Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously ...shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression.
We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point.
The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period.
The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.
β-Site APP-cleaving enzyme 1 (BACE1) is required for the penultimate cleavage of the amyloid-β precursor protein (APP) leading to the generation of amyloid-β peptides that is central to the ...pathogenesis of Alzheimer's disease. In addition to its role in endoproteolysis of APP, BACE1 participates in the proteolytic processing of neuregulin 1 (NRG1) and influences the myelination of central and peripheral axons. Although NRG1 has been genetically linked to schizophrenia and NRG1⁺/⁻ mice exhibit a number of schizophrenia-like behavioral traits, it is not known whether altered BACE1-dependent NRG1 signaling can cause similar behavioral abnormalities. To test this hypothesis, we analyze the behaviors considered to be rodent analogs of clinical features of schizophrenia in BACE1⁻/⁻ mice with impaired processing of NRG1. We demonstrate that BACE1⁻/⁻ mice exhibit deficits in prepulse inhibition, novelty-induced hyperactivity, hypersensitivity to a glutamatergic psychostimulant (MK-801), cognitive impairments, and deficits in social recognition. Importantly, some of these manifestations were responsive to treatment with clozapine, an atypical antipsychotic drug. Moreover, although the total amount of ErbB4, a receptor for NRG1 was not changed, binding of ErbB4 with postsynaptic density protein 95 (PSD95) was significantly reduced in the brains of BACE1⁻/⁻ mice. Consistent with the role of ErbB4 in spine morphology and synaptic function, BACE1⁻/⁻ mice displayed reduced spine density in hippocampal pyramidal neurons. Collectively, our findings suggest that alterations in BACE1-dependent NRG1/ErbB4 signaling may participate in the pathogenesis of schizophrenia and related psychiatric disorders.
Climate change is leading to a disproportionately large warming in the high northern latitudes, but the magnitude and sign of the future carbon balance of the Arctic are highly uncertain. Using 40 ...terrestrial biosphere models for the Alaskan Arctic from four recent model intercomparison projects – NACP (North American Carbon Program) site and regional syntheses, TRENDY (Trends in net land atmosphere carbon exchanges), and WETCHIMP (Wetland and Wetland CH4 Inter-comparison of Models Project) – we provide a baseline of terrestrial carbon cycle uncertainty, defined as the multi-model standard deviation (σ) for each quantity that follows. Mean annual absolute uncertainty was largest for soil carbon (14.0 ± 9.2 kg C m−2), then gross primary production (GPP) (0.22 ± 0.50 kg C m−2 yr−1), ecosystem respiration (Re) (0.23 ± 0.38 kg C m−2 yr−1), net primary production (NPP) (0.14 ± 0.33 kg C m−2 yr−1), autotrophic respiration (Ra) (0.09 ± 0.20 kg C m−2 yr−1), heterotrophic respiration (Rh) (0.14 ± 0.20 kg C m−2 yr−1), net ecosystem exchange (NEE) (−0.01 ± 0.19 kg C m−2 yr−1), and CH4 flux (2.52 ± 4.02 g CH4 m−2 yr−1). There were no consistent spatial patterns in the larger Alaskan Arctic and boreal regional carbon stocks and fluxes, with some models showing NEE for Alaska as a strong carbon sink, others as a strong carbon source, while still others as carbon neutral. Finally, AmeriFlux data are used at two sites in the Alaskan Arctic to evaluate the regional patterns; observed seasonal NEE was captured within multi-model uncertainty. This assessment of carbon cycle uncertainties may be used as a baseline for the improvement of experimental and modeling activities, as well as a reference for future trajectories in carbon cycling with climate change in the Alaskan Arctic and larger boreal region.
In northern peatlands, near‐saturated surface conditions promote valuable ecosystem services such as carbon storage and drinking water provision. Peat saturated hydraulic conductivity (Ksat) plays an ...important role in maintaining wet surface conditions by moderating drainage and evapotranspiration. Peat Ksat can exhibit intense spatial variability in three dimensions and can change rapidly in response to disturbance. The development of skillful predictive equations for peat Ksat and other hydraulic properties, akin to mineral soil pedotransfer functions, remains a subject of ongoing research. We report a meta‐analysis of 2,507 northern peat samples, from which we developed linear models that predict peat Ksat from other variables, including depth, dry bulk density, von Post score (degree of humification), and categorical information such as surface microform type and peatland trophic type (e.g., bog and fen). Peat Ksat decreases strongly with increasing depth, dry bulk density, and humification; and increases along the trophic gradient from bog to fen peat. Dry bulk density and humification are particularly important predictors and increase model skill greatly; our best model, which includes these variables, has a cross‐validated r2 of 0.75 and little bias. A second model that includes humification but omits dry bulk density, intended for rapid field estimations of Ksat, also performs well (cross‐validated r2 = 0.64). Two additional models that omit several predictors perform less well (cross‐validated r2 ∼ 0.5), and exhibit greater bias, but allow Ksat to be estimated from less comprehensive data. Our models allow improved estimation of peat Ksat from simpler, cheaper measurements.
Key Points
We report skillful statistical models to estimate saturated hydraulic conductivity in northern peats from simpler measurements
Peat dry bulk density and humification (von Post score) are particularly powerful predictors
Our models represent an improvement over existing pedotransfer functions for peat saturated hydraulic conductivity
Colonization of novel habitats can result in marked phenotypic responses to the new environment that include changes in body shape and opportunities for further morphological diversification. Fishes ...have repeatedly transitioned along the benthic–pelagic axis, with varying degrees of association with the substrate. Previous work focusing on individual lineages shows that these transitions are accompanied by highly predictable changes in body form. Here, we generalize expectations drawn from this literature to study the effects of habitat on body shape diversification across 3344 marine teleost fishes. We compare rates and patterns of evolution in eight linear measurements of body shape among fishes that live in pelagic, demersal and benthic habitats. While average body shape differs between habitats, these differences are subtle compared with the high diversity of shapes found within each habitat. Benthic living increases the rate of body shape evolution and has led to numerous lineages evolving extreme body shapes, including both exceptionally wide bodies and highly elongate, eel-like forms. By contrast, we find that benthic living is associated with the slowest diversification of structures associated with feeding. Though we find that habitat can serve as an impetus for predictable trait changes, we also highlight the diversity of responses in marine teleosts to opportunities presented by major habitats.
The effects of weather, terrain, fuels on fire severity were compared using remote sensing of the severity of two large fires in south-eastern Australian forests. The probability of contrasting ...levels of fire severity (fire confined to the understorey vs. tree canopies consumed) was analysed using logistic regression. These severities equate to extremes of fire intensity (<1,500 vs. >10,000 kW m⁻¹), consequent suppression potential (high vs. nil) and potential adverse ecological impacts on vertebrate fauna and soils (low vs. high). Weather was the major influence on fire severity. Crown fire was absent under non-extreme weather and but more likely under extreme weather, particularly on ridges in vegetation unburnt for >10 years. Crown fire probability was very low in recently burnt vegetation (1-5 years) and increased at higher fuel ages. In all cases, fire severity was lower in valleys, probably due to effects of wind protection and higher fuel moisture in moderating fire behaviour. Under non-extreme weather, fires are likely to be suppressible and burn heterogeneously, due to the influence of topographic position, slope and fuel load. Under extreme weather, fires are influenced only by fuel and topographic position, and probability of suppression on accessible ridges will be low except in recently burnt (i.e. 1-5 year old) fuels. Topographically imposed variation may mitigate adverse ecological effects on arboreal fauna and soil erosion potential.
Summary
Background
Low and high birthweight is known to increase the risk of acute and longer‐term adverse outcomes, such as stillbirth, infant mortality, obesity, type 2 diabetes and cardiovascular ...diseases. Gestational dyslipidaemia is associated with a numbers of adverse birth outcomes, but evidence regarding birthweight is still inconsistent to reliably inform clinical practice and treatment recommendations.
Objective
The aim of this study was to explore the relationship between maternal gestational dyslipidaemia and neonatal health outcomes, namely, birthweight, metabolic factors and inflammatory parameters.
Methods
We searched systematically Embase, MEDLINE, PubMed, CINAHL Plus and Cochrane Library up to 1 August 2016 (with an updated search in MEDLINE at the end of July 2017) for longitudinal studies that assessed the association of maternal lipid levels during pregnancy with neonatal birthweight, or metabolic and inflammatory parameters up to 3 years old.
Results
Data from 46 publications including 31,402 pregnancies suggest that maternal high triglycerides and low high‐density‐lipoprotein cholesterol levels throughout pregnancy are associated with increased birthweight, higher risk of large for gestational age and macrosomia and lower risk of small‐for‐gestational age. The findings were consistent across the studied populations, but stronger associations were observed in women who were overweight or obese prior to pregnancy.
Conclusions
This meta‐analysis suggested that the potential under‐recognized adverse effects of intrauterine exposure to maternal dyslipidaemia may warrant further investigation into the relationship between maternal dyslipidaemia and birthweight in large prospective cohorts or in randomized trials.
Accurate estimates of gestational age (GA) at birth are important for preterm birth surveillance but can be challenging to obtain in low income countries. Our objective was to develop machine ...learning models to accurately estimate GA shortly after birth using clinical and metabolomic data.
We derived three GA estimation models using ELASTIC NET multivariable linear regression using metabolomic markers from heel-prick blood samples and clinical data from a retrospective cohort of newborns from Ontario, Canada. We conducted internal model validation in an independent cohort of Ontario newborns, and external validation in heel prick and cord blood sample data collected from newborns from prospective birth cohorts in Lusaka, Zambia and Matlab, Bangladesh. Model performance was measured by comparing model-derived estimates of GA to reference estimates from early pregnancy ultrasound.
Samples were collected from 311 newborns from Zambia and 1176 from Bangladesh. The best-performing model accurately estimated GA within about 6 days of ultrasound estimates in both cohorts when applied to heel prick data (MAE 0.79 weeks (95% CI 0.69, 0.90) for Zambia; 0.81 weeks (0.75, 0.86) for Bangladesh), and within about 7 days when applied to cord blood data (1.02 weeks (0.90, 1.15) for Zambia; 0.95 weeks (0.90, 0.99) for Bangladesh).
Algorithms developed in Canada provided accurate estimates of GA when applied to external cohorts from Zambia and Bangladesh. Model performance was superior in heel prick data as compared to cord blood data.
Gene drive: progress and prospects Wedell, N; Price, T A R; Lindholm, A K
Proceedings - Royal Society. Biological sciences/Proceedings - Royal Society. Biological Sciences,
12/2019, Letnik:
286, Številka:
1917
Journal Article
Recenzirano
Odprti dostop
Gene drive is a naturally occurring phenomenon in which selfish genetic elements manipulate gametogenesis and reproduction to increase their own transmission to the next generation. Currently, there ...is great excitement about the potential of harnessing such systems to control major pest and vector populations. If synthetic gene drive systems can be constructed and applied to key species, they may be able to rapidly spread either modifying or eliminating the targeted populations. This approach has been lauded as a revolutionary and efficient mechanism to control insect-borne diseases and crop pests. Driving endosymbionts have already been deployed to combat the transmission of dengue and Zika virus in mosquitoes. However, there are a variety of barriers to successfully implementing gene drive techniques in wild populations. There is a risk that targeted organisms will rapidly evolve an ability to suppress the synthetic drive system, rendering it ineffective. There are also potential risks of synthetic gene drivers invading non-target species or populations. This Special Feature covers the current state of affairs regarding both natural and synthetic gene drive systems with the aim to identify knowledge gaps. By understanding how natural drive systems spread through populations, we may be able to better predict the outcomes of synthetic drive release.
Altering root morphology of rice (Oryza sativa L.) cultivars could improve yields in drought-prone upland ecosystems. Marker-assisted backcross breeding was used to introgress four QTLs for root ...traits into an upland rice cultivar. The QTLs had previously been identified under experimental conditions in a different genetic background. The introgressed lines and the recurrent parent were grown for 6 years by resource-poor farmers in upland sites in Eastern India and yields recorded. In combination the QTLs significantly increased yield by 1 t ha⁻¹ under relatively favourable field conditions. In less favourable trials, the QTL effects were not detected due to greater heterogeneity in soil–water availability in very low yielding environments and consequent yield variability. Root studies under controlled conditions showed that lines with the introgressions had longer roots throughout tillering than the recurrent parent (14 cm longer 2 weeks after sowing). Therefore, both improved roots and increased yield can be attributed to the introgression of QTLs. This is the first demonstration that marker-assisted backcross breeding (MABC) to introgress multiple root QTLs identified under controlled conditions is an effective strategy to improve farmers’ yields of upland rice. The strategy was used to breed a novel upland rice cultivar that has been released in India as Birsa Vikas Dhan 111.
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