Browsing by Subject "phenotype"
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Item Open Access Biomaterials-Mediated Regulation of Macrophage Cell Fate.(Frontiers in bioengineering and biotechnology, 2020-01) Liu, Yining; Segura, TatianaEndogenous regeneration aims to rebuild and reinstate tissue function through enlisting natural self-repairing processes. Promoting endogenous regeneration by reducing tissue-damaging inflammatory responses while reinforcing self-resolving inflammatory processes is gaining popularity. In this approach, the immune system is recruited as the principal player to deposit a pro-reparative matrix and secrete pro-regenerative cytokines and growth factors. The natural wound healing cascade involves many immune system players (neutrophils, macrophages, T cells, B cells, etc.) that are likely to play important and indispensable roles in endogenous regeneration. These cells support both the innate and adaptive arms of the immune system and collectively orchestrate host responses to tissue damage. As the early responders during the innate immune response, macrophages have been studied for decades in the context of inflammatory and foreign body responses and were often considered a cell type to be avoided. The view on macrophages has evolved and it is now understood that macrophages should be directly engaged, and their phenotype modulated, to guide the timely transition of the immune response and reparative environment. One way to achieve this is to design immunomodulating biomaterials that can be placed where endogenous regeneration is desired and actively direct macrophage polarization. Upon encountering these biomaterials, macrophages are trained to perform more pro-regenerative roles and generate the appropriate environment for later stages of regeneration since they bridge the innate immune response and the adaptive immune response. This new design paradigm necessitates the understanding of how material design elicits differential macrophage phenotype activation. This review is focused on the macrophage-material interaction and how to engineer biomaterials to steer macrophage phenotypes for better tissue regeneration.Item Restricted Fluorescent Labeling of Newborn Dentate Granule Cells in GAD67-GFP Transgenic Mice: A Genetic Tool for the Study of Adult Neurogenesis(2010) Zhao, Shengli; Zhou, Yang; Gross, Jimmy; Miao, Pei; Qiu, Li; Wang, Dongqing; Chen, Qian; Feng, GuopingNeurogenesis in the adult hippocampus is an important form of structural plasticity in the brain. Here we report a line of BAC transgenic mice (GAD67-GFP mice) that selectively and transitorily express GFP in newborn dentate granule cells of the adult hippocampus. These GFP+ cells show a high degree of colocalization with BrdU-labeled nuclei one week after BrdU injection and express the newborn neuron marker doublecortin and PSA-NCAM. Compared to mature dentate granule cells, these newborn neurons show immature morphological features: dendritic beading, fewer dendritic branches and spines. These GFP+ newborn neurons also show immature electrophysiological properties: higher input resistance, more depolarized resting membrane potentials, small and non-typical action potentials. The bright labeling of newborn neurons with GFP makes it possible to visualize the details of dendrites, which reach the outer edge of the molecular layer, and their axon (mossy fiber) terminals, which project to the CA3 region where they form synaptic boutons. GFP expression covers the whole developmental stage of newborn neurons, beginning within the first week of cell division and disappearing as newborn neurons mature, about 4 weeks postmitotic. Thus, the GAD67-GFP transgenic mice provide a useful genetic tool for studying the development and regulation of newborn dentate granule cells.Item Open Access Preclinical and Early Osteoarthritis(2023) Kraus, VirginiaThe term early osteoarthritis (OA) is often used to refer to mild or moderately severe radiographic OA. More recently, the term early OA has been used to refer to preradiographic or even earlier phases of disease. Diagnosis of OA in its early preradiographic stages could improve the likelihood of disease modification and thereby reduce medical costs, morbidity, and disability. The advent of sensitive imaging techniques has provided concrete evidence for joint structural abnormalities predating the quintessential radiographic changes we associate with OA. However, conventional OA risk factors function poorly for detection of preclinical and early OA. Therefore, it is currently difficult to define asymptomatic early stage (preclinical) OA in the absence of imaging abnormalities. Because not all radiographic OA progresses to a severe grade of disease or results in joint replacement, by inference, likely not all preclinical or preradiographic OA is expected to progress to early OA and more advanced stages of disease. The trajectory from preclinical to preradiographic to radiographic OA is influenced by the robustness of the endogenous cartilage repair responses, that vary by joint site, and genetic polymorphisms of growth factors implicated in OA susceptibility. The paradigm of joint tissue and biomarker alterations after joint injury is expected to provide a scenario for developing diagnostic algorithms for the early detection of idiopathic OA.Item Open Access Revising a Self-Regulation Phenotype for Depression Through Individual Differences in Macroscale Brain Organization.(Current directions in psychological science, 2023-08) Strauman, Timothy J; Hariri, Ahmad RSelf-regulation denotes the processes by which people initiate, maintain, and control their own thoughts, behaviors, or emotions to produce a desired outcome or avoid an undesired outcome. Self-regulation brings the influence of distal factors such as biology, temperament, and socialization history onto cognition, motivation, and behavior. Dysfunction in self-regulation represents a contributory causal factor for psychopathology. Accordingly, we previously proposed a risk phenotype model for depression drawing from regulatory focus theory and traditional task-based fMRI studies. In this article, we revise and expand our risk phenotype model using insights from new methodologies allowing quantification of individual differences in task-free macroscale brain organization. We offer a set of hypotheses as examples of how examination of intrinsic macroscale brain organization can extend and enrich investigations of self-regulation and depression. In doing so, we hope to promote a useful heuristic for model development and for identifying transdiagnostic risk phenotypes in psychopathology.Item Open Access The NKI-Rockland Sample: A Model for Accelerating the Pace of Discovery Science in Psychiatry.(Front Neurosci, 2012) Nooner, Kate Brody; Colcombe, Stanley J; Tobe, Russell H; Mennes, Maarten; Benedict, Melissa M; Moreno, Alexis L; Panek, Laura J; Brown, Shaquanna; Zavitz, Stephen T; Li, Qingyang; Sikka, Sharad; Gutman, David; Bangaru, Saroja; Schlachter, Rochelle Tziona; Kamiel, Stephanie M; Anwar, Ayesha R; Hinz, Caitlin M; Kaplan, Michelle S; Rachlin, Anna B; Adelsberg, Samantha; Cheung, Brian; Khanuja, Ranjit; Yan, Chaogan; Craddock, Cameron C; Calhoun, Vincent; Courtney, William; King, Margaret; Wood, Dylan; Cox, Christine L; Kelly, AM Clare; Di Martino, Adriana; Petkova, Eva; Reiss, Philip T; Duan, Nancy; Thomsen, Dawn; Biswal, Bharat; Coffey, Barbara; Hoptman, Matthew J; Javitt, Daniel C; Pomara, Nunzio; Sidtis, John J; Koplewicz, Harold S; Castellanos, Francisco Xavier; Leventhal, Bennett L; Milham, Michael PThe National Institute of Mental Health strategic plan for advancing psychiatric neuroscience calls for an acceleration of discovery and the delineation of developmental trajectories for risk and resilience across the lifespan. To attain these objectives, sufficiently powered datasets with broad and deep phenotypic characterization, state-of-the-art neuroimaging, and genetic samples must be generated and made openly available to the scientific community. The enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) is a response to this need. NKI-RS is an ongoing, institutionally centered endeavor aimed at creating a large-scale (N > 1000), deeply phenotyped, community-ascertained, lifespan sample (ages 6-85 years old) with advanced neuroimaging and genetics. These data will be publically shared, openly, and prospectively (i.e., on a weekly basis). Herein, we describe the conceptual basis of the NKI-RS, including study design, sampling considerations, and steps to synchronize phenotypic and neuroimaging assessment. Additionally, we describe our process for sharing the data with the scientific community while protecting participant confidentiality, maintaining an adequate database, and certifying data integrity. The pilot phase of the NKI-RS, including challenges in recruiting, characterizing, imaging, and sharing data, is discussed while also explaining how this experience informed the final design of the enhanced NKI-RS. It is our hope that familiarity with the conceptual underpinnings of the enhanced NKI-RS will facilitate harmonization with future data collection efforts aimed at advancing psychiatric neuroscience and nosology.