The evolution of binary populations in cool, clumpy star clusters

Observations and theory suggest that star clusters can form in a subvirial (cool) state and are highly substructured. Such initial conditions have been proposed to explain the level of mass segregation in clusters through dynamics, and have also been successful in explaining the origin of Trapezium-like systems. In this paper, we investigate, using N-body simulations, whether such a dynamical scenario is consistent with the observed binary properties in the Orion Nebula Cluster (ONC). We find that several different primordial binary populations are consistent with the overall fraction and separation distribution of visual binaries in the ONC (in the range 67-670 au), and that these binary systems are heavily processed. The substructured, cool-collapse scenario requires a primordial binary fraction approaching 100 per cent. We find that the most important factor in processing the primordial binaries is the initial level of substructure; a highly substructured cluster processes up to 20 per cent more systems than a less substructured cluster because of localized pockets of high stellar density in the substructure. Binaries are processed in the substructure before the cluster reaches its densest phase, suggesting that even clusters remaining in virial equilibrium or undergoing supervirial expansion would dynamically alter their primordial binary population. Therefore, even some expanding associations may not preserve their primordial binary populatio

The role of JAK-STAT signaling in adipose tissue function

Adipocytes play important roles in lipid storage, energy homeostasis and whole body insulin sensitivity. The JAK-STAT (Janus Kinase-Signal Transducer and Activator of Transcription) pathway mediates a variety of physiological processes including development, hematopoiesis, and inflammation. Although the JAK-STAT signaling pathway occurs in all cells, this pathway can mediate cell specific responses. Studies in the last two decades have identified hormones and cytokines that activate the JAK-STAT signaling pathway. These cytokines and hormones have profound effects on adipocytes. The content of this review will introduce the types of adipocytes and immune cells that make up adipose tissue, the impact of obesity on adipose cellular composition and function, and the general constituents of the JAK-STAT pathway and how its activators regulate adipose tissue development and physiology. A summary of the identification of STAT target genes in adipocytes reveals how these transcription factors impact various areas of adipocyte metabolism including insulin action, modulation of lipid stores, and glucose homeostasis. Lastly, we will evaluate exciting new data linking the JAK-STAT pathway and brown adipose tissue and consider the future outlook in this area of investigation. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. © 2013 The Authors

Emerging roles of JAK-STAT signaling pathways in adipocytes

Twenty years ago, adipocytes were largely considered to be inert energy-storage depots. We now know that fat cells are highly insulin-sensitive with significant endocrine functions. Alterations in adipocyte development or function can contribute to metabolic disease, in particular type 2 diabetes. The current obesity epidemic that plagues many nations provides a strong rationale for understanding basic adipocyte biology. The JAK-STAT signaling pathway mediates the action of a variety of hormones that have profound effects on adipocyte development and function. In addition, adipocytes secrete hormones that utilize this signaling pathway. This review summarizes research on the expression and function of JAKs and STATs in adipocytes and highlights the roles of JAK-STAT-activating cytokines in adipose tissue. © 2011 Elsevier Ltd

Pyruvate dehydrogenase complex (PDC) subunits moonlight as interaction partners of phosphorylated STAT5 in adipocytes and adipose tissue

© 2017 by The American Society for Biochemistry and Molecular Biology, Inc. STAT5 proteins play a role in adipocyte development and function, but their specific functions are largely unknown. To this end, we used an unbiased MS-based approach to identify novel STAT5-interacting proteins. We observed that STAT5A bound the E1 and E2 subunits of the pyruvate dehydrogenase complex (PDC). Whereas STAT5A typically localizes to the cytosol or nucleus, PDC normally resides within the mitochondrial matrix where it converts pyruvate to acetyl-CoA. We employed affinity purification and immunoblotting to validate the interaction between STAT5A and PDC subunits in murine and human cultured adipocytes, as well as in adipose tissue. We found that multiple PDC subunits interact with hormone-activated STAT5A in a dose- and time-dependent manner that coincides with tyrosine phosphorylation of STAT5. Using subcellular fractionation and immunofluorescence microscopy, we observed that PDC-E2 is present within the adipocyte nucleus where it associates with STAT5A. Because STAT5A is a transcription factor, we used chromatin immunoprecipitation (ChIP) to assess PDC’s ability to interact with STAT5 DNA-binding sites. These analyses revealed that PDC-E2 is bound to a STAT5-binding site in the promoter of the STAT5 target gene cytokine-inducible SH2-containing protein (cish). We have demonstrated a compelling interaction between STAT5A and PDC subunits in adipocytes under physiological conditions. There is previous evidence that PDC localizes to cancer cell nuclei where it plays a role in histone acetylation. On the basis of our ChIP data and these previous findings, we hypothesize that PDC may modulate STAT5’s ability to regulate gene expression by controlling histone or STAT5 acetylation

Secondary Structures in Long Compact Polymers

Compact polymers are self-avoiding random walks which visit every site on a lattice. This polymer model is used widely for studying statistical problems inspired by protein folding. One difficulty with using compact polymers to perform numerical calculations is generating a sufficiently large number of randomly sampled configurations. We present a Monte-Carlo algorithm which uniformly samples compact polymer configurations in an efficient manner allowing investigations of chains much longer than previously studied. Chain configurations generated by the algorithm are used to compute statistics of secondary structures in compact polymers. We determine the fraction of monomers participating in secondary structures, and show that it is self averaging in the long chain limit and strictly less than one. Comparison with results for lattice models of open polymer chains shows that compact chains are significantly more likely to form secondary structure.Comment: 14 pages, 14 figure

Temperature dependence and thermodynamics of klenow polymerase binding to primed-template DNA

DNA binding of Klenow polymerase has been characterized with respect to temperature to delineate the thermodynamic driving forces involved in the interaction of this polymerase with primed-template DNA. The temperature dependence of the binding affinity exhibits distinct curvature, with tightest binding at 25-30°C. Nonlinear temperature dependence indicates Klenow binds different primed-template constructs with large heat capacity (ΔCp) values (-870 to -1220 cal/mole K) and thus exhibits large temperature dependent changes in enthalpy and entropy. Binding is entropy driven at lower temperatures and enthalpy driven at physiological temperatures. Large negative ΔCp values have been proposed to be a \u27signature\u27 of site-specific DNA binding, but type I DNA polymerases do not exhibit significant DNA sequence specificity. We suggest that the binding of Klenow to a specific DNA structure, the primed-template junction, results in a correlated thermodynamic profile that mirrors what is commonly seen for DNA sequence-specific binding proteins. Klenow joins a small number of other DNA-sequence independent DNA binding proteins which exhibit unexpectedly large negative ΔCp values. Spectroscopic measurements show small conformational rearrangements of both the DNA and Klenow upon binding, and small angle x-ray scattering shows a global induced fit conformational compaction of the protein upon binding. Calculations from both crystal structure and solution structural data indicate that Klenow DNA binding is an exception to the often observed correlation between ΔCp and changes in accessible surface area. In the case of Klenow, surface area burial can account for only about half of the ΔCp of binding. © 2006 by the Biophysical Society

Loss of DBC1 (CCAR2) affects TNFα-induced lipolysis and Glut4 gene expression in murine adipocytes

© 2018 Society for Endocrinology Published by Bioscientifica Ltd. STAT5A (signal transducer and activator of transcription 5A) is a transcription factor that plays a role in adipocyte development and function. In this study, we report DBC1 (deleted in breast cancer 1 - also known as CCAR2) as a novel STAT5A-interacting protein. DBC1 has been primarily studied in tumor cells, but there is evidence that loss of this protein may promote metabolic health in mice. Currently, the functions of DBC1 in mature adipocytes are largely unknown. Using immunoprecipitation and immunoblotting techniques, we confirmed that there is an association between endogenous STAT5A and DBC1 proteins under physiological conditions in the adipocyte nucleus that is not dependent upon STAT5A tyrosine phosphorylation. We used siRNA to knockdown DBC1 in 3T3-L1 adipocytes to determine the impact on STAT5A activity, adipocyte gene expression and TNFα (tumor necrosis factor α)-regulated lipolysis. The loss of DBC1 did not affect the expression of several STAT5A target genes including Socs3, Cish, Bcl6, Socs2 and Igf1. However, we did observe decreased levels of TNFα-induced glycerol and free fatty acids released from adipocytes with reduced DBC1 expression. In addition, DBC1-knockdown adipocytes had increased Glut4 expression. In summary, DBC1 can associate with STAT5A in adipocyte nucleus, but it does not appear to impact regulation of STAT5A target genes. Loss of adipocyte DBC1 modestly increases Glut4 gene expression and reduces TNFα-induced lipolysis. These observations are consistent with in vivo observations that show loss of DBC1 promotes metabolic health in mice

On the mass segregation of stars and brown dwarfs in Taurus

We use the new minimum spanning tree (MST) method to look for mass segregation in the Taurus association. The method computes the ratio of MST lengths of any chosen subset of objects, including the most massive stars and brown dwarfs, to the MST lengths of random sets of stars and brown dwarfs in the cluster. This mass segregation ratio (ΛMSR) enables a quantitative measure of the spatial distribution of high- and low-mass stars, and brown dwarfs to be made in Taurus. We find that the most massive stars in Taurus are inversely mass segregated with ΛMSR= 0.70 ± 0.10 (ΛMSR= 1 corresponds to no mass segregation), which differs from the strong mass segregation signatures found in more dense and massive clusters such as Orion. The brown dwarfs in Taurus are not mass segregated, although we find evidence that some low-mass stars are, with an ΛMSR= 1.25 ± 0.15. Finally, we compare our results to previous measures of the spatial distribution of stars and brown dwarfs in Taurus, and briefly discuss their implication

Bromodomain and Extraterminal Inhibition by JQ1 Produces Divergent Transcriptional Regulation of Suppressors of Cytokine Signaling Genes in Adipocytes

© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: [email protected]. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway has cell-specific functions. Suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of JAK-STAT signaling. STAT5 plays a significant role in adipocyte development and function, and bromodomain and extraterminal (BET) proteins may be involved in STAT5 transcriptional activity. We treated 3T3-L1 adipocytes with the BET inhibitor JQ1 and observed that growth hormone (GH)-induced expression of 2 STAT5 target genes from the SOCS family, Socs3 and Cish, were inversely regulated (increased and decreased, respectively) by BET inhibition. Chromatin immunoprecipitation analyses revealed that changes in STAT5 binding did not correlate with gene expression changes. GH promoted the recruitment of the BET protein BRD2 to the Cish, but not Socs3, promoter. JQ1 treatment ablated this effect as well as the GH-induced binding of ribonucleic acid polymerase II (RNA Pol II) to the Cish transcription start site. BRD2 knockdown also suppressed GH induction of Cish, further supporting the role of BRD2 in Cish transcriptional activation. In contrast, JQ1 increased the binding of activated Pol II to the Socs3 coding region, suggesting enhanced messenger RNA (mRNA) elongation. Our finding that JQ1 transiently reduced the interaction between the positive transcription elongation factor (P-TEFb) and its inhibitor hexamethylene bis-acetamide inducible 1 (HEXIM1) is consistent with a previously described off-target effect of JQ1, whereby P-TEFb becomes more available to be recruited by genes that do not depend on BET proteins for activating transcription. These results demonstrate substantially different transcriptional regulation of Socs3 and Cish and suggest distinct roles in adipocytes for these 2 closely related proteins