Cross-Platform Comparison of Untargeted and Targeted Lipidomics Approaches on Aging Mouse Plasma.

Lipidomics - the global assessment of lipids - can be performed using a variety of mass spectrometry (MS)-based approaches. However, choosing the optimal approach in terms of lipid coverage, robustness and throughput can be a challenging task. Here, we compare a novel targeted quantitative lipidomics platform known as the Lipidyzer to a conventional untargeted liquid chromatography (LC)-MS approach. We find that both platforms are efficient in profiling more than 300 lipids across 11 lipid classes in mouse plasma with precision and accuracy below 20% for most lipids. While the untargeted and targeted platforms detect similar numbers of lipids, the former identifies a broader range of lipid classes and can unambiguously identify all three fatty acids in triacylglycerols (TAG). Quantitative measurements from both approaches exhibit a median correlation coefficient (r) of 0.99 using a dilution series of deuterated internal standards and 0.71 using endogenous plasma lipids in the context of aging. Application of both platforms to plasma from aging mouse reveals similar changes in total lipid levels across all major lipid classes and in specific lipid species. Interestingly, TAG is the lipid class that exhibits the most changes with age, suggesting that TAG metabolism is particularly sensitive to the aging process in mice. Collectively, our data show that the Lipidyzer platform provides comprehensive profiling of the most prevalent lipids in plasma in a simple and automated manner

Molecular Mechanisms Controlling HIV Transcription and Latency – Implications for Therapeutic Viral Reactivation

Persistence of transcriptionally silent replication competent HIV-1 is a major barrier to clearance of the virus from patients; current combinatorial antiretroviral therapies are successful in abrogating active viral replication, but are unable to eradicate latent HIV-1. A “shock and kill” strategy has been proposed as a curative approach in which latent virus is activated and infected cells are removed by immune clearance, while new rounds of infection are prevented by antiretroviral therapy. Much effort has been put toward understanding the molecular mechanisms maintaining HIV latency and the nature of reservoirs, to provide novel therapeutic targets. This has led to the development of latency reversal agents (LRAs), some of which are undergoing clinical trials. Targeting multiple mechanisms underlying HIV latency via a combination of LRAs is likely to result in more potent activation of the latent reservoir. Therefore, novel as well as synergistic combinations of therapeutic molecules are required to accomplish more potent latency reversal

The left atrial appendage in health and disease

Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmiaand results in significant morbidity and mortality. The left atrial appendage (LAA), a small embryonic remnant of the left atrium (LA), has been shown to play a key role in the pathophysiology of AF-related stroke and thromboembolism. As a consequence the LAA, in spite of its meagre size, has been described as ‘our most lethal human attachment’. Despite being a recognised harbinger of disease, the LAA has also been shown to play an important role in health. This review seeks to address our current understanding of this vital structure in both health and disease states

DNA looping induced by a transcriptional enhancer in vivo

Enhancers are DNA sequences that can activate gene transcription from remote positions. In yeast, regulatory sequences that are functionally equivalent to the metazoan enhancers are called upstream activating sequences (UASs). UASs show a lower degree of flexibility than their metazoan counterparts, but can nevertheless activate transcription from a distance of >1000 bp from the promoter. One of several models for the mechanism of action of transcriptional enhancers proposes that enhancer-bound activating proteins contact promoter-bound transcription factors and thereby get in close proximity to the promoter region with concomitant looping of the intervening DNA. We tested the mode of enhancer activity in yeast. A polymerase II-transcribed gene was paired with a remote, inducible enhancer. An independent reporter system was inserted next to the promoter to monitor the potential modes of enhancer activity. Our results show that the enhancer activated the reporter system only in the presence of a functional promoter. We also demonstrate that the heterologous expression of GAGA, a factor known to facilitate DNA loop formation, allows enhancer action in yeast over a distance of 3000 bp

A model for the break-up of a tuft of fibers

A simple model for the forces acting on a single fiber as it is withdrawn from a tangled fiber assembly is proposed. Particular emphasis is placed on understanding the dynamics of the reptating fiber with respect to the entanglement of fibers within the tuft. The resulting two-parameter model captures the qualitative features of experimental simulation. The model is extended to describe the break-up of a tuft. The results show good agreement with experiment and indicate where a fiber is most likely to fracture based on the density of fiber end-points

Can Hearing Aids Delay Time to Diagnosis of Dementia, Depression, or Falls in Older Adults?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153191/1/jgs16109-sup-0001-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153191/2/jgs16109_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153191/3/jgs16109.pd

Combining branched copolymers with additives generates stable thermoresponsive emulsions with in situ gelation upon exposure to body temperature

© 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Branched copolymer surfactants (BCS) containing thermoresponsive polymer components, hydrophilic components, and hydrophobic termini allow the formation of emulsions which switch from liquid at room temperature to a gel state upon heating. These materials have great potential as in situ gel-forming dosage forms for administration to external and internal body sites, where the emulsion system also allows effective solubilisation of a range of drugs with different chemistries. These systems have been reported previously, however there are many challenges to translation into pharmaceutical excipients. To transition towards this application, this manuscript describes the evaluation of a range of pharmaceutically-relevant oils in the BCS system as well as evaluation of surfactants and polymeric/oligomeric additives to enhance stability. Key endpoints for this study are macroscopic stability of the emulsions and rheological response to temperature. The effect of an optimal additive (methylcellulose) on the nanoscale processes occurring in the BCS-stabilised emulsions is probed by small-angle neutron scattering (SANS) to better comprehend the system. Overall, the study reports an optimal BCS/methylcellulose system exhibiting sol–gel transition at a physiologically-relevant temperature without macroscopic evidence of instability as an in situ gelling dosage form.Peer reviewe

La tribalidad posmoderna dentro del festival “Rock por la Vida” en Guadalajara: emoción colectiva de los asistentes del año 2007 al 2014

Este documento tiene como objetivo analizar las expresiones de los asistentes al festival ¨Rock por la Vida¨ (RXLV) en Guadalajara, a partir del concepto de Michael Maffesoli sobre la tribalidad posmoderna. Se detalla cómo es que los asistentes definen su sensibilidad o emoción colectiva, cómo van construyendo la socialidad dentro de la masa, es decir, cómo se van generando estas tribus. Se describen las experiencias de estar-juntos y se identifican las coincidencias en las emociones colectivas que se generan dentro del RXLV. This document´s objective is to analyze the expressions of those attending the festival Rock for Life in Guadalajara. From Michael Maffesoli postmodern concept of tribalism . It details how to define their collective feeling or emotion, how they build sociality within the mass , that is, how it is generating these tribus. The experience of being together are described . Coincidences in collective emotions that are generated within the RXLV are identified