Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4.

Postnatal/adult neural stem cells (NSCs) within the rodent subventricular zone (SVZ; also called subependymal zone) generate doublecortin (Dcx)(+) neuroblasts that migrate and integrate into olfactory bulb circuitry. Continuous production of neuroblasts is controlled by the SVZ microenvironmental niche. It is generally thought that enhancing the neurogenic activities of endogenous NSCs may provide needed therapeutic options for disease states and after brain injury. However, SVZ NSCs can also differentiate into astrocytes. It remains unclear whether there are conditions that favour astrogenesis over neurogenesis in the SVZ niche, and whether astrocytes produced there have different properties compared with astrocytes produced elsewhere in the brain. Here we show in mice that SVZ-generated astrocytes express high levels of thrombospondin 4 (Thbs4), a secreted homopentameric glycoprotein, in contrast to cortical astrocytes, which express low levels of Thbs4. We found that localized photothrombotic/ischaemic cortical injury initiates a marked increase in Thbs4(hi) astrocyte production from the postnatal SVZ niche. Tamoxifen-inducible nestin-creER(tm)4 lineage tracing demonstrated that it is these SVZ-generated Thbs4(hi) astrocytes, and not Dcx(+) neuroblasts, that home-in on the injured cortex. This robust post-injury astrogenic response required SVZ Notch activation modulated by Thbs4 via direct Notch1 receptor binding and endocytosis to activate downstream signals, including increased Nfia transcription factor expression important for glia production. Consequently, Thbs4 homozygous knockout mice (Thbs4(KO/KO)) showed severe defects in cortical-injury-induced SVZ astrogenesis, instead producing cells expressing Dcx migrating from SVZ to the injury sites. These alterations in cellular responses resulted in abnormal glial scar formation after injury, and significantly increased microvascular haemorrhage into the brain parenchyma of Thbs4(KO/KO) mice. Taken together, these findings have important implications for post-injury applications of endogenous and transplanted NSCs in the therapeutic setting, as well as disease states where Thbs family members have important roles

Influence of Wheat Straw Pelletizing and Inclusion Rate in Dry Rolled or Steam-flaked Corn-based Finishing Diets on Characteristics of Digestion for Feedlot Cattle.

Eight Holstein steers (216±48 kg body weight) fitted with ruminal and duodenal cannulas were used to evaluate effects of wheat straw processing (ground vs pelleted) at two straw inclusion rates (7% and 14%; dry matter basis) in dry rolled or steam-flaked corn-based finishing diets on characteristics of digestion. The experimental design was a split plot consisting of two simultaneous 4×4 Latin squares. Increasing straw level reduced ruminal (p<0.01) and total tract (p = 0.03) organic matter (OM) digestion. As expected, increasing wheat straw level from 7% to 14% decreased (p<0.05) ruminal and total tract digestion of OM. Digestion of neutral detergent fiber (NDF) and starch, per se, were not affected (p>0.10) by wheat straw level. Likewise, straw level did not influence ruminal acetate and propionate molar proportions or estimated methane production (p>0.10). Pelleting straw did not affect (p≥0.48) ruminal digestion of OM, NDF, and starch, or microbial efficiency. Ruminal feed N digestion was greater (7.4%; p = 0.02) for ground than for pelleted wheat straw diets. Although ruminal starch digestion was not affected by straw processing, post-ruminal (p<0.01), and total-tract starch (p = 0.05) digestion were greater for ground than for pelleted wheat straw diets, resulting in a tendency for increased post-ruminal (p = 0.06) and total tract (p = 0.07) OM digestion. Pelleting wheat straw decreased (p<0.01) ruminal pH, although ruminal volatile fatty acids (VFA) concentration and estimated methane were not affected (p≥0.27). Ruminal digestion of OM and starch, and post-ruminal and total tract digestion of OM, starch and N were greater (p<0.01) for steam-flaked than for dry rolled corn-based diets. Ruminal NDF digestion was greater (p = 0.02) for dry rolled than for steam-flaked corn, although total tract NDF digestion was unaffected (p = 0.94). Ruminal microbial efficiency and ruminal degradation of feed N were not affected (p>0.14) by corn processing. However, microbial N flow to the small intestine and ruminal N efficiency (non-ammonia N flow to the small intestine/N intake) were greater (p<0.01) for steam-flaked than for dry rolled corn-based diets. Ruminal pH and total VFA concentration were not affected (p≥ 0.16) by corn processing method. Compared with dry rolled corn, steam-flaked corn-based diets resulted in decreased acetate:propionate molar ratio (p = 0.02). It is concluded that at 7% or 14% straw inclusion rate, changes in physical characteristics of wheat straw brought about by pelleting negatively impact OM digestion of both steam-flaked and dry-rolled corn-based finishing diets. This effect is due to decreased post-ruminal starch digestion. Replacement of ground straw with pelleted straw also may decrease ruminal pH

Adolescent brain cognitive development (ABCD) study: Overview of substance use assessment methods.

One of the objectives of the Adolescent Brain Cognitive Development (ABCD) Study (https://abcdstudy.org/) is to establish a national longitudinal cohort of 9 and 10 year olds that will be followed for 10 years in order to prospectively study the risk and protective factors influencing substance use and its consequences, examine the impact of substance use on neurocognitive, health and psychosocial outcomes, and to understand the relationship between substance use and psychopathology. This article provides an overview of the ABCD Study Substance Use Workgroup, provides the goals for the workgroup, rationale for the substance use battery, and includes details on the substance use module methods and measurement tools used during baseline, 6-month and 1-year follow-up assessment time-points. Prospective, longitudinal assessment of these substance use domains over a period of ten years in a nationwide sample of youth presents an unprecedented opportunity to further understand the timing and interactive relationships between substance use and neurocognitive, health, and psychopathology outcomes in youth living in the United States

The public health benefit and burden of mass drug administration programs in Vietnamese schoolchildren : impact of mebendazole

Background: Mass anthelmintic drug administration is recommended in developing countries to address infection by soil-transmitted helminthiases (STH). We quantified the public health benefit of treatment with mebendazole in eight million Vietnamese children aged 5–14 years from 2006 to 2011. This was compared to the environmental impact of the pharmaceutical supply chain of mebendazole, as the resource use and emissions associated with pharmaceutical production can be associated with a public health burden, e.g. through emissions of fine particulate matter. Methodology: Through Markov modelling the disability due to STH was quantified for hookworm, Ascaris lumbricoides and Trichuris trichiura. For each worm type, four levels of intensity of infection were included: none, light, medium and heavy. The treatment effect on patients was quantified in Disability-Adjusted Life Years (DALYs). The public health burden induced by the pharmaceutical supply chain of mebendazole was quantified in DALYs through Life Cycle Assessment. Principal findings: Compared to ‘no treatment’, the modelled results of five-year treatment averted 116,587 DALYs (68% reduction) for the three worms combined and largely driven by A. lumbricoides. The main change in DALYs occurred in the first year of treatment, after which the results stabilized. The public health burden associated with the pharmaceutical supply chain was 6 DALYs. Conclusions: The public health benefit of the Mass Drug Administration (MDA) averted substantially more DALYs than those induced by the pharmaceutical supply chain. These results were verified in a sensitivity analysis. The starting prevalence for each worm was the most sensitive model parameter. This methodology is useful for policymakers interested in a holistic approach towards the public health performance of MDA programs, enveloping both the treatment benefit received by the patient and the public health burden associated with the resource consumption and environmental emissions of the pharmaceutical production and supply chain

Vehicle Signal Analysis Using Artificial Neural Networks for a Bridge Weigh-in-Motion System

This paper describes the procedures for development of signal analysis algorithms using artificial neural networks for Bridge Weigh-in-Motion (B-WIM) systems. Through the analysis procedure, the extraction of information concerning heavy traffic vehicles such as weight, speed, and number of axles from the time domain strain data of the B-WIM system was attempted. As one of the several possible pattern recognition techniques, an Artificial Neural Network (ANN) was employed since it could effectively include dynamic effects and bridge-vehicle interactions. A number of vehicle traveling experiments with sufficient load cases were executed on two different types of bridges, a simply supported pre-stressed concrete girder bridge and a cable-stayed bridge. Different types of WIM systems such as high-speed WIM or low-speed WIM were also utilized during the experiments for cross-checking and to validate the performance of the developed algorithms

The structure of cognition in 9 and 10 year-old children and associations with problem behaviors: Findings from the ABCD study\u27s baseline neurocognitive battery

The Adolescent Brain Cognitive Development (ABCD) study is poised to be the largest single-cohort long-term longitudinal study of neurodevelopment and child health in the United States. Baseline data on N= 4521 children aged 9-10 were released for public access on November 2, 2018. In this paper we performed principal component analyses of the neurocognitive assessments administered to the baseline sample. The neurocognitive battery included seven measures from the NIH Toolbox as well as five other tasks. We implemented a Bayesian Probabilistic Principal Components Analysis (BPPCA) model that incorporated nesting of subjects within families and within data collection sites. We extracted varimax-rotated component scores from a three-component model and associated these scores with parent-rated Child Behavior Checklist (CBCL) internalizing, externalizing, and stress reactivity. We found evidence for three broad components that encompass general cognitive ability, executive function, and learning/memory. These were significantly associated with CBCL scores in a differential manner but with small effect sizes. These findings set the stage for longitudinal analysis of neurocognitive and psychopathological data from the ABCD cohort as they age into the period of maximal adolescent risk-taking

Incidence of acute lower respiratory tract disease hospitalisations, including pneumonia, among adults in Bristol, UK, 2019, estimated using both a prospective and retrospective methodology

OBJECTIVES: To determine the disease burden of acute lower respiratory tract disease (aLRTD) and its subsets (pneumonia, lower respiratory tract infection (LRTI) and heart failure) in hospitalised adults in Bristol, UK. SETTING: Single-centre, secondary care hospital, Bristol, UK. DESIGN: We estimated aLRTD hospitalisations incidence in adults (≥18 years) in Bristol, UK, using two approaches. First, retrospective International Classification of Diseases 10th revision (ICD-10) code analysis (first five positions/hospitalisation) identified aLRTD events over a 12-month period (March 2018 to February 2019). Second, during a 21-day prospective review (19 August 2019 to 9 September 2019), aLRTD admissions were identified, categorised by diagnosis and subsequently annualised. Hospital catchment denominators were calculated using linked general practice and hospitalisation data, with each practice’s denominator contribution calculated based on practice population and per cent of the practices’ hospitalisations admitted to the study hospital. PARTICIPANTS: Prospective review: 1322 adults screened; 410 identified with aLRTD. Retrospective review: 7727 adult admissions. PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence of aLRTD and its subsets in the adult population of Southmead Hospital, Bristol UK. RESULTS: Based on ICD-10 code analysis, annual incidences per 100 000 population were: aLRTD, 1901; pneumonia, 591; LRTI, 739; heart failure, 402. aLRTD incidence was highest among those ≥65 years: 65–74 (3684 per 100 000 adults), 75–84 (6962 per 100 000 adults) and ≥85 (11 430 per 100 000 adults). During the prospective review, 410/1322 (31%) hospitalised adults had aLRTD signs/symptoms and annualised incidences closely replicated retrospective analysis results. CONCLUSIONS: The aLRTD disease burden was high, increasing sharply with age. The aLRTD incidence is probably higher than estimated previously due to criteria specifying respiratory-specific symptoms or radiological change, usage of only the first diagnosis code and mismatch between case count sources and population denominators. This may have significant consequences for healthcare planning, including usage of current and future vaccinations against respiratory infection

Using species A rotavirus reverse genetics to engineer chimeric viruses expressing SARS-CoV-2 spike epitopes:Heterologous viral peptide expression by rotavirus A

Species A rotavirus (RVA) vaccines based on live attenuated viruses are used worldwide in humans. The recent establishment of a reverse genetics system for rotoviruses (RVs) has opened the possibility of engineering chimeric viruses expressing heterologous peptides from other viral or microbial species in order to develop polyvalent vaccines. We tested the feasibility of this concept by two approaches. First, we inserted short SARS-CoV-2 spike peptides into the hypervariable region of the simian RV SA11 strain viral protein (VP) 4. Second, we fused the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, or the shorter receptor binding motif (RBM) nested within the RBD, to the C terminus of nonstructural protein (NSP) 3 of the bovine RV RF strain, with or without an intervening Thosea asigna virus 2A (T2A) peptide. Mutating the hypervariable region of SA11 VP4 impeded viral replication, and for these mutants, no cross-reactivity with spike antibodies was detected. To rescue NSP3 mutants, we established a plasmid-based reverse genetics system for the bovine RV RF strain. Except for the RBD mutant that demonstrated a rescue defect, all NSP3 mutants delivered endpoint infectivity titers and exhibited replication kinetics comparable to that of the wild-type virus. In ELISAs, cell lysates of an NSP3 mutant expressing the RBD peptide showed cross-reactivity with a SARS-CoV-2 RBD antibody. 3D bovine gut enteroids were susceptible to infection by all NSP3 mutants, but cross-reactivity with SARS-CoV-2 RBD antibody was only detected for the RBM mutant. The tolerance of large SARS-CoV-2 peptide insertions at the C terminus of NSP3 in the presence of T2A element highlights the potential of this approach for the development of vaccine vectors targeting multiple enteric pathogens simultaneously. IMPORTANCE We explored the use of rotaviruses (RVs) to express heterologous peptides, using SARS-CoV-2 as an example. Small SARS-CoV-2 peptide insertions (<34 amino acids) into the hypervariable region of the viral protein 4 (VP4) of RV SA11 strain resulted in reduced viral titer and replication, demonstrating a limited tolerance for peptide insertions at this site. To test the RV RF strain for its tolerance for peptide insertions, we constructed a reverse genetics system. NSP3 was C-terminally tagged with SARS-CoV-2 spike peptides of up to 193 amino acids in length. With a T2A-separated 193 amino acid tag on NSP3, there was no significant effect on the viral rescue efficiency, endpoint titer, and replication kinetics. Tagged NSP3 elicited cross-reactivity with SARS-CoV-2 spike antibodies in ELISA. We highlight the potential for development of RV vaccine vectors targeting multiple enteric pathogens simultaneously

Changing teaching practice: The evolving purpose of the teacher in higher education

open access journalIn this Editorial, we take the opportunity to expand on the second Journal of University Teaching and Learning theme, Developing Teaching Practice. Building on Editorial 18(4), which articulated changes to higher education in the period roughly between 1980 and 2021, we believe it is pertinent to explore the changing conceptions of academic as ‘teacher’. We use Engeström’s cultural-historical activity theory as a lens to consider how higher education teachers are situated in the current context of rapid changes arising from the COVID-19 pandemic. We explore possible future purposes of higher education to consider flow-on impacts on the purpose of its teachers and how their roles might change to accommodate future expectations. We assert the need to challenge the notion of the academic as a person who is recruited into higher education largely because of their subject matter expertise while maintaining strong commitment to teaching expertise that is grounded in scholarship, critical selfreflection, and agency. In our various teaching and leadership roles, and consistent with the literature, we have observed paradoxical outcomes from the nexus between risk, innovation and development, driving risk aversity and risk management, with significant (contradictory) impacts on teaching, teachers and student learning. The barriers to implementing innovative curricula include questions of do students get a standardised and ‘safe’ educational experience or are they challenged and afforded the opportunity to transform and grow? Are they allowed to fail? Related, do teachers have genuine agency, as an educator, or are they positioned as agents of a higher education system? We explore these questions and invite our readers to engage in serious reflexivity and identify strategies that help them question their attitudes, thought processes, and assumptions about teaching and student learning. We welcome papers that contribute values-based conversations and explore ways of dealing with and adapting to change in our teaching practices, case studies of learning through failure, change and adaptation and the development of the field

Study of the temperature dependence of the giant electric field-induced strain in Nb-doped BNT-BT-BKT piezoceramics

Dense Bi0.487Na0.427K0.06Ba0.026TiO3 (BNKBT) and Nb-doped Bi0.487Na0.427K0.06Ba0.026Ti0.98Nb0.02O3 (Nb-BNKBT) ceramics were prepared by the solid state reaction route. BNKBT is a non-ergodic relaxor and exhibits a piezoelectric response typical for a ferroelectric, whereas Nb-BNKBT is an ergodic relaxor and exhibits an electromechanical response typical for an incipient ferroelectric. The incorporation of 2 mol% of Nb into the BNKBT lattice is accompanied by an enhancement of the room-temperature unipolar field-induced strain from 0.19% to 0.43% at 75 kV/cm. BNKBT shows a depolarisation temperature of 90C, above which an electrostrictive response is observed, whereas Nb-BNKBT shows an electrostrictive response in the entire temperature range studied. At 40 kV/cm, Nb-BNKBT exhibits a temperature stable electromechanical response in comparison with undoped BNKBT, but it worsens under higher electric fields. These results may motivate further investigations on the impact of minor doping and driving electric fields on the electromechanical response of Bi0.5Na0.5TiO3–Bi0.5K0.5TiO3–BaTiO3-based ceramics