Protein misfolding underlies the pathology of a large number of human disorders, many of which are age-related. An exception to this is preeclampsia, a leading cause of pregnancy-associated morbidity ...and mortality in which misfolded proteins accumulate in body fluids and the placenta. We demonstrate that pregnancy zone protein (PZP), which is dramatically elevated in maternal plasma during pregnancy, efficiently inhibits in vitro the aggregation of misfolded proteins, including the amyloid beta peptide (Aβ) that is implicated in preeclampsia as well as with Alzheimer’s disease. The mechanism by which this inhibition occurs involves the formation of stable complexes between PZP and monomeric Aβ or small soluble Aβ oligomers formed early in the aggregation pathway. The chaperone activity of PZP is more efficient than that of the closely related protein alpha-2-macroglobulin (α₂M), although the chaperone activity of α₂M is enhanced by inducing its dissociation into PZP-like dimers. By immunohistochemistry analysis, PZP is found primarily in extravillous trophoblasts in the placenta. In severe preeclampsia, PZP-positive extravillous trophoblasts are adjacent to extracellular plaques containing Aβ, but PZP is not abundant within extracellular plaques. Our data support the conclusion that the up-regulation of PZP during pregnancy represents a major maternal adaptation that helps to maintain extracellular proteostasis during gestation in humans. We propose that overwhelming or disrupting the chaperone function of PZP could underlie the accumulation of misfolded proteins in vivo. Attempts to characterize extracellular proteostasis in pregnancy will potentially have broad-reaching significance for understanding disease-related protein misfolding.
The ribosome is increasingly becoming recognized as a key hub for integrating quality control processes associated with protein biosynthesis and cotranslational folding (CTF). The molecular ...mechanisms by which these processes take place, however, remain largely unknown, in particular in the case of intrinsically disordered proteins (IDPs). To address this question, we studied at a residue-specific level the structure and dynamics of ribosome-nascent chain complexes (RNCs) of α-synuclein (αSyn), an IDP associated with Parkinson’s disease (PD). Using solution-state nuclear magnetic resonance (NMR) spectroscopy and coarse-grained molecular dynamics (MD) simulations, we find that, although the nascent chain (NC) has a highly disordered conformation, its N-terminal region shows resonance broadening consistent with interactions involving specific regions of the ribosome surface. We also investigated the effects of the ribosome-associated molecular chaperone trigger factor (TF) on αSyn structure and dynamics using resonance broadening to define a footprint of the TF–RNC interactions. We have used these data to construct structural models that suggest specific ways by which emerging NCs can interact with the biosynthesis and quality control machinery.
The relative importance of life‐history variables to population growth rate (λ) has substantial consequences for the study of life‐history evolution and for the dynamics of biological populations. ...Using life‐history data for 142 natural populations of mammals, we estimated the elasticity of λ to changes in age at maturity (α), age at last reproduction (ω), juvenile survival (P
j), adult survival (P
a), and fertility (F). Elasticities were then used to quantify the relative importance of α, ω,P
j,P
a, andFto λ and to test theoretical predictions regarding the relative influence on λ of changes in life‐history variables. Neither α nor any other single life‐history variable had the largest relative influence on λ in the majority of the populations, and this pattern did not change substantially when effects of phylogeny and body size were statistically removed. Empirical support for theoretical predictions was poor at best. However, analyses of elasticities on the basis of the magnitude (F) and onset (α) of reproduction revealed that α, followed byF, had the largest relative influence on λ in populations characterized by early maturity and high reproductive rates, or when
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. When maturity was delayed and reproductive rates were low, or when
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, survival rates were overwhelmingly most influential, and reproductive parameters (α andF) had little relative influence on λ. Population dynamic consequences of likely responses of biological populations to perturbations in life‐history variables are examined, and predictions are made regarding the numerical dynamics of age‐structured populations on the basis of values of theF/α ratio.
The Lunar Environment heliospheric X-ray Imager (LEXI) is a wide field-of-view soft X-ray telescope developed to study solar wind-magnetosphere coupling. LEXI is part of the Blue Ghost 1 mission ...comprised of 10 payloads to be deployed on the lunar surface. LEXI monitors the dayside magnetopause position and shape as a function of time by observing soft X-rays (0.1–2 keV) emitted from solar wind charge-exchange between exospheric neutrals and high charge-state solar wind plasma in the dayside magnetosheath. Measurements of the shape and position of the magnetopause are used to test temporal models of meso- and macro-scale magnetic reconnection. To image the boundary, LEXI employs lobster-eye optics to focus X-rays to a microchannel plate detector with a 9.1
×
∘
9.1
∘
field of view.
The Cusp Plasma Imaging detector (CuPID) Cube Satellite Observatory is a six‐unit Cube Satellite developed to study macroscale properties of dayside magnetopause reconnection. Reconnection will be ...studied through imaging spatial and temporal ion dispersion signatures in the magnetospheric cusps. As reconnection enables shocked solar wind plasma to enter the cusp, high charge state solar wind ions will charge‐exchange with Earth's neutral exosphere. This process generates soft X‐rays imaged by the spacecraft. CuPID is in a circular, highly inclined (97.6°), sun‐synchronous, low Earth orbit (550 km), where it views upward through the cusp from its low altitude footprint. The mission carries three science instruments, an energetic (>50 keV) radiation detector, a soft X‐ray (0.1–2 keV) imager, and a body‐mounted magnetometer. The soft X‐ray imager employs a novel, wide field‐of‐view (4.6°) slumped micropore optical element to focus X‐rays. The radiation detector uses collimated micro‐dosimeters with blocking foils to discriminate particle species. The three‐axis magnetometer is part of the attitude determination and control system and has been calibrated to provide scientifically useful data.
Plain Language Summary
The Cusp Imaging Plasma Instrument Detector (CuPID) CubeSat Observatory is a small spacecraft designed to study soft X‐rays from space. These X‐rays will not penetrate the Earth's atmosphere, so an observer must make measurements from space, and CuPID will fly in a low altitude (550 km) polar orbit. The spacecraft will carry the first ever wide field‐of‐view soft X‐ray imager into orbit to make measurements of the Earth's space environment in soft X‐rays. Scientifically, soft X‐rays are useful as their intensity and dynamics in the Earth's polar cusps provide a proxy for the driving from the sun's solar wind. The spacecraft packs a modular set of avionics as well as soft X‐ray telescope and radiation sensor into a small 10 cm × 20 cm × 30 cm box. The self‐sustained mission will provide the first regular images of the Earth's magnetic field and space environment in soft X‐rays.
Key Points
The Cusp Plasma Imaging detector (CuPID) Cube Satellite Observatory is a small satellite built to study soft X‐rays in space
CuPID is a pioneering wide field‐of‐view soft X‐ray imager in orbit
CuPID studies solar wind‐magnetosphere coupling and magnetopause reconnection
Wild boars Sus scrofa have a social organization based on female groups that can include several generations of adults and offspring, and are thus likely matrilineal. However, little is known about ...the degree of relatedness between animals living in such groups or occupying the same core area of spatial activity. Also, polygynous male mating combined with matrilineal female groups can have strong influences on the genetic structure of populations. We used microsatellite genotyping combined with behavioral data to investigate the fine-scale population genetic structure and the mating system of wild boars in a multi-year study at Châteauvillain-Arc-en-Barrois (France). According to spatial genetic autocorrelation, females in spatial proximity were significantly inter-related. However, we found that numerous males contributed to the next generation, even within the same social group. Based on our genetic data and behavioral observations, wild boars in this population appear to have a low level of polygyny associated with matrilineal female groups, and infrequent multiple paternity. Mortality due to hunting may facilitate the breakup of what historically has been a more predominantly polygynous mating system, and likely accelerates the turnover of adults within the matrilineal groups.
The life history schedules of wild organisms have long attracted scientific interest, and, in light of ongoing climate change, an understanding of their genetic and environmental underpinnings is ...increasingly becoming of applied concern. We used a multi‐generation pedigree and detailed phenotypic records, spanning 18 years, to estimate the quantitative genetic influences on the timing of hibernation emergence in a wild population of Columbian ground squirrels (Urocitellus columbianus). Emergence date was significantly heritable h2 = 0.22 ± 0.05 (in females) and 0.34 ± 0.14 (in males), and there was a positive genetic correlation (rG = 0.76 ± 0.22) between male and female emergence dates. In adult females, the heritabilities of body mass at emergence and oestrous date were h2 = 0.23 ± 0.09 and h2 = 0.18 ± 0.12, respectively. The date of hibernation emergence has been hypothesized to have evolved so as to synchronize subsequent reproduction with upcoming peaks in vegetation abundance. In support of this hypothesis, although levels of phenotypic variance in emergence date were higher than oestrous date, there was a highly significant genetic correlation between the two (rG = 0.98 ± 0.01). Hibernation is a prominent feature in the annual cycle of many small mammals, but our understanding of its influences lags behind that for phenological traits in many other taxa. Our results provide the first insight into its quantitative genetic influences and thus help contribute to a more general understanding of its evolutionary significance.
Population genetics meets behavioral ecology Sugg, Derrick W.; Chesser, Ronald K.; Stephen Dobson, F. ...
Trends in ecology & evolution (Amsterdam),
08/1996, Letnik:
11, Številka:
8
Journal Article
Recenzirano
Populations are often composed of more than just randomly mating subpopulations - many organisms from social groups with distinct patterns of mating and dispersal. Such patterns have recieved much ...attention in behavioral ecology, yet theories of population genetics rarely take social structures into account. Consequently, population geneticists often report high levels of apparent in breeding and concomitantly low efective sizes, even for species that avoid mating between close kin. Recently, a view of gene dynamics has been introduced that takes dispersal and social structure into account. Accounting for social structure in population genetics leads to a different perspective on how genetic variation is partitoned and the rate at which genic diversity is lost in natural populations - a view that is more consistent with observed behaviors for the minimization of inbreeding.
Environmental factors influence the dynamics and regulation of biological populations through their influences on demographic variables, but demographic mechanisms of population regulation have ...received little attention. We investigated the demographic basis of regulation of Columbian ground squirrel (Spermophilus columbianus) populations under natural and experimentally food‐supplemented conditions. Food supplementation caused substantial increases in population density, and population densities returned to pretreatment levels when the supplementation ended. Control (untreated) populations remained relatively stable throughout the study period (1981–1986). Because food resources regulated the size of the ground squirrel populations, we used life‐table response experiment (LTRE) analyses to examine the demographic basis of changes in population growth rate and thus also demographic influences on population regulation. LTRE analyses of two foodmanipulated populations revealed that changes in age at maturity and fertility rate of females generally made the largest contributions to observed changes in population growth rate. Thus, our results suggested that abundance of food resources regulated the size of our study populations through the effects of food resources on age at maturity and fertility rates. Our results also indicated that different demographic mechanisms can underlie population regulation under different environmental conditions, because lower juvenile survival substantially contributed to population decline, but in only one of the populations. Demographic analyses of experimental data, such as those presented here, offer a rigorous and unambiguous means to elucidate the demographic basis of population regulation and to help identify environmental factors that underlie dynamics and regulation of biological populations.
Albatrosses exhibit extremely low reproductive rates, each pair brooding only one egg and subsequent chick at a time. Furthermore, in several of the species, the majority of successful pairs breed ...only once every second year (termed 'biennial' breeding). Thus, on average, these latter species have an annual fecundity of about half an offspring per year, while other albatrosses produce an egg and chick every year. Using our 40-year bank of demographic data, we compared 12 species of albatrosses according to these two breeding strategies to examine potential causes of biennial breeding. Biennial breeding could be due to physiological constraints, larger animals breeding more slowly, or ecological constraints, more distant pelagic feeding trips being energetically costly, or both. We tested these hypotheses by looking for predicted associations between the duration of the rearing period, the distance to the oceanic feeding zone and breeding frequency. We also looked for associations of these variables with other life-history traits. Body size had a strong influence on the duration of the rearing period, but not on the distance that birds travelled to the feeding zone. Both the duration of the rearing period and distance to the feeding zone appeared to have direct influences on breeding frequency, as revealed by a path analysis, and thus both hypotheses to explain biennial breeding were supported. Finally, breeding frequency exhibited a strong trade-off with adult survival and age at maturity, indicating that slower breeders live through more breeding seasons, perhaps mitigating their lower annual reproductive output.
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