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Jonathan Q Purnell, Geoffrey S Johnson, Abdus S Wahed, Chiara Dalla Man, Francesca Piccinini, Claudio Cobelli, Ronald L Prigeon, Bret H Goodpaster, David E Kelley, Myrlene A Staten, Karen E Foster-Schubert, David E Cummings, David R Flum, Anita P Courcoulas, Peter J Havel, Bruce M Wolfe
AIMS/HYPOTHESIS: In this prospective case-control study we tested the hypothesis that, while long-term improvements in insulin sensitivity (SI ) accompanying weight loss after Roux-en-Y gastric bypass (RYGB) would be similar in obese individuals with and without type 2 diabetes mellitus, stimulated-islet-cell insulin responses would differ, increasing (recovering) in those with diabetes but decreasing in those without. We investigated whether these changes would occur in conjunction with favourable alterations in meal-related gut hormone secretion and insulin processing...
February 10, 2018: Diabetologia
Matthias Kaiser, Florian Jug, Thomas Julou, Siddharth Deshpande, Thomas Pfohl, Olin K Silander, Gene Myers, Erik van Nimwegen
Much is still not understood about how gene regulatory interactions control cell fate decisions in single cells, in part due to the difficulty of directly observing gene regulatory processes in vivo. We introduce here a novel integrated setup consisting of a microfluidic chip and accompanying analysis software that enable long-term quantitative tracking of growth and gene expression in single cells. The dual-input Mother Machine (DIMM) chip enables controlled and continuous variation of external conditions, allowing direct observation of gene regulatory responses to changing conditions in single cells...
January 15, 2018: Nature Communications
Zhe Sun, Ting Wang, Ke Deng, Xiao-Feng Wang, Robert Lafyatis, Ying Ding, Ming Hu, Wei Chen
Motivation: Single cell transcriptome sequencing (scRNA-Seq) has become a revolutionary tool to study cellular and molecular processes at single cell resolution. Among existing technologies, the recently developed droplet-based platform enables efficient parallel processing of thousands of single cells with direct counting of transcript copies using Unique Molecular Identifier (UMI). Despite the technology advances, statistical methods and computational tools are still lacking for analyzing droplet-based scRNA-Seq data...
January 1, 2018: Bioinformatics
Jiangnan Luo, Yiting Liu, Dick R Nässel
Neuroendocrine cells store and secrete bulk amounts of neuropeptides, and display morphological and molecular characteristics distinct from neurons signaling with classical neurotransmitters. In Drosophila the transcription factor Dimmed (Dimm), is a prime organizer of neuroendocrine capacity in a majority of the peptidergic neurons. These neurons display large cell bodies and extensive axon terminations that commonly do not form regular synapses. We ask which molecular compartments of a neuron are affected by Dimm to generate these morphological features...
2017: Frontiers in Molecular Neuroscience
Johannes Stratmann, Stefan Thor
The extensive genetic regulatory flows underlying specification of different neuronal subtypes are not well understood at the molecular level. The Nplp1 neuropeptide neurons in the developing Drosophila nerve cord belong to two sub-classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1 neurons are specified by spatial cues; the Hox homeotic network and GATA factor grn, and temporal cues; the hb -> Kr -> Pdm -> cas -> grh temporal cascade. These spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp neurons that activate a common terminal selector feedforward cascade of col -> ap/eya -> dimm -> Nplp1...
April 2017: PLoS Genetics
Jan D Hirsch, Mark Bounthavong, Anisa Arjmand, David R Ha, Christine L Cadiz, Andrew Zimmerman, Heather Ourth, Anthony P Morreale, Steven V Edelman, Candis M Morello
BACKGROUND: In 2012 U.S. diabetes costs were estimated to be $245 billion, with $176 billion related to direct diabetes treatment and associated complications. Although a few studies have reported positive glycemic and economic benefits for diabetes patients treated under primary care physician (PCP)-pharmacist collaborative practice models, no studies have evaluated the cost-effectiveness of an endocrinologist-pharmacist collaborative practice model treating complex diabetes patients versus usual PCP care for similar patients...
March 2017: Journal of Managed Care & Specialty Pharmacy
Yiting Liu, Jiangnan Luo, Dick R Nässel
Growth of postmitotic neurons occurs during different stages of development, including metamorphosis, and may also be part of neuronal plasticity and regeneration. Recently we showed that growth of post-mitotic neuroendocrine cells expressing the basic helix loop helix (bHLH) transcription factor Dimmed (Dimm) in Drosophila could be regulated by insulin/IGF signaling and the insulin receptor (dInR). Dimm is also known to confer a secretory phenotype to neuroendocrine cells and can be part of a combinatorial code specifying terminal differentiation in peptidergic neurons...
2016: Frontiers in Molecular Neuroscience
Wenbo Hu, Chun Liu, Tingcai Cheng, Wei Li, Niannian Wang, Qingyou Xia
The molt-intermolt cycle is an essential feature in holometabolous and hemimetabolous insects' development. In the silkworm, silk glands are under dramatic morphological and functional changes with fibroin genes' transcription being repeatedly turned off and on during the molt-intermolt cycles. However, the molecular mechanisms controlling it are still unknown. Here, silk gland's histomorphology and transcriptome analysis were used to characterize changes in its structure and gene expression patterns from molt to intermolt stages...
September 2016: Insect Biochemistry and Molecular Biology
Hugo Gabilondo, Johannes Stratmann, Irene Rubio-Ferrera, Irene Millán-Crespo, Patricia Contero-García, Shahrzad Bahrampour, Stefan Thor, Jonathan Benito-Sipos
Specification of the myriad of unique neuronal subtypes found in the nervous system depends upon spatiotemporal cues and terminal selector gene cascades, often acting in sequential combinatorial codes to determine final cell fate. However, a specific neuronal cell subtype can often be generated in different parts of the nervous system and at different stages, indicating that different spatiotemporal cues can converge on the same terminal selectors to thereby generate a similar cell fate. However, the regulatory mechanisms underlying such convergence are poorly understood...
May 2016: PLoS Biology
Candis M Morello, Melissa L D Christopher, Linda Ortega, John Khoan, Taylor Rotunno, Steven V Edelman, Robert R Henry, Jan D Hirsch
BACKGROUND: No previous studies exist examining the impact of a short-term pharmacist-endocrinologist collaborative practice model on glycemic control in complex patients. OBJECTIVE: Evaluate outcomes associated with a PharmD-Endocrinologist Diabetes Intense Medical Management (DIMM) "tune up" clinic for complex patients. METHODS: A retrospective cohort study of 99 patients referred to DIMM clinic versus a comparator group of 56 primary care provider (PCP) patients meeting the same criteria (adult type 2 diabetes patients, glycosylated hemoglobin [A1C] ≥ 8%, follow-up visit within 6 months) in a Veterans Affairs Medical Center...
January 2016: Annals of Pharmacotherapy
Katherine Beebe, Dongkook Park, Paul H Taghert, Craig A Micchelli
The endocrine system employs peptide hormone signals to translate environmental changes into physiological responses. The diffuse endocrine system embedded in the gastrointestinal barrier epithelium is one of the largest and most diverse endocrine tissues. Furthermore, it is the only endocrine tissue in direct physical contact with the microbial environment of the gut lumen. However, it remains unclear how this sensory epithelium responds to specific pathogenic challenges in a dynamic and regulated manner. We demonstrate that the enteroendocrine cells of the adult Drosophila melanogaster midgut display a transient, sensitive, and systemic induction of the prosecretory factor dimmed (dimm) in response to the Gram-negative pathogen Pseudomonas entomophila (Pe)...
July 2015: G3: Genes—Genomes—Genetics
Tomoyuki Hida, Makoto Hamasaki, Shinji Matsumoto, Sosei Abe, Koji Takakura, Kenzo Hiroshima, Kazuki Nabeshima
A 67-year-old male with a history of asbestos exposure presented with fever, cough, and dyspnea and was found to have diffuse granular shadowing in both lungs, right pleural effusion, and hilar and mediastinal lymphadenopathy upon chest computed tomography. For definitive diagnosis, a thoracoscopic lung biopsy was performed. Intraoperative findings showed no remarkable macroscopic changes in the visceral and parietal pleura, although a high level of hyaluronic acid in the pleural effusion was noted. Histological findings showed proliferation of atypical cells with round-to-oval nuclei, prominent nucleoli, and eosinophilic cytoplasms...
June 2015: Pathology International
Tarik Hadžić, Dongkook Park, Katharine C Abruzzi, Lin Yang, Jennifer S Trigg, Remo Rohs, Michael Rosbash, Paul H Taghert
Neuroendocrine (NE) cells use large dense core vesicles (LDCVs) to traffic, process, store and secrete neuropeptide hormones through the regulated secretory pathway. The dimmed (DIMM) basic helix-loop-helix transcription factor of Drosophila controls the level of regulated secretory activity in NE cells. To pursue its mechanisms, we have performed two independent genome-wide analyses of DIMM's activities: (i) in vivo chromatin immunoprecipitation (ChIP) to define genomic sites of DIMM occupancy and (ii) deep sequencing of purified DIMM neurons to characterize their transcriptional profile...
February 27, 2015: Nucleic Acids Research
I A Kuznetsov, A V Kuznetsov
We developed a mathematical model for simulating neuropeptide transport inside dense core vesicles (DCVs) in axon terminals containing en passant boutons. The motivation for this research is a recent experimental study by Levitan and colleagues (Bulgari et al., 2014) which described DCV transport in nerve terminals of type Ib and type III as well as in nerve terminals of type Ib with the transcription factor DIMM. The goal of our modeling is validating the proposition put forward by Levitan and colleagues that the dramatic difference in DCV number in type Ib and type III terminals can be explained by the difference in DCV capture in type Ib and type III boutons rather than by differences in DCV anterograde transport and half-life of resident DCVs...
March 2015: Mathematical Biosciences
Dongkook Park, Peiyao Li, Adish Dani, Paul H Taghert
Bioactive peptides are packaged in large dense-core secretory vesicles, which mediate regulated secretion by exocytosis. In a variety of tissues, the regulated release of neurotransmitters and hormones is dependent on calcium levels and controlled by vesicle-associated synaptotagmin (SYT) proteins. Drosophila express seven SYT isoforms, of which two (SYT-α and SYT-β) were previously found to be enriched in neuroendocrine cells. Here we show that SYT-α and SYT-β tissue expression patterns are similar, though not identical...
September 24, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
David M Brown, Juan C Juarez, Andrea M Brown
A laser differential image-motion monitor (DIMM) system was designed and constructed as part of a turbulence characterization suite during the DARPA free-space optical experimental network experiment (FOENEX) program. The developed link measurement system measures the atmospheric coherence length (r0), atmospheric scintillation, and power in the bucket for the 1550 nm band. DIMM measurements are made with two separate apertures coupled to a single InGaAs camera. The angle of arrival (AoA) for the wavefront at each aperture can be calculated based on focal spot movements imaged by the camera...
December 1, 2013: Applied Optics
Jiangnan Luo, Yiting Liu, Dick R Nässel
Neurons and other cells display a large variation in size in an organism. Thus, a fundamental question is how growth of individual cells and their organelles is regulated. Is size scaling of individual neurons regulated post-mitotically, independent of growth of the entire CNS? Although the role of insulin/IGF-signaling (IIS) in growth of tissues and whole organisms is well established, it is not known whether it regulates the size of individual neurons. We therefore studied the role of IIS in the size scaling of neurons in the Drosophila CNS...
2013: PLoS Genetics
Frauke Bellos, Tamara Alpermann, Elena Gouberman, Claudia Haferlach, Susanne Schnittger, Torsten Haferlach, Wolfgang Kern
BACKGROUND: Myeloid nuclear differentiation antigen (MNDA) is expressed in myelomonocytic cells with highest levels in mature granulocytes and monocytes. It is suggested to be expressed more weakly in patients with myelodysplastic syndromes (MDS). The analysis of MNDA therefore may improve diagnostic capabilities of multiparameter flow cytometry (MFC) in MDS. METHODS: We used MFC for detection of MNDA expression in 269 patients with suspected or known MDS, acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML), cytopenia of unknown cause or without malignancy (negative controls)...
September 2012: Cytometry. Part B, Clinical Cytometry
Jason C Mills, Paul H Taghert
Developing cells acquire mature fates in part by selective (i.e. qualitatively different) expression of a few cell-specific genes. However, all cells share the same basic repertoire of molecular and subcellular building blocks. Therefore, cells must also specialize according to quantitative differences in cell-specific distributions of those common molecular resources. Here we propose the novel hypothesis that evolutionarily-conserved transcription factors called scaling factors (SFs) regulate quantitative differences among mature cell types...
January 2012: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Dongkook Park, Tarik Hadžić, Ping Yin, Jannette Rusch, Katharine Abruzzi, Michael Rosbash, James B Skeath, Satchidananda Panda, Jonathan V Sweedler, Paul H Taghert
BACKGROUND: In Drosophila, the basic-helix-loop-helix protein DIMM coordinates the molecular and cellular properties of all major neuroendocrine cells, irrespective of the secretory peptides they produce. When expressed by nonneuroendocrine neurons, DIMM confers the major properties of the regulated secretory pathway and converts such cells away from fast neurotransmission and toward a neuroendocrine state. RESULTS: We first identified 134 transcripts upregulated by DIMM in embryos and then evaluated them systematically using diverse assays (including embryo in situ hybridization, in vivo chromatin immunoprecipitation, and cell-based transactivation assays)...
September 27, 2011: Current Biology: CB
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