Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation

The apolipoprotein E E4 allele of the APOE gene is the strongest genetic factor for late-onset Alzheimer disease (LOAD). There is compelling evidence that apoE influences Alzheimer disease (AD) in large part by affecting amyloid β (Aβ) aggregation and clearance; however, the molecular mechanism underlying these findings remains largely unknown. Herein, we tested whether anti-human apoE antibodies can decrease Aβ pathology in mice producing both human Aβ and apoE4, and investigated the mechanism underlying these effects. We utilized APPPS1-21 mice crossed to apoE4-knockin mice expressing human apoE4 (APPPS1-21/APOE4). We discovered an anti-human apoE antibody, anti-human apoE 4 (HAE-4), that specifically recognizes human apoE4 and apoE3 and preferentially binds nonlipidated, aggregated apoE over the lipidated apoE found in circulation. HAE-4 also binds to apoE in amyloid plaques in unfixed brain sections and in living APPPS1-21/APOE4 mice. When delivered centrally or by peripheral injection, HAE-4 reduced Aβ deposition in APPPS1-21/APOE4 mice. Using adeno-associated virus to express 2 different full-length anti-apoE antibodies in the brain, we found that HAE antibodies decreased amyloid accumulation, which was dependent on Fcγ receptor function. These data support the hypothesis that a primary mechanism for apoE-mediated plaque formation may be a result of apoE aggregation, as preferentially targeting apoE aggregates with therapeutic antibodies reduces Aβ pathology and may represent a selective approach to treat AD

Mass Transfer by Stellar Wind

I review the process of mass transfer in a binary system through a stellar wind, with an emphasis on systems containing a red giant. I show how wind accretion in a binary system is different from the usually assumed Bondi-Hoyle approximation, first as far as the flow's structure is concerned, but most importantly, also for the mass accretion and specific angular momentum loss. This has important implications on the evolution of the orbital parameters. I also discuss the impact of wind accretion, on the chemical pollution and change in spin of the accreting star. The last section deals with observations and covers systems that most likely went through wind mass transfer: barium and related stars, symbiotic stars and central stars of planetary nebulae (CSPN). The most recent observations of cool CSPN progenitors of barium stars, as well as of carbon-rich post-common envelope systems, are providing unique constraints on the mass transfer processes.Comment: Chapter 7, in Ecology of Blue Straggler Stars, H.M.J. Boffin, G. Carraro & G. Beccari (Eds), Astrophysics and Space Science Library, Springe

Type Ia Supernovae as Stellar Endpoints and Cosmological Tools

Empirically, Type Ia supernovae are the most useful, precise, and mature tools for determining astronomical distances. Acting as calibrated candles they revealed the presence of dark energy and are being used to measure its properties. However, the nature of the SN Ia explosion, and the progenitors involved, have remained elusive, even after seven decades of research. But now new large surveys are bringing about a paradigm shift --- we can finally compare samples of hundreds of supernovae to isolate critical variables. As a result of this, and advances in modeling, breakthroughs in understanding all aspects of SNe Ia are finally starting to happen.Comment: Invited review for Nature Communications. Final published version. Shortened, update

Photometric and Spectroscopic study of a highly reddened type Ia supernova SN 2003hx in NGC 2076

We present $UBVRI$ CCD photometry and optical spectra of the type Ia supernova SN 2003hx which appeared in the galaxy NGC 2076, obtained till $\sim$ 146 days after the epoch of $B$ band maximum. The supernova reached at maximum brightness in $B$ band on JD 245 2893 $\pm$ 1.0 with an apparent magnitude of 14.92 $\pm$ 0.01 mag which was estimated by making template fits to the light curves. SN 2003hx is an example of a highly reddened supernova with $E(B-V)$ = 0.56 $\pm$ 0.23. We estimate $R_v$ = 1.97 $\pm$ 0.54 which indicates the small size of dust particles as compared to their galactic counterparts. The luminosity decline rate is $\Delta m_{15}(B)$ = 1.17 $\pm$ 0.12 mag and the absolute $B$ band magnitude obtained from the luminosity versus decline rate relation (Phillips et al. 1999) is $M^B_{max}$ = -19.20 $\pm$ 0.18 mag. The peak bolometric luminosity indicates that $\sim$ 0.66 $M_\odot$ mass of $^{56}$ Ni was ejected by the supernova. The spectral evolution indicates the supernova to be a normal type Ia event.Comment: 16 pages, 21 figures, 5 tables, Accepted for publication in MNRA

How to enhance service quality through organizational facilitators, collective work engagement, and relational service competence

This study aims to test how collective work engagement and relational service competence, as affective and cognitive-competent collective states, mediate the relationship between organizational facilitators and customers' perceptions of service quality. In all, 107 service-oriented units were aggregated from 615 service workers and 2165 customers. Structural equation modelling confirmed that organizational facilitators are related to collective work engagement andrelational service competence, which play a mediating role between organizational facilitators and service quality. Whereas collective work engagement plays a partially mediating role between organizational facilitators and relational service competence, relational service competence plays a fully mediating role between collective work engagement and service quality. A discussion and limitations are also provided

Lifetime fitness consequences of early-life ecological hardship in a wild mammal population

1. Early-life ecological conditions have major effects on survival and reproduction. Numerous studies in wild systems show fitness benefits of good quality early-life ecological conditions (‘silver spoon’ effects). 2. Recently, however, some studies have reported that poor quality early-life ecological conditions are associated with later-life fitness advantages and that the effect of early-life conditions can be sex-specific. Furthermore, few studies have investigated the effect of the variability of early-life ecological conditions on later-life fitness. 3. Here we test how the mean and variability of early-life ecological conditions affect the longevity and reproduction of males and females using 14 years of data on wild banded mongooses (Mungos mungo). 4. Males that experienced highly variable ecological conditions during development lived longer and had greater lifetime fitness, while those that experienced poor early-life conditions lived longer but at a cost of reduced fertility. In females there were no such effects. 5. Our study suggests that exposure to more variable environments in early life can result in lifetime fitness benefits whereas differences in the mean early-life conditions experienced mediates a life history trade-off between survival and reproduction. It also demonstrates how early-life ecological conditions can produce different selection pressures on males and female

Carnivore abundance near motorways related to prey and roadkills

"This is the pre-peer reviewed version of the following article: Aimara Planillo, Cristina Mata, Andrea Manica y Juan E. Malo, Carnivore abundance near motorways related to prey and roadkills, The Journal of Wildlife Management 82.2 (2018):319-327 , which has been published in final form at https://doi.org/10.1002/jwmg.21384. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions"Landscape disturbance by roads may increase abundance of prey in verges (i.e., strips of terrain adjacent to roadways) or create other features that can attract carnivores and expose them to a higher risk of mortality by vehicle collision. We studied a system that included European rabbits (Oryctolagus cuniculus) and their predators in central Spain near 3 motorways during 2011 and 2012. We analyzed carnivore and rabbit abundance and the potential effect of prey populations on carnivore roadkill. We estimated rabbit and carnivore abundance index by surveying scats in 1-km transects in the landscape, and calculated a roadkill index in motorway stretches parallel to the transects from roadkill data obtained in a roadkill monitoring survey from 2007 to 2011. We analyzed carnivore response for the entire carnivore community and for 2 groups of species: the red fox, which is the most synanthropic carnivore in our study area, and the other carnivores. Fox abundance was higher near motorways compared to control sites, whereas the abundance of other species was related only to rabbit abundance. Furthermore, motorway stretches with higher carnivore abundance presented higher values of carnivore roadkills. Thus, motorways are a source of mortality for carnivores that should be managed carefully. The potential cascading effect of food resources near roads on carnivore mortality should be considered in management and food abundance near roads should be minimized in areas inhabited by carnivores of conservation concernA. P. was supported by a Ph.D. grant of the Basque Government (BFI09.362). This study forms part of the CENIT-OASIS Project funded by a consortium of companies supported by the Centro para el Desarrollo Tecnológico e Industrial of the Spanish Ministry of Science and Innovation (CENIT-2008 1016). The Comunidad de Madrid, together with the European Social Fund, supports the TEG research group through the REMEDINAL-3 Research Network (S2013/MAE-2719

Measurement of gravitational and thermal effects in a liquid-actuated torsion pendulum

We describe a proof-of-principle experiment aiming to investigate the inverse-square law of gravitation at the centimeter scale. The sensor is a two-stage torsion pendulum, while actuation is accomplished by a variable liquid mass. The time-varying gravitational force is related to the level of the circulating fluid in one or two containers at a short distance from the test mass, with all moving mechanical parts positioned at a large distance. We provide a description of the apparatus and present the first results. We identified a systematic effect of thermal origin, producing offsets of few fNm in torque and of about 10 pN in force. When this effect is neutralized, the measurements agree well with the predictions of simulations. We also discuss the upcoming instrument upgradations and the expected sensitivity improvement that will allow us to perform measurements with adequate accuracy to investigate the unexplored regions of the α−λ parameter space of a Yukawa-like deviation from the Newtonian potential

Tubulin isoform composition tunes microtubule dynamics

Microtubules polymerize and depolymerize stochastically, a behavior essential for cell division, motility and differentiation. While many studies advanced our understanding of how microtubule-associated proteins tune microtubule dynamics in trans, we have yet to understand how tubulin genetic diversity regulates microtubule functions. The majority of in vitro dynamics studies are performed with tubulin purified from brain tissue. This preparation is not representative of tubulin found in many cell types. Here we report the 4.2Å cryo-EM structure and in vitro dynamics parameters of α1B/βI+βIVb microtubules assembled from tubulin purified from a human embryonic kidney cell line with isoform composition characteristic of fibroblasts and many immortalized cell lines. We find that these microtubules grow faster and transition to depolymerization less frequently compared to brain microtubules. Cryo-EM reveals that the dynamic ends of α1B/βI+βIVb microtubules are less tapered and that these tubulin heterodimers display lower curvatures. Interestingly, analysis of EB1 distributions at dynamic ends suggests no differences in GTP cap sizes. Lastly, we show that the addition of recombinant α1A/βIII tubulin, a neuronal isotype overexpressed in many tumors, proportionally tunes the dynamics of α1B/βI+βIVb microtubules. Our study is an important step towards understanding how tubulin isoform composition tunes microtubule dynamics