95 research outputs found
Exploring universal patterns in human home-work commuting from mobile phone data
Home-work commuting has always attracted significant research attention
because of its impact on human mobility. One of the key assumptions in this
domain of study is the universal uniformity of commute times. However, a true
comparison of commute patterns has often been hindered by the intrinsic
differences in data collection methods, which make observation from different
countries potentially biased and unreliable. In the present work, we approach
this problem through the use of mobile phone call detail records (CDRs), which
offers a consistent method for investigating mobility patterns in wholly
different parts of the world. We apply our analysis to a broad range of
datasets, at both the country and city scale. Additionally, we compare these
results with those obtained from vehicle GPS traces in Milan. While different
regions have some unique commute time characteristics, we show that the
home-work time distributions and average values within a single region are
indeed largely independent of commute distance or country (Portugal, Ivory
Coast, and Boston)--despite substantial spatial and infrastructural
differences. Furthermore, a comparative analysis demonstrates that such
distance-independence holds true only if we consider multimodal commute
behaviors--as consistent with previous studies. In car-only (Milan GPS traces)
and car-heavy (Saudi Arabia) commute datasets, we see that commute time is
indeed influenced by commute distance
Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration.
The regenerative capacity of skeletal muscle declines with age. Previous studies suggest that this process can be reversed by exposure to young circulation; however, systemic age-specific factors responsible for this phenomenon are largely unknown. Here we report that oxytocin--a hormone best known for its role in lactation, parturition and social behaviours--is required for proper muscle tissue regeneration and homeostasis, and that plasma levels of oxytocin decline with age. Inhibition of oxytocin signalling in young animals reduces muscle regeneration, whereas systemic administration of oxytocin rapidly improves muscle regeneration by enhancing aged muscle stem cell activation/proliferation through activation of the MAPK/ERK signalling pathway. We further show that the genetic lack of oxytocin does not cause a developmental defect in muscle but instead leads to premature sarcopenia. Considering that oxytocin is an FDA-approved drug, this work reveals a potential novel and safe way to combat or prevent skeletal muscle ageing
Electromagnetic Wave Theory and Applications
Contains table of contents for Section 3 and reports on four research projects.California Institute of Technology/Jet Propulsion Laboratory Agreement 959548National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Agreement 958461U.S. Navy - Office of Naval Research Grant N00014-89-J-1107U.S. Navy - Office of Naval Research Grant N00014-92-J-1616U.S. Navy - Office of Naval Research Grant N00014-92-J-4098Digital Equipment CorporationJoint Services Electronics Program Contract DAAL03-92-C-0001U.S. Navy - Office of Naval Research Agreement N00014-90-J-1002U.S. Navy - Office of Naval Research Agreement N00014-89-J-1019DEMACOU.S. Army Cold Regions Research and Engineering Laboratory Contract DACA89-93-K-0009U.S. Department of Transportation Agreement DTRS-57-92-C-00054TTD1Advanced Research Projects Agency/Consortium for Superconducting Electronics Contract MDA972-90-C-0021National Science Foundation Fellowship MIP 88-58764National Science Foundatio
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Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis
Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. PKM2 interaction with phosphotyrosine-containing proteins inhibits enzyme activity and increases availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small molecule PKM2 activators inhibit growth of xenograft tumors. Structural studies reveal that small molecule activators bind PKM2 at the subunit interaction interface, a site distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small molecule activation of PKM2 can interfere with anabolic metabolism
Inactivation of a Single Copy of Crebbp Selectively Alters Pre-mRNA Processing in Mouse Hematopoietic Stem Cells
Global expression analysis of fetal liver hematopoietic stem cells (FL HSCs) revealed the presence of unspliced pre-mRNA for a number of genes in normal FL HSCs. In a subset of these genes, Crebbp+/− FL HSCs had less unprocessed pre-mRNA without a corresponding reduction in total mRNA levels. Among the genes thus identified were the key regulators of HSC function Itga4, Msi2 and Tcf4. A similar but much weaker effect was apparent in Ep300+/− FL HSCs, indicating that, in this context as in others, the two paralogs are not interchangeable. As a group, the down-regulated intronic probe sets could discriminate adult HSCs from more mature cell types, suggesting that the underlying mechanism is regulated with differentiation stage and is active in both fetal and adult hematopoiesis. Consistent with increased myelopoiesis in Crebbp hemizygous mice, targeted reduction of CREBBP abundance by shRNA in the multipotent EML cell line triggered spontaneous myeloid differentiation in the absence of the normally required inductive signals. In addition, differences in protein levels between phenotypically distinct EML subpopulations were better predicted by taking into account not only the total mRNA signal but also the amount of unspliced message present. CREBBP thus appears to selectively influence the timing and degree of pre-mRNA processing of genes essential for HSC regulation and thereby has the potential to alter subsequent cell fate decisions in HSCs
Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase as a Target in LKB1-Mutant Lung Cancer
The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase which coordinates cell growth, polarity, motility, and metabolism. In non-small cell lung cancer, LKB1 is somatically inactivated in 25-30% of cases, often concurrently with activating KRAS mutation. Here, we employed an integrative approach to define novel therapeutic targets in KRAS-driven LKB1 mutant lung cancers. High-throughput RNAi screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase which catalyzes dTTP biosynthesis, as synthetically lethal with Lkb1 deficiency in mouse and human lung cancer lines. Global metabolite profiling demonstrated that Lkb1-null cells had striking decreases in multiple nucleotide metabolites as compared to the Lkb1-wt cells. Thus, LKB1 mutant lung cancers have deficits in nucleotide metabolism conferring hypersensitivity to DTYMK inhibition, suggesting that DTYMK is a potential therapeutic target in this aggressive subset of tumors
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