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Developmental myelination is a protracted process in the mammalian brain1. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age2-4. We tested this theory in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity5. During adolescence, visual experience modulated the rate of oligodendrocyte maturation in visual cortex. To determine whether oligodendrocyte maturation in turn regulates neuronal plasticity, we genetically blocked oligodendrocyte differentiation and myelination in adolescent mice. In adult mice lacking adolescent oligodendrogenesis, a brief period of monocular deprivation led to a significant decrease in visual cortex responses to the deprived eye, reminiscent of the plasticity normally restricted to adolescence. This enhanced functional plasticity was accompanied by a greater turnover of dendritic spines and coordinated reductions in spine size following deprivation. Furthermore, inhibitory synaptic transmission, which gates experience-dependent plasticity at the circuit level, was diminished in the absence of adolescent oligodendrogenesis. These results establish a critical role for oligodendrocytes in shaping the maturation and stabilization of cortical circuits and support the concept of developmental myelination acting as a functional brake on neuronal plasticity.

Introduction: Asking family members to leave during invasive procedures has historically been common practice; however, evidence-based recommendations have altered the trend of family presence during pediatric procedures. The aim of this study was to determine factors related to family members’ choice to be present or absent during fracture reductions in a pediatric emergency department (ED), and their satisfaction with that choice.Methods: We administered role-specific, anonymous surveys to a convenience sample of patients’ family members in the ED of a Level I pediatric trauma center. All family members were given a choice of where to be during the procedure.Results: Twenty-five family members of 18 patients completed surveys. Seventeen family members chose to stay in the room. Family member satisfaction with their decision to be inside or outside the room during the procedure (median = very satisfied) was almost uniformly high and not associated with any of the following variables: previous presence during a medical procedure; provider-reported procedure difficulty, or anxiety levels. Family member perception of procedure success (median = extremely well) was also high and not associated with other variables. Location during the procedure was associated with a desire to be in the same location in the future (Fisher’s exact test, p=0.001). Common themes found among family members’ reasons for their location decisions and satisfaction levels were a desire to support the patient, high staff competence, and their right as parents to choose their location.Conclusion: Family members self-select their location during their child’s fracture reduction to high levels of satisfaction, and they considered the ability to choose their location as important.

Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here, we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4. Therefore, our study reveals the function of glia-neuron gap junctions in neuronal axon specification and shows that calcium originated from glial cells can regulate neuronal intracellular pathways through gap junctions.

Super-Earths orbiting M dwarf stars may be the most common habitable planets in the Universe. However, their habitability is threatened by intense irradiation from their host stars, which drives the escape of water to space and can lead to surface desiccation. We present simulation results of a box model incorporating deep-water cycling between interior and atmosphere and water loss to space for terrestrial planets of mass 1–8 M ⊕ orbiting in the habitable zone of a late M dwarf. Energy-limited loss decreases with planetary mass, while diffusion-limited loss increases with mass. Depending on where it orbits in the habitable zone, a 1 M ⊕ planet that starts with 3–8 Earth Oceans can end up with an Earthlike surface of oceans and exposed continents; for an 8 M ⊕ super-Earth, that range is 3–12 Earth Oceans. Planets initialized with more water end up as waterworlds with no exposed continents, while planets that start with less water have desiccated surfaces by 5 Gyr. Since the mantles of terrestrial planets can hold much more water than is currently present in Earth's atmosphere, none of our simulations result in Dune planets—such planets may be less common than previously thought. Further, more water becomes sequestered within the mantle for larger planets. A super-Earth at the inner edge of the habitable zone tends to end up as either a waterworld or with a desiccated surface; only a narrow range of initial water inventory yields an Earthlike surface. [ABSTRACT FROM AUTHOR]

Slime's increasing popularity has caused children to be more frequently exposed to glue. There is no comprehensive literature describing pediatric glue-related injuries. This study's purpose is to characterize pediatric glue-related injuries presented to U.S. emergency departments (EDs). We queried the National Electronic Injury Surveillance System for pediatric glue-related injuries from 2009 to 2018. Data were abstracted from discrete and case narrative data. Odds ratios were calculated to determine age-related differences in injuries. An estimated 18,126 pediatric patients were treated in U.S. EDs for glue-related injuries. Injury incidence increased over time. The most frequently injured body part was the eye, and the most common diagnosis was foreign body without documented sequelae. The most common injury mechanism was unintentional splash/squirt/explosion. Younger children were more likely to accidentally ingest glue; older children were more likely to sustain burns. Preventive efforts should focus on personal protective equipment, proper storage/labeling, and supervision of use. [ABSTRACT FROM AUTHOR]

Glia make up roughly half of all cells in the mammalian nervous system and play a major part in nervous system development, function, and disease. Although research in the past few decades has shed light on their morphological and functional diversity, there is still much to be known about key aspects of their development such as the generation of glial diversity and the factors governing proper morphogenesis. Glia of the nematode C. elegans possess many developmental and morphological similarities with their vertebrate counterparts and can potentially be used as a model to understand certain aspects of glial biology owing to advantages such as its genetic tractability and fully mapped cell lineage. In this review, we summarize recent progress in our understanding of genetic pathways that regulate glial development in C. elegans and discuss how some of these findings may be conserved. [ABSTRACT FROM AUTHOR]

Coordination of cell growth is essential for the development of the brain, but the molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. To investigate the mechanisms involved in glial size regulation, we used Caenorhabditis elegans amphid sheath (AMsh) glia as a model and show that a conserved cis-Golgi membrane protein eas-1/GOLT1B negatively regulates glial growth. We found that eas-1 inhibits a conserved E3 ubiquitin ligase rnf-145/RNF145, which, in turn, promotes nuclear activation of sbp-1/ SREBP, a key regulator of sterol and fatty acid synthesis, to restrict cell growth. At early developmental stages, rnf-145 in the cis-Golgi network inhibits sbp-1 activation to promote the growth of glia, and when animals reach the adult stage, this inhibition is released through an eas-1-dependent shuttling of rnf-145 from the cis-Golgi to the trans-Golgi network to stop glial growth. Furthermore, we identified long-chain polyunsaturated fatty acids (LC-PUFAs), especially eicosapentaenoic acid (EPA), as downstream products of the eas-1-rnf-145-sbp-1 pathway that functions to prevent the overgrowth of glia. Together, our findings reveal a novel and potentially conserved mechanism underlying glial size control. The molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. This study in nematodes reveals eicosapentaenoic acid as the downstream product of a pathway that functions to prevent the overgrowth of glia, suggesting a novel and potentially conserved mechanism underlying glial size control. [ABSTRACT FROM AUTHOR]

As one of the most-studied receptors, Robo plays functions in many biological processes, and its functions highly depend on Slit, the ligand of Robo. Here we uncover a Slitindependent role of Robo in glial migration and show that neurons can release an extracellular fragment of Robo upon cleavage to attract glia during migration in Caenorhabditis elegans. Furthermore, we identified the conserved cell adhesion molecule SYG-1/Neph as a receptor for the cleaved extracellular Robo fragment to mediate glial migration and SYG-1/Neph functions through regulation of the WAVE complex. Our studies reveal a previously unknown Slit-independent function and regulatory mechanism of Robo and show that the cleaved extracellular fragment of Robo can function as a ligand for SYG-1/Neph to guide glial migration. As Robo, the cleaved region of Robo, and SYG-1/Neph are all highly conserved across the animal kingdom, our findings may present a conserved Slit-independent Robo mechanism during brain development. [ABSTRACT FROM AUTHOR]

The Delaware Basin, an evaporite sequence spanning west Texas and southeast New Mexico, is well known for the mining of potassium salts, known as potash. Several companies operate mines in the region, primarily using room-and-pillar techniques. However, the region's karst topography is prone to ground subsidence and sinkhole development when triggered by anthropogenic activities. We explored a region of significant ground subsidence encompassing a potash mine. Incorporating synthetic aperture radar (SAR) images from the advanced land-observing satellite (ALOS) and Sentinel-1A sensors, we used interferometric SAR techniques to detect a significant amount of subsidence located in several distinct areas from 2007 to 2011 and from January to November 2016. To investigate the origin of this subsidence, we considered potash mining by analysing the mine operator's production records. We observed a strong correlation between the total subsidence rate in our area and the potash production rate during 2007-2011. Furthermore, we observed a considerable amount of continuous subsidence during 2016, despite the mine operator suspending potash production on 6 May 2016. As such, the observed subsidence could result in deleterious consequences throughout the region if further action is not taken. [ABSTRACT FROM AUTHOR]

Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here, we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4. Therefore, our study reveals the function of glia-neuron gap junctions in neuronal axon specification and shows that calcium originated from glial cells can regulate neuronal intracellular pathways through gap junctions. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Serviceberry or Saskatoon berry [Amelanchier alnifolia (Nutt.) Nutt. ex. M. Roem (Rosaceae)], native to the North Glacier forests of the Rocky Mountains in Montana, has been used by the Blackfeet Indian tribe in alleviation of diabetes. Anecdotally, tea made from twigs and leaves have been used for optimum health and diabetes management. However, such traditional knowledge of the medicinal properties of Amelanchier alnifolia has not been validated by scientific studies. The goal of this study was to identify potential antidiabetic mechanisms of serviceberry. Materials and Methods: Serviceberry plant samples consisting of leaves, twigs, and leaves with berries were extracted and fractionated. Ethyl acetate and water fractions were tested for inhibition of α-glucosidase activity in vitro. Diet-induced obese, hyperglycemic C57Bl6 mice were administered serviceberry leaf extract prior to sucrose-, starch-, or glucose-loading to test for α-glucosidase inhibition and decreased post-prandial glycemic response. Results: In the course of screening for potential antidiabetic mechanisms, serviceberry leaf extracts and subfractions demonstrated potent inhibitory activity against mammalian intestinal α-glucosidase activity (EC 3.2.1.20). Further, in an animal model of diet-induced obesity and hyperglycemia, serviceberry leaf subfraction demonstrated significant inhibition of intestinal α-glucosidase activity, and delayed the absorption of carbohydrates, resulting in significant lowering of post-prandial blood glucose concentrations, similar to the antidiabetic drug Acarbose™. Conclusions: These findings indicating that serviceberry leaf extract may lower post-prandial glycemic response corroborate traditional knowledge of the Blackfeet Indians of Montana, and potentially offer a complementary approach in the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Expanding upon Pimbblet's 2011 analysis of career h-indices for members of the Astronomical Society of Australia, we provide additional citation metrics which are geared to quantifying the current performance of all professional astronomers in Australia. We have trawled the staff web-pages of Australian Universities, Observatories and Research Organisations hosting professional astronomers, and identified 384 PhD-qualified, research-active, astronomers in the nation. 132 of these are not members of the Astronomical Society of Australia. Using the SAO/NASA Astrophysics Data System, we provide the three following common metrics based on publications in the first decade of the 21st century (2001-2010): h-index, author-normalised citation count and lead-author citation count. We additionally present a somewhat more inclusive analysis, applicable for many early-career researchers, that is based on publications from 2006-2010. Histograms and percentiles, plus top-performer lists, are presented for each category. Finally, building on Hirsch's empirical equation, we find that the (10-year) h-index and (10-year) total citation count T can be approximated by the relation for h >~ 5. Expanding upon Pimbblet's 2011 analysis of career h-indices for members of the Astronomical Society of Australia, we provide additional citation metrics which are geared to quantifying the current performance of all professional astronomers in Australia. [ABSTRACT FROM AUTHOR]

Previously, we described an APC-adenovirus (APC-Ad) FasL cell gene therapy method which could be used to deplete autoreactive T cells in vivo. FasL was toxic, however, and controlled regulation of FasL was not achieved. Here we describe an improved approach to delivering TNF-related apoptosis-inducing ligand (TRAIL) in vivo in which collagen II-induced (CII-incluced) arthritis-susceptible (CIA-susceptible) DBA/lj mice were treated with CII-pulsed DCs that had been transfected with a novel Ad system. The Ad was engineered to exhibit inducible TRAIL under the control of the doxycycline-inducible (DOX-inducible) tetracycline response element (TRE). Four groups of mice were treated with CII-DCAdTRAIL+DOX, CII-DC-AdTRAIL (no DOX), CII-DC-AdGFP+DOX, or DC-AdTRAIL+DOX (no CII), beginning 2 weeks after priming with CII in CFA. The incidence of arthritis and infiltration of T cells in the joint was significantly decreased in CII-DC-AdTRAIL+DOX-treated mice. The in vitro splenic T cell proliferative response and induction of IFN-γ to bovine CII stimulation were also significantly reduced in mice treated with CII-DC-AdTRAIL+DOX. AdTRAIL+DOX was not toxic to DCs or mice but could induce activated T cells to undergo apoptosis in the spleen. Our results suggest that CII-DCAdTRAILd)OX cell gene therapy is a safe and effective method for inhibiting the development of CIA. [ABSTRACT FROM AUTHOR]

Background: Developmental myelination is a protracted process in the mammalian brain. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age. We tested this hypothesis in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity., Objectives/methods: To prevent myelin progression, we conditionally deleted Myrf, a transcription factor necessary for oligodendrocyte maturation, from oligodendrocyte precursor cells (Myrf cKO) in adolescent mice. To induce experience-dependent plasticity, adult control and Myrf cKO mice were monocularly deprived by eyelid suture. Functional and structural neuronal plasticity in the visual cortex were assessed in vivo by intrinsic signal optical imaging and longitudinal two photon imaging of dendritic spines, respectively., Results: During adolescence, visual experience modulated the rate of oligodendrocyte maturation in visual cortex. Myrf deletion from oligodendrocyte precursors during adolescence led to inhibition of oligodendrocyte maturation and myelination that persisted into adulthood. Following monocular deprivation, visual cortex activity in response to visual stimulation of the deprived eye remained stable in adult control mice, as expected for post-critical period animals. By contrast, visual cortex responses to the deprived eye decreased significantly following monocular deprivation in adult Myrf cKO mice, reminiscent of the plasticity observed in adolescent mice. Furthermore, visual cortex neurons in adult Myrf cKO mice had fewer dendritic spines and a higher level of spine turnover. Finally, monocular deprivation induced spatially coordinated spine size decreases in adult Myrf cKO, but not control, mice., Conclusions: These results demonstrate a critical role for oligodendrocytes in shaping the maturation and stabilization of cortical circuits and support the concept of myelin acting as a brake on neuronal plasticity during development., Competing Interests: Competing interests: The authors declare no competing interests.

RNA-seq datasets can contain millions of intron reads per library that are typically removed from downstream analysis. Only reads overlapping annotated exons are considered to be informative since mature mRNA is assumed to be the major component sequenced, especially for poly(A) RNA libraries. In this study, we show that intron reads are informative, and through exploratory data analysis of read coverage that intron signal is representative of both pre-mRNAs and intron retention. We demonstrate how intron reads can be utilized in differential expression analysis using our index method where a unique set of differentially expressed genes can be detected using intron counts. In exploring read coverage, we also developed the superintronic software that quickly and robustly calculates user-defined summary statistics for exonic and intronic regions. Across multiple datasets, superintronic enabled us to identify several genes with distinctly retained introns that had similar coverage levels to that of neighbouring exons. The work and ideas presented in this paper is the first of its kind to consider multiple biological sources for intron reads through exploratory data analysis, minimizing bias in discovery and interpretation of results. Our findings open up possibilities for further methods development for intron reads and RNA-seq data in general., (© The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

The regulation of gliogenesis is a fundamental process for nervous system development, as the appropriate glial number and identity is required for a functional nervous system. To investigate the molecular mechanisms involved in gliogenesis, we used C. elegans as a model and identified the function of the proneural gene lin-32 / Atoh1 in gliogenesis. We found that lin-32 functions during embryonic development to negatively regulate the number of AMsh glia. The ectopic AMsh cells at least partially arise from cells originally fated to become CEPsh glia, suggesting that lin-32 is involved in the specification of specific glial subtypes. Moreover, we show that lin-32 acts in parallel with cnd-1 / NeuroD1 and ngn-1 / Neurog1 in negatively regulating an AMsh glia fate. Furthermore, expression of murine Atoh1 fully rescues lin-32 mutant phenotypes, suggesting lin-32 /Atoh1 may have a conserved role in glial specification., (Copyright © 2020 Zhang et al.)

Survival prediction is very important in medical treatment. However, recent leading research is challenged by two factors: 1) the datasets usually come with multi-modality; and 2) sample sizes are relatively small. To solve the above challenges, we developed a deep survival learning model to predict patients' survival outcomes by integrating multi-view data. The proposed network contains two sub-networks, one view-specific and one common sub-network. We designated one CNN-based and one FCN-based sub-network to efficiently handle pathological images and molecular profiles, respectively. Our model first explicitly maximizes the correlation among the views and then transfers feature hierarchies from view commonality and specifically fine-tunes on the survival prediction task. We evaluate our method on real lung and brain tumor data sets to demonstrate the effectiveness of the proposed model using data with multiple modalities across different tumor types.