Acute Hypoxia Alters Extracellular Vesicle Signatures and the Brain Citrullinome of Naked Mole-Rats (Heterocephalus glaber)

Peptidylarginine deiminases (PADs) and extracellular vesicles (EVs) may be indicative biomarkers of physiological and pathological status and adaptive responses, including to diseases and disorders of the central nervous system (CNS) and related to hypoxia. While these markers have been studied in hypoxia-intolerant mammals, in vivo investigations in hypoxia-tolerant species are lacking. Naked mole-rats (NMR) are among the most hypoxia-tolerant mammals and are thus a good model organism for understanding natural and beneficial adaptations to hypoxia. Thus, we aimed to reveal CNS related roles for PADs in hypoxia tolerance and identify whether circulating EV signatures may reveal a fingerprint for adaptive whole-body hypoxia responses in this species. We found that following in vivo acute hypoxia, NMR: (1) plasma-EVs were remodelled, (2) whole proteome EV cargo contained more protein hits (including citrullinated proteins) and a higher number of associated KEGG pathways relating to the total proteome of plasma-EVs Also, (3) brains had a trend for elevation in PAD1, PAD3 and PAD6 protein expression, while PAD2 and PAD4 were reduced, while (4) the brain citrullinome had a considerable increase in deiminated protein hits with hypoxia (1222 vs. 852 hits in normoxia). Our findings indicate that circulating EV signatures are modified and proteomic content is reduced in hypoxic conditions in naked mole-rats, including the circulating EV citrullinome, while the brain citrullinome is elevated and modulated in response to hypoxia. This was further reflected in elevation of some PADs in the brain tissue following acute hypoxia treatment. These findings indicate a possible selective role for PAD-isozymes in hypoxia response and tolerance

The concept of quality of life in dementia in the different stages of the disease

In order to conceptually define quality of life (QOL) in dementia, the literature on QOL in the elderly population, in chronic disease and in dementia was studied. Dementia is a progressive, age-related, chronic condition and to avoid omissions within the dementia-specific concept of QOL, a broad orientation was the preferred approach in this literature study. Adaptation is a major outcome in studies investigating interventions aimed at improving QOL in chronic conditions, but to date, it has not been used in the definition of QOL. It is argued that adaptation is an important indication of QOL in people with chronic diseases and therefore also in dementia. Some crucial issues in assessing dementia-related QOL that are relevant to clarify the continuing debate on whether QOL, particularly in dementia, can be measured at all, are discussed. Then the following conceptual definition is offered: dementia-specific QOL is the multidimensional evaluation of the person-environment system of the individual, in terms of adaptation to the perceived consequences of the dementi

Illiberal Norm Diffusion: How Do Governments Learn to Restrict Non-Governmental Organizations?

Recent decades have witnessed a global cascade of restrictive and repressive measures against nongovernmental organizations (NGOs). We theorize that state learning from observing the regional environment, rather than NGO growth per se or domestic unrest, explains this rapid diffusion of restrictions. We develop and test two hypotheses: (1) states adopt NGO restrictions in response to nonarmed bottom-up threats in their regional environment (“learning from threats”); (2) states adopt NGO restrictions through imitation of the legislative behavior of other states in their regional environment (“learning from examples”). Using an original dataset on NGO restrictions in ninety-six countries over a period of twenty-five years (1992–2016), we test these hypotheses by means of negative binomial regression and survival analyses, using spatially weighted techniques. We find very limited evidence for learning from threats, but consistent evidence for learning from examples. We corroborate this finding through close textual comparison of laws adopted in the Middle East and Africa, showing legal provisions being taken over almost verbatim from one law into another. In our conclusion, we spell out the implications for the quality of democracy and for theories of transition to a postliberal order, as well as for policy-makers, lawyers, and civil-society practitioners.The politics and administration of institutional chang

Galaxy and Mass Assembly (GAMA): The stellar mass budget of galaxy spheroids and discs

We build on a recent photometric decomposition analysis of 7506 Galaxy and Mass Assembly (GAMA) survey galaxies to derive stellar mass function fits to individual spheroid and disc component populations down to a lower mass limit of log(M*/M⊙) = 8. We find that the spheroid/disc mass distributions for individual galaxy morphological types are well described by single Schechter function forms. We derive estimates of the total stellar mass densities in spheroids (ρspheroid = 1.24 ± 0.49 × 108 M⊙ Mpc −3h0.7) and discs (ρdisc = 1.20 ± 0.45 × 108 M⊙ Mpc −3h0.7), which translates to approximately 50 per cent of the local stellar mass density in spheroids and 48 per cent in discs. The remaining stellar mass is found in the dwarf ‘little blue spheroid’ class, which is not obviously similar in structure to either classical spheroid or disc populations. We also examine the variation of component mass ratios across galaxy mass and group halo mass regimes, finding the transition from spheroid to disc mass dominance occurs near galaxy stellar mass ∼1011 M⊙ and group halo mass ∼1012.5 M⊙h−1. We further quantify the variation in spheroid-to-total mass ratio with group halo mass for central and satellite populations as well as the radial variation of this ratio within groups

Geotechnical Offshore Seabed Tool (GOST): CPTu measurements and operations in New Zealand.

The Geotechnical Offshore Seabed Tool (GOST) was used in three field campaigns in on-and offshore areas in Tauranga, Bay of Plenty, New Zealand. Offshore measurements were performed along the main shipping channel in the Tauranga Harbor and onshore measurements were conducted at the locations of two landslides at Pyes Pa and Omokoroa. From each of these sites a sample static CPTu profile is described and reviewed. Additionally, a vibratory CPTu from the Pyes Pa landslide is presented. The CPTu results were used for subsurface sediments investigations at the tested locations

Monitoring the landslide at Bramley Drive, Tauranga, NZ

Omokoroa Peninsula, Tauranga Harbour, is prone to landslides in sensitive pyroclastic soils, especially in coastal bluffs. The largest is the landslide at Bramley Drive that first occurred in 1979, and was reactivated in 2011 and 2012. Since 2012 the landslide has been monitored with laser scans, vibro-and static-CPT, pore water logging at 3 depths, and a borehole inclinometer. Laser scan results track degradation of the scarp and allow development of a preliminary magnitude-frequency curve for failure events on the scarp. To date the borehole inclinometer has shown no obvious shear surface development. However, deformations in phase with the solid earth tides are evident in the cumulative displacement plots. Layers of weak soils separated by sharp boundaries are believed to exaggerate the deformations of the solid earth tides to the extent that they are measurable with a simple inclinometer. Residual deformation after subtraction of the earth tide effects indicate some movement over winter of 2014 associated with sensitive soils at or near the failure surface. The depth of this movement corresponds with a zone of high induced pore water pressures under vibratory CPTu. Pore water pressures indicate two discrete aquifers: an upper aquifer in tephra layers high in the upper part of the sequence that responds to atmospheric pressures; and a second aquifer in the underlying ignimbrites. Pressures in the bottom aquifer are lower than in the overlying aquifer in summer and higher in winter. Large spikes in pore water pressure have been observed during winter of 2014; these coincide with the time of deformation noted in the inclinometer traces

No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial

Background: The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). Methods and Findings: Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1:1:1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1:1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after tr Conclusions: In this trial, temporary cART during PHI was found to transiently lower the viral set point and defer the restart of cART during chronic HIV infection

Precision Pion-Proton Elastic Differential Cross Sections at Energies Spanning the Delta Resonance

A precision measurement of absolute pi+p and pi-p elastic differential cross sections at incident pion laboratory kinetic energies from T_pi= 141.15 to 267.3 MeV is described. Data were obtained detecting the scattered pion and recoil proton in coincidence at 12 laboratory pion angles from 55 to 155 degrees for pi+p, and six angles from 60 to 155 degrees for pi-p. Single arm measurements were also obtained for pi+p energies up to 218.1 MeV, with the scattered pi+ detected at six angles from 20 to 70 degrees. A flat-walled, super-cooled liquid hydrogen target as well as solid CH2 targets were used. The data are characterized by small uncertainties, ~1-2% statistical and ~1-1.5% normalization. The reliability of the cross section results was ensured by carrying out the measurements under a variety of experimental conditions to identify and quantify the sources of instrumental uncertainty. Our lowest and highest energy data are consistent with overlapping results from TRIUMF and LAMPF. In general, the Virginia Polytechnic Institute SM95 partial wave analysis solution describes our data well, but the older Karlsruhe-Helsinki PWA solution KH80 does not.Comment: 39 pages, 22 figures (some with quality reduced to satisfy ArXiv requirements. Contact M.M. Pavan for originals). Submitted to Physical Review

Gravitational Coupling and Dynamical Reduction of The Cosmological Constant

We introduce a dynamical model to reduce a large cosmological constant to a sufficiently small value. The basic ingredient in this model is a distinction which has been made between the two unit systems used in cosmology and particle physics. We have used a conformal invariant gravitational model to define a particular conformal frame in terms of large scale properties of the universe. It is then argued that the contributions of mass scales in particle physics to the vacuum energy density should be considered in a different conformal frame. In this manner, a decaying mechanism is presented in which the conformal factor appears as a dynamical field and plays a key role to relax a large effective cosmological constant. Moreover, we argue that this model also provides a possible explanation for the coincidence problem.Comment: To appear in GR

Sex-Dependent Effects of Cardiometabolic Health and APOE4 on Brain Age: A Longitudinal Cohort Study.

The aging population is growing faster than all other demographic strata. With older age comes a greater risk of health conditions such as obesity and high blood pressure (BP). These cardiometabolic risk factors (CMRs) exhibit prominent sex differences in midlife and aging, yet their influence on brain health in females vs males is largely unexplored. In this study, we investigated sex differences in relationships between BP, body mass index (BMI), and brain age over time and tested for interactions with APOE ε4 genotype (APOE4), a known genetic risk factor of Alzheimer disease. The sample included participants from 2 United Kingdom-based longitudinal birth cohorts, the Lothian Birth Cohort (1936) and Insight 46 (1946). Participants with MRI data from at least 1 time point were included to evaluate sex differences in associations between CMRs and brain age. The open-access software package brainageR 2.1 was used to estimate brain age for each participant. Linear mixed-effects models were used to assess the relationships between brain age, BMI, BP, and APOE4 status (i.e., carrier vs noncarrier) in males and females over time. The combined sample comprised 1,120 participants (48% female) with a mean age (SD) of 73 (0.72) years in the Lothian Birth Cohort and 71 (0.68) years in Insight 46 at the time point 1 assessment. Approximately 30% of participants were APOE4 carriers. Higher systolic and diastolic BP was significantly associated with older brain age in females only (β = 0.43-0.56, p < 0.05). Among males, higher BMI was associated with older brain age across time points and APOE4 groups (β = 0.72-0.77, p < 0.05). In females, higher BMI was linked to older brain age among APOE4 noncarriers (β = 0.68-0.99, p < 0.05), whereas higher BMI was linked to younger brain age among carriers, particularly at the last time point (β = -1.75, p < 0.05). This study indicates sex-dependent and time-dependent relationships between CMRs, APOE4 status, and brain age. Our findings highlight the necessity of sex-stratified analyses to elucidate the role of CMRs in individual aging trajectories, providing a basis for developing personalized preventive interventions