ORCID Profile
0000-0001-9752-4756
Current Organisations
University of California, San Diego
,
Universitair Medisch Centrum Groningen
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 02-07-2021
Abstract: Recent work has suggested that macrophages may regulate adiposity, but the mechanisms underlying this process remain unresolved. Cox et al. report that a macrophage-derived growth factor, Pvf3, and its receptor on fat body cells are needed for lipid storage in fruit fly larvae (see the Perspective by O'Brien and Domingos). The mouse Pvf3 ortholog, PDGFcc, was similarly required to store fat in newborn and adult mice. When PDGFcc was blocked or deleted, food intake and absorption were normal, but mice increased their energy expenditure partly due to enhanced brown adipose tissue thermogenesis. PDGFcc was produced exclusively by fat-resident macrophages rather than by those mediating inflammation and insulin resistance. This work may inform future treatments for lipodystrophy, cachexia, and obesity. Science , abe9383, this issue p. eabe9383 see also abj5072, p. 24
Publisher: American Accounting Association
Date: 2008
DOI: 10.2308/JMAR.2008.20.1.25
Abstract: ABSTRACT: This study examines empirically the association between joint strategies and the design of manufacturing performance measurement systems. Drawing on data collected from production managers in 84 industrial firms, the study seeks evidence of links between the implementation of differentiation, low-cost and joint strategies in production, and reliance on efficiency, financial, and customer-focused performance measures. The results indicate the paradoxical situation where virtually all units in the s le pursue competitive advantage in differentiation yet many rely intensely on efficiency and financial measures to measure manufacturing performance. Reliance on efficiency measures is observed to be associated with the pursuit of low-cost and differentiation strategies jointly. Reliance on financial measures, on the other hand, appears to be related to differentiation and not related to the strategic importance of low cost. The findings suggest that financial measures may have a role in monitoring the financial impact of differentiation and curbing excessive differentiation. However, efficiency measures are primarily related to the extent of strategic focus on low cost and may be observed in differentiating units when differentiation is pursued jointly with low cost.
Publisher: Emerald
Date: 17-08-2015
Publisher: Informa UK Limited
Date: 13-12-2018
Publisher: Cold Spring Harbor Laboratory
Date: 23-09-2022
DOI: 10.1101/2022.09.22.22280158
Abstract: Brain disorders, including neurodegenerative diseases and mental illnesses, are often difficult to diagnose and study due to clinical and pathological heterogeneity, overlap in clinical manifestations between disorders, and frequent comorbidities, h ering drug development and fundamental research. Hence, there is a clear need for data-driven approaches to disentangle these complex disorders. Here, we established a computational pipeline to process clinical summaries from donors with a wide range of brain disorders that were neuropathologically diagnosed by the Netherlands Brain Bank. First, we identified and defined 90 cross-disorder signs and symptoms within cognitive, motor, sensory, psychiatric, and general domains. Second, we trained and optimized natural language processing (NLP) models to identify these signs and symptoms in in idual sentences of the extensive clinical summaries from donors of the NBB, resulting in temporal disease trajectories. Third, we studied the temporal manifestation and survival profiles across rare and complex dementias, alpha-synucleinopathies, frontotemporal dementia subtypes, and mental illnesses, giving new insight into how symptomatology differs in manifestation and temporal profiles across brain disorders. Lastly, we trained a recurrent neural network to predict the Neuropathological Diagnosis. Taken together, this integrated approach resulted in a highly unique resource that can facilitate research into cross-disorder symptomatology.
Publisher: Public Library of Science (PLoS)
Date: 06-02-2015
Publisher: Elsevier BV
Date: 09-2020
Publisher: Cold Spring Harbor Laboratory
Date: 15-06-2020
DOI: 10.1101/2020.06.15.152397
Abstract: Macrophages control inflammation in obese animals, and may also directly or indirectly regulate energy storage. In a genetic screen we identify a PDGF-family growth factor, Pvf3 , produced by macrophages and required for lipid storage in Drosophila larvae’s fat body cells. We next demonstrate using genetic and pharmacological approaches that Pvf3 ortholog PDGFcc, produced by Ccr2 -independent embryo-derived tissue macrophages, is also required for storage in mammalian white adipose tissue. PDGFcc production by resident macrophages is regulated by diet, acts on white adipocytes in a paracrine manner, and controls adipocyte hypertrophy in high-fat diet fed and genetically hyperphagic mice. Upon PDGFcc blockade, excess lipids are redirected at the organismal level toward thermogenesis and hepatic storage in adults. This process is altogether independent from inflammation and insulin resistance promoted by Ccr2 -dependent monocytes/macrophages. Our data identify a conserved macrophagedependent mechanism that controls energy storage, conducive to the design of pharmacological interventions.
Location: United States of America
No related grants have been discovered for Inge R. Holtman.