Retinoid X Receptor Signaling Mediates Cancer Cell Lipid Metabolism in the Leptomeninges.

Cancer cells metastatic to the leptomeninges encounter a metabolically-challenging extreme microenvironment. To understand adaptations to this space, we subjected leptomeningeal-metastatic (LeptoM) mouse breast and lung cancers isolated from either the leptomeninges or orthotopic primary sites to ATAC-and RNA-sequencing. When inhabiting the leptomeninges, the LeptoM cells demonstrated transcription downstream of retinoid-X-receptors (RXRs).

Leptomeningeal anti-tumor immunity follows unique signaling principles.

Metastasis to the cerebrospinal fluid (CSF)-filled leptomeninges, or leptomeningeal metastasis (LM), represents a fatal complication of cancer. Proteomic and transcriptomic analyses of human CSF reveal a substantial inflammatory infiltrate in LM. We find the solute and immune composition of CSF in the setting of LM changes dramatically, with notable enrichment in IFN-γ signaling.

CXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis.

Proinflammatory signaling is a hallmark feature of human cancer, including in myeloproliferative neoplasms (MPNs), most notably myelofibrosis (MF). Dysregulated inflammatory signaling contributes to fibrotic progression in MF; however, the individual cytokine mediators elicited by malignant MPN cells to promote collagen-producing fibrosis and disease evolution are yet to be fully elucidated. Previously, we identified a critical role for combined constitutive JAK/STAT and aberrant NF-κB proinflammatory signaling in MF development.

Classifying Young Children with Attention-Deficit/Hyperactivity Disorder Based on Child, Parent, and Family Characteristics: A Cross-Validation Study.

We aimed to identify subgroups of young children with differential risks for ADHD, and cross-validate these subgroups with an independent sample of children. All children in Study 1 (N = 120) underwent psychological assessments and were diagnosed with ADHD before age 7. Latent class analysis (LCA) classified children into risk subgroups.

Characterization, isolation, and in vitro culture of leptomeningeal fibroblasts.

Meninges, or the membranous coverings of the brain and spinal cord, play host to dozens of morbid pathologies. In this study we provide a method to isolate the leptomeningeal cell layer, identify leptomeninges in histologic slides, and maintain leptomeningeal fibroblasts in in vitro culture. Using an array of transcriptomic, histological, and cytometric analyses, we identified ICAM1 and SLC38A2 as two novel markers of leptomeningeal cells in vivo and in vitro.

Preferential uptake of antibody targeted calcium phosphosilicate nanoparticles by metastatic triple negative breast cancer cells in co-cultures of human metastatic breast cancer cells plus bone osteoblasts.

Calcium phosphosilicate nanoparticles (CPSNPs) are bioresorbable nanoparticles that can be bioconjugated with targeting molecules and encapsulate active agents and deliver them to tumor cells without causing damage to adjacent healthy tissue. Data obtained in this study demonstrated that an anti-CD71 antibody on CPSNPs targets these nanoparticles and enhances their internalization by triple negative breast cancer cells in-vitro. Caspase 3,7 activation, DNA damage, and fluorescent microscopy confirmed the apoptotic breast cancer response caused by targeted anti-CD71-CPSNPs encapsulated with gemcitabine monophosphate, the active metabolite of the chemotherapeutic gemcitabine used to treat cancers including breast and ovarian.

History of conditioned reward association disrupts inhibitory control: an examination of neural correlates.

The neural processes that support inhibitory control in the face of stimuli with a history of reward association are not yet well understood. Yet, the ability to flexibly adapt behavior to changing reward-contingency contexts is important for daily functioning and warrants further investigation. This study aimed to characterize neural and behavioral impacts of stimuli with a history of conditioned reward association on motor inhibitory control in healthy young adults by investigating group-level effects as well as individual variation in the ability to inhibit responses to stimuli with a reward history.

Examining cognitive control and reward interactions in adolescent externalizing symptoms.

During adolescence, rapid development and reorganization of the dopaminergic system supports increasingly sophisticated reward learning and the ability to exert behavioral control. Disruptions in the ability to exert control over previously rewarded behavior may underlie some forms of adolescent psychopathology. Specifically, symptoms of externalizing psychopathology may be associated with difficulties in flexibly adapting behavior in the context of reward.

Resting-state EEG Connectivity in Young Children with ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing neurodevelopmental disorder. While early childhood is a crucial time for early intervention, it is characterized by instability of ADHD diagnosis. Neural correlates of ADHD have potential to improve diagnostic accuracy; however, minimal research has focused on early childhood.

Registration-free analysis of diffusion MRI tractography data across subjects through the human lifespan.

Diffusion MRI tractography produces massive sets of streamlines that need to be clustered into anatomically meaningful white-matter bundles. Conventional clustering techniques group streamlines based on their proximity in Euclidean space. We have developed AnatomiCuts, an unsupervised method for clustering tractography streamlines based on their neighboring anatomical structures, rather than their coordinates in Euclidean space.

Differential Associations of Deprivation and Threat With Cognitive Control and Fear Conditioning in Early Childhood.

Early-life adversity (ELA) is strongly associated with risk for psychopathology. Within adversity, deprivation, and threat may lead to psychopathology through different intermediary pathways. Specifically, deprivation, defined as the absence of expected cognitive and social inputs, is associated with lower performance on complex cognitive tasks whereas threatening experiences, defined as the presence of experiences that reflect harm to the child, are associated with atypical fear learning and emotional processes.

Development of Prefrontal Cortical Connectivity and the Enduring Effect of Learned Value on Cognitive Control.

Inhibitory control, the capacity to suppress an inappropriate response, is a process employed for guiding action selection in the service of goal-directed behavior. Under neutral circumstances, inhibitory control success improves from childhood to adulthood and has been associated with developmental shifts in functional activation and connectivity of the PFC. However, the ability to exercise inhibitory control is challenged in certain contexts by including appetitive cues, a phenomenon that may be particularly pronounced in youths.

MGH-USC Human Connectome Project datasets with ultra-high b-value diffusion MRI.

The MGH-USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300 mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH-USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU-Minn Connectome Database (ConnectomeDB).