Inhibitor of DNA binding 1 as a secreted angiogenic transcription factor in rheumatoid arthritis

Abstract Introduction Rheumatoid arthritis (RA) is characterized by enhanced blood vessel development in joint synovium. This involves the recruitment of endothelial progenitor cells (EPCs), allowing for de novo vessel formation and pro-inflammatory cell infiltration. Inhibitor of DNA Binding 1 (Id1) is a transcription factor characteristic of EPCs that influences cell maturation. Method Enzyme-linked immunosorbant assay (ELISA) and polymerase chain reaction (PCR) were used to examine Id1 levels in synovial fluid (SF) and endothelial cells (ECs), respectively. Immunohistology was used to determine the expression of Id1 in synovial tissue (ST). Human dermal microvascular EC (HMVEC) migration and tube forming assays were used to determine if recombinant human Id1 (rhuId1) and/or RA SF immunodepleted Id1 showed angiogenic activity. We also utilized the RA ST severe combined immunodeficient (SCID) mouse chimera to examine if Id1 recruits EPCs to RA synovium. Results ST samples immunostained for Id1 showed heightened expression in RA compared to osteoarthritis (OA) and normal (NL) ST. By immunofluorescence staining, we found significantly more Id1 in RA compared to OA and NL vasculature, showing that Id1 expressing cells, and therefore EPCs, are most active in vascular remodeling in the RA synovium. We also detected significantly more Id1 in RA compared to OA and other arthritis SFs by ELISA, which correlates highly with Chemokine (C-X-C motif) ligand 16 (CXCL16) levels. In vitro chemotaxis assays showed that Id1 is highly chemotactic for HMVECs and can be attenuated by inhibition of Nuclear Factor κB and phosphoinositide 3-kinase. Using in vitro Matrigel assays, we found that HMVECs form tubes in response to rhuId1 and that Id1 immunodepleted from RA SF profoundly decreases tube formation in Matrigel in vitro. PCR showed that Id1 mRNA could be up-regulated in EPCs compared to HMVECs in response to CXCL16. Finally, using the K/BxN serum induced arthritis model, we found that EC CXCR6 correlated with Id1 expression by immunohistochemistry. Conclusions We conclude that Id1 correlates highly with CXCL16 expression, EPC recruitment, and blood vessel formation in the RA joint, and that Id1 is potently angiogenic and can be up-regulated in EPCs by CXCL16.http://deepblue.lib.umich.edu/bitstream/2027.42/110805/1/13075_2013_Article_4258.pd

Inflammatory properties of inhibitor of DNA binding 1 secreted by synovial fibroblasts in rheumatoid arthritis

Abstract Background Inhibitor of DNA binding 1 (Id1) is a nuclear protein containing a basic helix-loop-helix (bHLH) domain that regulates cell growth by selective binding and prevention of gene transcription. Sources of Id1 production in rheumatoid arthritis synovial tissue (RA ST) and its range of functional effects in RA remain to be clarified. Methods We analyzed Id1 produced from synovial fibroblasts and endothelial cells (ECs) with histology and real-time polymerase chain reaction (RT-PCR). Fibroblast supernatants subjected to differential centrifugation to isolate and purify exosomes were measured for Id1 by enzyme-linked immunosorbent assay (ELISA). Western blotting of Id1-stimulated ECs was performed to determine the kinetics of intracellular protein phosphorylation. EC intracellular signaling pathways induced by Id1 were subsequently targeted with silencing RNA (siRNA) for angiogenesis inhibition. Results By PCR and histologic analysis, we found that the primary source of Id1 in STs is from activated fibroblasts that correlate with inflammatory scores in human RA ST and in joints from K/BxN serum-induced mice. Normal (NL) and RA synovial fibroblasts increase Id1 production with stimulation by transforming growth factor beta (TGF-β). Most of the Id1 released by RA synovial fibroblasts is contained within exosomes. Endothelial progenitor cells (EPCs) and human dermal microvascular ECs (HMVECs) activate the Jnk signaling pathway in response to Id1, and Jnk siRNA reverses Id1-induced HMVEC vessel formation in Matrigel plugs in vivo. Conclusions Id1 is a pleotropic molecule affecting angiogenesis, vasculogenesis, and fibrosis. Our data shows that Id1 is not only an important nuclear protein, but also can be released from fibroblasts via exosomes. The ability of extracellular Id1 to activate signaling pathways expands the role of Id1 in the orchestration of tissue inflammation.http://deepblue.lib.umich.edu/bitstream/2027.42/134552/1/13075_2016_Article_984.pd

LOFAR discovery of a double radio halo system in Abell 1758 and radio/X-ray study of the cluster pair

Radio halos and radio relics are diffuse synchrotron sources that extend over Mpc-scales and are found in a number of merger galaxy clusters. They are believed to form as a consequence of the energy that is dissipated by turbulence and shocks in the intra-cluster medium (ICM). However, the precise physical processes that generate these steep synchrotron spectrum sources are still poorly constrained. We present a new LOFAR observation of the double galaxy cluster Abell 1758. This system is composed of A1758N, a massive cluster hosting a known giant radio halo, and A1758S, which is a less massive cluster whose diffuse radio emission is confirmed here for the first time. Our observations have revealed a radio halo and a candidate radio relic in A1758S, and a suggestion of emission along the bridge connecting the two systems which deserves confirmation. We combined the LOFAR data with archival VLA and GMRT observations to constrain the spectral properties of the diffuse emission. We also analyzed a deep archival Chandra observation and used this to provide evidence that A1758N and A1758S are in a pre-merger phase. The ICM temperature across the bridge that connects the two systems shows a jump which might indicate the presence of a transversal shock generated in the initial stage of the merger

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

SDSS-IV MaNGA-resolved Star Formation and Molecular Gas Properties of Green Valley Galaxies: A First Look with ALMA and MaNGA

We study the role of cold gas in quenching star formation in the green valley by analyzing ALMA 12 CO (1-0) observations of three galaxies with resolved optical spectroscopy from the MaNGA survey. We present resolution-matched maps of the star formation rate and molecular gas mass. These data are used to calculate the star formation efficiency (SFE) and gas fraction (f gas ) for these galaxies separately in the central "bulge" regions and outer disks. We find that, for the two galaxies whose global specific star formation rate (sSFR) deviates most from the star formation main sequence, the gas fraction in the bulges is significantly lower than that in their disks, supporting an "inside-out" model of galaxy quenching. For the two galaxies where SFE can be reliably determined in the central regions, the bulges and disks share similar SFEs. This suggests that a decline in f gas is the main driver of lowered sSFR in bulges compared to disks in green valley galaxies. Within the disks, there exist common correlations between the sSFR and SFE and between sSFR and f gas on kiloparsec scales - the local SFE or f gas in the disks declines with local sSFR. Our results support a picture in which the sSFR in bulges is primarily controlled by f gas , whereas both SFE and f gas play a role in lowering the sSFR in disks. A larger sample is required to confirm if the trend established in this work is representative of the green valley as a whole.The work is supported by the Ministry of Science & Technology of Taiwan under the grant MOST 103-2112-M-001-031-MY3 and 106-2112-M-001-034. R.M. and F.B. acknowledge support by the UK Science and Technology Facilities Council (STFC). R.M. acknowledges ERC Advanced Grant 695671 "QUENCH.

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Tailored education for older patients to facilitate engagement in falls prevention strategies after hospital discharge—A pilot randomized controlled trial

Background The aims of the study were to evaluate the effect of providing tailored falls prevention education in hospital on: i) engagement in targeted falls prevention behaviors in the month after discharge: ii) patients’ self-perceived risk and knowledge about falls and falls prevention strategies after receiving the education. Methods A pilot randomized controlled trial (n = 50): baseline and outcome assessments conducted by blinded researchers. Participants: hospital inpatients 60 years or older, discharged to the community. Participants were randomized into two groups. The intervention was a tailored education package consisting of multimedia falls prevention information with trained health professional follow-up, delivered in addition to usual care. Outcome measures were engagement in falls prevention behaviors in the month after discharge measured at one month after discharge with a structured survey, and participants’ knowledge, confidence and motivation levels before and after receiving the education. The feasibility of providing the intervention was examined and falls outcomes (falls, fall-related injuries) were also collected. Results Forty-eight patients (98%) provided follow-up data. The complete package was provided to 21 (84%) intervention group participants. Participants in the intervention group were significantly more likely to plan how to safely restart functional activities [Adjusted odds ratio 3.80, 95% CI (1.07, 13.52), p = 0.04] and more likely to complete other targeted behaviors such as completing their own home exercise program [Adjusted odds ratio 2.76, 95% CI (0.72, 10.50), p = 0.14] than the control group. The intervention group was significantly more knowledgeable, confident and motivated to engage in falls prevention strategies after receiving the education than the control group. There were 23 falls (n = 5 intervention; n = 18 control) and falls rates were 5.4/1000 patient days (intervention); 18.7/1000 patient days (control). Conclusion This tailored education was received positively by older people, resulted in increased engagement in falls prevention strategies after discharge and is feasible to deliver to older hospital patients. Trial registration The study was registered with the Australian New Zealand Clinical Trials Registry; ACTRN12611000963921 on 8th November 2011

Radiocarbon Protocols and First Intercomparison Results From The Chronos¹⁴ Carbon-Cycle Facility, University Of New South Wales, Sydney, Australia

The Chronos 14Carbon-Cycle Facility is a new radiocarbon laboratory at the University of New South Wales, Australia. Built around an Ionplus 200 kV MIni-CArbon DAting System (MICADAS) Accelerator Mass Spectrometer (AMS) installed in October 2019, the facility was established to address major challenges in the Earth, Environmental and Archaeological sciences. Here we report an overview of the Chronos facility, the pretreatment methods currently employed (bones, carbonates, peat, pollen, charcoal, and wood) and results of radiocarbon and stable isotope measurements undertaken on a wide range of sample types. Measurements on international standards, known-age and blank samples demonstrate the facility is capable of measuring 14C samples from the Anthropocene back to nearly 50,000 years ago. Future work will focus on improving our understanding of the Earth system and managing resources in a future warmer world

The Cerebellum Link to Neuroticism: A Volumetric MRI Association Study in Healthy Volunteers

Prior research suggests an association between reduced cerebellar volumes and symptoms of depression and anxiety in patients with mood disorders. However, whether a smaller volume in itself reflects a neuroanatomical correlate for increased susceptibility to develop mood disorders remains unclear. The aim of the present study was to examine the relationship between cerebellar volume and neurotic personality traits in a non-clinical subject sample. 3T Structural magnetic resonance imaging scans were acquired, and trait depression and anxiety scales of the revised NEO personality inventory were assessed in thirty-eight healthy right-handed volunteers. Results showed that cerebellar volume corrected for total brain volume was inversely associated with depressive and anxiety-related personality traits. Cerebellar gray and white matter contributed equally to the observed associations. Our findings extend earlier clinical observations by showing that cerebellar volume covaries with neurotic personality traits in healthy volunteers. The results may point towards a possible role of the cerebellum in the vulnerability to experience negative affect. In conclusion, cerebellar volumes may constitute a clinico-neuroanatomical correlate for the development of depression- and anxiety-related symptoms

Scale-up of Malaria Rapid Diagnostic Tests and Artemisinin-Based Combination Therapy: Challenges and Perspectives in Sub-Saharan Africa.

Guido Bastiaens and colleagues describe barriers to achieving scale-up and appropriate use of rapid diagnostic tests and artemisinin-based combination therapy for malaria in sub-Saharan Africa. Please see later in the article for the Editors' Summary