Petroleum hydrocarbon contamination is a global problem which can cause long-term environmental damage and impacts water security. Natural source zone depletion (NSZD) is the natural degradation of ...such contaminants. Chemotaxis is an aspect of NSZD which is not fully understood, but one that grants microorganisms the ability to alter their motion in response to a chemical concentration gradient potentially enhancing petroleum NSZD mass removal rates. This study investigates the distribution of potentially chemotactic and hydrocarbon degrading microbes (CD) across the water table of a legacy petroleum hydrocarbon site near Perth, Western Australia in areas impacted by crude oil, diesel and jet fuel. Core samples were recovered and analysed for hydrocarbon contamination using gas chromatography. Predictive metagenomic profiling was undertaken to infer functionality using a combination of 16 S rRNA sequencing and PICRUSt2 analysis. Naphthalene contamination was found to significantly increase the occurrence of potential CD microbes, including members of the Comamonadaceae and Geobacteraceae families, which may enhance NSZD. Further work to explore and define this link is important for reliable estimation of biodegradation of petroleum hydrocarbon fuels. Furthermore, the outcomes suggest that the chemotactic parameter within existing NSZD models should be reviewed to accommodate CD accumulation in areas of naphthalene contamination, thereby providing a more accurate quantification of risk from petroleum impacts in subsurface environments, and the scale of risk mitigation due to NSZD.
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•Unprecedented view of the microbial metabolic groups at petroleum legacy site.•Chemotactic and hydrocarbon degrading bacteria (CD) are inferred in soil cores.•Naphthalene drives the occurrence of CD operational taxonomic units (OTUs).•Provides a basis for modelling to account for CD distribution and function.
This review was generated from discussions by the Pharmacologic and Somatic Treatments Section of the National Institute of Mental Health Strategic Plan for Mood Disorders Committee on advancing ...novel pharmacologic and somatic treatments for mood disorders. The opening section of the article summarizes in broad strokes, current pharmacologic treatments, and new directions in the field. Thereafter the topics focus on specific research initiatives that could advance the current therapeutics for mood disorders including new basic and clinical research in vivo human imaging procedures, somatic therapeutics, and the vast new area of pharmacogenetics. New scientific and technical opportunities exist today based on advances in basic neuroscience, opportunities in clinical testing, industry interest in advancing central nervous system therapeutics, and on active consumer advocacy groups. The question of how to bring all of these positive forces together to accelerate discovery in mood disorder thera-peutics is the topic of this article.
Neuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential ...descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons constitute more than 85 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.
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•Efficient pipeline for brain-wide imaging and reconstruction of individual neurons•Searchable database containing more than 1,000 fully reconstructed neurons•In some brain areas projection neurons fall into discrete classes•Other projection neurons form a continuum of projection types
An efficient pipeline for brain-wide imaging and morphological reconstruction of individual neurons, including long-range projection neurons, is presented along with a searchable database containing more than 1,000 fully reconstructed neurons in the mouse neocortex, hippocampus, thalamus, and hypothalamus.
The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. Partial lipid analysis is now a ...regular part of every patient's blood test and physicians readily and regularly prescribe drugs that alter the levels of major plasma lipids such as cholesterol and triglycerides. Plasma contains many thousands of distinct lipid molecular species that fall into six main categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenols. The physiological contributions of these diverse lipids and how their levels change in response to therapy remain largely unknown. As a first step toward answering these questions, we provide herein an in-depth lipidomics analysis of a pooled human plasma obtained from healthy individuals after overnight fasting and with a gender balance and an ethnic distribution that is representative of the US population. In total, we quantitatively assessed the levels of over 500 distinct molecular species distributed among the main lipid categories. As more information is obtained regarding the roles of individual lipids in health and disease, it seems likely that future blood tests will include an ever increasing number of these lipid molecules.
The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. Partial lipid analysis is now a ...regular part of every patient's blood test and physicians readily and regularly prescribe drugs that alter the levels of major plasma lipids such as cholesterol and triglycerides. Plasma contains many thousands of distinct lipid molecular species that fall into six main categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenols. The physiological contributions of these diverse lipids and how their levels change in response to therapy remain largely unknown. As a first step toward answering these questions, we provide herein an in-depth lipidomics analysis of a pooled human plasma obtained from healthy individuals after overnight fasting and with a gender balance and an ethnic distribution that is representative of the US population. In total, we quantitatively assessed the levels of over 500 distinct molecular species distributed among the main lipid categories. As more information is obtained regarding the roles of individual lipids in health and disease, it seems likely that future blood tests will include an ever increasing number of these lipid molecules.
The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, ...particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.
Inflammation and macrophage foam cells are characteristic features of atherosclerotic lesions, but the mechanisms linking cholesterol accumulation to inflammation and LXR-dependent response pathways ...are poorly understood. To investigate this relationship, we utilized lipidomic and transcriptomic methods to evaluate the effect of diet and LDL receptor genotype on macrophage foam cell formation within the peritoneal cavities of mice. Foam cell formation was associated with significant changes in hundreds of lipid species and unexpected suppression, rather than activation, of inflammatory gene expression. We provide evidence that regulated accumulation of desmosterol underlies many of the homeostatic responses, including activation of LXR target genes, inhibition of SREBP target genes, selective reprogramming of fatty acid metabolism, and suppression of inflammatory-response genes, observed in macrophage foam cells. These observations suggest that macrophage activation in atherosclerotic lesions results from extrinsic, proinflammatory signals generated within the artery wall that suppress homeostatic and anti-inflammatory functions of desmosterol.
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► Desmosterol is the dominant LXR ligand formed in macrophage foam cells ► Desmosterol integrates cholesterol and fatty acid homeostasis in the macrophage ► Desmosterol inhibits activation of inflammatory responses in macrophages ► Macrophage activation in atherosclerosis is likely due to extrinsic mediators
Cholesterol accumulation in peritoneal macrophages results in unexpected suppression, rather than activation, of inflammatory gene expression, suggesting that this response is suppressed in atherosclerotic lesions by extrinsic proinflammatory signals.
Despite a rich phenomenology, γ-ray bursts (GRBs) are divided into two classes based on their duration and spectral hardness-the long-soft and the short-hard bursts. The discovery of afterglow ...emission from long GRBs was a watershed event, pinpointing their origin to star-forming galaxies, and hence the death of massive stars, and indicating an energy release of about 1051 erg. While theoretical arguments suggest that short GRBs are produced in the coalescence of binary compact objects (neutron stars or black holes), the progenitors, energetics and environments of these events remain elusive despite recent localizations. Here we report the discovery of the first radio afterglow from the short burst GRB 050724, which unambiguously associates it with an elliptical galaxy at a redshift z = 0.257. We show that the burst is powered by the same relativistic fireball mechanism as long GRBs, with the ejecta possibly collimated in jets, but that the total energy release is 10-1,000 times smaller. More importantly, the nature of the host galaxy demonstrates that short GRBs arise from an old (> 1 Gyr) stellar population, strengthening earlier suggestions and providing support for coalescing compact object binaries as the progenitors.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Trastuzumab targets the extracellular domain of the HER2 protein. Adding trastuzumab to chemotherapy for patients with early-stage, HER2-positive breast cancer reduces the risk of recurrence and ...death, but is associated with cardiac toxicity. We investigated the long-term benefits and risks of adjuvant trastuzumab on breast cancer recurrence and cause-specific mortality.
We did a collaborative meta-analysis of individual patient data from randomised trials assessing chemotherapy plus trastuzumab versus the same chemotherapy alone. Randomised trials that enrolled women with node-negative or node-positive, operable breast cancer were included. We collected individual patient-level data on baseline characteristics, dates and sites of first distant breast cancer recurrence and any previous local recurrence or second primary cancer, and the date and underlying cause of death. Primary outcomes were breast cancer recurrence, breast cancer mortality, death without recurrence, and all-cause mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, oestrogen receptor (ER) status, and trial yielded first-event rate ratios (RRs).
Seven randomised trials met the inclusion criteria, and included 13 864 patients enrolled between February, 2000, and December, 2005. Mean scheduled treatment duration was 14·4 months and median follow-up was 10·7 years (IQR 9·5 to 11·9). The risks of breast cancer recurrence (RR 0·66, 95% CI 0·62 to 0·71; p<0·0001) and death from breast cancer (0·67, 0·61 to 0·73; p<0·0001) were lower with trastuzumab plus chemotherapy than with chemotherapy alone. Absolute 10-year recurrence risk was reduced by 9·0% (95% CI 7·4 to 10·7; p<0·0001) and 10-year breast cancer mortality was reduced by 6·4% (4·9 to 7·8; p<0·0001), with a 6·5% reduction (5·0 to 8·0; p<0·0001) in all-cause mortality, and no increase in death without recurrence (0·4%, –0·3 to 1·1; p=0·35). The proportional reduction in recurrence was largest in years 0–1 after randomisation (0·53, 99% CI 0·46 to 0·61), with benefits persisting through years 2–4 (0·73, 0·62 to 0·85) and 5–9 (0·80, 0·64 to 1·01), and little follow-up beyond year 10. Proportional recurrence reductions were similar irrespective of recorded patient and tumour characteristics, including ER status. The more high risk the tumour, the larger the absolute reductions in 5-year recurrence (eg, 5·7% 95% CI 3·1 to 8·3, 6·8% 4·7 to 9·0, and 10·7% 7·7 to 13·6 in N0, N1–3, and N4+ disease).
Adding trastuzumab to chemotherapy for early-stage, HER2-positive breast cancer reduces recurrence of, and mortality from, breast cancer by a third, with worthwhile proportional reductions irrespective of recorded patient and tumour characteristics.
Cancer Research UK, UK Medical Research Council.
Listeria monocytogenes was associated with more than 60 produce recalls, including tomato, cherry, broccoli, lemon, and lime, between 2017 and 2020. This study describes the effects of temperature, ...time, and food substrate as factors influencing L. monocytogenes behavior on whole intact raw fruits and vegetables. Ten intact whole fruit and vegetable commodities were chosen based on data gaps identified in a systematic literature review. Produce investigated belong to major commodity families: Ericaceae (blackberry, raspberry, and blueberry), Rutaceae (lemon and mandarin orange), Roseaceae (sweet cherry), Solanaceae (tomato), Brassaceae (cauliflower and broccoli), and Apiaceae (carrot). A cocktail of five L. monocytogenes strains that included clinical, food, or environmental isolates linked to foodborne outbreaks was used to inoculate intact whole fruits and vegetables. Samples were incubated at 2, 12, 22, 30, and 35°C with relative humidities matched to typical real-world conditions. Foods were sampled (n = 6) for up to 28 days, depending on temperature. Growth and decline rates were estimated using DMFit, an Excel add-in. Growth rates were compared with ComBase modeling predictions for L. monocytogenes. Almost every experiment showed initial growth, followed by subsequent decline. L. monocytogenes was able to grow on the whole intact surface of all produce tested, except for carrot. The 10 produce commodities supported growth of L. monocytogenes at 22 and 35°C. Growth and survival at 2 and 12°C varied by produce commodity. The standard deviation of the square root growth and decline rates showed significantly larger variability in both growth and decline rates within replicates as temperature increased. When L. monocytogenes growth occurred, it was conservatively modeled by ComBase Predictor, and growth was generally followed by decreases in concentration. This research will assist in understanding the risks of foodborne disease outbreaks and recalls associated with L. monocytogenes on fresh whole produce.
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