Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains

Background: Magnetic Resonance Imaging (MRI) analysis method “brain-age” paradigm could offer an intuitive prognostic metric (brain-predicted age difference: brain-PAD) for disability in Multiple Sclerosis (MS), reflecting structural brain health adjusted for aging. Equally, cellular senescence has been reported in MS using T-cell biomarker CD8+CD57+. Objective: Here we explored links between MRI-derived brain-age and blood-derived cellular senescence. We examined the value of combining brain-PAD with CD8+CD57+(ILT2+PD-1+) T-cells when predicting disability score in MS and considered whether age-related biological mechanisms drive disability. Methods: Brain-age analysis was applied to T1-weighted MRI images. Disability was assessed and peripheral blood was examined for CD8+CD57+ T-cell phenotypes. Linear regression models were used, adjusted for sex, age and normalized brain volume. Results: We included 179 mainly relapsing-remitting MS patients. A high brain-PAD was associated with high physical disability (mean brain-PAD = +6.54 [5.12–7.95]). CD8+CD57+(ILT2+PD-1+) T-cell frequency was neither associated with disability nor with brain-PAD. Physical disability was predicted by the interaction between brain-PAD and CD8+CD57+ILT2+PD-1+ T-cell frequency (AR2 = 0.196), yet without improvement compared to brain-PAD alone (AR2 = 0.206; AICc = 1.8). Conclusion: Higher frequency of CD8+CD57+ILT2+PD-1+ T-cells in the peripheral blood in patients with an older appearing brain was associated with worse disability scores, suggesting a role of these cells in the development of disability in MS patients with poorer brain health

Supervoid Origin of the Cold Spot in the Cosmic Microwave Background

We use a WISE-2MASS-Pan-STARRS1 galaxy catalog to search for a supervoid in the direction of the Cosmic Microwave Background Cold Spot. We obtain photometric redshifts using our multicolor data set to create a tomographic map of the galaxy distribution. The radial density profile centred on the Cold Spot shows a large low density region, extending over 10's of degrees. Motivated by previous Cosmic Microwave Background results, we test for underdensities within two angular radii, $5^\circ$, and $15^\circ$. Our data, combined with an earlier measurement by Granett et al 2010, are consistent with a large $R_{\rm void}=(192 \pm 15)h^{-1} Mpc$ $(2\sigma)$ supervoid with $\delta \simeq -0.13 \pm 0.03$ centered at $z=0.22\pm0.01$. Such a supervoid, constituting a $\sim3.5 \sigma$ fluctuation in the $\Lambda CDM$ model, is a plausible cause for the Cold Spot.Comment: 4 pages, 2 figures, Proceedings of IAU 306 Symposium: Statistical Challenges in 21st Century Cosmolog

MicroRNA profiling reveals marker of motor neuron disease in ALS models

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining thein vivomiRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents.SIGNIFICANCE STATEMENTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease progresses, suggesting that it may be a clinically useful marker of disease status. Furthermore, rats treated with ALS therapy have restored expression of this MN RNA marker, making it an MN-specific and drug-responsive marker for ALS rodents.</jats:p

What makes you not a Sikh? : a preliminary mapping of values

This study sets out to establish which Sikh values contrasted with or were shared by non-Sikh adolescents. A survey of attitude toward a variety of Sikh values was fielded in a sample of 364 non-Sikh schoolchildren aged between 13 and 15 in London. Values where attitudes were least positive concerned Sikh duties/code of conduct, festivals, rituals, prayer Gurdwara attendance, listening to scripture recitation, the amrit initiation. Sikh values empathized with by non-Sikhs concerned family pride, charity, easy access to ordination and Gurdwaras, maintaining the five Ks, seeing God in all things, abstaining from meat and alcohol and belief in the stories of Guru Nanak. Further significant differences of attitude toward Sikhism were found in comparisons by sex, age and religious affiliation. Findings are applied to teaching Sikhism to pupils of no faith adherence. The study recommends the extension of values mapping to specifically Sikh populations

Fishing for ecosystem services

Ecosystems are commonly exploited and manipulated to maximize certain human benefits. Such changes can degrade systems, leading to cascading negative effects that may be initially undetected, yet ultimately result in a reduction, or complete loss, of certain valuable ecosystem services. Ecosystembased management is intended to maintain ecosystem quality and minimize the risk of irreversible change to natural assemblages of species and to ecosystem processes while obtaining and maintaining long-term socioeconomic benefits. We discuss policy decisions in fishery management related to commonly manipulated environments with a focus on influences to ecosystem services. By focusing on broader scales, managing for ecosystem services, and taking a more proactive approach, we expect sustainable, quality fisheries that are resilient to future disturbances. To that end, we contend that: (1) management always involves tradeoffs; (2) explicit management of fisheries for ecosystem services could facilitate a transition from reactive to proactive management; and (3) adaptive co-management is a process that could enhance management for ecosystem services. We propose adaptive co-management with an ecosystem service framework where actions are implemented within ecosystem boundaries, rather than political boundaries, through strong interjurisdictional relationships