The timing of TCRα expression critically influences T cell development and selection

Sequential rearrangement of the T cell receptor for antigen (TCR) β and α chains is a hallmark of thymocyte development. This temporal control is lost in TCR transgenics because the α chain is expressed prematurely at the CD4−CD8− double negative (DN) stage. To test the importance of this, we expressed the HYα chain at the physiological CD4+CD8+ double positive (DP) stage. The reduced DP and increased DN cellularity typically seen in TCR transgenics was not observed when the α chain was expressed at the appropriate stage. Surprisingly, antigen-driven selection events were also altered. In male mice, thymocyte deletion now occurred at the single positive or medullary stage. In addition, no expansion of CD8αα intestinal intraepithelial lymphocytes (IELs) was observed, despite the fact that HY transgenics have been used to model IEL development. Collectively, these data establish the importance of proper timing of TCR expression in thymic development and selection and emphasize the need to use models that most accurately reflect the physiologic process

Public health response to a measles outbreak in a large correctional facility, Queensland, 2013

This report documents the prompt, co-ordinated and effective public health response to a measles outbreak in Queensland in 2013. There were 17 cases in a large, high-security, regional correctional facility, a setting with unique challenges. Recommendations are provided to reduce the likelihood and magnitude of measles outbreaks in correctional facilities

Structure and function of the bacterial heterodimeric ABC transporter CydDC: stimulation of ATPase activity by thiol and heme compounds.

In Escherichia coli, the biogenesis of both cytochrome bd-type quinol oxidases and periplasmic cytochromes requires the ATP-binding cassette-type cysteine/GSH transporter, CydDC. Recombinant CydDC was purified as a heterodimer and found to be an active ATPase both in soluble form with detergent and when reconstituted into a lipid environment. Two-dimensional crystals of CydDC were analyzed by electron cryomicroscopy, and the protein was shown to be made up of two non-identical domains corresponding to the putative CydD and CydC subunits, with dimensions characteristic of other ATP-binding cassette transporters. CydDC binds heme b. Detergent-solubilized CydDC appears to adopt at least two structural states, each associated with a characteristic level of bound heme. The purified protein in detergent showed a weak basal ATPase activity (approximately 100 nmol Pi/min/mg) that was stimulated ∼3-fold by various thiol compounds, suggesting that CydDC could act as a thiol transporter. The presence of heme (either intrinsic or added in the form of hemin) led to a further enhancement of thiol-stimulated ATPase activity, although a large excess of heme inhibited activity. Similar responses of the ATPase activity were observed with CydDC reconstituted into E. coli lipids. These results suggest that heme may have a regulatory role in CydDC-mediated transmembrane thiol transport

Single nucleus and spatial transcriptomic profiling of healthy human hamstring tendon

The molecular and cellular basis of health in human tendons remains poorly understood. Among human tendons, hamstring tendon has markedly low pathology and can provide a prototypic healthy tendon reference. The aim of this study was to determine the transcriptomes and location of all cell types in healthy hamstring tendon. Using single nucleus RNA sequencing, we profiled the transcriptomes of 10 533 nuclei from four healthy donors and identified 12 distinct cell types. We confirmed the presence of two fibroblast cell types, endothelial cells, mural cells, and immune cells, and identified cell types previously unreported in tendons, including different skeletal muscle cell types, satellite cells, adipocytes, and undefined nervous system cells. The location of these cell types within tendon was defined using spatial transcriptomics and imaging, and potential transcriptional networks and cell–cell interactions were analyzed. We demonstrate that fibroblasts have the highest number of potential cell–cell interactions in our dataset, are present throughout the tendon, and play an important role in the production and organization of extracellular matrix, thus confirming their role as key regulators of hamstring tendon homeostasis. Overall, our findings underscore the complexity of the cellular networks that underpin healthy human tendon function and the central role of fibroblasts as key regulators of hamstring tendon tissue homeostasis

The Vehicle, 1966, Vol. 8

Vol. 8 Table of Contents CommentaryBill Moser & Avis Eaglestonpage 3 The Vengeance of the DeadStephen W. Gibbspage 5 Ode To A MeadowKathleen McCormackpage 12 Row OnDavid Helmpage 13 Sonnet 63R.L. Hudsonpage 14 UntitledKathleen McCormackpage 14 The Pure GoldDavid Helmpage 15 CommunionDavid Helmpage 15 PreludeMichael Baldwinpage 15 The AlbatrossKaren Cooleypage 16 The Albatross (photo)DeWittpage 17 Ruff and the VaseDavid Helmpage 18 LaBelleKathleen McCormackpage 19 Not Quite SoR.L. Hudsonpage 20 Feeling (no number)David Reifpage 21 Song at DuskDavid Helmpage 21 Arcadia RuminationsR.L. Hudsonpage 22 The BarWayne Johnsonpage 25 HelloWilliam Framepage 26 The ProcessJerry DeWittpage 27 The KillingAdrian Beardpage 30 The Amusement Park GameStephen W. Gibbspage 38 DamnMel Tylerpage 40 PainWilliam Framepage 40 UntitledSusan Champlinpage 41 Portrait of A Scholar As A Young ManStephen W. Gibbspage 42 The TimesW.D.Mpage 46 ParadoxW.D.M.page 46 MankindDavid Helmpage 47https://thekeep.eiu.edu/vehicle/1014/thumbnail.jp

The Vehicle, 1966, Vol. 8

Vol. 8 Table of Contents CommentaryBill Moser & Avis Eaglestonpage 3 The Vengeance of the DeadStephen W. Gibbspage 5 Ode To A MeadowKathleen McCormackpage 12 Row OnDavid Helmpage 13 Sonnet 63R.L. Hudsonpage 14 UntitledKathleen McCormackpage 14 The Pure GoldDavid Helmpage 15 CommunionDavid Helmpage 15 PreludeMichael Baldwinpage 15 The AlbatrossKaren Cooleypage 16 The Albatross (photo)DeWittpage 17 Ruff and the VaseDavid Helmpage 18 LaBelleKathleen McCormackpage 19 Not Quite SoR.L. Hudsonpage 20 Feeling (no number)David Reifpage 21 Song at DuskDavid Helmpage 21 Arcadia RuminationsR.L. Hudsonpage 22 The BarWayne Johnsonpage 25 HelloWilliam Framepage 26 The ProcessJerry DeWittpage 27 The KillingAdrian Beardpage 30 The Amusement Park GameStephen W. Gibbspage 38 DamnMel Tylerpage 40 PainWilliam Framepage 40 UntitledSusan Champlinpage 41 Portrait of A Scholar As A Young ManStephen W. Gibbspage 42 The TimesW.D.Mpage 46 ParadoxW.D.M.page 46 MankindDavid Helmpage 47https://thekeep.eiu.edu/vehicle/1014/thumbnail.jp

The allantoin transport protein, PucI, from Bacillus subtilis: evolutionary relationships, amplified expression, activity and specificity

This work reports the evolutionary relationships, amplified expression, functional characterisation and purification of the putative allantoin transport protein, PucI, from Bacillus subtilis. Sequence alignments and phylogenetic analysis confirmed close evolutionary relationships between PucI and membrane proteins of the nucleobase-cation-symport-1 family of secondary active transporters. These include the sodium-coupled hydantoin transport protein, Mhp1, from Microbacterium liquefaciens and related proteins from bacteria, fungi and plants. Membrane topology predictions for PucI were consistent with twelve putative transmembrane-spanning α-helices with both N- and C-terminal ends at the cytoplasmic side of the membrane. The pucI gene was cloned into the IPTG-inducible plasmid pTTQ18 upstream from an in-frame hexahistidine tag and conditions are described for optimal amplified expression of the PucI(His6) protein in Escherichia coli to a level of about 5% in inner membranes. Initial rates of inducible PucI-mediated uptake of 14C-allantoin into energised Escherichia coli whole cells conformed to Michaelis-Menten kinetics with an apparent affinity (Kmapp) of 24 ± 3M, therefore confirming that PucI is a medium affinity transporter of allantoin. Dependence of allantoin transport on sodium was not apparent. Competitive uptake experiments showed that PucI recognises some additional hydantoin compounds, including hydantoin itself, and to a lesser extent a range of nucleobases and nucleosides. PucI(His6) was solubilised from inner membranes using n-dodecyl-β-D-maltoside and purified. The isolated protein comprised a substantial proportion of α-helix secondary structure, consistent with the predictions, and a three-dimensional model was therefore constructed on a template of the Mhp1 structure, which aided localisation of the potential ligand binding site in PucI

A search for AGN in the most extreme UV-selected starbursts using the European VLBI Network

We have used the European VLBI Network (EVN) to observe a sample of Lyman Break Analogs (LBAs), nearby (z < 0.3) galaxies with properties similar to the more distant Lyman Break Galaxies (LBGs). The study of LBGs may help define the feed-back relationship between black holes (BHs) and their host galaxies. Previous VLA observations have shown that the kpc-scale radio emission from LBAs is dominated by starbursts. The main targets of this VLBI experiment were selected because they possessed emission-line properties between starbursts and Type 2 (obscured) AGN. Eight targets (three star-forming LBAs, four composite LBAs, and one Type 1 AGN) were observed at 5 GHz, four of which were also observed at 1.7 GHz. One star-forming LBA and one composite LBA were detected above 5 \sigma at 1.7 GHz (only), while the AGN was detected at 5 GHz. In both LBAs, the radio luminosity (LR) exceeds that expected from supernovae (remnants) based on a comparison with Arp220, Arp229A and Mrk273, by factors of 2 - 8. The composite LBA exhibits a compact core emitting around 10% of the VLA flux density. The high Tb of 3.5E7 K and excess core L_R with respect to the L_R/L_X relation of radio-quiet AGN indicate that this LBA possesses an obscured AGN (MBH ~ E5-E7 M_sun). While weak AGN may co-exist with the starbursts as shown in at least one of the LBAs, their contribution to the total radio flux is fairly minimal. Our results show that the detection of such weak AGN presents a challenge at radio, X-ray and optical emission-line wavelengths at z ~ 0.2, indicating the great difficulties that need to be overcome in order to study similar processes at high redshift when these types of galaxies were common.Comment: 10 pages, 4 figures, accepted for publication in MNRA

Situating dissemination and implementation sciences within and across the translational research spectrum

The efficient and effective movement of research into practice is acknowledged as crucial to improving population health and assuring return on investment in healthcare research. The National Center for Advancing Translational Science which sponsors Clinical and Translational Science Awards (CTSA) recognizes that dissemination and implementation (D&I) sciences have matured over the last 15 years and are central to its goals to shift academic health institutions to better align with this reality. In 2016, the CTSA Collaboration and Engagement Domain Task Force chartered a D&I Science Workgroup to explore the role of D&I sciences across the translational research spectrum. This special communication discusses the conceptual distinctions and purposes of dissemination, implementation, and translational sciences. We propose an integrated framework and provide real-world examples for articulating the role of D&I sciences within and across all of the translational research spectrum. The framework\u27s major proposition is that it situates D&I sciences as targeted sub-sciences of translational science to be used by CTSAs, and others, to identify and investigate coherent strategies for more routinely and proactively accelerating research translation. The framework highlights the importance of D&I thought leaders in extending D&I principles to all research stages