Addressing the ‘wicked problem’ of nutrient pollution requires coordinated policies spanning across diverse sectors and environmental systems. Using a case study of Canadian legislation, we apply ...semantic network analysis to identify thematic links across an inventory of 245 nutrient-related policies. Our analysis identifies twelve topics with unique types of connections across multiple facets of Canadian society. ‘Hub’ policies include broad environmental protection, land use planning, and climate-related legislation with close ties to multiple other topics. ‘Bridge’ policies create connections among otherwise disconnected topics in the network, representing opportunities to inform new policy proposals. Some legislation, such as food processing regulations, indirectly relates to nutrient use but could inform policy integration towards more coordinated and holistic nutrient management across the food system. A computational text network approach can be useful for addressing challenges in complex policy analysis, including by identifying unique entry points to guide more cross-cutting nutrient policy development.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sphingosine 1‐phosphate receptors (S1PR) are G protein‐coupled and compose a family with five subtypes, S1P1R–S1P5R. The drug Gilenya® (Novartis, Basel, Switzerland) (Fingolimod; FTY720) targets ...S1PRs and was the first oral therapy for patients with relapsing‐remitting multiple sclerosis (MS). The phosphorylated form of FTY720 (pFTY720) binds S1PRs causing initial agonism, then subsequent receptor internalization and functional antagonism. Internalization of S1P1R attenuates sphingosine 1‐phosphate (S1P)‐mediated egress of lymphocytes from lymph nodes, limiting aberrant immune function in MS. pFTY720 also exerts direct actions on neurons and glial cells which express S1PRs. In this study, we investigated the regulation of pro‐inflammatory chemokine release by S1PRs in enriched astrocytes and microglial cultures. Astrocytes and microglia were stimulated with lipopolysaccharide (LPS) and increases in C‐X‐C motif chemokine 5 (CXCL5), also known as LIX (lipopolysaccharide‐induced CXC chemokine) expression were quantified. Results showed that pFTY720 attenuated LPS‐induced CXCL5 (LIX) protein release from astrocytes, as did the S1P1R selective agonist, SEW2871. In addition, pFTY720 blocked messenger ribonucleic acid (mRNA) transcription of the chemokines, (i) CXCL5/LIX, (ii) C‐X‐C motif chemokine 10 (CXCL10) also known as interferon gamma‐induced protein 10 (IP10) and (iii) chemokine (C‐C motif) ligand 2 (CCL2) also known as monocyte chemoattractant protein 1 (MCP1). Interestingly, inhibition of sphingosine kinase attenuated LPS‐induced increases in mRNA levels of all three chemokines, suggesting that LPS‐TLR4 (Toll‐like receptor 4) signalling may enhance chemokine expression via S1P‐S1PR transactivation. Lastly, these observations were not limited to astrocytes since we also found that pFTY720 attenuated LPS‐induced release of CXCL5 from microglia. These data highlight a role for S1PR signalling in regulating the levels of chemokines in glial cells and support the notion that pFTY720 efficacy in multiple sclerosis may involve the direct modulation of astrocytes and microglia.
In addition to its immunomodulatory actions, the multiple sclerosis (MS) drug FTY720 binds to membrane sphingosine 1‐phosphate (S1P) receptors and regulates the release of inflammatory mediators from glial cells in the central nervous system. In this study, we found that lipopolysaccharide (LPS) induced the release of chemokines, in particular C‐X‐C motif chemokine 5 (CXCL5), from astrocytes and microglia and that phosphorylated FTY720 (pFTY720) blocks this process. Our data suggest that LPS induces transactivation of glial S1P receptors, in a sphingosine kinase‐dependent manner, resulting in chemokine synthesis and that pFTY720 interrupts this signalling cascade by causing intracellular accumulation of membrane S1P1R. Therefore, FTY720's therapeutic effects in MS may include modulation of neuroinflammation through direct regulation of S1PR signalling in astrocytes and microglia.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aerial predators adopt a variety of different hunting styles, with divergent flight morphologies typically adapted either to high-speed interception or manoeuvring through clutter, but how are their ...sensorimotor systems tuned in relation to habitat structure and prey behavior? Falcons intercept prey at high-speed using the same proportional navigation guidance law as homing missiles. This classical guidance law works well in the open, but performs sub-optimally against highly-manoeuvrable targets, and may not produce a feasible path through the cluttered environments frequented by hawks and other raptors. Here we identify the guidance law of n = 5 Harris' Hawks Parabuteo unicinctus chasing erratically manoeuvring artificial targets. Harris' Hawks use a mixed guidance law, coupling low-gain proportional navigation with a low-gain proportional pursuit element. This guidance law promotes tail-chasing and is not thrown off by erratic manoeuvres, making it well suited to the hawks' natural hunting style, involving close pursuit of agile prey through clutter.
Learning in a constant environment, and adapting flexibly to a changing one, through changes in reinforcement contingencies or valence-free cues, depends on overlapping circuitry that interconnects ...the prefrontal cortex (PFC) with the striatum and is subject to several forms of neurochemical modulation. We present evidence from recent studies in animals employing electrophysiological, pharmacological and lesion techniques, and neuroimaging, neuropsychological and pharmacological investigations of healthy humans and clinical patients. Dopamine (DA) neurotransmission in the medial striatum and PFC is critical for basic reinforcement learning and the integration of negative feedback during reversal learning, whilst orbitofrontal 5-hydroxytryptamine (5-HT) likely mediates this type of low level flexibility, perhaps by reducing interference from salient stimuli. The role of prefrontal noradrenaline (NA) in higher order flexibility indexed through attentional set-shifting has recently received significant empirical support, and similar avenues appear promising in the field of task switching.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The COVID-19 pandemic has led to dramatic social and economic changes in daily life. First studies report an impact on mental health of the general population showing increased levels of anxiety, ...stress and depression. In this study, we compared the impact of the pandemic on two culturally and economically similar European countries: the UK and Germany.
Participants (UK = 241, German = 541) completed an online-survey assessing COVID-19 exposure, impact on financial situation and work, substance and media consumption, mental health using the Symptom-Check-List-27 (SCL-27) and the Schizotypal Personality Questionnaire.
We found distinct differences between the two countries. UK responders reported a stronger direct impact on health, financial situation and families. UK responders had higher clinical scores on the SCL-27, and higher prevalence. Interestingly, German responders were less hopeful for an end of the pandemic and more concerned about their life-stability.
As 25% of both German and UK responders reported a subjective worsening of the general psychological symptoms and 20-50% of German and UK responders reached the clinical cut-off for depressive and dysthymic symptoms as well as anxieties, it specifically shows the need for tailored intervention systems to support large proportions of the general public.
The global number of dam constructions has increased dramatically over the past six decades and is forecast to continue to rise, particularly in less industrialized regions. Identifying development ...pathways that can deliver the benefits of new infrastructure while also maintaining healthy and productive river systems is a great challenge that requires understanding the multifaceted impacts of dams at a range of scales. New approaches and advanced methodologies are needed to improve predictions of how future dam construction will affect biodiversity, ecosystem functioning, and fluvial geomorphology worldwide, helping to frame a global strategy to achieve sustainable dam development. Here, we respond to this need by applying a graph-based river routing model to simultaneously assess flow regulation and fragmentation by dams at multiple scales using data at high spatial resolution. We calculated the cumulative impact of a set of 6374 large existing dams and 3377 planned or proposed dams on river connectivity and river flow at basin and subbasin scales by fusing two novel indicators to create a holistic dam impact matrix for the period 1930-2030. Static network descriptors such as basin area or channel length are of limited use in hierarchically nested and dynamic river systems, so we developed the river fragmentation index and the river regulation index, which are based on river volume. These indicators are less sensitive to the effects of network configuration, offering increased comparability among studies with disparate hydrographies as well as across scales. Our results indicate that, on a global basis, 48% of river volume is moderately to severely impacted by either flow regulation, fragmentation, or both. Assuming completion of all dams planned and under construction in our future scenario, this number would nearly double to 93%, largely due to major dam construction in the Amazon Basin. We provide evidence for the importance of considering small to medium sized dams and for the need to include waterfalls to establish a baseline of natural fragmentation. Our versatile framework can serve as a component of river fragmentation and connectivity assessments; as a standardized, easily replicable monitoring framework at global and basin scales; and as part of regional dam planning and management strategies.
IMPORTANCE: Polygenic risk scores (PRS) are predictors of the genetic susceptibilities of individuals to diseases. All individuals have DNA risk variants for all common diseases, but genetic ...susceptibility differences between people reflect the cumulative burden of these. Polygenic risk scores for an individual are calculated as weighted counts of thousands of risk variants that they carry, where the risk variants and their weights have been identified in genome-wide association studies. Here, we review the underlying basic science of PRS, providing a foundation for understanding the potential clinical utility and limitations of PRS. OBSERVATIONS: Polygenic risk scores can be calculated for a wide range of diseases from a saliva or blood sample using genotyping technologies that are inexpensive. While genotyping only needs to be done once for each individual in their lifetime, the PRS can be recalculated as identification of risk variants improves. On their own, PRS will never be able to establish or definitively predict future diagnoses of common complex conditions because genetic factors only contribute part of the risk, and PRS will only ever capture part of the genetic contributions. Nonetheless, just as clinical medicine uses a multitude of other predictive measures, PRS either on their own or as part of multivariable predictive algorithms could play a role. CONCLUSIONS AND RELEVANCE: Utility of PRS in clinical medicine and ethical issues related to their use should be evaluated in the context of realistic expectations of what PRS can and cannot deliver. For different diseases, PRS could have utility in community settings (stratification to better triage people into established screening programs) or could contribute to clinical decision-making for those presenting with symptoms but where formal diagnosis is unclear. In principle, PRS could contribute to treatment choices, but more data are needed to allow development of PRS in this context.
Flapping flight is the most energetically demanding form of sustained forwards locomotion that vertebrates perform. Flock dynamics therefore have significant implications for energy expenditure. ...Despite this, no studies have quantified the biomechanical consequences of flying in a cluster flock or pair relative to flying solo. Here, we compared the flight characteristics of homing pigeons (Columba livia) flying solo and in pairs released from a site 7 km from home, using high-precision 5 Hz global positioning system (GPS) and 200 Hz tri-axial accelerometer bio-loggers. As expected, paired individuals benefitted from improved homing route accuracy, which reduced flight distance by 7% and time by 9%. However, realising these navigational gains involved substantial changes in flight kinematics and energetics. Both individuals in a pair increased their wingbeat frequency by 18% by decreasing the duration of their upstroke. This sharp increase in wingbeat frequency caused just a 3% increase in airspeed but reduced the oscillatory displacement of the body by 22%, which we hypothesise relates to an increased requirement for visual stability and manoeuvrability when flying in a flock or pair. The combination of the increase in airspeed and a higher wingbeat frequency would result in a minimum 2.2% increase in the total aerodynamic power requirements if the wingbeats were fully optimised. Overall, the enhanced navigational performance will offset any additional energetic costs as long as the metabolic power requirements are not increased above 9%. Our results demonstrate that the increases in wingbeat frequency when flying together have previously been underestimated by an order of magnitude and force reinterpretation of their mechanistic origin. We show that, for pigeons flying in pairs, two heads are better than one but keeping a steady head necessitates energetically costly kinematics.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The architectural and morphological adaptations of the hamstrings in response to training with different exercises have not been explored.
To evaluate changes in biceps femoris long head (BF
) ...fascicle length and hamstring muscle size following 10-weeks of Nordic hamstring exercise (NHE) or hip extension (HE) training.
30 recreationally active male athletes (age, 22.0±3.6 years; height, 180.4±7 cm; weight, 80.8±11.1 kg) were allocated to 1 of 3 groups: (1) HE training (n=10), NHE training (n=10), or no training (control, CON) (n=10). BF
fascicle length was assessed before, during (Week 5) and after the intervention with a two-dimensional ultrasound. Hamstring muscle size was determined before and after training via MRI.
Compared with
, BF
fascicles were lengthened in the NHE and HE groups at
(d=1.12-1.39, p<0.001) and
(d=1.77-2.17, p<0.001) and these changes did not differ significantly between exercises (d=0.49-0.80, p=0.279-0.976). BF
volume increased more for the HE than the NHE (d=1.03, p=0.037) and CON (d=2.24, p<0.001) groups. Compared with the CON group, both exercises induced significant increases in semitendinosus volume (d=2.16-2.50, ≤0.002) and these increases were not significantly different (d=0.69, p=0.239).
NHE and HE training both stimulate significant increases in BF
fascicle length; however, HE training may be more effective for promoting hypertrophy in the BF
.
Abstract
Nitrogen (N) footprints are one method to quantify consumer driven reactive nitrogen (Nr) emissions. Canada is a highly urbanized yet economically natural resource-dependent country, ...providing an illustrative case study to examine attribution of Nr emissions to per capita consumption, either domestically or abroad. Yet, considered only at the national scale, N footprints may obscure absolute and relative contributions of local drivers to Nr emissions. We apply a top-down N footprint approach drawing from national N budgets, emissions inventories, and agricultural statistics to estimate sub-national (provincial) drivers of Nr emissions across Canada. We calculate per capita provincial Nr footprints from four primary sectors in 2018: (a) crop production, (b) animal production, (c) wastewater treatment, and (d) fossil fuel burning. We estimate that Canada’s total N footprint is 995.7 Gg Nr yr
−1
, which equates to an average per capita footprint nationally of 27.1 kg Nr capita
−1
yr
−1
. The largest national contributions come from a few key (sub)sectors, including transport, beef consumption, and wastewater treatment. Provincial per capita N footprints vary widely, with the largest (Saskatchewan 50.3 kg Nr cap
−1
yr
−1
) more than double the smallest (Ontario 22.0 kg Nr cap
−1
yr
−1
). Most variation across provinces is due to the fossil fuels sector, including emissions from energy generation and the oil and gas industry. We therefore compare our top-down approach for the fossil fuels sector with bottom-up N footprints and territorial emissions methodologies. Per capita N emissions vary considerably across these approaches. For example, Alberta’s per-capita fossil fuel Nr emissions are 45.9, 23.0, and 6.3 kg Nr cap
−1
yr
−1
using territorial, top-down and bottom-up footprint approaches, respectively. This analysis demonstrates the challenges of attributing Nr emission for export-oriented economies. Our study provides novel insights on sub-national drivers of Nr emissions, emphasizing the need to consider how heterogeneous geographic contexts contribute to national N footprints.
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