Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons.

The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed. To investigate their properties, we isolated glia and neurons from Cln3-deficient mice and studied their basic biology in culture. Upon stimulation, both Cln3-deficient astrocytes and microglia also showed an attenuated ability to transform morphologically, and an altered protein secretion profile. These defects were more pronounced in astrocytes, including the reduced secretion of a range of neuroprotective factors, mitogens, chemokines and cytokines, in addition to impaired calcium signalling and glutamate clearance. Cln3-deficient neurons also displayed an abnormal organization of their neurites. Most importantly, using a co-culture system, Cln3-deficient astrocytes and microglia had a negative impact on the survival and morphology of both Cln3-deficient and wildtype neurons, but these effects were largely reversed by growing mutant neurons with healthy glia. These data provide evidence that CLN3 disease astrocytes are functionally compromised. Together with microglia, they may play an active role in neuron loss in this disorder and can be considered as potential targets for therapeutic interventions

Post-fire Recovery of Wyoming Big Sagebrush Steppe in Central and Southeast Montana

Big sagebrush (Artemisia tridentata Nutt.) steppe is a widespread habitat throughout eastern Montana and supports several sagebrush-dependent species including Greater Sage-grouse (Centrocercus urophasianus). We sampled 24 burned-unburned paired sites in central and southeastern Montana dominated by Wyoming big sagebrush (ssp. wyomingensis). Time since fire ranged from 4 to 67 years. Prescribed burns and wildfires typically resulted in the complete mortality of big sagebrush. We found negligible post-fire Wyoming big sagebrush recovery for 17 of the 24 sites and the oldest burn (67 years) was only 8 percent recovered. Perennial grass cover increased 27 percent and 20 percent following prescribed fire and wildfire, respectively; western wheatgrass (Pascopyrum smithii) accounted for most of this increase. Annual grass cover increased by 11 percent due primarily to field brome (Bromus arvensis, formerly B. japonicus). Plant species richness significantly declined in burned plots compared to unburned controls. There was no change after burning in overall sub-shrub or forb cover or the density of Cichorieae forbs that are important for successful Greater Sage-grouse brood rearing. Managers concerned about Greater Sage-grouse and other sage-dependent species should be extremely cautious with prescribed burns and wildfires in this region. Fire will likely eliminate sagebrush habitat, increase weedy annual grass cover and reduce species richness; sagebrush cover could take a century or more to recover to pre-burn conditions

Analytic and Numerical Study of Preheating Dynamics

We analyze the phenomenon of preheating,i.e. explosive particle production due to parametric amplification of quantum fluctuations in the unbroken case, or spinodal instabilities in the broken phase, using the Minkowski space $O(N)$ vector model in the large $N$ limit to study the non-perturbative issues involved. We give analytic results for weak couplings and times short compared to the time at which the fluctuations become of the same order as the tree level,as well as numerical results including the full backreaction.In the case where the symmetry is unbroken, the analytic results agree spectacularly well with the numerical ones in their common domain of validity. In the broken symmetry case, slow roll initial conditions from the unstable minimum at the origin, give rise to a new and unexpected phenomenon: the dynamical relaxation of the vacuum energy.That is, particles are abundantly produced at the expense of the quantum vacuum energy while the zero mode comes back to almost its initial value.In both cases we obtain analytically and numerically the equation of state which turns to be written in terms of an effective polytropic index that interpolates between vacuum and radiation-like domination. We find that simplified analysis based on harmonic behavior of the zero mode, giving rise to a Mathieu equation forthe non-zero modes miss important physics. Furthermore, analysis that do not include the full backreaction do not conserve energy, resulting in unbound particle production. Our results do not support the recent claim of symmetry restoration by non-equilibrium fluctuations.Finally estimates of the reheating temperature are given,as well as a discussion of the inconsistency of a kinetic approach to thermalization when a non-perturbatively large number of particles is created.Comment: Latex file, 52 pages and 24 figures in .ps files. Minor changes. To appear in Physical Review D, 15 December 199

Differential expression, function and response to inflammatory stimuli of 11β-hydroxysteroid dehydrogenase type 1 in human fibroblasts: a mechanism for tissue-specific regulation of inflammation

Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation. We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Expression, activity and function of 11β-HSD1 was assessed in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid arthritis or osteoarthritis. 11β-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis factor-α or IL-1β (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4-fold and 14-fold; synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-γ was without effect, and there was no difference in 11β-HSD1 expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the presence of 100 nmol/l cortisone, IL-6 production – a characteristic feature of synovial derived fibroblasts – was significantly reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11β-HSD inhibitor, emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences in fibroblast-derived glucocorticoid production (via the enzyme 11β-HSD1) between cells from distinct anatomical locations may play a key role in the predeliction of certain tissues to develop persistent inflammation

Standardized Measures of Coastal Wetland Condition: Implementation at a Laurentian Great Lakes Basin-Wide Scale

Since European settlement, over 50 % of coastal wetlands have been lost in the Laurentian Great Lakes basin, causing growing concern and increased monitoring by government agencies. For over a decade, monitoring efforts have focused on the development of regional and organism-specific measures. To facilitate collaboration and information sharing between public, private, and government agencies throughout the Great Lakes basin, we developed standardized methods and indicators used for assessing wetland condition. Using an ecosystem approach and a stratified random site selection process, birds, anurans, fish, macroinvertebrates, vegetation, and physico-chemical conditions were sampled in coastal wetlands of all five Great Lakes including sites from the United States and Canada. Our primary objective was to implement a standardized basin-wide coastal wetland monitoring program that would be a powerful tool to inform decision-makers on coastal wetland conservation and restoration priorities throughout the Great Lakes basin

Design and validation of a mechanically flexible and ultra-lightweight high-density diffuse optical tomography system for functional neuroimaging of newborns

Neonates are a highly vulnerable population. The risk of brain injury is greater during the first days and weeks after birth than at any other time of life. Functional neuroimaging that can be performed longitudinally and at the cot-side has the potential to improve our understanding of the evolution of multiple forms of neurological injury over the perinatal period. However, existing technologies make it very difficult to perform repeated and/or long-duration functional neuroimaging experiments at the cot-side. We aimed to create a modular, high-density diffuse optical tomography (HD-DOT) technology specifically for neonatal applications that is ultra-lightweight, low profile and provides high mechanical flexibility. We then sought to validate this technology using an anatomically accurate dynamic phantom. An advanced 10-layer rigid-flexible printed circuit board technology was adopted as the basis for the DOT modules, which allows for a compact module design that also provides the flexibility needed to conform to the curved infant scalp. Two module layouts were implemented: dual-hexagon and triple-hexagon. Using in-built board-to-board connectors, the system can be configured to provide a vast range of possible layouts. Using epoxy resin, thermochromic dyes, and MRI-derived 3D-printed moulds, we constructed an electrically switchable, anatomically accurate dynamic phantom. This phantom was used to quantify the imaging performance of our flexible, modular HD-DOT system. Using one particular module configuration designed to cover the infant sensorimotor system, the device provided 36 source and 48 detector positions, and over 700 viable DOT channels per wavelength, ranging from 10 to over an area of approximately . The total weight of this system is only 70 g. The signal changes from the dynamic phantom, while slow, closely simulated real hemodynamic response functions. Using difference images obtained from the phantom, the measured 3D localization error provided by the system at the depth of the cortex was in the of range 3 to 6 mm, and the lateral image resolution at the depth of the neonatal cortex is estimated to be as good as 10 to 12 mm. The HD-DOT system described is ultra-low weight, low profile, can conform to the infant scalp, and provides excellent imaging performance. It is expected that this device will make functional neuroimaging of the neonatal brain at the cot-side significantly more practical and effective. [Abstract copyright: © 2021 The Authors.

The Stars of the HETDEX Survey. I. Radial Velocities and Metal-Poor Stars from Low-Resolution Stellar Spectra

The Hobby-Eberly Telescope Dark Energy Experiment (HETDEX) is an unbiased, massively multiplexed spectroscopic survey, designed to measure the expansion history of the universe through low-resolution (R∼750) spectra of Lyman-Alpha Emitters. In its search for these galaxies, HETDEX will also observe a few 105 stars. In this paper, we present the first stellar value-added catalog within the internal second data release of the HETDEX Survey (HDR2). The new catalog contains 120,571 low-resolution spectra for 98,736 unique stars between 10∘) Galactic latitudes. With these spectra, we measure radial velocities (RVs) for ∼42,000 unique FGK-type stars in the catalog and show that the HETDEX spectra are sufficient to constrain these RVs with a 1σ precision of 28.0 km/s and bias of 3.5 km/s with respect to the LAMOST surveys and 1σ precision of 27.5 km/s and bias of 14.0 km/s compared to the SEGUE survey. Since these RVs are for faint (G≥16) stars, they will be complementary to Gaia. Using t-Distributed Stochastic Neighbor Embedding (t-SNE), we also demonstrate that the HETDEX spectra can be used to determine a star's Teff, and log g and its [Fe/H]. With the t-SNE projection of the FGK-type stars with HETDEX spectra we also identify 416 new candidate metal-poor ([Fe/H] <−1~dex) stars for future study. These encouraging results illustrate the utility of future low-resolution stellar spectroscopic surveys

Activity patterns of free-ranging koalas (Phascolarctos cinereus) revealed by accelerometry

An understanding of koala activity patterns is important for measuring the behavioral response of this species to environmental change, but to date has been limited by the logistical challenges of traditional field methodologies. We addressed this knowledge gap by using tri-axial accelerometer data loggers attached to VHF radio collars to examine activity patterns of adult male and female koalas in a high-density population at Cape Otway, Victoria, Australia. Data were obtained from 27 adult koalas over two 7-d periods during the breeding season: 12 in the early-breeding season in November 2010, and 15 in the late-breeding season in January 2011. Multiple 15 minute observation blocks on each animal were used for validation of activity patterns determined from the accelerometer data loggers. Accelerometry was effective in distinguishing between inactive (sleeping, resting) and active (grooming, feeding and moving) behaviors. Koalas were more active during the early-breeding season with a higher index of movement (overall dynamic body acceleration [ODBA]) for both males and females. Koalas showed a distinct temporal pattern of behavior, with most activity occurring from mid-afternoon to early morning. Accelerometry has potential for examining fine-scale behavior of a wide range of arboreal and terrestrial species

Experimental warming differentially affects vegetative and reproductive phenology of tundra plants

Rapid climate warming is altering Arctic and alpine tundra ecosystem structure and function, including shifts in plant phenology. While the advancement of green up and flowering are well-documented, it remains unclear whether all phenophases, particularly those later in the season, will shift in unison or respond divergently to warming. Here, we present the largest synthesis to our knowledge of experimental warming effects on tundra plant phenology from the International Tundra Experiment. We examine the effect of warming on a suite of season-wide plant phenophases. Results challenge the expectation that all phenophases will advance in unison to warming. Instead, we find that experimental warming caused: (1) larger phenological shifts in reproductive versus vegetative phenophases and (2) advanced reproductive phenophases and green up but delayed leaf senescence which translated to a lengthening of the growing season by approximately 3%. Patterns were consistent across sites, plant species and over time. The advancement of reproductive seasons and lengthening of growing seasons may have significant consequences for trophic interactions and ecosystem function across the tundra