Molecular Imaging of Stem Cells: Tracking Survival, Biodistribution, Tumorigenicity, and Immunogenicity

Being able to self-renew and differentiate into virtually all cell types, both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have exciting therapeutic implications for myocardial infarction, neurodegenerative disease, diabetes, and other disorders involving irreversible cell loss. However, stem cell biology remains incompletely understood despite significant advances in the field. Inefficient stem cell differentiation, difficulty in verifying successful delivery to the target organ, and problems with engraftment all hamper the transition from laboratory animal studies to human clinical trials. Although traditional histopathological techniques have been the primary approach for ex vivo analysis of stem cell behavior, these postmortem examinations are unable to further elucidate the underlying mechanisms in real time and in vivo. Fortunately, the advent of molecular imaging has led to unprecedented progress in understanding the fundamental behavior of stem cells, including their survival, biodistribution, immunogenicity, and tumorigenicity in the targeted tissues of interest. This review summarizes various molecular imaging technologies and how they have advanced the current understanding of stem cell survival, biodistribution, immunogenicity, and tumorigenicity

Quantitative mass spectrometry reveals a role for the GTPase Rho1p in actin organization on the peroxisome membrane

We have combined classical subcellular fractionation with large-scale quantitative mass spectrometry to identify proteins that enrich specifically with peroxisomes of Saccharomyces cerevisiae. In two complementary experiments, isotope-coded affinity tags and tandem mass spectrometry were used to quantify the relative enrichment of proteins during the purification of peroxisomes. Mathematical modeling of the data from 306 quantified proteins led to a prioritized list of 70 candidates whose enrichment scores indicated a high likelihood of them being peroxisomal. Among these proteins, eight novel peroxisome-associated proteins were identified. The top novel peroxisomal candidate was the small GTPase Rho1p. Although Rho1p has been shown to be tethered to membranes of the secretory pathway, we show that it is specifically recruited to peroxisomes upon their induction in a process dependent on its interaction with the peroxisome membrane protein Pex25p. Rho1p regulates the assembly state of actin on the peroxisome membrane, thereby controlling peroxisome membrane dynamics and biogenesis

Why have asset price properties changed so little in 200 years

We first review empirical evidence that asset prices have had episodes of large fluctuations and been inefficient for at least 200 years. We briefly review recent theoretical results as well as the neurological basis of trend following and finally argue that these asset price properties can be attributed to two fundamental mechanisms that have not changed for many centuries: an innate preference for trend following and the collective tendency to exploit as much as possible detectable price arbitrage, which leads to destabilizing feedback loops.Comment: 16 pages, 4 figure

System-based proteomic analysis of the interferon response in human liver cells

BACKGROUND: Interferons (IFNs) play a critical role in the host antiviral defense and are an essential component of current therapies against hepatitis C virus (HCV), a major cause of liver disease worldwide. To examine liver-specific responses to IFN and begin to elucidate the mechanisms of IFN inhibition of virus replication, we performed a global quantitative proteomic analysis in a human hepatoma cell line (Huh7) in the presence and absence of IFN treatment using the isotope-coded affinity tag (ICAT) method and tandem mass spectrometry (MS/MS). RESULTS: In three subcellular fractions from the Huh7 cells treated with IFN (400 IU/ml, 16 h) or mock-treated, we identified more than 1,364 proteins at a threshold that corresponds to less than 5% false-positive error rate. Among these, 54 were induced by IFN and 24 were repressed by more than two-fold, respectively. These IFN-regulated proteins represented multiple cellular functions including antiviral defense, immune response, cell metabolism, signal transduction, cell growth and cellular organization. To analyze this proteomics dataset, we utilized several systems-biology data-mining tools, including Gene Ontology via the GoMiner program and the Cytoscape bioinformatics platform. CONCLUSIONS: Integration of the quantitative proteomics with global protein interaction data using the Cytoscape platform led to the identification of several novel and liver-specific key regulatory components of the IFN response, which may be important in regulating the interplay between HCV, interferon and the host response to virus infection

UniPep - a database for human N-linked glycosites: a resource for biomarker discovery

There has been considerable recent interest in proteomic analyses of plasma for the purpose of discovering biomarkers. Profiling N-linked glycopeptides is a particularly promising method because the population of N-linked glycosites represents the proteomes of plasma, the cell surface, and secreted proteins at very low redundancy and provides a compelling link between the tissue and plasma proteomes. Here, we describe UniPep - a database of human N-linked glycosites - as a resource for biomarker discovery

Loss of synergistic transcriptional feedback loops drives diverse B-cell cancers

BACKGROUND: The most common B-cell cancers, chronic lymphocytic leukemia/lymphoma (CLL), follicular and diffuse large B-cell (FL, DLBCL) lymphomas, have distinct clinical courses, yet overlapping cell-of-origin . Dynamic changes to the epigenome are essential regulators of B-cell differentiation. Therefore, we reasoned that these distinct cancers may be driven by shared mechanisms of disruption in transcriptional circuitry. METHODS: We compared purified malignant B-cells from 52 patients with normal B-cell subsets (germinal center centrocytes and centroblasts, naïve and memory B-cells) from 36 donor tonsils using \u3e325 high-resolution molecular profiling assays for histone modifications, open chromatin (ChIP-, FAIRE-seq), transcriptome (RNA-seq), transcription factor (TF) binding, and genome copy number (microarrays). FINDINGS: From the resulting data, we identified gains in active chromatin in enhancers/super-enhancers that likely promote unchecked B-cell receptor signaling, including one we validated near the immunoglobulin superfamily receptors FCMR and PIGR. More striking and pervasive was the profound loss of key B-cell identity TFs, tumor suppressors and their super-enhancers, including EBF1, OCT2(POU2F2), and RUNX3. Using a novel approach to identify transcriptional feedback, we showed that these core transcriptional circuitries are self-regulating. Their selective gain and loss form a complex, iterative, and interactive process that likely curbs B-cell maturation and spurs proliferation. INTERPRETATION: Our study is the first to map the transcriptional circuitry of the most common blood cancers. We demonstrate that a critical subset of B-cell TFs and their cognate enhancers form self-regulatory transcriptional feedback loops whose disruption is a shared mechanism underlying these diverse subtypes of B-cell lymphoma. FUNDING: National Institute of Health, Siteman Cancer Center, Barnes-Jewish Hospital Foundation, Doris Duke Foundation

Near-Infrared Imaging Polarimetry of Inner Region of GG Tau A Disk

By performing non-masked polarization imaging with Subaru/HiCIAO, polarized scattered light from the inner region of the disk around the GG Tau A system was successfully detected in the $H$ band with a spatial resolution of approximately 0.07\arcsec, revealing the complicated inner disk structures around this young binary. This paper reports the observation of an arc-like structure to the north of GG Tau Ab and part of a circumstellar structure that is noticeable around GG Tau Aa extending to a distance of approximately 28 AU from the primary star. The speckle noise around GG Tau Ab constrains its disk radius to <13 AU. Based on the size of the circumbinary ring and the circumstellar disk around GG Tau Aa, the semi-major axis of the binary's orbit is likely to be 62 AU. A comparison of the present observations with previous ALMA and near-infrared (NIR) H$_2$ emission observations suggests that the north arc could be part of a large streamer flowing from the circumbinary ring to sustain the circumstellar disks. According to the previous studies, the circumstellar disk around GG Tau Aa has enough mass and can sustain itself for a duration sufficient for planet formation; thus, our study indicates that planets can form within close (separation $\lesssim$ 100 AU) young binary systems.Comment: Accepted for publication in AJ, 12 pages, 5 figure

Subaru/HiCIAO HKsHK_{\rm s} imaging of LkHα\alpha 330 - multi-band detection of the gap and spiral-like structures

We present $H$- and $K_{\rm s}$-bands observations of the LkH$\alpha$ 330 disk with a multi-band detection of the large gap and spiral-like structures. The morphology of the outer disk ($r\sim$0\farcs3) at PA=0--45$^\circ$ and PA=180--290$^\circ$ are likely density wave-induced spirals and comparison between our observational results and simulations suggests a planet formation. We have also investigated the azimuthal profiles at the ring and the outer-disk regions as well as radial profiles in the directions of the spiral-like structures and semi-major axis. Azimuthal analysis shows a large variety in wavelength and implies that the disk has non-axisymmetric dust distributions. The radial profiles in the major-axis direction (PA=$271^\circ$) suggest that the outer region (r\geq0\farcs25) may be influenced by shadows of the inner region of the disk. The spiral-like directions (PA=10$^\circ$ and 230$^\circ$) show different radial profiles, which suggests that the surfaces of the spiral-like structures are highly flared and/or have different dust properties. Finally, a color-map of the disk shows a lack of an outer eastern region in the $H$-band disk, which may hint the presence of an inner object that casts a directional shadow onto the disk.Comment: 12pages, 16 figures, 2 tables, accepted for publication in A

Human Plasma PeptideAtlas

Peptide identifications of high probability from 28 LC-MS/MS human serum and plasma experiments from eight different laboratories, carried out in the context of the HUPO Plasma Proteome Project, were combined and mapped to the EnsEMBL human genome. The 6929 distinct observed peptides were mapped to approximately 960 different proteins. The resulting compendium of peptides and their associated samples, proteins, and genes is made publicly available as a reference for future research on human plasma