Towards an integrated understanding of low-dose chemical exposures in the development of human cancer

Both genetic and environmental factors can play a role in an individual’s cancer susceptibility, and lifestyle-related factors have been a primary focus of our prevention efforts for several decades. However, advances in our understanding of cancer causation have resulted in additional concerns being raised about exposures to chronic, low-level exposures to combinations of chemicals. In this project, a large multinational task force comprised of twelve teams was organized to review 11 hallmark phenotypes of cancer and identify priority target sites for disruption in each area. Prototypical chemical disruptors for all targets were then identified, and dose-response information was gathered. Evidence of low-dose effects for each chemical was noted and cross-hallmark effects for all targets and chemicals were documented. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). This analysis reveals that every day exposures to individual (non-carcinogenic) chemicals that act on a range of mechanisms, pathways, and systems could conspire to instigate environmental carcinogenesis. Additional research on carcinogenesis is needed and the carcinogenic potential of low-dose exposures to mixtures of chemical that act selectively to enable these hallmark phenotypes also needs to be explored. Current models of risk assessment will also need to be revisited as they are not at aligned with our current understanding of cancer biology

The Effect of Large Scale Magnetic Turbulence on the Acceleration of Electrons by Perpendicular Collisionless Shocks

We study the physics of electron acceleration at collisionless shocks that move through a plasma containing large-scale magnetic fluctuations. We numerically integrate the trajectories of a large number of electrons, which are treated as test particles moving in the time dependent electric and magnetic fields determined from 2-D hybrid simulations (kinetic ions, fluid electron). The large-scale magnetic fluctuations effect the electrons in a number of ways and lead to efficient and rapid energization at the shock front. Since the electrons mainly follow along magnetic lines of force, the large-scale braiding of field lines in space allows the fast-moving electrons to cross the shock front several times, leading to efficient acceleration. Ripples in the shock front occuring at various scales will also contribute to the acceleration by mirroring the electrons. Our calculation shows that this process favors electron acceleration at perpendicular shocks. The current study is also helpful in understanding the injection problem for electron acceleration by collisionless shocks. It is also shown that the spatial distribution of energetic electrons is similar to in-situ observations (e.g., Bale et al. 1999; Simnett et al. 2005). The process may be important to our understanding of energetic electrons in planetary bow shocks and interplanetary shocks, and explaining herringbone structures seen in some type II solar radio bursts.Comment: 23 pages, 6 figures, accepted by Ap

Simulations of Electron Acceleration at Collisionless Shocks: The Effects of Surface Fluctuations

Energetic electrons are a common feature of interplanetary shocks and planetary bow shocks, and they are invoked as a key component of models of nonthermal radio emission, such as solar radio bursts. A simulation study is carried out of electron acceleration for high Mach number, quasi-perpendicular shocks, typical of the shocks in the solar wind. Two dimensional self-consistent hybrid shock simulations provide the electric and magnetic fields in which test particle electrons are followed. A range of different shock types, shock normal angles, and injection energies are studied. When the Mach number is low, or the simulation configuration suppresses fluctuations along the magnetic field direction, the results agree with theory assuming magnetic moment conserving reflection (or Fast Fermi acceleration), with electron energy gains of a factor only 2 - 3. For high Mach number, with a realistic simulation configuration, the shock front has a dynamic rippled character. The corresponding electron energization is radically different: Energy spectra display: (1) considerably higher maximum energies than Fast Fermi acceleration; (2) a plateau, or shallow sloped region, at intermediate energies 2 - 5 times the injection energy; (3) power law fall off with increasing energy, for both upstream and downstream particles, with a slope decreasing as the shock normal angle approaches perpendicular; (4) sustained flux levels over a broader region of shock normal angle than for adiabatic reflection. All these features are in good qualitative agreement with observations, and show that dynamic structure in the shock surface at ion scales produces effective scattering and can be responsible for making high Mach number shocks effective sites for electron acceleration.Comment: 26 pages, 12 figure

The effective stability parameter for two-component galactic discs: Is 1/Q ~ 1/Q_stars + 1/Q_gas ?

The Wang-Silk approximation, 1/Q ~ 1/Q_stars + 1/Q_gas, is frequently used for estimating the effective Q parameter in two-component discs of stars and gas. Here we analyse this approximation in detail, and show how its accuracy depends on the radial velocity dispersions and Toomre parameters of the two components. We then propose a much more accurate but still simple approximation for the effective Q parameter, which further takes into account the stabilizing effect of disc thickness. Our effective Q parameter is a natural generalization of Toomre's Q, and as such can be used in a wide variety of contexts, e.g. for predicting star formation thresholds in galaxies or for measuring the stability level of galactic discs at low and high redshifts.Comment: MNRAS, in pres

Milled cereal straw accelerates earthworm (Lumbricus terrestris) growth more than selected organic amendments

Earthworms benefit agriculture by providing several ecosystem services. Therefore, strategies to increase earthworm abundance and activity in agricultural soils should be identified, and encouraged. Lumbricus terrestris earthworms primarily feed on organic inputs to soils but it is not known which organic amendments are the most effective for increasing earthworm populations. We conducted earthworm surveys in the field and carried out experiments in single-earthworm microcosms to determine the optimum food source for increasing earthworm biomass using a selection of crop residues and organic wastes available to agriculture. We found that although farmyard manure increased earthworm populations more than cereal straw in the field, straw increased earthworm biomass more than manures when milled and applied to microcosms. Earthworm growth rates were positively correlated with the calorific value of the amendment and straw had a much higher calorific value than farmyard manure, greenwaste compost, or anaerobic digestate. Reducing the particle size of straw by milling to < 3 mm made the energy in the straw more accessible to earthworms. The benefits and barriers to applying milled straw to arable soils in the field are discussed

The feeling of anger: From brain networks to linguistic expressions.

This review of the neuroscience of anger is part of The Human Affectome Project, where we attempt to map anger and its components (i.e., physiological, cognitive, experiential) to the neuroscience literature (i.e., genetic markers, functional imaging of human brain networks) and to linguistic expressions used to describe anger feelings. Given the ubiquity of anger in both its normative and chronic states, specific language is used in humans to express states of anger. Following a review of the neuroscience literature, we explore the language that is used to convey angry feelings, as well as metaphors reflecting inner states of anger experience. We then discuss whether these linguistic expressions can be mapped on to the neural circuits during anger experience and to distinct components of anger. We also identify relationships between anger components, brain networks, and other affective research relevant to motivational states of dominance and basic needs for safety

The neuroscience of sadness: A multidisciplinary synthesis and collaborative review

Sadness is typically characterized by raised inner eyebrows, lowered corners of the mouth, reduced walking speed, and slumped posture. Ancient subcortical circuitry provides a neuroanatomical foundation, extending from dorsal periaqueductal grey to subgenual anterior cingulate, the latter of which is now a treatment target in disorders of sadness. Electrophysiological studies further emphasize a role for reduced left relative to right frontal asymmetry in sadness, underpinning interest in the transcranial stimulation of left dorsolateral prefrontal cortex as an antidepressant target. Neuroimaging studies – including meta-analyses – indicate that sadness is associated with reduced cortical activation, which may contribute to reduced parasympathetic inhibitory control over medullary cardioacceleratory circuits. Reduced cardiac control may – in part – contribute to epidemiological reports of reduced life expectancy in affective disorders, effects equivalent to heavy smoking. We suggest that the field may be moving toward a theoretical consensus, in which different models relating to basic emotion theory and psychological constructionism may be considered as complementary, working at different levels of the phylogenetic hierarchy.Fil: Arias, Juan A.. Swansea University; Reino Unido. Universidad de Santiago de Compostela; EspañaFil: Williams, Claire. Swansea University; Reino UnidoFil: Raghvani, Rashmi. Swansea University; Reino UnidoFil: Aghajani, Moji. No especifíca;Fil: Baez, Sandra. Universidad de los Andes; ColombiaFil: Belzung, Catherine. Universite de Tours; FranciaFil: Booij, Linda. Concordia University Montreal; CanadáFil: Busatto, Geraldo. Universidade de Sao Paulo; BrasilFil: Chiarella, Julian. Concordia University Montreal; CanadáFil: Fu, Cynthia. University Of East London; Reino UnidoFil: Ibañez, Agustin Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina. Universidad Adolfo Ibañez; Chile. Universidad Autónoma del Caribe; ColombiaFil: Liddell, Belinda J.. University of New South Wales; AustraliaFil: Lowe, Leroy. No especifíca;Fil: Penninx, Brenda W.J.H.. No especifíca;Fil: Rosa, Pedro. Universidade de Sao Paulo; BrasilFil: Kemp, Andrew H.. Universidade de Sao Paulo; Brasil. Swansea University; Reino Unid

The neuroscience of social feelings:mechanisms of adaptive social functioning

Social feelings have conceptual and empirical connections with affect and emotion. In this review, we discuss how they relate to cognition, emotion, behavior and well-being. We examine the functional neuroanatomy and neurobiology of social feelings and their role in adaptive social functioning. Existing neuroscience literature is reviewed to identify concepts, methods and challenges that might be addressed by social feelings research. Specific topic areas highlight the influence and modulation of social feelings on interpersonal affiliation, parent-child attachments, moral sentiments, interpersonal stressors, and emotional communication. Brain regions involved in social feelings were confirmed by meta-analysis using the Neurosynth platform for large-scale, automated synthesis of functional magnetic resonance imaging data. Words that relate specifically to social feelings were identfied as potential research variables. Topical inquiries into social media behaviors, loneliness, trauma, and social sensitivity, especially with recent physical distancing for guarding public and personal health, underscored the increasing importance of social feelings for affective and second person neuroscience research with implications for brain development, physical and mental health, and lifelong adaptive functioning

Anticipatory feelings: Neural correlates and linguistic markers

This review introduces anticipatory feelings (AF) as a new construct related to the process of anticipation and prediction of future events. AF, defined as the state of awareness of physiological and neurocognitive changes that occur within an oganism in the form of a process of adapting to future events, are an important component of anticipation and expectancy. They encompass bodily-related interoceptive and affective components and are influenced by intrapersonal and dispositional factors, such as optimism, hope, pessimism, or worry. In the present review, we consider evidence from animal and human research, including neuroimaging studies, to characterize the brain structures and brain networks involved in AF. The majority of studies reviewed revealed three brain regions involved in future oriented feelings: 1) the insula; 2) the ventromedial prefrontal cortex (vmPFC); and 3) the amygdala. Moreover, these brain regions were confirmed by a meta-analysis, using a platform for large-scale, automated synthesis of fMRI data. Finally, by adopting a neurolinguistic and a big data approach, we illustrate how AF are expressed in language