Mine waters are widely regarded as environmental pollutants, but are also potential sources of valuable metals. Water draining the Maurliden mine (Sweden) is highly acidic (pH 2.3) and rich in zinc ...(∼460 mg L–1) and iron (∼400 mg L–1), and contains smaller concentrations (0.3–49 mg L–1) of other transition metals and arsenic. We have developed novel techniques that promote the concurrent amelioration of acidic waste waters and selective recovery of metals, and have used these systems to treat synthetic Maurliden mine water in the laboratory. The two major metals present were removed via controlled biomineralization: zinc as ZnS in a sulfidogenic bioreactor, and iron as schwertmannite by microbial iron oxidation and precipitation of ferric iron. A small proportion (∼11%) of the schwertmannite produced was used to remove arsenic as the initial step in the process, and other chalcophilic metals (copper, cadmium and cobalt) were removed (as sulfides) in the stage 1 metal sulfide precipitation reactor. Results from this work have demonstrated that modular biomineralization units can be effective at processing complex mine waters and generating metal products that may be recycled. The economic and environmental benefits of using an integrated biological approach for treating metal-rich mine waters is discussed.
Increased hepatocyte death contributes to the pathology of acute and chronic liver diseases. However, the role of hepatocyte pyroptosis and extracellular inflammasome release in liver disease is ...unknown.
We used primary mouse and human hepatocytes, hepatocyte-specific leucine 351 to proline Nlrp3KICreA mice, and GsdmdKO mice to investigate pyroptotic cell death in hepatocytes and its impact on liver inflammation and damage. Extracellular NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasomes were isolated from mutant NLRP3-YFP HEK cells and internalisation was studied in LX2 and primary human hepatic stellate cells. We also examined a cohort of 154 adult patients with biopsy-proven non-alcoholic fatty liver disease (Sir Charles Gairdner Hospital, Nedlands, Western Australia).
We demonstrated that primary mouse and human hepatocytes can undergo pyroptosis upon NLRP3 inflammasome activation with subsequent release of NLRP3 inflammasome proteins that amplify and perpetuate inflammasome-driven fibrogenesis. Pyroptosis was inhibited by blocking caspase-1 and gasdermin D activation. The activated form of caspase-1 was detected in the livers and in serum from patients with non-alcoholic steatohepatitis and correlated with disease severity. Nlrp3KICreA mice showed spontaneous liver fibrosis under normal chow diet, and increased sensitivity to liver damage and inflammation after treatment with low dose lipopolysaccharide. Mechanistically, hepatic stellate cells engulfed extracellular NLRP3 inflammasome particles leading to increased IL-1β secretion and α-smooth muscle actin expression. This effect was abrogated when cells were pre-treated with the endocytosis inhibitor cytochalasin B.
These results identify hepatocyte pyroptosis and release of inflammasome components as a novel mechanism to propagate liver injury and liver fibrosis development.
Our findings identify a novel mechanism of inflammation in the liver. Experiments in cell cultures, mice, and human samples show that a specific form of cell death, called pyroptosis, leads to the release of complex inflammatory particles, the NLRP3 inflammasome, from inside hepatocytes into the extracellular space. From there they are taken up by other cells and thereby mediate inflammatory and pro-fibrogenic stress signals. The discovery of this mechanism may lead to novel treatments for chronic liver diseases in the future.
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•Human and murine hepatocytes undergo pyroptosis and release NLRP3 inflammasome proteins.•Pyroptotic cell death in hepatocytes is dependent on caspase-1 and gasdermin D activation.•Caspase-1 activity is increased in livers and serum from NASH patients.•Nlrp3KICreA mice develop fibrosis and show increased sensitivity to liver damage.•Human hepatic stellate cells internalise extracellular NLRP3-YFP oligomeric particles.•Extracellular NLRP3 oligomeric particles perpetuate inflammation and fibrogenesis.
Acid mine drainage (AMD) causes environmental pollution that affects many countries having historic or current mining industries. Preventing the formation or the migration of AMD from its source is ...generally considered to be the preferable option, although this is not feasible in many locations, and in such cases, it is necessary to collect, treat, and discharge mine water. There are various options available for remediating AMD, which may be divided into those that use either chemical or biological mechanisms to neutralise AMD and remove metals from solution. Both abiotic and biological systems include those that are classed as “active” (i.e., require continuous inputs of resources to sustain the process) or “passive” (i.e., require relatively little resource input once in operation). This review describes the current abiotic and bioremediative strategies that are currently used to mitigate AMD and compares the strengths and weaknesses of each. New and emerging technologies are also described. In addition, the factors that currently influence the selection of a remediation system, and how these criteria may change in the future, are discussed.
The evolution of overconfidence JOHNSON, Dominic D. P; FOWLER, James H
Nature (London),
09/2011, Letnik:
477, Številka:
7364
Journal Article
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Confidence is an essential ingredient of success in a wide range of domains ranging from job performance and mental health to sports, business and combat. Some authors have suggested that not just ...confidence but overconfidence--believing you are better than you are in reality--is advantageous because it serves to increase ambition, morale, resolve, persistence or the credibility of bluffing, generating a self-fulfilling prophecy in which exaggerated confidence actually increases the probability of success. However, overconfidence also leads to faulty assessments, unrealistic expectations and hazardous decisions, so it remains a puzzle how such a false belief could evolve or remain stable in a population of competing strategies that include accurate, unbiased beliefs. Here we present an evolutionary model showing that, counterintuitively, overconfidence maximizes individual fitness and populations tend to become overconfident, as long as benefits from contested resources are sufficiently large compared with the cost of competition. In contrast, unbiased strategies are only stable under limited conditions. The fact that overconfident populations are evolutionarily stable in a wide range of environments may help to explain why overconfidence remains prevalent today, even if it contributes to hubris, market bubbles, financial collapses, policy failures, disasters and costly wars.
The human respiratory tract hosts a diverse community of cocirculating viruses that are responsible for acute respiratory infections. This shared niche provides the opportunity for virus–virus ...interactions which have the potential to affect individual infection risks and in turn influence dynamics of infection at population scales. However, quantitative evidence for interactions has lacked suitable data and appropriate analytical tools. Here, we expose and quantify interactions among respiratory viruses using bespoke analyses of infection time series at the population scale and coinfections at the individual host scale. We analyzed diagnostic data from 44,230 cases of respiratory illness that were tested for 11 taxonomically broad groups of respiratory viruses over 9 y. Key to our analyses was accounting for alternative drivers of correlated infection frequency, such as age and seasonal dependencies in infection risk, allowing us to obtain strong support for the existence of negative interactions between influenza and noninfluenza viruses and positive interactions among noninfluenza viruses. In mathematical simulations that mimic 2-pathogen dynamics, we show that transient immune-mediated interference can cause a relatively ubiquitous common cold-like virus to diminish during peak activity of a seasonal virus, supporting the potential role of innate immunity in driving the asynchronous circulation of influenza A and rhinovirus. These findings have important implications for understanding the linked epidemiological dynamics of viral respiratory infections, an important step towards improved accuracy of disease forecasting models and evaluation of disease control interventions.
The first national single-step, full-information (phenotype, pedigree, and marker genotype) genetic evaluation was developed for final score of US Holsteins. Data included final scores recorded from ...1955 to 2009 for 6,232,548 Holsteins cows. BovineSNP50 (Illumina, San Diego, CA) genotypes from the Cooperative Dairy DNA Repository (Beltsville, MD) were available for 6,508 bulls. Three analyses used a repeatability animal model as currently used for the national US evaluation. The first 2 analyses used final scores recorded up to 2004. The first analysis used only a pedigree-based relationship matrix. The second analysis used a relationship matrix based on both pedigree and genomic information (single-step approach). The third analysis used the complete data set and only the pedigree-based relationship matrix. The fourth analysis used predictions from the first analysis (final scores up to 2004 and only a pedigree-based relationship matrix) and prediction using a genomic based matrix to obtain genetic evaluation (multiple-step approach). Different allele frequencies were tested in construction of the genomic relationship matrix. Coefficients of determination between predictions of young bulls from parent average, single-step, and multiple-step approaches and their 2009 daughter deviations were 0.24, 0.37 to 0.41, and 0.40, respectively. The highest coefficient of determination for a single-step approach was observed when using a genomic relationship matrix with assumed allele frequencies of 0.5. Coefficients for regression of 2009 daughter deviations on parent-average, single-step, and multiple-step predictions were 0.76, 0.68 to 0.79, and 0.86, respectively, which indicated some inflation of predictions. The single-step regression coefficient could be increased up to 0.92 by scaling differences between the genomic and pedigree-based relationship matrices with little loss in accuracy of prediction. One complete evaluation took about 2h of computing time and 2.7 gigabytes of memory. Computing times for single-step analyses were slightly longer (2%) than for pedigree-based analysis. A national single-step genetic evaluation with the pedigree relationship matrix augmented with genomic information provided genomic predictions with accuracy and bias comparable to multiple-step procedures and could account for any population or data structure. Advantages of single-step evaluations should increase in the future when animals are pre-selected on genotypes.
Recent Advances in Thermoregulation Tansey, Etain A; Johnson, Christopher D
Advances in physiology education,
09/2015, Letnik:
39, Številka:
3
Journal Article
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Thermoregulation is the maintenance of a relatively constant core body temperature. Humans normally maintain a body temperature at 37°C, and maintenance of this relatively high temperature is ...critical to human survival. This concept is so important that control of thermoregulation is often the principal example cited when teaching physiological homeostasis. A basic understanding of the processes underpinning temperature regulation is necessary for all undergraduate students studying biology and biology-related disciplines, and a thorough understanding is necessary for those students in clinical training. Our aim in this review is to broadly present the thermoregulatory process taking into account current advances in this area. First, we summarize the basic concepts of thermoregulation and subsequently assess the physiological responses to heat and cold stress, including vasodilation and vasoconstriction, sweating, nonshivering thermogenesis, piloerection, shivering, and altered behavior. Current research is presented concerning the body's detection of thermal challenge, peripheral and central thermoregulatory control mechanisms, including brown adipose tissue in adult humans and temperature transduction by the relatively recently discovered transient receptor potential channels. Finally, we present an updated understanding of the neuroanatomic circuitry supporting thermoregulation.
The D‐dimer assay Johnson, Eric D.; Schell, John C.; Rodgers, George M.
American journal of hematology,
July 2019, Letnik:
94, Številka:
7
Journal Article
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D‐dimer is an indirect marker of fibrinolysis and fibrin turnover; this molecule exhibits unique properties as a biological marker of hemostatic abnormalities as well as an indicator of intravascular ...thrombosis. D‐dimer is a soluble fibrin degradation product that results from the systematic degradation of vascular thrombi through the fibrinolytic mechanism. Because of this, the D‐dimer serves as a valuable marker of activation of coagulation and fibrinolysis in a number of clinical scenarios. Most commonly, D‐dimer has been extensively investigated for excluding the diagnosis of venous thromboembolism (VTE) and is used routinely for this indication. In addition, D‐dimer has been evaluated for determining the optimal duration of anticoagulation in VTE patients, for diagnosing and monitoring disseminated intravascular coagulation, and for monitoring other conditions in which the patient is at high risk of bleeding or thrombosis. Limitations of the assay include D‐dimer elevation in a constellation of clinical scenarios (age, pregnancy, and cancer) and lack of clinical standardization.
In this paper, we provide a physical model for the origin of variations in the shapes and bump strengths of dust attenuation laws in galaxies by combining a large suite of cosmological "zoom-in" ...galaxy formation simulations with 3D Monte Carlo dust radiative transfer calculations. We model galaxies over three orders of magnitude in stellar mass, ranging from Milky Way-like systems to massive galaxies at high redshift. Critically, for these calculations, we employ a constant underlying dust extinction law in all cases and examine how the role of geometry and radiative transfer effects impacts the resultant attenuation curves. Our main results follow. Despite our usage of a constant dust extinction curve, we find dramatic variations in the derived attenuation laws. The slopes of normalized attenuation laws depend primarily on the complexities of star-to-dust geometry. Increasing fractions of unobscured young stars flatten normalized curves, while increasing fractions of unobscured old stars steepen curves. Similar to the slopes of our model attenuation laws, we find dramatic variation in the 2175 ultraviolet bump strength, including a subset of curves with little to no bump. These bump strengths are primarily influenced by the fraction of unobscured O and B stars in our model, with the impact of scattered light having only a secondary effect. Taken together, these results lead to a natural relationship between the attenuation curve slope and 2175 bump strength. Finally, we apply these results to a 25 Mpc h−1 box cosmological hydrodynamic simulation in order to model the expected dispersion in attenuation laws at integer redshifts from z = 0 to 6. A significant dispersion is expected at low redshifts and decreases toward z = 6. We provide tabulated results for the best-fit median attenuation curve at all redshifts.
Inflammasome activation plays a central role in the development of drug‐induced and obesity‐associated liver disease. However, the sources and mechanisms of inflammasome‐mediated liver damage remain ...poorly understood. Our aim was to investigate the effect of NLRP3 inflammasome activation on the liver using novel mouse models. We generated global and myeloid cell‐specific conditional mutant Nlrp3 knock‐in mice expressing the D301N Nlrp3 mutation (ortholog of D303N in human NLRP3), resulting in a hyperactive NLRP3. To study the presence and significance of NLRP3‐initiated pyroptotic cell death, we separated hepatocytes from nonparenchymal cells and developed a novel flow‐cytometry–based (fluorescence‐activated cell sorting; FACS) strategy to detect and quantify pyroptosis in vivo based on detection of active caspase 1 (Casp1)‐ and propidium iodide (PI)‐positive cells. Liver inflammation was quantified histologically by FACS and gene expression analysis. Liver fibrosis was assessed by Sirius Red staining and quantitative polymerase chain reaction for markers of hepatic stellate cell (HSC) activation. NLRP3 activation resulted in shortened survival, poor growth, and severe liver inflammation; characterized by neutrophilic infiltration and HSC activation with collagen deposition in the liver. These changes were partially attenuated by treatment with anakinra, an interleukin‐1 receptor antagonist. Notably, hepatocytes from global Nlrp3‐mutant mice showed marked hepatocyte pyroptotic cell death, with more than a 5‐fold increase in active Casp1/PI double‐positive cells. Myeloid cell‐restricted mutant NLRP3 activation resulted in a less‐severe liver phenotype in the absence of detectable pyroptotic hepatocyte cell death. Conclusions: Our data demonstrate that global and, to a lesser extent, myeloid‐specific NLRP3 inflammasome activation results in severe liver inflammation and fibrosis while identifying hepatocyte pyroptotic cell death as a novel mechanism of NLRP3‐mediated liver damage. (Hepatology 2014;59:898–910)
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