Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium.

Dendritic spines are small subcompartments that protrude from the dendrites of neurons and are important for signaling activity and synaptic communication. These subcompartments have been characterized to have different shapes. While it is known that these shapes are associated with spine function, the specific nature of these shape-function relationships is not well understood. In this work, we systematically investigated the relationship between the shape and size of both the spine head and spine apparatus, a specialized endoplasmic reticulum compartment within the spine head, in modulating rapid calcium dynamics using mathematical modeling. We developed a spatial multicompartment reaction-diffusion model of calcium dynamics in three dimensions with various flux sources, including N-methyl-D-aspartate receptors (NMDARs), voltage-sensitive calcium channels (VSCCs), and different ion pumps on the plasma membrane. Using this model, we make several important predictions. First, the volume to surface area ratio of the spine regulates calcium dynamics. Second, membrane fluxes impact calcium dynamics temporally and spatially in a nonlinear fashion. Finally, the spine apparatus can act as a physical buffer for calcium by acting as a sink and rescaling the calcium concentration. These predictions set the stage for future experimental investigations of calcium dynamics in dendritic spines

“Back to Basics:” Converging Mattering, Dialogue, and Love within Pedagogy, Research, and Community-Engaged Work

This article highlights the intersections of Mattering, Dialogue, and Love— three seemingly distinct concepts, within schooling and research. Using sister circles, book presentations, and a critical ethnography, we underscore how a critical examination of one’s lived experiences can serve as a platform for anti-racist and social justice work. In this way, this article functions as a medium through which we acknowledge systemic inequities perpetuated within schools and recenter schools as extensions of the communities they serve

Increasing phytoremediation efficiency and reliability using novel omics approaches

Phytoremediation is a cost-effective green alternative to traditional soil remediation technologies, but has experienced varied success in practice. The recent omics revolution has led to leaps in our understanding of soil microbial communities and plant metabolism, and some of the conditions that promote predictable activity in contaminated soils and heterogeneous environments. Combinations of omics tools and new bioinformatics approaches will allow us to understand integrated activity patterns between plants and microbes, and determine how this metaorganism can be modified to maximize growth, appropriate assembly of microbial communities, and, ultimately, phytoremediation activity. Here we provide an overview of how new omics-mediated discoveries can potentially be translated into an effective and reliable environmental technology

Absolute Proper Motion of the Fornax Dwarf Spheroidal Galaxy from Photographic and HST WFPC2 Data

We have measured the absolute proper motion of the Fornax dwarf spheroidal galaxy from a combination of photographic plate material and HST WFPC2 data that provide a time baseline of up to 50 years. The extragalactic reference frame consists of 8 QSO images and 48 galaxies. The absolute proper motion is mu_alpha cos(delta) = 0.59 +-0.16 mas/yr and mu_delta = -0.15 +- 0.16 mas/yr. The corresponding orbit of Fornax is polar, with an eccentricity of 0.27, and a radial period of 4.5 Gyr. Fornax's current location is near pericenter. The direction of the motion of Fornax supports the notion that Fornax belongs to the Fornax-LeoI-LeoII-Sculptor-Sextans stream as hypothesized by Lynden-Bell (1976, 1982) and Majewski (1994). According to our orbit determination, Fornax crossed the Magellanic plane \~190 Myr ago, a time that coincides with the termination of the star-formation process in Fornax. We propose that ram-pressure stripping due to the passage of Fornax through a gaseous medium denser than the typical intragalactic medium left behind from the LMC may have caused the end of star formation in Fornax. The excess, anomalous clouds within the South Galactic pole region of the Magellanic Stream whose origin has long been debated in the literature as constituents of either the Magellanic Stream or of the extragalactic Sculptor group, are found to lie along the orbit of Fornax. We speculate that these clouds are stripped material from Fornax as the dwarf crossed the Magellanic Clouds' orbit.Comment: Accepted for publication in Astronomical Journal. The version with high resolution figures can be found at ftp://pegasus.astro.yale.edu/pub/dana/paper

Phylogenetic Signal, Root Morphology, Mycorrhizal Type, and Macroinvertebrate Exclusion: Exploring Wood Decomposition in Soils Conditioned by 13 Temperate Tree Species

Woodlands are pivotal to carbon stocks, but the process of cycling C is slow and may be most effective in the biodiverse root zone. How the root zone impacts plants has been widely examined over the past few decades, but the role of the root zone in decomposition is understudied. Here, we examined how mycorrhizal association and macroinvertebrate activity influences wood decomposition across diverse tree species. Within the root zone of six predominantly arbuscular mycorrhizal (AM) (Acer negundo, Acer saccharum, Prunus serotina, Juglans nigra, Sassafras albidum, and Liriodendron tulipfera) and seven predominantly ectomycorrhizal (EM) tree species (Carya glabra, Quercus alba, Quercus rubra, Betula alleghaniensis, Picea rubens, Pinus virginiana, and Pinus strobus), woody litter was buried for 13 months. Macroinvertebrate access to woody substrate was either prevented or not using 0.22 mm mesh in a common garden site in central Pennsylvania. Decomposition was assessed as proportionate mass loss, as explained by root diameter, phylogenetic signal, mycorrhizal type, canopy tree trait, or macroinvertebrate exclusion. Macroinvertebrate exclusion significantly increased wood decomposition by 5.9%, while mycorrhizal type did not affect wood decomposition, nor did canopy traits (i.e., broad leaves versus pine needles). Interestingly, there was a phylogenetic signal for wood decomposition. Local indicators for phylogenetic associations (LIPA) determined high values of sensitivity value in Pinus and Picea genera, while Carya, Juglans, Betula, and Prunus yielded low values of sensitivity. Phylogenetic signals went undetected for tree root morphology. Despite this, roots greater than 0.35 mm significantly increased woody litter decomposition by 8%. In conclusion, the findings of this study suggest trees with larger root diameters can accelerate C cycling, as can trees associated with certain phylogenetic clades. In addition, root zone macroinvertebrates can potentially limit woody C cycling, while mycorrhizal type does not play a significant role

Manipulating Wild and Tamed Phytobiomes: Challenges and Opportunities

This white paper presents a series of perspectives on current and future phytobiome management, discussed at the Wild and Tamed Phytobiomes Symposium in University Park, PA, USA, in June 2018. To enhance plant productivity and health, and to translate lab- and greenhouse-based phytobiome research to field applications, the academic community and end-users need to address a variety of scientific, practical, and social challenges. Prior discussion of phytobiomes has focused heavily on plant-associated bacterial and fungal assemblages, but the phytobiomes concept covers all factors that influence plant function. Here we discuss various management considerations, including abiotic conditions (e.g. soil, nutrient applications), microorganisms (e.g. bacterial and fungal assemblages, bacterial and fungal inoculants, viruses), macroorganisms (e.g. arthropods, plant genetics), and societal factors (e.g. communication approaches, technology diffusion). An important near-term goal for this field should be to estimate the potential relative contribution of different components of the phytobiome to plant health, as well as the potential and risk of modifying each in the near-future

Orbits of Globular Clusters in the Outer Galaxy: NGC 7006

We present a proper motion study of the distant globular cluster NGC 7006 based on the measurement of 25 photographic plates spanning a 40-year interval. The absolute proper motion determined with respect to extragalactic objects is (-0.96, -1.14) +- (0.35, 0.40) mas/yr. The total space velocity of NGC 7006 in a Galactocentric rest frame is 279 km/s, placing the cluster on one of the most energetic orbits (Ra =102 kpc) known to date for clusters within 40-kpc from the Galactic center. We compare the orbits of four clusters that have apocentric radii larger than 80 kpc (NGC 5466, NGC 6934, NGC 7006 and Pal 13) with those of Galactic satellites with well-measured proper motions. These clusters have orbits that are highly eccentric and of various inclinations with respect to the Galactic plane. In contrast, the orbits of the Galactic satellites are of low to moderate eccentricity and highly inclined. Based on orbit types, chemical abundances and cluster parameters, we discuss the properties of the hypothetical host systems of the remote globular clusters in the Searle-Zinn paradigm. It is apparent that clusters such as NGC 5466, NGC 6934 and NGC 7006 formed in systems that more likely resemble the Fornax dSph, rather than the Sagittarius dSph. We also discuss plausible causes for the difference found so far between the orbit type of outer halo clusters and that of Galactic satellites and for the tentative, yet suggestive phase-space scatter found among outer halo clusters.Comment: 27 pages, 5 figures, to be published in the Astronomical Journa

Complex Independent Component Analysis of Frequency-Domain Electroencephalographic Data

Independent component analysis (ICA) has proven useful for modeling brain and electroencephalographic (EEG) data. Here, we present a new, generalized method to better capture the dynamics of brain signals than previous ICA algorithms. We regard EEG sources as eliciting spatio-temporal activity patterns, corresponding to, e.g., trajectories of activation propagating across cortex. This leads to a model of convolutive signal superposition, in contrast with the commonly used instantaneous mixing model. In the frequency-domain, convolutive mixing is equivalent to multiplicative mixing of complex signal sources within distinct spectral bands. We decompose the recorded spectral-domain signals into independent components by a complex infomax ICA algorithm. First results from a visual attention EEG experiment exhibit (1) sources of spatio-temporal dynamics in the data, (2) links to subject behavior, (3) sources with a limited spectral extent, and (4) a higher degree of independence compared to sources derived by standard ICA.Comment: 21 pages, 11 figures. Added final journal reference, fixed minor typo

Successful use of axonal transport for drug delivery by synthetic molecular vehicles

We report the use of axonal transport to achieve intraneural drug delivery. We constructed a novel tripartite complex of an axonal transport facilitator conjugated to a linker molecule bearing up to a hundred reversibly attached drug molecules. The complex efficiently enters nerve terminals after intramuscular or intradermal administration and travels within axonal processes to neuron cell bodies. The tripartite agent provided 100-fold amplification of saturable neural uptake events, delivering multiple drug molecules per complex. _In vivo_, analgesic drug delivery to systemic and to non-targeted neural tissues was greatly reduced compared to existing routes of administration, thus exemplifying the possibility of specific nerve root targeting and effectively increasing the potency of the candidate drug gabapentin 300-fold relative to oral administration

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

BackgroundCurrent treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.MethodsWe performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).ResultsRituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of$61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and$110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.ConclusionsOur results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug