Paying for free delivery: dependent self-employment as a measure of precarity in parcel delivery

This article explores supply chain pressures in parcel delivery and how the drive to contain costs to ‘preserve value in motion’, including the costs of failed delivery, underpins contractual differentiation. It focuses on owner-drivers and home couriers paid by delivery. It considers precarity through the lens of the labour process, while locating it within the supply chain, political economy and ‘instituted economic process’ that define it. Focus on the labour process shows how ‘self-employment’ is used to remove so-called ‘unproductive’ time from the remit of paid labour. Using Smith’s concept of double indeterminacy the article captures the dynamic relationship between those on standard and non-standard contracts and interdependency of effort power and mobility power. It exposes the apparent mobility and autonomy of dependent selfemployed drivers while suggesting that their presence, alongside the increased use of technology, reconfigures the work-effort bargain across contractual status

Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart

Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis

Reduced isolation-induced pup ultrasonic communication in mouse pups lacking brain serotonin

BACKGROUND: Serotonin (5-hydroxytryptamine, 5-HT) is a key modulatory neurotransmitter in the mammalian central nervous system (CNS) that plays an important role as a developmental signal. Several lines of evidence associate altered 5-HT signaling with psychopathology in humans, particularly neurodevelopmental disorders such as autism spectrum disorders (ASD). ASD are characterized by persistent social and communication deficits along with stereotyped and repetitive patterns of behavior, with all symptoms emerging early during development. METHODS: Here, we employed a mouse model devoid of brain 5-HT due to the lack of the gene encoding tryptophan hydroxylase 2 (Tph2), the initial and rate-limiting enzyme of 5-HT synthesis in the CNS. Tph2 null mutant (Tph2 (-/-) ) mice show normal prenatal development; however, they display for yet unknown reasons severe growth retardation during the first postnatal weeks. We investigated, therefore, whether Tph2 (-/-) mice display deficits in isolation-induced ultrasonic vocalizations (USV) as pups during early life. Isolation-induced USV are the most commonly studied behavioral measure to assess developmental delays and communication deficits in rodent models for ASD, particularly as they serve an important communicative function in coordinating mother-pup interactions. RESULTS: Tph2 (-/-) mouse pups displayed a clear deficit in the emission of isolation-induced USV, as compared to heterozygous and wildtype littermates, exactly during growth retardation onset, including reduced call numbers and deficits in call clustering and temporal organization. CONCLUSIONS: The ultrasonic communication impairment displayed by Tph2 (-/-) mouse pups is likely to result in a deficient mother-infant interaction, presumably contributing to their growth retardation phenotype, and represents a prominent feature relevant to ASD

Deep and fast live imaging with two-photon scanned light-sheet microscopy

We implemented two-photon scanned light-sheet microscopy, combining nonlinear excitation with orthogonal illumination of light-sheet microscopy, and showed its excellent performance for in vivo, cellular-resolution, three-dimensional imaging of large biological samples. Live imaging of fruit fly and zebrafish embryos confirmed that the technique can be used to image up to twice deeper than with one-photon light-sheet microscopy and more than ten times faster than with point-scanning two-photon microscopy without compromising normal biology

Serotonin is required for exercise-induced adult hippocampal neurogenesis

Voluntary wheel running has long been known to induce precursor cell proliferation in adult hippocampal neurogenesis in rodents. However, mechanisms that couple activity with the promitotic effect are not yet fully understood. Using tryptophan hydroxylase (TPH) 2 deficient (Tph2-deficient) mice that lack brain serotonin, we explored the relationship between serotonin signaling and exercise-induced neurogenesis. Surprisingly, Tph2-deficient mice exhibit normal baseline hippocampal neurogenesis but impaired activity-induced proliferation. Our data demonstrate that the proproliferative effect of running requires the release of central serotonin in young-adult and aged mice. Lack of brain serotonin further results in alterations at the stage of Sox2-positive precursor cells, suggesting physiological adaptations to changes in serotonin supply to maintain homeostasis in the neurogenic niche. We conclude that serotonin plays a direct and acute regulatory role in activity-dependent hippocampal neurogenesis. The understanding of exercise-induced neurogenesis might offer preventive but also therapeutic opportunities in depression and age-related cognitive decline

The potential contribution of disruptive low-carbon innovations to 1.5 °C climate mitigation

This paper investigates the potential for consumer-facing innovations to contribute emission reductions for limiting warming to 1.5 °C. First, we show that global integrated assessment models which characterise transformation pathways consistent with 1.5 °C mitigation are limited in their ability to analyse the emergence of novelty in energy end-use. Second, we introduce concepts of disruptive innovation which can be usefully applied to the challenge of 1.5 °C mitigation. Disruptive low-carbon innovations offer novel value propositions to consumers and can transform markets for energy-related goods and services while reducing emissions. Third, we identify 99 potentially disruptive low-carbon innovations relating to mobility, food, buildings and cities, and energy supply and distribution. Examples at the fringes of current markets include car clubs, mobility-as-a-service, prefabricated high-efficiency retrofits, internet of things, and urban farming. Each of these offers an alternative to mainstream consumer practices. Fourth, we assess the potential emission reductions from subsets of these disruptive low-carbon innovations using two methods: a survey eliciting experts’ perceptions and a quantitative scaling-up of evidence from early-adopting niches to matched segments of the UK population. We conclude that disruptive low-carbon innovations which appeal to consumers can help efforts to limit warming to 1.5 °C

UK grid electricity carbon intensity can be reduced by enhanced oil recovery with CO2 sequestration

Enhanced Oil Recovery (EOR) using CO2 coupled with Carbon Capture and Storage (CCS) can potentially accelerate CO2 storage investment through creation of a large commercial market for EOR . This article assesses how coupled a CCS-EOR scenario might contribute to decarbonization of UK grid electricity. Progressive introduction of 11 CCS-to-EOR gas-power plant projects from 2020 is estimated to store 52 Mt CO2 yr−1 from 2030. These 11 projects produce extra revenue of 1100 MM bbls of taxable EOR oil from 2020 to 2049. After each 20-year EOR project ceases, its infrastructure is paid for, and has many years of life. UK climate change targets would necessitate continued CO2 storage at low cost. Considering all greenhouse gas emissions – from power generation, CCS-EOR operations, and oil production and combustion – this project suite emits an estimated 940–1068 Mt CO2e from 2020 to 2049, while storing 1358 Mt CO2. The total average electricity grid factor in the UK reduces to 90–142 kg CO2e MWh−1, with gas generating 132 TWh yr-1. This life-cycle analysis (LCA) is unusual in linking oil production and combustion with CCS and gas-fueled electricity, yet provides a net carbon reduction, and progressively reduces net oil combustion emissions beyond 2040

Exaggerated aggression and decreased anxiety in mice deficient in brain serotonin

Serotonin is a major neurotransmitter in the central nervous system (CNS). Dysregulation of serotonin transmission in the CNS is reported to be related to different psychiatric disorders in humans including depression, impulsive aggression and anxiety disorders. The most frequently prescribed antidepressants and anxiolytics target the serotonergic system. However, these drugs are not effective in 20–30% of cases. The causes of this failure as well as the molecular mechanisms involved in the origin of psychological disorders are poorly understood. Biosynthesis of serotonin in the CNS is initiated by tryptophan hydroxylase 2 (TPH2). In this study, we used Tph2-deficient (Tph2−/−) mice to evaluate the impact of serotonin depletion in the brain on mouse behavior. Tph2−/− mice exhibited increased depression-like behavior in the forced swim test but not in the tail suspension test. In addition, they showed decreased anxiety-like behavior in three different paradigms: elevated plus maze, marble burying and novelty-suppressed feeding tests. These phenotypes were accompanied by strong aggressiveness observed in the resident–intruder paradigm. Despite carrying only one copy of the gene, heterozygous Tph2+/− mice showed only 10% reduction in brain serotonin, which was not sufficient to modulate behavior in the tested paradigms. Our findings provide unequivocal evidence on the pivotal role of central serotonin in anxiety and aggression

Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production.

Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology