functional hyperemia - activity-dependent increases in local blood perfusion - underlies the on-demand delivery of blood to regions of enhanced neuronal activity, a process that is crucial for brain health. Importantly, functional hyperemia deficits have been linked to multiple dementia risk factors, including aging, chronic hypertension, and cerebral small vessel disease (cSVD). We previously reported crippled functional hyperemia in a mouse model of genetic cSVD that was likely caused by depletion of phosphatidylinositol 4,5-bisphosphate (PIP) in capillary endothelial cells (EC) downstream of impaired epidermal growth factor receptor (EGFR) signaling.

LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction.

Lymphoid restricted membrane protein (LRMP) is a specific regulator of the hyperpolarization-activated cyclic nucleotide-sensitive isoform 4 (HCN4) channel. LRMP prevents cAMP-dependent potentiation of HCN4 but the interaction domains, mechanisms of action, and basis for isoform-specificity remain unknown. Here we identify the domains of LRMP essential for regulation.

Inceptor as a regulator of brain insulin sensitivity.

While historically viewed as an insulin insensitive organ, it is now accepted that insulin has a role in brain physiology. Changes in brain insulin and IGF1 signaling have been associated with neurological diseases, however the molecular factors regulating brain insulin sensitivity remain uncertain. In this study, we proposed that a recently described protein, termed Inceptor, may play a role in brain insulin and IGF1 resistance.

Altered circadian behavior and light sensing in mouse models of Alzheimer's disease.

Circadian symptoms have long been observed in Alzheimer's disease (AD) and often appear before cognitive symptoms, but the mechanisms underlying circadian alterations in AD are poorly understood. We studied circadian re-entrainment in AD model mice using a "jet lag" paradigm, observing their behavior on a running wheel after a 6 h advance in the light:dark cycle. Female 3xTg mice, which carry mutations producing progressive amyloid beta and tau pathology, re-entrained following jet lag more rapidly than age-matched wild type controls at both 8 and 13 months of age.

1 year mortality after hip fracture in an Irish urban trauma centre.

Background: Hip fracture accounts for a considerable burden of disease in older adults, yet there is a paucity of data pertaining to longer-term outcomes in the Irish Hip Fracture population. Understanding the factors that influence longer-term survival would allow care pathways to be refined to optimise patient outcomes. In Ireland, there is no linkage to death registration at a national or regional level, nor are longer-term outcomes captured by the Irish Hip Fracture Database.

Altered circadian behavior and light sensing in mouse models of Alzheimer's disease.

Circadian symptoms have long been observed in Alzheimer's disease (AD) and often appear before cognitive symptoms, but the mechanisms underlying circadian alterations in AD are poorly understood. We studied circadian re-entrainment in AD model mice using a "jet lag" paradigm, observing their behavior on a running wheel after a six hour advance in the light:dark cycle. Female 3xTg mice, which carry mutations producing progressive amyloid beta and tau pathology, re-entrained following jet lag more rapidly than age-matched wild type controls at both 8 and 13 months of age.

Global profiling identifies a stress-responsive tyrosine site on EDC3 regulating biomolecular condensate formation.

RNA granules are cytoplasmic condensates that organize biochemical and signaling complexes in response to cellular stress. Functional proteomic investigations under RNA-granule-inducing conditions are needed to identify protein sites involved in coupling stress response with ribonucleoprotein regulation. Here, we apply chemical proteomics using sulfonyl-triazole (SuTEx) probes to capture cellular responses to oxidative and nutrient stress.

Development of a Frailty Index in the Irish Hip Fracture Database.

Introduction: In older people, hip fracture can lead to adverse outcomes. Frailty, capturing biological age and vulnerability to stressors, can indicate those at higher risk. We derived a frailty index (FI) in the Irish Hip Fracture Database (IHFD) and explored associations with prolonged length of hospital stay (LOS ≥ 30 days), delirium, inpatient mortality and new nursing home admission.

SOD1 mediates lysosome-to-mitochondria communication and its dysregulation by amyloid-β oligomers.

Altered mitochondrial DNA (mtDNA) occurs in neurodegenerative disorders like Alzheimer's disease (AD); how mtDNA synthesis is linked to neurodegeneration is poorly understood. We previously discovered Nutrient-induced Mitochondrial Activity (NiMA), an inter-organelle signaling pathway where nutrient-stimulated lysosomal mTORC1 activity regulates mtDNA replication in neurons by a mechanism sensitive to amyloid-β oligomers (AβOs), a primary factor in AD pathogenesis (Norambuena et al., 2018).

Impact of COVID-19 on hip fracture care in Ireland: findings from the Irish Hip Fracture Database.

Purpose: To describe the impact of COVID-19 on hip fracture care during the first 6 months of the pandemic.

Methods: A secondary analysis of 4385 cases in the Irish Hip Fracture Database from 1st June 2019 to 31st August 2020 was conducted.

Results: Hip fracture admissions decreased by 15% during the study period (p < 0.

Cost of hospitalisation for hip fracture-findings from the Irish hip fracture database.

Unlabelled: The authors utilised the Irish Hip Fracture Database (IHFD) to quantify the impact of hip fracture on the health service in terms of incidence, bed days and financial costs. The absolute number of hip fracture cases recorded by the IHFD has increased, as has the associated costs of hospitalisation.

Introduction: Hip fracture places a considerable clinical and financial burden on the healthcare system, with acute hospitalisation accounting for a substantial proportion of the costs incurred.

Characteristics of Centenarians in the Irish Hip Fracture Database.

Aim Hip fractures are common amongst older people and result in significant morbidity and mortality. The Irish Hip Fracture Database (IHFD) collects data, from the 16 trauma orthopaedic units in Ireland, on patients aged 60 years and older who sustain hip fractures. This study aims to describe the characteristics of those patients aged 100 years and older in this database.

Neutrophil Enzyme Myeloperoxidase Modulates Neuronal Response in a Model of Subarachnoid Hemorrhage by Venous Injury.

Background And Purpose: Aneurysmal subarachnoid hemorrhage (SAH) is associated with the development of delayed cognitive deficits. Neutrophil infiltration into the central nervous system is linked to the development of these deficits after SAH. It is however unclear how neutrophil activity influences central nervous system function in SAH.

Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol.

Alzheimer's disease (AD) is characterized by the presence of amyloid β (Aβ) plaques, tau tangles, inflammation, and loss of cognitive function. Genetic variation in a cholesterol transport protein, apolipoprotein E (apoE), is the most common genetic risk factor for sporadic AD. In vitro evidence suggests that apoE links to Aβ production through nanoscale lipid compartments (lipid clusters), but its regulation in vivo is unclear.

Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease.

Dementia resulting from small vessel diseases (SVDs) of the brain is an emerging epidemic for which there is no treatment. Hypertension is the major risk factor for SVDs, but how hypertension damages the brain microcirculation is unclear. Here, we show that chronic hypertension in a mouse model progressively disrupts on-demand delivery of blood to metabolically active areas of the brain (functional hyperemia) through diminished activity of the capillary endothelial cell inward-rectifier potassium channel, Kir2.