The Effect of Natural Dissolved Organic Carbon on the Acute Toxicity of Copper to Larval Freshwater Mussels (\u3cem\u3eGlochidia\u3c/em\u3e)

The present study examined the effect of dissolved organic carbon (DOC), both added and inherent, on Cu toxicity in glochidia, the larvae of freshwater mussels. Using incremental additions of natural DOC concentrate and reconstituted water, a series of acute copper toxicity tests were conducted. An increase in DOC from 0.7 to 4.4 mg C/L resulted in a fourfold increase (36–150 μg Cu/L) in the 24-h median effective concentration (EC50) and a significant linear relationship (r2=0.98, p=0.0008) between the DOC concentration and the Cu EC50 of Lampsilis siliquoidea glochidia. The ameliorating effect of added DOC on Cu toxicity was confirmed using a second mussel species, the endangered (in Canada) Lampsilis fasciola. The effect of inherent (i.e., not added) DOC on Cu toxicity was also assessed in eight natural waters (DOC 5–15 mg C/L). These experiments revealed a significant relationship between the EC50 and the concentration of inherent DOC (r2=0.79, p=0.0031) with EC50s ranging from 27 to 111 μg Cu/L. These laboratory tests have demonstrated that DOC provides glochidia with significant protection from acute Cu toxicity. The potential risk that Cu poses to mussel populations was assessed by comparing Cu and DOC concentrations from significant mussel habitats in Ontario to the EC50s. Although overall mean Cu concentration in the mussel’s habitat was well below the acutely toxic level given the concentration of DOC, episodic Cu releases in low DOC waters may be a concern for the recovery of endangered freshwater mussels. The results are examined in the context of current Cu water quality regulations including the U.S. Environmental Protection Agency’s (U.S. EPA) biotic ligand model

Moving Stories: Agency, Emotion and Practical Rationality

What is it to be an agent? One influential line of thought, endorsed by G. E. M. Anscombe and David Velleman, among others, holds that agency depends on practical rationality—the ability to act for reasons, rather than being merely moved by causes. Over the past 25 years, Velleman has argued compellingly for a distinctive view of agency and the practical rationality with which he associates it. On Velleman’s conception, being an agent consists in having the capacity to be motivated by a drive to act for reasons. Your bodily movements qualify as genuine actions insofar as they are motivated in part by your desire to behave in a way that makes sense to yourself. However, there are at least two distinct ways of spelling out what this drive towards self-intelligibility consists in, both present in Velleman’s work. It might consist in a drive towards intelligibility in causal-psychological terms: roughly, a drive to maximize the rational coherence of your psychological states. Alternatively, it might consist in a drive towards narrative intelligibility: a drive to make your ongoing activity conform to a recognizable narrative structure, where that structure is understood emotionally. Velleman originally saw these options as basically equivalent, but later came to prioritize the drive towards causal-psychological intelligibility over that towards narrative intelligibility. I argue that this gets things the wrong way round—we should instead understand our capacities to render ourselves intelligible in causal-psychological terms as built upon a bedrock of emotionally suffused narrative understanding. In doing so, we resolve several problems for Velleman’s view, and pave the way for an embodied, embedded and affective account of practical rationality and agency. According to the picture that emerges, practical rationality is essential to agency, narrative understanding is essential to practical rationality, and the rhythms and structures patterning the ebb and flow of our emotional lives are essential to narrative understanding

Estructura agraria y dinámica de pobreza rural en el Perú

A partir de un panel provincial para el periodo entre los censos agropecuarios de 1994 y el 2012, este estudio pretende esclarecer el signo de la relación entre estructura agraria y dinámicas de pobreza rural en el Perú. Los resultados descriptivos revelan que las provincias con reducciones importantes en las tasas de pobreza rural son aquellas cuyas unidades agropecuarias tenían, al inicio del periodo, una mayor cantidad de tierra agrícola - en equivalente de riego -, una estructura de propiedad menos fragmentada, una distribución de la tierra más equitativa y una mayor proporción de productores con capacidad de innovación tecnológica. Por otro lado, los resultados econométricos sugieren que un importante determinante de la dinámica de pobreza rural observada es el tamaño de la propiedad, y no la estructura agraria. Asimismo, se muestra que las provincias cuya tasa de emigración es más alta y cuya tasa de inmigración es más baja son las que sufren un mayor aumento de la pobreza rural. Por último, junto con variables que pueden estar determinando un acceso diferenciado a los mercados, persiste un impacto positivo del grado de diversificación de la actividad productiva sobre las posibilidades de generar dinámicas de reducción de la pobreza en áreas rurales

Philosophy of Hope

The philosophy of hope centers on two interlocking sets of questions. The first concerns the nature of hope. Specific questions here include how to analyze hope, how hope motivates us, and whether there is only one type of hope. The second set concerns the value of hope. Key questions here include whether and when it is good to hope and whether there is a virtue of hope. Philosophers of hope tend to proceed from the first set of questions to the second. This is a natural approach, for one might expect that you must develop a basic understanding of what hope is before you can determine its value. The structure of this chapter thus follows this approach. But readers should not be misled: there is in fact a good deal of feedback between the two sets of questions. A theory of hope is more plausible to the extent that it fits well with plausible ideas about the value of hope. So the movement from hope’s nature to its value is one of emphasis rather than a strict, step-wise process

Epidemiology of influenza-associated hospitalization in adults, Toronto, 2007/8

The purpose of this investigation was to identify when diagnostic testing and empirical antiviral therapy should be considered for adult patients requiring hospitalization during influenza seasons. During the 2007/8 influenza season, six acute care hospitals in the Greater Toronto Area participated in active surveillance for laboratory-confirmed influenza requiring hospitalization. Nasopharyngeal (NP) swabs were obtained from patients presenting with acute respiratory or cardiac illness, or with febrile illness without clear non-respiratory etiology. Predictors of influenza were analyzed by multivariable logistic regression analysis and likelihoods of influenza infection in various patient groups were calculated. Two hundred and eighty of 3,917 patients were found to have influenza. Thirty-five percent of patients with influenza presented with a triage temperature ≥38.0°C, 80% had respiratory symptoms in the emergency department, and 76% were ≥65 years old. Multivariable analysis revealed a triage temperature ≥38.0°C (odds ratio [OR] 3.1; 95% confidence interval [CI] 2.3–4.1), the presence of respiratory symptoms (OR 1.7; 95% CI 1.2–2.4), admission diagnosis of respiratory infection (OR 1.8; 95% CI 1.3–2.4), admission diagnosis of exacerbation of chronic obstructive pulmonary disease (COPD)/asthma or respiratory failure (OR 2.3; 95% CI 1.6–3.4), and admission in peak influenza weeks (OR 4.2; 95% CI 3.1–5.7) as independent predictors of influenza. The likelihood of influenza exceeded 15% in patients with respiratory infection or exacerbation of COPD/asthma if the triage temperature was ≥38.0°C or if they were admitted in the peak weeks during the influenza season. During influenza season, diagnostic testing and empiric antiviral therapy should be considered in patients requiring hospitalization if respiratory infection or exacerbation of COPD/asthma are suspected and if either the triage temperature is ≥38.0°C or admission is during the weeks of peak influenza activity

Minimalistic control of biped walking in rough terrain

Toward our comprehensive understanding of legged locomotion in animals and machines, the compass gait model has been intensively studied for a systematic investigation of complex biped locomotion dynamics. While most of the previous studies focused only on the locomotion on flat surfaces, in this article, we tackle with the problem of bipedal locomotion in rough terrains by using a minimalistic control architecture for the compass gait walking model. This controller utilizes an open-loop sinusoidal oscillation of hip motor, which induces basic walking stability without sensory feedback. A set of simulation analyses show that the underlying mechanism lies in the “phase locking” mechanism that compensates phase delays between mechanical dynamics and the open-loop motor oscillation resulting in a relatively large basin of attraction in dynamic bipedal walking. By exploiting this mechanism, we also explain how the basin of attraction can be controlled by manipulating the parameters of oscillator not only on a flat terrain but also in various inclined slopes. Based on the simulation analysis, the proposed controller is implemented in a real-world robotic platform to confirm the plausibility of the approach. In addition, by using these basic principles of self-stability and gait variability, we demonstrate how the proposed controller can be extended with a simple sensory feedback such that the robot is able to control gait patterns autonomously for traversing a rough terrain.National Science Foundation (U.S.) (grant 0746194)Swiss National Science Foundation (grant PBZH2-114461)Swiss National Science Foundation (grant PP00P2_123387/1

The Toll→NFκB Signaling Pathway Mediates the Neuropathological Effects of the Human Alzheimer's Aβ42 Polypeptide in Drosophila

Alzheimer's (AD) is a progressive neurodegenerative disease that afflicts a significant fraction of older individuals. Although a proteolytic product of the Amyloid precursor protein, the Αβ42 polypeptide, has been directly implicated in the disease, the genes and biological pathways that are deployed during the process of Αβ42 induced neurodegeneration are not well understood and remain controversial. To identify genes and pathways that mediated Αβ42 induced neurodegeneration we took advantage of a Drosophila model for AD disease in which ectopically expressed human Αβ42 polypeptide induces cell death and tissue degeneration in the compound eye. One of the genes identified in our genetic screen is Toll (Tl). It encodes the receptor for the highly conserved Tl→NFkB innate immunity/inflammatory pathway and is a fly homolog of the mammalian Interleukin-1 (Ilk-1) receptor. We found that Tl loss-of-function mutations dominantly suppress the neuropathological effects of the Αβ42 polypeptide while gain-of-function mutations that increase receptor activity dominantly enhance them. Furthermore, we present evidence demonstrating that Tl and key downstream components of the innate immunity/inflammatory pathway play a central role in mediating the neuropathological activities of Αβ42. We show that the deleterious effects of Αβ42 can be suppressed by genetic manipulations of the Tl→NFkB pathway that downregulate signal transduction. Conversely, manipulations that upregulate signal transduction exacerbate the deleterious effects of Aβ42. Since postmortem studies have shown that the Ilk-1→NFkB innate immunity pathway is substantially upregulated in the brains of AD patients, the demonstration that the Tl→NFkB signaling actively promotes the process of Αβ42 induced cell death and tissue degeneration in flies points to possible therapeutic targets and strategies

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways

Neurodegeneration, induced by misfolded tau protein, and neuroinflammation, driven by glial cells, represent the salient features of Alzheimer's disease (AD) and related human tauopathies. While tau neurodegeneration significantly correlates with disease progression, brain inflammation seems to be an important factor in regulating the resistance or susceptibility to AD neurodegeneration. Previously, it has been shown that there is a reciprocal relationship between the local inflammatory response and neurofibrillary lesions. Numerous independent studies have reported that inflammatory responses may contribute to the development of tau pathology and thus accelerate the course of disease. It has been shown that various cytokines can significantly affect the functional and structural properties of intracellular tau. Notwithstanding, anti-inflammatory approaches have not unequivocally demonstrated that inhibition of the brain immune response can lead to reduction of neurofibrillary lesions. On the other hand, our recent data show that misfolded tau could represent a trigger for microglial activation, suggesting the dual role of misfolded tau in the Alzheimer's disease inflammatory cascade. On the basis of current knowledge, we can conclude that misfolded tau is located at the crossroad of the neurodegenerative and neuroinflammatory pathways. Thus disease-modified tau represents an important target for potential therapeutic strategies for patients with Alzheimer's disease