ALBERT

Description: The blood-brain barrier (BBB) is essential for maintaining brain homeostasis and protecting neural tissue from damaging blood-borne agents. The barrier is characterized by endothelial tight junctions that limit passive paracellular diffusion of polar solutes and macromolecules from blood to brain. Decreased brain clearance of the neurotoxic amyloid-β (Aβ) peptide is a central event in the pathogenesis of Alzheimer’s disease (AD). Whereas transport of Aβ across the BBB can occur via transcellular endothelial receptors, the paracellular movement of Aβ has not been described. We show that soluble human Aβ(1–40) monomers can diffuse across the paracellular pathway of the BBB in tandem with a decrease in the tight junction proteins claudin-5 and occludin in the cerebral vascular endothelium. In a murine model of AD (Tg2576), plasma Aβ(1–40) levels were significantly increased, brain Aβ(1–40) levels were decreased, and cognitive function was enhanced when both claudin-5 and occludin were suppressed. Furthermore, Aβ can cause a transient down-regulation of claudin-5 and occludin, allowing for its own paracellular clearance across the BBB. Our results show, for the first time, the involvement of the paracellular pathway in autoregulated Aβ movement across the BBB and identify both claudin-5 and occludin as potential therapeutic targets for AD. These findings also indicate that controlled modulation of tight junction components at the BBB can enhance the clearance of Aβ from the brain.

Description: Abstract Many of the processes that govern the viability of animal populations vary spatially, yet population viability analyses (PVAs) that account explicitly for spatial variation are rare. We develop a PVA model that incorporates autocorrelation into the analysis of local demographic information to produce spatially explicit estimates of demography and viability at relatively fine spatial scales across a large spatial extent. We use a hierarchical, spatial, autoregressive model for capture–recapture data from multiple locations to obtain spatially explicit estimates of adult survival (ϕad), juvenile survival (ϕjuv), and juvenile‐to‐adult transition rates (ψ), and a spatial autoregressive model for recruitment data from multiple locations to obtain spatially explicit estimates of recruitment (R). We combine local estimates of demographic rates in stage‐structured population models to estimate the rate of population change (λ), then use estimates of λ (and its uncertainty) to forecast changes in local abundance and produce spatially explicit estimates of viability (probability of extirpation, Pex). We apply the model to demographic data for the Sonoran desert tortoise (Gopherus morafkai) collected across its geographic range in Arizona. There was modest spatial variation in λ^ (0.94–1.03), which reflected spatial variation in ϕ^ad (0.85–0.95), ϕ^juv (0.70–0.89), and ψ^ (0.07–0.13). Recruitment data were too sparse for spatially explicit estimates; therefore, we used a range‐wide estimate (R^ = 0.32 1‐yr‐old females per female per year). Spatial patterns in demographic rates were complex, but ϕ^ad, ϕ^juv, and λ^ tended to be lower and ψ^ higher in the northwestern portion of the range. Spatial patterns in Pex varied with local abundance. For local abundances 〉500, Pex was near zero (〈0.05) across most of the range after 100 yr; as abundances decreased, however, Pex approached one in the northwestern portion of the range and remained low elsewhere. When local abundances were 〈50, western and southern populations were vulnerable (Pex 〉 0.25). This approach to PVA offers the potential to reveal spatial patterns in demography and viability that can inform conservation and management at multiple spatial scales, provide insight into scale‐related investigations in population ecology, and improve basic ecological knowledge of landscape‐level phenomena.

Description: Author(s): H. Heylen, C. Babcock, J. Billowes, M. L. Bissell, K. Blaum, P. Campbell, B. Cheal, R. F. Garcia Ruiz, Ch. Geppert, W. Gins, M. Kowalska, K. Kreim, S. M. Lenzi, I. D. Moore, R. Neugart, G. Neyens, W. Nörtershäuser, J. Papuga, and D. T. Yordanov The odd-odd Mn 54 , 56 , 58 , 60 , 62 , 64 isotopes ( Z = 25 ) were studied using bunched-beam collinear laser spectroscopy at ISOLDE, CERN. From the measured hyperfine spectra the spins and magnetic moments of Mn isotopes up to N = 39 were extracted. The previous tentative ground state spin assignments of Mn 58 , 60 , 6… [Phys. Rev. C 92, 044311] Published Tue Oct 13, 2015

Description: Langmuir DOI: 10.1021/acs.langmuir.6b01444

Description: A capture cross section value is often assigned to Si–SiO 2 interface defects. Using a kinetic variation of the charge pumping technique and transition state theory, we show that the value of capture cross section is extremely sensitive to the measurement approach and does not provide any meaningful insight into the physics involved. We argue that capture cross section is neither a physical property of interface defects nor is there any need to assign capture cross section values.

Description: Analytical Chemistry DOI: 10.1021/acs.analchem.5b00487

Description: Helper T cells are critical for protective immunity, CD8+ T-cell memory, and CD4+ recall responses, but whether the same or distinct CD4+ T cells are involved in these responses has not been established. Here we describe two CD4+ T cells, LLO118 and LLO56, specific for an immunodominant Listeria monocytogenes epitope, with dramatically different responses to primary and secondary infection. Comparing in vivo responses, LLO118 T cells proliferate more strongly to primary infection, whereas surprisingly, LLO56 has a superior CD4+ recall response to secondary infection. LLO118 T cells provide more robust help for CD8+ T-cell responses to secondary infection than LLO56. We found no detectable differences in antigen sensitivity, but naive LLO118 T cells have much lower levels of CD5 and their T-cell receptor levels are dramatically down-regulated after their strong primary response. Thus, distinct CD4+ helper T cells are specialized to help either in primary or secondary responses to infection.

Description: The mechanism by which antifreeze proteins (AFPs) irreversibly bind to ice has not yet been resolved. The ice-binding site of an AFP is relatively hydrophobic, but also contains many potential hydrogen bond donors/acceptors. The extent to which hydrogen bonding and the hydrophobic effect contribute to ice binding has been debated for over 30 years. Here we have elucidated the ice-binding mechanism through solving the first crystal structure of an Antarctic bacterial AFP. This 34-kDa domain, the largest AFP structure determined to date, folds as a Ca2+-bound parallel beta-helix with an extensive array of ice-like surface waters that are anchored via hydrogen bonds directly to the polypeptide backbone and adjacent side chains. These bound waters make an excellent three-dimensional match to both the primary prism and basal planes of ice and in effect provide an extensive X-ray crystallographic picture of the AFP∶ice interaction. This unobstructed view, free from crystal-packing artefacts, shows the contributions of both the hydrophobic effect and hydrogen bonding during AFP adsorption to ice. We term this mode of binding the “anchored clathrate” mechanism of AFP action.

Description: The reference rock site condition has two important applications for ground-motion prediction in the stable continental region of central and eastern North America (CENA). (1) It represents the site condition for which ground motions are computed using semiempirical ground-motion prediction equations. In addition, (2) it represents the site condition to which site amplification factors, which are used to modify ground-motion intensity measures for softer site condition, are referenced (i.e., site amplification is unity for reference rock). We define reference rock by its shear ( S )- and compression ( P )-wave velocities, as well as a site attenuation parameter ( 0 ), which is used in stochastic ground-motion simulation methods. Prior definitions of reference rock conditions in CENA were based mostly on indirect large-scale crustal velocity inversions and judgment. We compile and interpret a unique database of direct velocity measurements to develop criteria for assessing the presence of reference rock site condition based on measured seismic velocities and their gradient with respect to depth. We apply the criteria to available profiles and perform rigorous statistical analysis from which we recommend S - and P -wave velocities of 3000 and 5500 m/s, respectively, for the reference rock condition. We recommend that, for practical applications, use ranges of reference S - and P -wave velocities of 2700–3300 m/s and 5000–6100 m/s, respectively. The ranges are based on a ±5% change in amplification using quarter-wavelength theory. We do not find evidence for regional dependence of the reference velocities, which are derived principally from three general geographic regions: (1) Atlantic coast, (2) continental interior, and (3) Appalachian Mountains. Our data do not provide reference velocities for the Gulf Coast region. The recommended velocity-compatible reference rock site kappa is 0.006 s.

Description: Pennsylvanian rocks of the northern U.S. Rocky Mountains are mature quartzose sandstones. This paper uses detrital zircon geochronology on seven samples from the Wood River Formation, Tensleep Sandstone, and Weber Sandstone to determine if these sandstones have a common provenance, representing eastern Laurentian and Appalachian sand reworked within shallow-marine and eolian environments from the Wyoming craton westward to the Pioneer thrust plate of south-central Idaho. Our work suggests that this continental sand blanket was mixed with local sources on the south in the Yavapai-Mazatzal provinces of the Ancestral Rocky Mountains and in samples from the western Cordilleran thrust belt in south-central Idaho. In total, these Pennsylvanian sandstones contain a broad spectrum of detrital zircon U-Pb ages including, from old to young: A) minor Archean-age (3300–2550 Ma) populations; B) Paleoproterozoic (2000–1600 Ma), Mesoproterozoic (1470–1350 Ma), and major "Grenvillian" (1250–950 Ma) populations; and C) Cryogenian- to Ediacaran-age (665–565 Ma) and minor Paleozoic (495–410 Ma) populations. We interpret these detrital zircon ages to represent provenance mainly from the Appalachian mountain belt of eastern North America; however, central Appalachian versus northern Appalachian derivation is not clearly distinguished. The Weber Sandstone from the north flank of the Uinta Mountains in northeast Utah contains a strong 1700–1640 Ma age population derived from the Yavapai-Mazatzal provinces in the adjacent Ancestral Rocky Mountains. The shallow-marine Hailey Member of the Wood River Formation in south-central Idaho yields a population of 〉1800 Ma detrital zircons reworked from the uplifted Mississippian Copper Basin Formation. Both the Hailey and Wilson Creek Members of the Wood River Formation contain unique 640–490 Ma grains that may represent provenance from the Big Creek-Beaverhead plutonic belt of east-central Idaho and/or eastern Klamath terrane in the Klamath Mountains of northwest California and southwest Oregon. These new data support published models for Pennsylvanian–Permian transport of siliciclastic sediment with sources mainly from the North American craton, north of the Ancestral Rocky Mountains, into continental margin basins.