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Regulatory gene circuits with positive-feedback loops control stem cell differentiation, but several mechanisms can contribute to positive feedback. Here, we dissect feedback mechanisms through which the transcription factor PU.l controls lymphoid and myeloid differentiation. Quantitative live-cell imaging revealed that developing B cells decrease PU.l levels by reducing PU.l transcription, whereas developing macrophages increase PU.l levels by lengthening their cell cycles, which causes stable PU.l accumulation. Exogenous PU.l expression in progenitors increases endogenous PU.l levels by inducing cell cycle lengthening, implying positive feedback between a regulatory factor and the cell cycle. Mathematical modeling showed that this cell cycle-coupled feedback architecture effectively stabilizes a slow-dividing differentiated state. These results show that cell cycle duration functions as an integral part of a positive autoregulatory circuit to control cell fate. [ABSTRACT FROM AUTHOR]

To mount an immune response, lymphocytes must recirculate between the blood and lymph nodes, recognize antigens upon contact with specialized presenting cells, proliferate to expand a small number of clonally relevant tymphocytes, differentiate to antibody-producing plasma cells or effector T cells, exit from lymph nodes, migrate to tissues, and engage in host-protective activities. All of these processes involve motility and cellular interactions--events that were hidden from view until recently. Introduced to immunology by three papers in this journal in 2002, in vivo live-cell imaging studies are revealing the behavior of cells mediating adaptive and innate immunity in diverse tissue environments, providing quantitative measurement of cellular motility, interactions, and response dynamics. Here, we review themes emerging from such studies and speculate on the future of immunoimaging. [ABSTRACT FROM AUTHOR]

Photoacoustic tomography (PAT) can create multiscale multicontrast images of living biological structures ranging from organelles to organs. This emerging technology overcomes the high degree of scattering of optical photons in biological tissue by making use of the photoacoustic effect. Light absorption by molecules creates a thermally induced pressure jump that launches ultrasonic waves, which are received by acoustic detectors to form images. Different implementations of PAT allow the spatial resolution to be scaled with the desired imaging depth in tissue while a high depth-to-resolution ratio is maintained. As a rule of thumb, the achievable spatial resolution is on the order of 1/200 of the desired imaging depth, which can reach up to 7 centimeters. PAT provides anatomical, functional, metabolic, molecular, and genetic contrasts of vasculature, hemodynamics, oxygen metabolism, biomarkers, and gene expression. We review the state of the art of PAT for both biological and clinical studies and discuss future prospects. [ABSTRACT FROM AUTHOR]

Engineered fluorescent protein (FP) chimeras that modulate their fluorescence in response to changes in calcium ion (Ca2+) concentration are powerful tools for visualizing intracellular signaling activity. However, despite a decade of availability, the palette of single FP-based Ca2+ indicators has remained limited to a single green hue. We have expanded this palette by developing blue, improved green, and red intensiometric indicators, as well as an emission ratiometric indicator with an 11,000% ratio change. This series enables improved single-color Ca2+ imaging in neurons and transgenic Caenorhabditis elegans. In HeLa cells, Ca2+ was imaged in three subcellular compartments, and, in conjunction with a cyan FP-yellow FP-based indicator, Ca2+ and adenosine 5'-triphosphate were simultaneously imaged. This palette of indicators paints the way to a colorful new era of Ca2+ imaging. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is an increasingly common technique used to selectively modify neural processing. However, application of TMS is limited by uncertainty concerning its physiological effects. We applied TMS to the cat visual cortex and evaluated the neural and hemodynamic consequences. Short TMS pulse trains elicited initial activation (-1 minute) and prolonged suppression (5 to 10 minutes) of neural responses. Furthermore, TMS disrupted the temporal structure of activity by altering phase relationships between neural signals. Despite the complexity of this response, neural changes were faithfully reflected in hemodynamic signals; quantitative coupling was present over a range of stimulation parameters. These results demonstrate long-lasting neural responses to TMS and support the use of hemodynamic-based neuroimaging to effectively monitor these changes over time. [ABSTRACT FROM AUTHOR]

The mechanisms controlling the establishment of the embryonic-abembryonic (E-Ab) axis of the mammalian blastocyst are controversial. We used in vitro time-lapse imaging and in vivo lineage labeling to provide evidence that the E-Ab axis of the mouse blastocyst is generated independently of early cell lineage. Rather, both the boundary between two-cell blastomeres and the E-Ab axis of the blastocyst align relative to the ellipsoidal shape of the zona pellucida (ZP), an extraembryonic structure. Lack of correlation between cell lineage and the E-Ab axis can be explained by the rotation of the embryo within the ZP. [ABSTRACT FROM AUTHOR]

Noninvasive molecular-imaging technologies are providing researchers with exciting new opportunities to study small-animal models of human disease. With continued improvements in instrumentation, identification of better imaging targets by genome-based approaches, and design of better imaging probes by innovative chemistry, these technologies promise to play increasingly important roles in disease diagnosis and therapy. [ABSTRACT FROM AUTHOR]

This article focuses on diffusion dynamics of glycine receptors revealed by single-quantum dot tracking. Semiconductor quantum dots (QDs) are nanometer-sized fluorescent probes suitable for advanced biological imaging. Authors of this article used QDs to track individual glycine receptors (GlyRs) and analyze their lateral dynamics in the neuronal membrane of living cells for periods ranging from milliseconds to minutes. They had characterized multiple diffusion domains in relation to the synaptic, perisynaptic, or extrasynaptic GlyR localization.

Fluorescent semiconductor nanocrystals (quantum dots) have the potential to revolutionize biological imaging, but their use has been limited by difficulties in obtaining nanocrystals that are biocompatible. To address this problem, we encapsulated individual nanocrystals in phospholipid block-copolymer micelles and demonstrated both in vitro and in vivo imaging. When conjugated to DNA, the nanocrystal-micelles acted as in vitro fluorescent probes to hybridize to specific complementary sequences. Moreover, when injected into Xenopus embryos, the nanocrystal-micelles were stable, nontoxic (<5 × 10[sup9] nanocrystals per cell), cell autonomous, and slow to photobleach. Nanocrystal fluorescence could be followed to the tadpole stage, allowing lineage-tracing experiments in embryogenesis. [ABSTRACT FROM AUTHOR]

Looks at a computer-based system that permits the analysis and archiving of 3D image data taken over time. Discussion of design considerations for a 4D image archival system; The integrated microscopy resource 4D image archival system; Applications of the 4D image archival system; How the system provides a valuable tool for the study of embryogenesis and cytoplasmic movements within cells.

Focuses on the effect of technological innovations on structural biology advancement and information proliferation. Imaging science and protein structure representation; Use of computers; Timeliness; Historical progress; Essential technologies; Cloning; Crystal formation; DNA replication; Sociological impact; Use of the Internet computer network. INSETS: Now even weaklings can image proteins!, by S.H.;Industrial-strength protein structures, by S.H..

The article presents an overview of life science research applications for mass spectrometry imaging (MSI), which allows for the detection and spatial mapping of molecules. Several MSI methods are reviewed, such as matrix-assisted laser desorption ionization (MALDI)-MSI, secondary ion mass spectrometry (SIMS), and desorption electrospray ionization (DESI). Various research uses of MSI are described, including differentiation of brain cancer samples using lipid analysis, biological maker identification, and surgical tissue histology.

Optical imaging in vivo with molecular specificity is important in biomedicine because of its high spatial resolution and sensitivity compared with magnetic resonance imaging. Stimulated Raman scattering (SRS) microscopy allows highly sensitive optical imaging based on vibrational spectroscopy without adding toxic or perturbative labels. However, SRS imaging in living animals and humans has not been feasible because light cannot be collected through thick tissues, and motion-blur arises from slow imaging based on backscattered light. In this work, we enable in vivo SRS imaging by substantially enhancing the collection of the backscattered signal and increasing the imaging speed by three orders of magnitude to video rate. This approach allows label-free in vivo imaging of water, lipid, and protein in skin and mapping of penetration pathways of topically applied drugs in mice and humans. [ABSTRACT FROM AUTHOR]

The article discusses technological advances in imaging equipment used in life science research and characterization of cellular dynamics. Cell biology professor and microscopist Greenfield Sluder is cited regarding advances in imaging technology. The article explains that the barrier to microscopic resolution called the diffraction limit that had prevented scientists from viewing intracellular biology was circumvented with technology awarded the 2008 Method of the Year by the journal "Nature Methods." The article discusses advanced technologies including stimulated emission depletion (STED) microscopy, photoactivated localization microscopy (PALM), and stochastic optical reconstruction microscopy (STORM).

This article discusses the emerging prominence of molecular imaging in biomedical research. This discipline allows for the noninvasive examination of genetics and molecules within living animals. A specific type of molecular imaging, known as multimodal imaging, is becoming increasingly more common and should accelerate the development of diagnostics and therapeutics. The difficulty of multiplexing numerous signals simultaneously in Raman spectroscopy using Raman nanoparticles is discussed by Sanjiv Gambhir of Stanford University.

The article offers information on several products including the FLIR Systems A8200sc and A8300sc midwave infrared cameras from FLIR Systems, the TissueScan Cancer and Normal Tissue cDNA Arrays from Origene Technologies, and the MuviCyte live imaging system from PerkinElmer.

Looks at the use of multiphoton imaging to illuminate living cells for study. Horizons opened up by the technique; Advances in cytology made as a result of the technology; How the technology works; Prospects for the future. INSET: Jellyfish proteins light up cells..

The article discusses the role that machine learning and what are referred to as molecular paints play in understanding cells' responses to toxins and drugs, including through referencing a study led by cell biologist Anne Carpenter to be published in the journal "Nature Protocols." An overview of the cell imagining techniques used to track drugs' effects on cells is provided.

The article discusses efforts undertaken to visualize interactions between cells and viruses and the way viruses establish infections through imaging process, referencing an study on mice in the issue coauthored by scientist X. Sewald. An overview of the imaging of the mouse leukemia virus (MLV) and the HIV infection is provided.

The article reports on the development of a technique for filtering anatomical images after clearing and staining, described in the September 2018 issue of the journal "Copeia," developed by researchers at the University of Kansas at Lawrence and St. Cloud State University in Minnesota.

A summary is presented of findings on the use of adaptive optics and lattice light-sheet microscopy in the three-dimensional imaging of the cells of multicellular organisms and the cell biology applications of such imaging. The comparison of different cell types allegedly enabled by such imaging is described.

The article discusses the hypothesis that the cell contains structures called lipid rafts, functional formations of lipids and membrane proteins collected in the cell's plasma membrane. Critics of the theory dispute the efficacy of detergent extraction methodology to detect lipid rafts, and highlight problems in determining the size and organizational process of these structures. Advocates argue that improved imaging technology is providing more detailed evidence of the existence of lipid rafts.

The article discusses a report in a 2011 issue of "Science" Express regarding cell biology research by Friedman and colleagues who discovered that endoplasmic reticulum (ER)-mitochondria interaction sites mark the sites of mitochondrial fission, which suggests the active participation of the ER in mitochondrial division. Topics include a brief overview of the role of mitochondria in cell physiology and metabolic functions, the diversity in the shape of mitochondria, which is a result of fission into smaller forms and fusion into larger forms, and imaging techniques by Friedman and colleagues showing mitochondrial fission occurring at regions of contact between mitochondria and ER.

An essay is presented on fluorescence microscopy. It offers a brief history of its use in the study of molecular and cell biology and discusses some drawbacks to its use, such as limited spatial resolution. The author offers his thoughts on the development of an imaging modality that combines electron microscopy and fluorescence imaging and the development of an approach that focuses on single-molecule detection and localization.

The constant regeneration of the blood system during hematopoiesis requires tightly controlled lineage decisions of hematopoietic progenitor cells (HPCs). Because of technical limitations, differentiation of individual HPCs could not previously be analyzed continuously. It was therefore disputed whether cell-extrinsic cytokines can instruct HPC lineage choice or only allow survival of cells that are already lineage-restricted. Here, we used bioimaging approaches that allow the continuous long-term observation of individual differentiating mouse HPCs. We demonstrate that the physiological cytokines, macrophage colony-stimulating factor and granulocyte colony- stimulating factor, can instruct hematopoietic lineage choice. [ABSTRACT FROM AUTHOR]

The article discusses the study which reviews recent efforts that have pushed the boundary of the vibrational spectroscopic imaging field in terms of spectral acquisition speed, detection sensitivity, spatial resolution, and imaging depth relative to imaging of living cells and tissues. It specifically focuses on coherent Raman scattering microscopy as an emerging high-speed vibrational imaging platform. The two central challenges facing the field are also mentioned.

Discusses uses for green fluorescent protein (GFP) in live-cell imaging. Value of GFP for studying cellular responses; Source of GFP; GFP-based indicators that reflect their chemical environment; Limitations of GFP; Smallest protein tag; Labels using phytofluors; Smallest taggable domain; GFP as an indicator of gene expression; Four ways in which spectroscopic monitoring should continue to expand.

The article evaluates laboratory equipment and supplies including cellSens imaging software from Olympus, a five-layer cell culture flask from Porvair Sciences, and the Flowmi Cell Strainer from Bel-Art Products.

The article discusses a 2013 report in the journal "Nature Communications" regarding materials science research by Gu et al. describing the use of photoluminescent porous silicon nanoparticles for imaging.

The article discusses the winning images of the 2013 Federation of American Societies for Experimental Biology (FASEB) BioArt competition, which depict subjects such as an embryonic skate on its yolk sac, water dynamics in the monkey brain, and silica bead transport in human fibroblasts.

A summary is presented of the article "Imaging Morphogenesis: Technological Advances and Biological Insights," by Philipp J. Keller, which was published in the online version of the periodical in 2013.

The article reviews several life science laboratory automation products, including the Biomek 4000 Laboratory Automation Workstation by Beckman Coulter, the Preddator System Liquid Handling System from Redd & Whyte, and the acumen high-content imaging (HCI) system by TTP Labtech.

The article discusses fluorescence imaging of cellular metabolites with RNA. Topics include the use of genetically encoded sensors, such as fluorescent proteins with a ligand-binding domain, in real-time imaging of small molecules in living cells and an overview of the team's research methodology for the the development of RNA sensors.

The article reviews several laboratory products, including the In-Vivo Xtreme small animal imaging system by Carestream, the Applied Biosystems QuantStudio 12K Flex Real-Time polymerase chain reaction (PCR) system by Life Technologies, and the Allegra X-14 benchtop centrifuge from Beckman Coulter.

This article reports that the ability to measure tiny magnetic fields with good sensitivity can be found in many applications, from biological imaging to prospecting for buried treasure. However, the most sensitive magnetometers that operate in ambient conditions tend to be power-hungry, bulky, and heavy. The magnetic field splits the energy levels of rubidium atoms, and the extent of the splitting depends on the strength of the magnetic field. Changes in the magnetic field are then detected and tracked optically by the relative absorption changes of a laser light tuned to the split energy levels.

Scientists reviews the recent crossover of quantum dots, clusters of roughly a few thousand inorganic atoms with favorable properties for biological imaging. They illustrate their use with epidermal growth factor which are quantum dot (EGF-QD) conjugates. EGF binds to members of the erbB family of receptor tyrosine kinases, and inappropriate expression of these receptors is implicated in some types of cancer. Fortunately, EGF-QD also bind to these receptors, making it feasible to monitor endocytosis and intracellular trafficking of the growth factor. Coupling the use of these ligands to expression of various fluorescent pairs of erbB receptors suggested that heterodimerization of erbB1 and B2 is triggered by the interaction with EGF.

This article introduces various articles related to genomic medicine published in the October 24, 2003 issue of the journal "Science." Researchers have noted that for certain diseases, such as type II diabetes or alcohol dependence, resources might be better placed in environmental or behavioral interventions that can have a major impact on public health rather than in gene-hunting. Genomic knowledge is slowly wending its way into medical practice. For instance, researchers are using the rapidly expanding knowledge about the genomes of microorganisms to speed efforts to develop vaccines. Molecular imaging is providing an increasing power to studies of animal models of disease and is beginning to be used in clinical trials as a noninvasive means of monitoring disease progress and response to therapeutic agents

Reports that scientists have discovered a way to improve sub-surface molecular imaging. The use of chemically identical fluorescent molecules and their response to light; How molecular imaging has been hampered; The problem of the diffraction limit, an intrinsic blurring of light that prevents two sources from being resolved when they are close together.