GalNAc glycoprotein expression by breast cell lines, primary breast cancer and normal breast epithelial membrane

Over-expression of N-acetylgalactosamine glycoproteins as detected by binding of the lectin from Helix pomatia (HPA), is associated with metastatic competence and poor patient prognosis in a range of human adenocarcinomas. These glycoproteins remain poorly characterised, and their functional role has yet to be elucidated. This study describes characterisation of a range of human breast/breast cancer cell lines for the expression of the N-acetylgalactosaminylated glycoproteins of interest, and their comparison with normal breast epithelium and a range of clinical breast carcinoma samples. Confocal and light microscopy studies revealed cytochemical HPA-binding patterns consistent with a fundamental disruption in normal glycobiosynthetic pathways attending increasing metastatic potential. We report the most complete comparative analysis of HPA-binding ligands from cultured breast cells, clinical breast carcinoma samples and normal breast epithelium to date. Lectin blotting identified 11 major HPA-binding glycoprotein bands common to both clinical tumour samples and breast cell lines and 6 of these bands were also expressed by samples of normal breast epithelium, albeit at much lower levels. Moreover, very marked quantitative but not qualitative differences in levels of expression consistent with metastatic capability were noted. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

History of Adverse Pregnancy Outcomes, Blood Pressure, and Subclinical Vascular Measures in Late Midlife: SWAN (Study of Women’s Health Across the Nation)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142563/1/jah32800_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142563/2/jah32800.pd

TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.

HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion

Interaction of ENSO-driven Flood Variability and Anthropogenic Changes in Driving Channel Evolution: Corryong/ Nariel Creek, Australia

This is an Accepted Manuscript of an article published by Taylor & Francis in Australian Geographer on 03/09/2015, available online: 10.1080/00049182.2015.1048595Understanding the relative contributions of climatic and anthropogenic drivers of channel change are important to inform river management, especially in the context of environmental change. This global debate is especially pertinent in Australia as catchments have been severely altered since recent European settlement, and there is also strong evidence of cyclical climate variability controlling environmental systems. Corryong/Nariel Creek is an ideal setting to further study the interaction between climate and anthropogenic changes on channel evolution as it has experienced both significant periods of flood and drought, controlled by the El Niño Southern Oscillation (ENSO), and extensive anthropogenic changes. Since European settlement the floodplain has been completely cleared, the riparian zone almost entirely invaded by willows, and every reach of the channel has experienced some form of direct channel modification. Through the combined analysis of channel evolution, climate changes and anthropogenic history of the river it was found that both the ENSO-driven climate and anthropogenic drivers are significant, although at different scales of channel change. Significant straightening in response to land clearing in the early twentieth century occurred before any records of direct channel modifications. Following this, most river management works were in response to instabilities created in the clearing period, or to instabilities created by flooding triggering a new phase of instability in reaches which had already undergone stabilisation works. Overall, human activities triggered channel instability via land clearing, and management works since then generally exacerbated erosion during high flows that are driven by climate fluctuations. This research raises the interesting question of whether rivers in Australia have become more responsive to the ENSO cycle since the clearing of catchment and riparian vegetation, or whether the past response to climate variability was different

Relative contributions to vergence eye movements of two binocular cues for motion-in-depth

When we track an object moving in depth, our eyes rotate in opposite directions. This type of "disjunctive" eye movement is called horizontal vergence. The sensory control signals for vergence arise from multiple visual cues, two of which, changing binocular disparity (CD) and inter-ocular velocity differences (IOVD), are specifically binocular. While it is well known that the CD cue triggers horizontal vergence eye movements, the role of the IOVD cue has only recently been explored. To better understand the relative contribution of CD and IOVD cues in driving horizontal vergence, we recorded vergence eye movements from ten observers in response to four types of stimuli that isolated or combined the two cues to motion-in-depth, using stimulus conditions and CD/IOVD stimuli typical of behavioural motion-in-depth experiments. An analysis of the slopes of the vergence traces and the consistency of the directions of vergence and stimulus movements showed that under our conditions IOVD cues provided very little input to vergence mechanisms. The eye movements that did occur coinciding with the presentation of IOVD stimuli were likely not a response to stimulus motion, but a phoria initiated by the absence of a disparity signal

School-level factors associated with teacher connectedness: : A multilevel analysis of the structural and relational school determinants of young people’s health

© The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.ABSTRACT Background Conducting research on the antecedents of teacher connectedness (TC) is key to inform intervention and policy that can leverage the public health potential of teachers for young people’s well-being. As part of the EU-funded Teacher Connectedness Project, this study aims to examine the contribution of a variety of school-level factors (including type of school, school size, student–teacher ratio, students per class and teacher gender). Methods Sample consisted of 5335 adolescents aged 11, 13 and 15 years that had participated in the HBSC study in England. Multilevel multinomial regression was used to examine the contributions of sociodemographic and school-level factors to TC. Results TC was lower in older adolescents and those from less affluent families, but similar in boys and girls. Regarding school-level factors, it was not the size of the school but the ratio of students per teacher which was significantly associated to TC, with higher student–teacher ratio being significantly associated with lower odds of medium-to-high TC. Some differences between mixed and all-girls schools were also found. Conclusions Health promotion strategies targeting student–teacher relationships need to consider how TC changes by age and SES and give attention to school-level factors, in particular the student–teacher ratio. Keywords educational settings, social determinants, young peoplePeer reviewedFinal Published versio

First Results from The GlueX Experiment

The GlueX experiment at Jefferson Lab ran with its first commissioning beam in late 2014 and the spring of 2015. Data were collected on both plastic and liquid hydrogen targets, and much of the detector has been commissioned. All of the detector systems are now performing at or near design specifications and events are being fully reconstructed, including exclusive production of $\pi^{0}$, $\eta$ and $\omega$ mesons. Linearly-polarized photons were successfully produced through coherent bremsstrahlung and polarization transfer to the $\rho$ has been observed.Comment: 8 pages, 6 figures, Invited contribution to the Hadron 2015 Conference, Newport News VA, September 201

Galectin-9 Mediates HIV Transcription by Inducing TCR-Dependent ERK Signaling

Endogenous plasma levels of the immunomodulatory carbohydrate-binding protein galectin-9 (Gal-9) are elevated during HIV infection and remain elevated after antiretroviral therapy (ART) suppression. We recently reported that Gal-9 regulates HIV transcription and potently reactivates latent HIV. However, the signaling mechanisms underlying Gal-9-mediated viral transcription remain unclear. Given that galectins are known to modulate T cell receptor (TCR)-signaling, we hypothesized that Gal-9 modulates HIV transcriptional activity, at least in part, through inducing TCR signaling pathways. Gal-9 induced T cell receptor ζ chain (CD3ζ) phosphorylation (11.2 to 32.1%; P = 0.008) in the J-Lat HIV latency model. Lck inhibition reduced Gal-9-mediated viral reactivation in the J-Lat HIV latency model (16.8–0.9%; P < 0.0001) and reduced both Gal-9-mediated CD4+ T cell activation (10.3 to 1.65% CD69 and CD25 co-expression; P = 0.0006), and IL-2/TNFα secretion (P < 0.004) in primary CD4+ T cells from HIV-infected individuals on suppressive ART. Using phospho-kinase antibody arrays, we found that Gal-9 increased the phosphorylation of the TCR-downstream signaling molecules ERK1/2 (26.7-fold) and CREB (6.6-fold). ERK and CREB inhibitors significantly reduced Gal-9-mediated viral reactivation (16.8 to 2.6 or 12.6%, respectively; P < 0.0007). Given that the immunosuppressive rapamycin uncouples HIV latency reversal from cytokine-associated toxicity, we also investigated whether rapamycin could uncouple Gal-9-mediated latency reactivation from its concurrent pro-inflammatory cytokine production. Rapamycin reduced Gal-9-mediated secretion of IL-2 (4.4-fold, P = 0.001) and TNF (4-fold, P = 0.02) without impacting viral reactivation (16.8% compared to 16.1%; P = 0.2). In conclusion, Gal-9 modulates HIV transcription by activating the TCR-downstream ERK and CREB signaling pathways in an Lck-dependent manner. Our findings could have implications for understanding the role of endogenous galectin interactions in modulating TCR signaling and maintaining chronic immune activation during ART-suppressed HIV infection. In addition, uncoupling Gal-9-mediated viral reactivation from undesirable pro-inflammatory effects, using rapamycin, may increase the potential utility of recombinant Gal-9 within the reversal of HIV latency eradication framework