Stabilizing milk-derived extracellular vesicles (mEVs) through lyophilization: a novel trehalose and tryptophan formulation for maintaining structure and Bioactivity during long-term storage.

Extracellular vesicles (EVs) are widely investigated for their implications in cell-cell signaling, immune modulation, disease pathogenesis, cancer, regenerative medicine, and as a potential drug delivery vector. However, maintaining integrity and bioactivity of EVs between Good Manufacturing Practice separation/filtration and end-user application remains a consistent bottleneck towards commercialization. Milk-derived extracellular vesicles (mEVs), separated from bovine milk, could provide a relatively low-cost, scalable platform for large-scale mEV production; however, the reliance on cold supply chain for storage remains a logistical and financial burden for biologics that are unstable at room temperature.

Molecular Basis of Oncogenic PI3K Proteins.

The dysregulation of phosphatidylinositol 3-kinase (PI3K) signaling plays a pivotal role in driving neoplastic transformation by promoting uncontrolled cell survival and proliferation. This oncogenic activity is primarily caused by mutations that are frequently found in PI3K genes and constitutively activate the PI3K signaling pathway. However, tumorigenesis can also arise from nonmutated PI3K proteins adopting unique active conformations, further complicating the understanding of PI3K-driven cancers.

Emotional words evoke region- and valence-specific patterns of concurrent neuromodulator release in human thalamus and cortex.

Words represent a uniquely human information channel-humans use words to express thoughts and feelings and to assign emotional valence to experience. Work from model organisms suggests that valence assignments are carried out in part by the neuromodulators dopamine, serotonin, and norepinephrine. Here, we ask whether valence signaling by these neuromodulators extends to word semantics in humans by measuring sub-second neuromodulator dynamics in the thalamus (N = 13) and anterior cingulate cortex (N = 6) of individuals evaluating positive, negative, and neutrally valenced words.

The Experimental Beverage Marketplace: Feasibility and preliminary validation of a tool to experimentally study sugar-sweetened beverage taxes and beverage purchasing.

Sugar sweetened-beverage (SSB) consumption contributes to poor diet quality and diet-related chronic diseases. One effective public health strategy to reduce SSB consumption is to tax SSB. Laboratory approaches can complement existing methods to improve understanding of how taxes on SSB influence purchasing.

Beyond the first try: How many quit attempts are necessary to achieve substance use cessation?

Unlabelled: Substance use disorder (SUD) is a chronically relapsing disorder; thus, individuals with SUD may require several attempts before achieving abstinence. The goal of the present study was to investigate what variables are associated with the number of quit attempts before successful abstinence was achieved. Data were collected from 421 International Quit & Recovery Registry participants.

Engineering the physical characteristics of biomaterials for innate immune-mediated cancer immunotherapy.

It has recently been recognized that the physical characteristics of biomaterials - such as size, structure, shape, charge, mechanical strength, hydrophobicity, and multivalency - regulate immunological functions in innate immune cells. In immuno-oncology applications, biomaterials are engineered with distinct physical properties to achieve desired innate immune responses. In this review, we discuss how physical characteristics influence effector functions and innate immune signaling pathways in distinct innate immune cell subtypes.

Longitudinal Pathways From Maltreatment to Substance Use Through Delay Discounting During Adolescence and Into Young Adulthood.

Objective: Children and adolescents exposed to maltreatment are at a greater risk for substance use disorders in adulthood. However, developmental processes that explain how maltreatment experiences may influence substance use behaviors remain unclear. We investigated whether delay discounting (ie, the preference for immediate over delayed rewards), a critical indicator of self-regulation, serves as a key mechanism linking maltreatment and substance use.

Optimizing infant neuroimaging methods to understand the neurodevelopmental impacts of early nutrition and feeding.

There is strong evidence proper nutrition is imperative for healthy infant neurodevelopment, providing the neural foundations for later cognition and behavior. Over the first years of life infants are supported by unique sources of nutrition (e.g.

Effects of early maternal care on anxiety and threat learning in adolescent nonhuman primates.

Early life adverse experiences, including childhood maltreatment, are major risk factors for psychopathology, including anxiety disorders with dysregulated fear responses. Consistent with human studies, maltreatment by the mother (MALT) leads to increased emotional reactivity in rhesus monkey infants. Whether this persists and results in altered emotion regulation, due to enhanced fear learning or impaired utilization of safety signals as shown in human stress-related disorders, is unclear.

More Than a Small Brain: The Importance of Studying Neural Function during Development.

The nervous system contains complex circuits comprising thousands of cell types and trillions of connections. Here, we discuss how the field of "developmental systems neuroscience" combines the molecular and genetic perspectives of developmental neuroscience with the (typically adult-focused) functional perspective of systems neuroscience. This combination of approaches is critical to understanding how a handful of cells eventually produce the wide range of behaviors necessary for survival.

PERM1 regulates mitochondrial energetics through O-GlcNAcylation in the heart.

PERM1 was initially identified as a new downstream target of PGC-1α and ERRs that regulates mitochondrial bioenergetics in skeletal muscle. Subsequently, we and other groups demonstrated that PERM1 is also a positive regulator of mitochondrial bioenergetics in the heart. However, the exact mechanisms of regulatory functions of PERM1 remain poorly understood.

The phenotype of recovery XII: A reinforcer pathology perspective on associations between delay discounting and pain catastrophizing in substance use disorder recovery.

Background: Substance use disorder (SUD) and pain are highly comorbid conditions and several pain indices (e.g., pain intensity) are associated with an increased risk of relapse.

Child maltreatment and executive function development throughout adolescence and into young adulthood.

Child maltreatment impacts approximately one in seven children in the United States, leading to adverse outcomes throughout life. Adolescence is a time period critical for the development of executive function, but there is little research examining how abuse and neglect may differently affect the developmental trajectories of executive function throughout adolescence and into young adulthood. In the current study, 167 adolescents participated at six time points from ages 14 to 20.

Regulation of craving for real-time fMRI neurofeedback based on individual classification.

In previous real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) studies on smoking craving, the focus has been on within-region activity or between-region connectivity, neglecting the potential predictive utility of broader network activity. Moreover, there is debate over the use and relative predictive power of individual-specific and group-level classifiers. This study aims to further advance rtfMRI-NF for substance use disorders by using whole-brain rtfMRI-NF to assess smoking craving-related brain patterns, evaluate the performance of group-level or individual-level classification ( = 31) and evaluate the performance of an optimized classifier across repeated NF runs.

Neural and metabolic factors in carbohydrate reward: Rationale, design, and methods for a flavor-nutrient learning paradigm in humans.

Overconsumption of ultra-processed foods (UPFs), which are linked with adverse health outcomes, is a growing public health concern. UPFs deliver highly bioavailable calories rapidly, which may contribute to their reinforcing potential and drive overconsumption. Our primary aim is to test the role of speed of nutrient availability on reward learning.

Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life.

Biospecimens in the HEALthy Brain and Child Development (HBCD) Study: Rationale and protocol.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The longitudinal collection of biological samples from over 7000 birthing parents and their children within the HBCD study enables research on pre- and postnatal exposures (e.g.

Polygenicity in a box: Copy number variants, neural circuit development, and neurodevelopmental disorders.

Clinically defined neurodevelopmental disorders (cd-NDDs), including Autistic Spectrum Disorder (ASD) and Schizophrenia (Scz), are primarily polygenic: Multiple risk genes distributed across the genome, in potentially infinite combinations, account for variable pathology. Polygenicity raises a fundamental question: Can "core" cd-NDD pathogenic mechanisms be identified given this genomic complexity? With the right models and analytic targets, a distinct class of polygenic mutations-Copy Number Variants (CNVs): contiguous gene deletions or duplications associated with cd-NDD risk-provide a singular opportunity to define cd-NDD pathology. CNVs orthologous to those that confer cd-NDD risk have been engineered in animals as well as human stem cells.

Input-specific localization of NMDA receptor GluN2 subunits in thalamocortical neurons.

Molecular and functional diversity among synapses is generated, in part, by differential expression of neurotransmitter receptors and their associated protein complexes. -methyl--aspartate receptors (NMDARs) are tetrameric ionotropic glutamate receptors that most often comprise two GluN1 and two GluN2 subunits. NMDARs generate functionally diverse synapses across neuron populations through cell-type-specific expression patterns of GluN2 subunits (GluN2A - 2D), which have vastly different functional properties and distinct downstream signaling.