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

Estimated Entrainment of Dungeness Crab During Dredging For The Columbia River Channel Improvement Project

The studies reported here focus on issues regarding the entrainment of Dungeness crab related to the proposed Columbia River Channel Improvement Project and provided direct measurements of crab entrainment rates at three locations (Desdomona Shoals, Upper Sands, and Miller Sands) from RM4 to RM24 during summer 2002. Entrainment rates for all age classes of crabs ranged from zero at Miller Sands to 0.224 crabs per cy at Desdemona Shoals in June 2002. The overall entrainment rate at Desdomona Shoals in September was 0.120 crabs per cy. A modified Dredge Impact Model (DIM) used the summer 2002 entrainment rates to project crab entrainment and adult equivalent loss and loss to the fishery for the Channel Improvement Project. To improve the projections, entrainment data from Flavel Bar is needed. The literature, analyses of salinity intrusion scenarios, and the summer 2002 site-specific data on entrainment and salinity all indicate that bottom salinity influences crab distribution and entrainment, especially at lower salinities. It is now clear from field measurements of entrainment rates and salinity during a period of low river flow (90-150 Kcfs) and high salinity intrusion that entrainment rates are zero where bottom salinity is less than 16 o/oo most of the time. Further, entrainment rates of 2+ and older crab fall with decreasing salinity in a clear and consistent manner. More elaboration of the crab distribution- salinity model, especially concerning salinity and the movements of 1+ crab, is needed

Dancing to the Partisan Beat: A First Analysis of Political Communication on TikTok

TikTok is a video-sharing social networking service, whose popularity is increasing rapidly. It was the world's second-most downloaded app in 2019. Although the platform is known for having users posting videos of themselves dancing, lip-syncing, or showcasing other talents, user-videos expressing political views have seen a recent spurt. This study aims to perform a primary evaluation of political communication on TikTok. We collect a set of US partisan Republican and Democratic videos to investigate how users communicated with each other about political issues. With the help of computer vision, natural language processing, and statistical tools, we illustrate that political communication on TikTok is much more interactive in comparison to other social media platforms, with users combining multiple information channels to spread their messages. We show that political communication takes place in the form of communication trees since users generate branches of responses to existing content. In terms of user demographics, we find that users belonging to both the US parties are young and behave similarly on the platform. However, Republican users generated more political content and their videos received more responses; on the other hand, Democratic users engaged significantly more in cross-partisan discussions.Comment: Accepted as a full paper at the 12th International ACM Web Science Conference (WebSci 2020). Please cite the WebSci version; Second version includes corrected typo

Terrain Features and Architecture of Wolverine (Gulo gulo) Resting Burrows and Reproductive Dens on Arctic Tundra

Burrowing species rely on subterranean and subnivean sites to fulfill important life-history and behavioral processes, including predator avoidance, thermoregulation, resting, and reproduction. For these species, burrow architecture can affect the quality and success of such processes, since characteristics like tunnel width and chamber depth influence access by predators, thermal insulation, and energy spent digging. Wolverines (Gulo gulo) living in Arctic tundra environments dig burrows in snow during winter for resting sites and reproductive dens, but there are few published descriptions of such burrows. We visited 114 resting burrows and describe associated architectural characteristics and non-snow structure. Additionally, we describe characteristics of 15 reproductive den sites that we visited during winter and summer. Although many resting burrows were solely excavated in snow, most incorporated terrain structures including cliffs, talus, river shelf ice, thermokarst caves, and stream cutbanks. Burrows typically consisted of a single tunnel leading to a single chamber, though some burrows had multiple entrances, branching tunnels, or both. Tunnels in resting burrows were shorter than those in reproductive dens, and resting chambers were typically located at the deepest part of the burrow. Reproductive dens were associated with snowdrift-forming terrain features such as streambeds, cutbanks on lake edges, thermokarst caves, and boulders. Understanding such characteristics of Arctic wolverine resting and reproductive structures is critical for assessing anthropogenic impacts as snowpack undergoes climate-driven shifts.Les espèces fouisseuses dépendent de lieux enfouis sous la terre et sous la neige pour satisfaire leurs importants processus de vie et de comportement, y compris l’évitement des prédateurs, la thermorégulation, le repos et la reproduction. Pour ces espèces, l’architecture des terriers peut avoir des effets sur la qualité et la réussite des processus, car des caractéristiques comme la largeur des tunnels et la profondeur des chambres influencent l’accès aux terriers par les prédateurs, l’isolation thermique et l’énergie dépensée pour creuser. L’hiver, les carcajous (Gulo gulo) qui vivent dans les environnements de la toundra de l’Arctique creusent des terriers dans la neige afin de s’en servir comme aires de repos et comme tanières de reproduction. Cependant, peu de descriptions de tels terriers ont été publiées. Nous avons visité 114 terriers de repos, puis nous avons décrit leurs caractéristiques architecturales et les structures connexes n’étant pas recouvertes de neige. Par ailleurs, nous décrivons les caractéristiques de 15 tanières de reproduction que nous avons visitées en hiver et en été. Même si de nombreux terriers de repos ont été uniquement creusés dans la neige, la plupart des terriers incorporaient des structures topographiques, dont des falaises, des talus, de la glace de banquise, des grottes thermokarstiques et des hautes berges de cours d’eau. En général, les terriers étaient composés d’un seul tunnel menant à une seule chambre, bien que certains avaient plusieurs entrées, des galeries, ou les deux. Les tunnels des aires de repos étaient moins longs que ceux des tanières de reproduction, et les chambres de repos étaient généralement situées dans la partie la plus profonde des terriers. Les tanières de reproduction étaient installées dans des caractéristiques topographiques où s’amoncelle la neige, comme les lits de cours d’eau, les hautes berges de lacs, les grottes thermokarstiques et les rochers. Il est essentiel de comprendre les caractéristiques des structures de repos et de reproduction des carcajous de l’Arctique afin d’être en mesure d’évaluer les incidences anthropiques au moment où le manteau neigeux subit des changements liés au climat

A vortex description of the first-order phase transition in type-I superconductors

Using both analytical arguments and detailed numerical evidence we show that the first order transition in the type-I 2D Abelian Higgs model can be understood in terms of the statistical mechanics of vortices, which behave in this regime as an ensemble of attractive particles. The well-known instabilities of such ensembles are shown to be connected to the process of phase nucleation. By characterizing the equation of state for the vortex ensemble we show that the temperature for the onset of a clustering instability is in qualitative agreement with the critical temperature. Below this point the vortex ensemble collapses to a single cluster, which is a non-extensive phase, and disappears in the absence of net topological charge. The vortex description provides a detailed mechanism for the first order transition, which applies at arbitrarily weak type-I and is gauge invariant unlike the usual field-theoretic considerations, which rely on asymptotically large gauge coupling.Comment: 4 pages, 6 figures, uses RevTex. Additional references added, some small corrections to the tex

Assessing Juvenile Salmonid Passage Through Culverts: Field Research in Support of Protocol Development

The primary goal of our research this spring/ summer was to refine techniques and examine scenarios under which a standardized protocol could be applied to assess juvenile coho salmon (O. kisutch) passage through road culverts. Field evaluations focused on capture-mark- recapture methods that allowed analysis of fish movement patterns, estimates of culvert passability, and potential identification of cues inducing these movements. At this stage, 0+ age coho salmon fry 30 mm to 65 mm long (fork length) were the species and age class of interest. Ultimately, the protocol will provide rapid, statistically rigorous methods for trained personnel to perform standardized biological assessments of culvert passability to a number of juvenile salmon species. Questions to be addressed by the research include the following: ? Do hydraulic structures such as culverts restrict habitat for juvenile salmonids? ? How do existing culverts and retrofits perform relative to juvenile salmonid passage? ? Do some culvert characteristics and hydraulic conditions provide better passage than others? ? Does the culvert represent a barrier to certain size classes of fish? Recommendations addressed issues of study site selection, initial capture, marking, recapture/observations, and estimating movement

Preliminary Assessment of Potential Impacts to Dungeness Crabs from Disposal of Dredged Materials from the Columbia River

Dredging of the Columbia River navigation channel has raised concerns about dredging-related impacts on Dungeness crabs (Cancer magister). The overall objectives of this effort are to synthesize what is known about disposal effects on Dungeness crabs (Phase 1) and to offer approaches to quantify the effects, including approaches to gain a population-level perspective on any effects found in subsequent studies (Phase 2). This report documents Phase 1, which included (1) development of a conceptual model to integrate knowledge about crab biology and the physical processes occurring during disposal, (2) application of physics-based numerical modeling of the disposal event to understand the physical forces and processes to which a crab might be exposed during disposal, (3) conduct of a vulnerability analysis to identify the potential mechanisms by which crabs may be injured, and (4) recommendations of topics and approaches for future studies to assess the potential population-level effects of disposal on Dungeness crabs. The conceptual model first recognizes that disposal of dredged materials is a physically dynamic process with three aspects: (1) convective descent and bottom encounter, (2) dynamic collapse and spreading, and (3) mounding. Numerical modeling was used to assess the magnitude of the potentially relevant forces and extent of mounding in single disposal events. The modeling outcomes show that predicted impact pressure, shear stress, and mound depth are greatly reduced by discharge in deep water, and somewhat reduced at longer discharge duration. The analysis of numerical modeling results and vulnerabilities indicate that the vulnerability of crabs to compression forces under any of the disposal scenarios is low. For the deep-water disposal scenarios, the maximum forces and mounding do not appear to be sufficiently high enough to warrant concern for surge currents or burial at the depths involved (over 230 ft). For the shallow-water (45 to 65 ft), short-duration disposal scenarios, the shear force and surge currents estimated from the modeling and observed previously in the field at Palos Verdes, California appear to be sufficiently high to mobilize and transport the bottom sediment and at least juvenile crab. Behavioral response to surge currents probably occurs and may reduce the occurrence and extent of movement and any associated impacts. There evidence that burial by dredged materials can effect crab survival, but confounding factors in previous experiments preclude conclusions about thresholds and extent of effects. We recommend that future studies focus on burial effects during shallow water, short duration disposal events and take into account the potential for behavioral responses to mitigate any effects

Intratumoral T-cell receptor repertoire composition predicts overall survival in patients with pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is refractory to immune checkpoint inhibitor therapy. However, intratumoral T-cell infiltration correlates with improved overall survival (OS). Herein, we characterized the diversity and antigen specificity of the PDAC T-cell receptor (TCR) repertoire to identify novel immune-relevant biomarkers. Demographic, clinical, and TCR-beta sequencing data were collated from 353 patients across three cohorts that underwent surgical resection for PDAC. TCR diversity was calculated using Shannon Wiener index, Inverse Simpson index, and True entropy. Patients were clustered by shared repertoire specificity. TCRs predictive of OS were identified and their associated transcriptional states were characterized by single-cell RNAseq. In multivariate Cox regression models controlling for relevant covariates, high intratumoral TCR diversity predicted OS across multiple cohorts. Conversely, in peripheral blood, high abundance of T-cells, but not high diversity, predicted OS. Clustering patients based on TCR specificity revealed a subset of TCRs that predicts OS. Interestingly, these TCR sequences were more likely to encode CD