Cell Membrane Fatty Acids and PIPs Modulate the Etiology of Pancreatic Cancer by Regulating AKT.

Pancreatic ductal adenocarcinoma (PDAC) is one of the worst solid malignancies in regard to outcomes and metabolic dysfunction leading to cachexia. It is alarming that PDAC incidence rates continue to increase and warrant the need for innovative approaches to combat this disease. Due to its relatively slow progression (10-20 years), prevention strategies represent an effective means to improve outcomes.

Synaptopodin: a key regulator of Hebbian plasticity.

Synaptopodin, an actin-associated protein found in a subset of dendritic spines in telencephalic neurons, has been described to influence both functional and morphological plasticity under various plasticity paradigms. Synaptopodin is necessary and sufficient for the formation of the spine apparatus, stacks of smooth endoplasmic reticulum cisternae. The spine apparatus is a calcium store that locally regulates calcium dynamics in response to different patterns of activity and is also thought to be a site for local protein synthesis.

Health Disparities and the Influence of Culturally Competent Care in Overall Health and Healthcare Utilization among Hispanics in a Southeastern US Community.

This study sought to assess disparities in health/healthcare utilization for Hispanic immigrant community in Greenville County, SC. The study also assessed the role of culturally competent care perceptions on health/healthcare utilization within this growing community. Secondary administrative data collected by a large health care system in the county facilitated the assessment of health/healthcare utilization disparities using multivariate regression.

Impaired hippocampal plasticity associated with loss of recycling endosomal SLC9A6/NHE6 is ameliorated by the TrkB agonist 7,8-dihydroxyflavone.

Proper maintenance of intracellular vesicular pH is essential for cargo trafficking during synaptic function and plasticity. Mutations in the SLC9A6 gene encoding the recycling endosomal pH regulator (Na, K)/H exchanger isoform 6 (NHE6) are causal for Christianson syndrome (CS), a severe form of X-linked intellectual disability. NHE6 expression is also downregulated in other neurodevelopmental and neurodegenerative disorders, such as autism spectrum disorder and Alzheimer's disease, suggesting its dysfunction could contribute more broadly to the pathophysiology of other neurological conditions.

Sex-Specific ADNP/NAP (Davunetide) Regulation of Cocaine-Induced Plasticity.

Cocaine use disorder (CUD) is a chronic neuropsychiatric disorder estimated to effect 1-3% of the population. Activity-dependent neuroprotective protein (ADNP) is essential for brain development and functioning, shown to be protective in fetal alcohol syndrome and to regulate alcohol consumption in adult mice. The goal of this study was to characterize the role of ADNP, and its active peptide NAP (NAPVSIPQ), which is also known as davunetide (investigational drug) in mediating cocaine-induced neuroadaptations.

The ISR downstream target ATF4 represses long-term memory in a cell type-specific manner.

The integrated stress response (ISR), a pivotal protein homeostasis network, plays a critical role in the formation of long-term memory (LTM). The precise mechanism by which the ISR controls LTM is not well understood. Here, we report insights into how the ISR modulates the mnemonic process by using targeted deletion of the activating transcription factor 4 (ATF4), a key downstream effector of the ISR, in various neuronal and non-neuronal cell types.

Eta-secretase-like processing of the amyloid precursor protein (APP) by the rhomboid protease RHBDL4.

The amyloid precursor protein (APP) is a key protein in Alzheimer's disease synthesized in the endoplasmic reticulum (ER) and translocated to the plasma membrane where it undergoes proteolytic cleavages by several proteases. Conversely, to other known proteases, we previously elucidated rhomboid protease RHBDL4 as a novel APP processing enzyme where several cleavages likely occur already in the ER. Interestingly, the pattern of RHBDL4-derived large APP C-terminal fragments resembles those generated by the η-secretase or MT5-MMP, which was described to generate so-called Aη fragments.

Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated With Psychopathology Across Independent Cohorts.

Background: Patients with early psychosis (EP) (within 3 years after psychosis onset) show significant variability, which makes predicting outcomes challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, which limits the development of early interventions.

Methods: A data-driven approach, partial least squares correlation, was used across 2 independent datasets to examine multivariate relationships between white matter properties and symptomatology and to identify stable and generalizable signatures in EP.

Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

Background: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions.

Methods: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP.

Synaptopodin is required for long-term depression at Schaffer collateral-CA1 synapses.

Synaptopodin (SP), an actin-associated protein found in telencephalic neurons, affects activity-dependant synaptic plasticity and dynamic changes of dendritic spines. While being required for long-term depression (LTD) mediated by metabotropic glutamate receptor (mGluR-LTD), little is known about its role in other forms of LTD induced by low frequency stimulation (LFS-LTD) or spike-timing dependent plasticity (STDP). Using electrophysiology in ex vivo hippocampal slices from SP-deficient mice (SPKO), we show that absence of SP is associated with a deficit of LTD at Sc-CA1 synapses induced by LFS-LTD and STDP.

Novel forms of ventilation in neonates: Neurally adjusted ventilatory assist and proportional assist ventilation.

Patient-triggered modes of ventilation are currently the standard of practice in the care of term and preterm infants. Maintaining spontaneous breathing during mechanical ventilation promotes earlier weaning and possibly reduces ventilator-induced diaphragmatic dysfunction. A further development of assisted ventilation provides support in proportion to the respiratory effort and enables the patient to have full control of their ventilatory cycle.

Substance Use Screening in Geriatric Primary Care: Cultural Issues and Alcohol Consumption in the Deep South.

Objectives: To investigate indicators of potentially hazardous alcohol use among older adults living in a region with high substance use stigma.

Methods: Patients at a university-affiliated geriatrics clinic in the Deep South of theUS completed behavioral health screenings including self-reported alcohol use, symptoms of depression or anxiety, and cognitive functioning between 2018 and 2022.

Results: Participants ( = 278) averaged 76.

Loss of synaptopodin impairs mGluR5 and protein synthesis-dependent mGluR-LTD at CA3-CA1 synapses.

Metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) is an important form of synaptic plasticity that occurs in many regions of the central nervous system and is the underlying mechanism for several learning paradigms. In the hippocampus, mGluR-LTD is manifested by the weakening of synaptic transmission and elimination of dendritic spines. Interestingly, not all spines respond or undergo plasticity equally in response to mGluR-LTD.

Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes.

Background: Compared to minimally invasive brain metastases (MI BrM), highly invasive (HI) lesions form abundant contacts with cells in the peritumoral brain parenchyma and are associated with poor prognosis. Reactive astrocytes (RAs) labeled by phosphorylated STAT3 (pSTAT3) have recently emerged as a promising therapeutic target for BrM. Here, we explore whether the BrM invasion pattern is influenced by pSTAT3+ RAs and may serve as a predictive biomarker for STAT3 inhibition.

Prostate Cancer Treatment via CRISPR-Cas9 Gene Editing Facilitated by Polyethyleneimine-Derived Graphene Quantum Dots.

CRISPR-Cas9 is a programmable gene editing tool with a promising potential for cancer gene therapy. This therapeutic function is enabled in the present work via the non-covalent delivery of CRISPR ribonucleic protein (RNP) by cationic glucosamine/PEI-derived graphene quantum dots (PEI-GQD) that aid in overcoming physiological barriers and tracking genes of interest. PEI-GQD/RNP complex targeting the TP53 mutation overexpressed in ~50% of cancers successfully produces its double-stranded breaks in solution and in PC3 prostate cancer cells.

Chronic Volar Distal Radial Ulnar Joint Dislocation: A Case Report with Proposed Treatment Algorithm.

Case: We report the case of a 34-year-old woman with a chronic right volar dislocation of the distal radioulnar joint (DRUJ) and associated ulnar styloid fracture. The patient presented 1 month after a dog bite injury with wrist pain and limited range of motion, and radiographs demonstrated volar DRUJ dislocation. Closed reduction was unsuccessful, and thus, open reduction was performed.

Geographical and seasonal patterns in the carbonate chemistry of Narragansett Bay, RI.

This study examined geographical and seasonal patterns in carbonate chemistry and will facilitate assessment of acidification conditions and the current state of the seawater carbonate chemistry system in Narragansett Bay. Direct measurements of total alkalinity, dissolved inorganic carbon, dissolved oxygen percent saturation, water temperature, salinity and pressure were performed during monthly sampling cruises carried out over three years. These measurements were used to calculate the following biologically relevant carbonate system parameters: total pH , the partial pressure of carbon dioxide in the gas phase , and the aragonite saturation state .

Loss of synaptopodin impairs mGluR5 and protein synthesis dependent mGluR-LTD at CA3-CA1 synapses.

Unlabelled: Metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) is an important form of synaptic plasticity that occurs in many regions of the CNS and is the underlying mechanism for several learning paradigms. In the hippocampus, mGluR-LTD is manifested by the weakening of synaptic transmission and elimination of dendritic spines. Interestingly, not all spines respond or undergo plasticity equally in response to mGluR-LTD.